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Sample records for rat hippocampal pyramidal

  1. EFFECTS OF GLUTAMATE ON SODIUM CHANNEL IN ACUTELY DISSOCIATED HIPPOCAMPAL CA1 PYRAMIDAL NEURONS OF RATS

    Institute of Scientific and Technical Information of China (English)

    高宾丽; 伍国锋; 杨艳; 刘智飞; 曾晓荣

    2011-01-01

    Objective To observe the effects of glutamate on sodium channel in acutely dissociated hippocampal CA1 pyramidal neurons of rats.Methods Voltage-dependent sodium currents (INa) in acutely dissociated hippocampal CA1 pyramidal neurons of neonate rats were recorded by whole-cell patchclamp of the brain slice technique when a series of doses of glutamate (100-1000μmol/L) were applied.Results Different concentrations of glutamate could inhibit INa,and higher concentration of glutamate affected greater inhibitio...

  2. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

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    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  3. Electrophysiological actions of cyclosporin A and tacrolimus on rat hip-pocampal CA1 pyramidal neurons

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    Yong YU; Xue-qin CHEN; Yao-yuan CUI; Guo-yuan HU

    2007-01-01

    Aim: The aim of the present study was to investigate the electrophysiological actions of cyclosporin A (CsA) and tacrolimus (FK506) on neurons in the brain, and to elucidate the relevant mechanisms. Methods: Whole-cell current-clamp recording was made in CA1 pyramidal neurons in rat hippocampal slices; whole- cell voltage-clamp recording was made in dissociated hippocampal CA1 pyrami- dal neurons of rats. Results: CsA (100 μmol/L) and FKS06 (50 μmol/L) did not significantly alter the passive electrical properties of hippocampal CA1 pyramidal neurons, but slowed down the repolarizing phase of the action potential. CsA (10-100 μmol/L) selectively inhibited the delayed rectifier K~ current (IK,) in a concentration-dependent manner. CsA did not affect the kinetic properties of IK. Intracellular dialysis of CsA (100 μmol/L) had no effect on IK. The inhibition of IK by CsA (100/μmol/L) persisted under the low Ca2+ conditions that blocked the basal activity of calcineurin. Conclusion: CsA exerted calcineurin-independent inhibition on the IK in rat hippocampal pyramidal neurons. Taken together with our previous finding with FK506, it is conceivable that the spike broadening caused by the immunosuppressant drugs is due to direct inhibition on the IK.

  4. Somatosensory stimulation suppresses the excitability of pyramidal cells in the hippocampal CA1 region in rats

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    Yang Wang; Zhouyan Feng; Jing Wang; Xiaojing Zheng

    2014-01-01

    The hippocampal region of the brain is important for encoding environment inputs and memory formation. However, the underlying mechanisms are unclear. To investigate the behavior of indi-vidual neurons in response to somatosensory inputs in the hippocampal CA1 region, we recorded and analyzed changes in local ifeld potentials and the ifring rates of individual pyramidal cells and interneurons during tail clamping in urethane-anesthetized rats. We also explored the mechanisms underlying the neuronal responses. Somatosensory stimulation, in the form of tail clamping, chan-ged local ifeld potentials into theta rhythm-dominated waveforms, decreased the spike ifring of py-ramidal cells, and increased interneuron ifring. In addition, somatosensory stimulation attenuated orthodromic-evoked population spikes. These results suggest that somatosensory stimulation sup-presses the excitability of pyramidal cells in the hippocampal CA1 region. Increased inhibition by local interneurons might underlie this effect. These ifndings provide insight into the mechanisms of signal processing in the hippocampus and suggest that sensory stimulation might have thera-peutic potential for brain disorders associated with neuronal hyperexcitability.

  5. Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons

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    TAN Hong-yu; SUN Li-na; WANG Xiao-liang; YE Tie-hu

    2010-01-01

    Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current (I_((K(DR))) and transient outward potassium current (I_((K(A))) in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student's paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited I_(K(DR)) by 49.2% at +40 mV when depolarized from -110 mV (P 0.05). The IC_(50) value of etomidate for blocking I_(K(DR)) was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V_(1/2) of activation curve was shifted from (17.3±1.5) mV to (10.7±9.9) mV (n=8, P <0.05), the V_(1/2) of inactivation curve was shifted from (-18.3±2.2) mV to (-45.3±9.4) mV (n=8, P <0.05). Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of I_(K(DR)) to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited I_(K(DR)) but not I_(K(A)) in rat hippocampal pyramidal neurons. I_(K(DR)) was inhibited by etomidate in a concentration-dependent manner, while I_(K(A)) remained unaffected.

  6. Persistent sodium current properties in hippocampal CA1 pyramidal neurons of young and adult rats.

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    Lunko, Oleksii; Isaev, Dmytro; Maximyuk, Oleksandr; Ivanchick, Gleb; Sydorenko, Vadym; Krishtal, Oleg; Isaeva, Elena

    2014-01-24

    Persistent tetrodotoxin-sensitive sodium current (INaP) plays an important role in cellular and neuronal network excitability in physiological conditions and under different pathological circumstances. However, developmental changes in INaP properties remain largely unclear. In the present study using whole cell patch clamp technique we evaluated INaP properties in CA1 hippocampal pyramidal neurons isolated from young (postnatal day (P) 12-16) and adult (P60-75) rats. We show that the INaP density is substantially larger in the adult group. Although INaP inactivation characteristics were found to be similar in both groups, voltage dependence of INaP activation is shifted to more negative membrane potentials (young: -48.6±0.5mV vs. adult: -52.4±0.2mV, p<0.01). Our data indicates the increase of INaP contribution in the basal membrane sodium conductivity in the mature hippocampus.

  7. Repeated transcranial magnetic stimulation prevents kindling-induced changes in electrophysiological properties of rat hippocampal CA1 pyramidal neurons.

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    Shojaei, A; Semnanian, S; Janahmadi, M; Moradi-Chameh, H; Firoozabadi, S M; Mirnajafi-Zadeh, J

    2014-11-01

    The mechanisms underlying antiepileptic or antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS) are poorly understood. In this study, we investigated the effect of rTMS applied during rapid amygdala kindling on some electrophysiological properties of hippocampal CA1 pyramidal neurons. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (1Hz for 4min) 5min after termination of daily kindling stimulations. Twenty four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using whole-cell patch-clamp technique. Amygdala kindling significantly depolarized the resting membrane potential and increased the input resistance, spontaneous firing activity, number of evoked spikes and half-width of the first evoked spike. Kindling also decreased the first-spike latency and amplitude significantly. Application of rTMS during kindling somehow prevented the development of seizures and protected CA1 pyramidal neurons of hippocampus against deleterious effect of kindling on both passive and active neuronal electrophysiological properties. Interestingly, application of rTMS alone enhanced the excitability of CA1 pyramidal neurons significantly. Based on the results of our study, it may be suggested that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced changes in electrophysiological properties of hippocampal CA1 pyramidal neurons. It seems that rTMS exerts protective effects on the neural circuits involved in spreading the seizures from the focus to other parts of the brain.

  8. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices.

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    Greene, R W; Haas, H L

    1985-09-01

    Intracellular recordings with a bridge amplifier of CA1 pyramidal neurones in vitro were employed to study the mechanisms of action of exogenously applied adenosine in the hippocampal slice preparation of the rat. Adenosine enhanced the calcium-dependent, long-duration after-hyperpolarization (a.h.p.) at least in part by a reduction in the rate of decay of the a.h.p. Both the reduced rate of decay and that of the control can be described with a single exponential. Antagonism of the calcium-dependent potassium current (and as a result, the a.h.p.) by bath application of CdCl2 or intracellular injection of EGTA (ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid) did not reduce the adenosine-evoked hyperpolarization or decrease in input resistance. Similarly, TEA (tetraethylammonium), which antagonizes both the voltage- and calcium-sensitive, delayed, outward rectification, had no effect on the adenosine-evoked changes in resting membrane properties. Adenosine did not affect the early, transient, outward rectification. During exposure to 4-aminopyridine (4-AP) in concentrations sufficient to antagonize this early rectification, the changes in resting membrane properties evoked by adenosine were unaffected. We conclude that the enhancement of the a.h.p. and accommodation by adenosine may be mediated by a change in the regulation of intracellular calcium. However, the mechanism responsible for the hyperpolarization and decrease in input resistance evoked by adenosine is both calcium and voltage insensitive. Thus, it appears distinct from that mediating the enhancement of the a.h.p. and accommodation.

  9. Penicillin-induced epileptogenesis in immature rat CA3 hippocampal pyramidal cells.

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    Swann, J W; Brady, R J

    1984-02-01

    Penicillin's ability to produce epileptiform discharges in the CA3 region of hippocampus was examined both extracellularly and intracellularly in slices taken from immature rats 3-25 days of age. Comparisons were made to similar recordings from slices taken from mature rats. Between postnatal days 9 and 19 penicillin treatment resulted in spontaneous extracellular epileptiform bursts and coincident intracellular depolarization shifts. These events were more prolonged and less frequent than in slices from mature rats, and the bursts were followed by prolonged afterdischarges, often 20-30 s in duration. Intracellularly these afterdischarges consisted of large, rhythmic slow depolarizing potentials, which resulted in one or more action potentials in individual CA3 pyramidal cells. Extracellular field recordings showed these events to be simultaneous with synchronous discharges of a large population of CA3 pyramidal cells. In pups 1-2 weeks of age the ability of hippocampus to produce prolonged afterdischarges was associated with a slow depolarizing afterpotential, which followed the downstroke of the depolarization shift. Coincident with this afterpotential was a prolonged negative field in the CA3 pyramidal cell body layer. By postnatal days 24 and 25 the tendency to generate afterdischarges was greatly reduced. In addition, afterdischarges were observed infrequently in slices taken during the first postnatal week. Spike trains produced by prolonged intracellular current injection in slices taken on postnatal days 9-19 were followed by large afterhyperpolarizations and were unable to produce afterdischarges in individual CA3 pyramidal cells. Intracellular recordings from presumed glial cells suggest that extracellular K+ accumulation may play a role in the pronounced capacity of hippocampus from 1- and 2-week-old rat pups to generate prolonged afterdischarges.

  10. The protective role of ascorbic acid on hippocampal CA1 pyramidal neurons in a rat model of maternal lead exposure.

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    Sepehri, Hamid; Ganji, Farzaneh

    2016-07-01

    Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead+100mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons' somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl's analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (Pascorbic acid. Sholl's analysis revealed a significant increase in apical dendritic branch points near cell body (PAscorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.

  11. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

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    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  12. Muscarinic activation of inwardly rectifying K+ conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells

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    Seeger, Thomas; Alzheimer, Christian

    2001-01-01

    To determine how acetylcholine (ACh) modulates the somatodendritic processing of EPSPs, we performed whole-cell recordings from CA1 pyramidal cells of hippocampal slices and examined the effect of the cholinergic agonist, carbachol (CCh), on α-amino-3-hydroxy-5-methyl isoxazole-4-propionate (AMPA) EPSPs, miniature EPSPs, and EPSP-like waveforms evoked by brief dendritic glutamate pulses (glutamate-evoked postsynaptic potentials, GPSPs). Although CCh is known to enhance the intrinsic excitability of the neuron in several ways, activation of atropine-sensitive (muscarinic) receptors on the apical dendrite or the soma of CA1 pyramidal cells consistently reduced the amplitude of EPSPs and GPSPs. Cholinergic inhibition of evoked and simulated EPSP waveforms displayed considerable voltage dependence, with the amplitude of the postsynaptic potentials progressively declining with membrane hyperpolarization indicating the involvement of an inwardly rectifying current. Extracellular Ba2+ (200 μm) and tertiapin (30 nm), a novel and selective blocker of G protein-activated, inwardly rectifying K+ (GIRK) channels, completely blocked the effect of CCh on GPSP amplitude. Muscarinic reduction of GPSPs was not sensitive to the M1 receptor-preferring antagonist, pirenzepine, but was suppressed by the M2 receptor-preferring antagonist, methoctramine, and by the allosteric M2 receptor antagonist, gallamine. In voltage-clamp recordings, CCh induced an ion current displaying inward rectification in the hyperpolarizing direction, which was identified as a GIRK current based on its sensitivity to low Ba2+ and tertiapin. Its pharmacological profile paralleled that of the cholinergic GPSP reduction. We link the observed reduction of postsynaptic potentials to the cholinergic activation of a GIRK conductance, which serves to partially shunt excitatory synaptic input. PMID:11533131

  13. [PI 3 K/Akt signaling pathway contributed to the protective effect of acupuncture intervention on epileptic seizure-induced injury of hippocampal pyramidal cells in epilepsy rats].

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    Yang, Fan; Ang, Wen-Ping; Shen, De-Kai; Liu, Xiang-Guo; Yang, Yong-Qing; Ma, Yun

    2013-02-01

    To observe the protective effect of acupuncture stimulation on pyramidal cells in hippocampal CA 1 and CA 3 regions and to analyze the involvement of phosphatidy linositol-3-kinase (PI 3 K)/protein kinase B(PKB or Akt) signaling pathway in the acupuncture effect in epilepsy rats. A total of 120 SD rats were randomly divided into normal control group, model group, LY 294002 (a specific antagonist for PI 3 K/Akt signaling) group, acupuncture+ LY 294002 group and acupuncture group (n = 24 in each group, 12 for H. E. staining, and 12 for electron microscope observation). Epilepsy model was established by intraperitoneal injection of pentylenetetrazol (PTZ, 5 microL). Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) once daily for 5 days. Dimethyl Sulfoxide (DMSO, 5 microL, a control solvent) was given to rats of the normal, model and acupuncture groups, and LY294002 (5 microL, dissolved in DMSO) given to rats of the LY 294002 and acupuncture+ LY 294002 groups by lateral ventricular injection. Four hours and 24 h after modeling, the hippocampus tissues were sampled for observing pathological changes of CA 1 and CA 3 regions after H. E. staining under light microscope and for checkin ultrastructural changes of the pyramidal cells under transmission electron microscope. In comparison with the normal control group, the numbers of pyramidal cells of hippocampal CA 3 region in the model group were decreased significantly 4 h and 24 h after epileptic seizure (P acupuncture group were increased considerably in the number at both 4 h and 24 h after seizure (P acupuncture+ LY 294002 and model groups in the numbers of pyramidal cells at 4 h and 24 h after seizure (P > 0.05). Findings of the light microscope and electron microscope showed that the injury severity of pyramidal cells of hippocampal CA 1 and CA 3 regions was moderate 4 h after epileptic seizure and even worse 24 h after seizure in the model group, LY 294002 group and acupuncture+ LY

  14. Hippocampal CA3 pyramidal cells selectively innervate aspiny interneurons.

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    Wittner, Lucia; Henze, Darrell A; Záborszky, László; Buzsáki, György

    2006-09-01

    The specific connectivity among principal cells and interneurons determines the flow of activity in neuronal networks. To elucidate the connections between hippocampal principal cells and various classes of interneurons, CA3 pyramidal cells were intracellularly labelled with biocytin in anaesthetized rats and the three-dimensional distribution of their axon collaterals was reconstructed. The sections were double-stained for substance P receptor (SPR)- or metabotropic glutamate receptor 1alpha (mGluR-1alpha)-immunoreactivity to investigate interneuron targets of the CA3 pyramidal cells. SPR-containing interneurons represent a large portion of the GABAergic population, including spiny and aspiny classes. Axon terminals of CA3 pyramidal cells contacted SPR-positive interneuron dendrites in the hilus and in all hippocampal strata in both CA3 and CA1 regions (7.16% of all boutons). The majority of axons formed single contacts (87.5%), but multiple contacts (up to six) on single target neurons were also found. CA3 pyramidal cell axon collaterals innervated several types of morphologically different aspiny SPR-positive interneurons. In contrast, spiny SPR-interneurons or mGluR-1alpha-positive interneurons in the hilus, CA3 and CA1 regions were rarely contacted by the filled pyramidal cells. These findings indicate a strong target selection of CA3 pyramidal cells favouring the activation of aspiny classes of interneurons.

  15. The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons.

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    Sergiy V Korol

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diazepam. In whole-cell recordings in rat brain slices, diazepam (1 μM, an allosteric positive modulator of GABAA receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABAA current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM plus diazepam (1 μM, only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diazepam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABAA receptors in the CA3 pyramidal neurons.

  16. Sub-millisecond firing synchrony of closely neighboring pyramidal neurons in hippocampal CA1 of rats during delayed non-matching to sample task

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    Susumu Takahashi

    2009-09-01

    Full Text Available Firing synchrony among neurons is thought to play functional roles in several brain regions. In theoretical analyses, firing synchrony among neurons within sub-millisecond precision is feasible to convey information. However, little is known about the occurrence and the functional significance of the sub-millisecond synchrony among closely neighboring neurons in the brain of behaving animals because of a technical issue: spikes simultaneously generated from closely neighboring neurons are overlapped in the extracellular space and are not easily separated. As described herein, using a unique spike sorting technique based on independent component analysis together with extracellular 12-channel multi-electrodes (dodecatrodes, we separated such overlapping spikes and investigated the firing synchrony among closely neighboring pyramidal neurons in the hippocampal CA1 of rats during a delayed non-matching to sample task. Results showed that closely neighboring pyramidal neurons in the hippocampal CA1 can co-fire with sub-millisecond precision. The synchrony generally co-occurred with the firing rate modulation in relation to both internal (retention and comparison and external (stimulus input and motor output events during the task. However, the synchrony occasionally occurred in relation to stimulus inputs even when rate modulation was clearly absent, suggesting that the synchrony is not simply accompanied with firing rate modulation and that the synchrony and the rate modulation might code similar information independently. We therefore conclude that the sub-millisecond firing synchrony in the hippocampus is an effective carrier for propagating information—as represented by the firing rate modulations—to downstream neurons.

  17. Weak sinusoidal electric fields entrain spontaneous Ca transients in the dendritic tufts of CA1 pyramidal cells in rat hippocampal slice preparations.

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    Maeda, Kazuma; Maruyama, Ryuichi; Nagae, Toru; Inoue, Masashi; Aonishi, Toru; Miyakawa, Hiroyoshi

    2015-01-01

    Neurons might interact via electric fields and this notion has been referred to as ephaptic interaction. It has been shown that various types of ion channels are distributed along the dendrites and are capable of supporting generation of dendritic spikes. We hypothesized that generation of dendritic spikes play important roles in the ephaptic interactions either by amplifying the impact of electric fields or by providing current source to generate electric fields. To test if dendritic activities can be modulated by electric fields, we developed a method to monitor local Ca-transients in the dendrites of a neuronal population in acute rat hippocampal slices by applying spinning-disk confocal microscopy and multi-cell dye loading technique. In a condition in which the dendrites of CA1 pyramidal neurons show spontaneous Ca-transients due to added 50 μM 4-aminopyridine to the bathing medium and adjusted extracellular potassium concentration, we examined the impact of sinusoidal electric fields on the Ca-transients. We have found that spontaneously occurring fast-Ca-transients in the tufts of the apical dendrites of CA1 pyramidal neurons can be blocked by applying 1 μM tetrodotoxin, and that the timing of the transients become entrained to sub-threshold 1-4 Hz electric fields with an intensity as weak as 0.84 mV/mm applied parallel to the somato-dendritic axis of the neurons. The extent of entrainment increases with intensity below 5 mV/mm, but does not increase further over the range of 5-20 mV/mm. These results suggest that population of pyramidal cells might be able to detect electric fields with biologically relevant intensity by modulating the timing of dendritic spikes.

  18. Extrinsic and local glutamatergic inputs of the rat hippocampal CA1 area differentially innervate pyramidal cells and interneurons.

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    Takács, Virág T; Klausberger, Thomas; Somogyi, Peter; Freund, Tamás F; Gulyás, Attila I

    2012-06-01

    The two main glutamatergic pathways to the CA1 area, the Schaffer collateral/commissural input and the entorhinal fibers, as well as the local axons of CA1 pyramidal cells innervate both pyramidal cells and interneurons. To determine whether these inputs differ in their weights of activating GABAergic circuits, we have studied the relative proportion of pyramidal cells and interneurons among their postsynaptic targets in serial electron microscopic sections. Local axons of CA1 pyramidal cells, intracellularly labeled in vitro or in vivo, innervated a relatively high proportion of interneuronal postsynaptic targets (65.9 and 53.8%, in vitro and in vivo, respectively) in stratum (str.) oriens and alveus. In contrast, axons of in vitro labeled CA3 pyramidal cells in str. oriens and str. radiatum of the CA1 area made synaptic junctions predominantly with pyramidal cell spines (92.9%). The postsynaptic targets of anterogradely labeled medial entorhinal cortical boutons in CA1 str. lacunosum-moleculare were primarily pyramidal neuron dendritic spines and shafts (90.8%). The alvear group of the entorhinal afferents, traversing str. oriens, str. pyramidale, and str. radiatum showed a higher preference for innervating GABAergic cells (21.3%), particularly in str. oriens/alveus. These data demonstrate that different glutamatergic pathways innervate CA1 GABAergic cells to different extents. The results suggest that the numerically smaller CA1 local axonal inputs together with the alvear part of the entorhinal input preferentially act on GABAergic interneurons in contrast to the CA3, or the entorhinal input in str. lacunosum-moleculare. The results highlight differences in the postsynaptic target selection of the feed-forward versus recurrent glutamatergic inputs to the CA1 and CA3 areas.

  19. Convergence of entorhinal and CA3 inputs onto pyramidal neurons and interneurons in hippocampal area CA1--an anatomical study in the rat.

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    Kajiwara, Riichi; Wouterlood, Floris G; Sah, Anupam; Boekel, Amber J; Baks-te Bulte, Luciënne T G; Witter, Menno P

    2008-01-01

    The entorhinal cortex (EC) conveys information to hippocampal field CA1 either directly by way of projections from principal neurons in layer III, or indirectly by axons from layer II via the dentate gyrus, CA3, and Schaffer collaterals. These two pathways differentially influence activity in CA1, yet conclusive evidence is lacking whether and to what extent they converge onto single CA1 neurons. Presently we studied such convergence. Different neuroanatomical tracers injected into layer III of EC and into CA3, respectively, tagged simultaneously the direct entorhino-hippocampal fibers and the indirect innervation of CA1 neurons by Schaffer collaterals. In slices of fixed brains we intracellularly filled CA1 pyramidal cells and interneurons in stratum lacunosum-moleculare (LM) and stratum radiatum (SR). Sections of these slices were scanned in a confocal laser scanning microscope. 3D-reconstruction was used to determine whether boutons of the labeled input fibers were in contact with the intracellularly filled neurons. We analyzed 12 pyramidal neurons and 21 interneurons. Perforant path innervation to pyramidal neurons in our material was observed to be denser than that from CA3. All pyramidal neurons and 17 of the interneurons received contacts of both perforant pathway and Schaffer input on their dendrites and cell bodies. Four interneurons, which were completely embedded in LM, received only labeled perforant pathway input. Thus, we found convergence of both projection systems on single CA1 pyramidal and interneurons with dendrites that access the layers where perforant pathway fibers and Schaffer collaterals end.

  20. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

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    Kim, Sooyun; Guzman, Segundo J.; Hu, Hua; Jonas, Peter

    2012-01-01

    CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic dom...

  1. Dendritic potassium channels in hippocampal pyramidal neurons.

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    Johnston, D; Hoffman, D A; Magee, J C; Poolos, N P; Watanabe, S; Colbert, C M; Migliore, M

    2000-05-15

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

  2. Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

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    Ting Ju

    2016-12-01

    Full Text Available Background: Streptozotocin (STZ has served as an agent to generate an Alzheimer's disease (AD model in rats, while edaravone (EDA, a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs, AMPAR-mediated eEPSCs (eEPSCsAMPA, evoked inhibitory postsynaptic currents (eIPSCs, evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR, it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

  3. The neuroprotective effect of topiramate on the ultrastructure of pyramidal neurons of the hippocampal CA1 and CA3 sectors in an experimental model of febrile seizures in rats.

    Science.gov (United States)

    Sobaniec-Lotowska, Maria E; Lotowska, Joanna M

    2011-01-01

    The objective of the current ultrastructural study was to explore the potentiality of the neuroprotective effect of TPM against damage of pyramidal neurons in the hippocampal CA1 and CA3 sectors in an experimental model of febrile seizures (FS) in rats. The FS group exhibited variously pronounced submicroscopic lesions of the neuronal perikarya, including total cell disintegration. Advanced changes induced by hyperthermic stress were manifested by marked degenerative abnormalities, such as substantial swelling of the mitochondria, dilation, degranulation and disintegration of the granular endoplasmic reticulum, and vacuolar changes in the Golgi complex. The most substantially damaged pyramidal neurons showed features of aponecrosis (so-called "dark neurons"), resulting in a marked neuronal loss in the explored areas of the hippocampal cortex. The neurodegenerative changes were accompanied by distinct damage to the blood-brain barrier components. The administration of topiramate at a dose of 80/kg b.m. prior to the induction of hyperthermic stress (as prevention against febrile seizures) caused a substantial neuroprotective action - the drug efficiently lightened the neuronal damage, basically reduced cell aponecrosis and enhanced cell viability. However, TPM applied directly after FS induction did not exert any distinct neuroprotective effect on the perikarya of pyramidal neurons in the hippocampal cortex.

  4. Modulation of Hyperpolarization-Activated Cation Currents (Ih) by Ethanol in Rat Hippocampal CA3 Pyramidal Neurons

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    Licheri, Valentina

    2015-01-01

    It is well established that ethanol (EtOH), through the interaction with several membrane proteins, as well as intracellular pathways, is capable to modulate many neuronal function. Recent reports show that EtOH increases the firing rate of hippocampal GABAergic interneurons through the positive modulation of the hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels. This effect might be consistent with the increase of GABA release from presynaptic terminals...

  5. Closed head injury causes hyperexcitability in rat hippocampal CA1 but not in CA3 pyramidal cells.

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    Griesemer, Désirée; Mautes, Angelika M

    2007-12-01

    Traumatic brain injury frequently elicits epileptic seizures hours or days after the impact. The mechanisms on cellular level are poorly understood. Because posttraumatic epilepsy appears in many cases as a temporal-lobe epilepsy which originated the hippocampus, we studied trauma-induced hyperexcitability on the cellular level in this brain area. We used the model of closed head injury to analyse the electrophysiological changes in CA1 and CA3 pyramidal cells and in interneurones of the CA1 field, which is extremely sensitive to ischemia. We found that morphologically closed head injury (CHI) led to a gradual progressive, cell type specific time course in neuronal degeneration. To analyse electrophysiological impairment we measured resting membrane potential, recorded spontaneous action potentials and induced action potentials by current pulses at different times after CHI. We found a dramatic increase in the frequency of spontaneous action potentials of CA1 but not of CA3 pyramidal cells after CHI. This hyperexcitability was maximal at 2 h (4.5-fold higher than sham), was also observed at 24 h after CHI and disappeared after 3 days. We found that CA1 interneurones responded by a much weaker increase of AP frequency after CHI. We conclude that the strong hyperexcitability after CHI is cell-type specific and transient. The understanding of the complex neuronal interactions probably offers a promising possibility for pharmacological intervention to prevent posttraumatic epilepsy.

  6. Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

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    Ashhad, Sufyan; Johnston, Daniel

    2014-01-01

    The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if InsP3R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of d-myo-InsP3 in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP3 concentration, emphasizing the graded dependence of such plasticity on InsP3R activation. Mechanistically, we found that this InsP3-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP3Rs, the influx of calcium through N-methyl-d-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP3Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis. PMID:25552640

  7. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

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    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.

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    Kim, Jinhyun; Wei, Dong-Sheng; Hoffman, Dax A

    2005-11-15

    A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.

  9. Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations.

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    Stark, Eran; Roux, Lisa; Eichler, Ronny; Senzai, Yuta; Royer, Sebastien; Buzsáki, György

    2014-07-16

    High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation, frequency control, and spatial coherence of the rhythm are poorly understood. Using multisite optogenetic manipulations in freely behaving rodents, we found that depolarization of a small group of nearby pyramidal cells was sufficient to induce high-frequency oscillations, whereas closed-loop silencing of pyramidal cells or activation of parvalbumin- (PV) or somatostatin-immunoreactive interneurons aborted spontaneously occurring ripples. Focal pharmacological blockade of GABAA receptors abolished ripples. Localized PV interneuron activation paced ensemble spiking, and simultaneous induction of high-frequency oscillations at multiple locations resulted in a temporally coherent pattern mediated by phase-locked interneuron spiking. These results constrain competing models of ripple generation and indicate that temporally precise local interactions between excitatory and inhibitory neurons support ripple generation in the intact hippocampus.

  10. Phase precession in hippocampal interneurons showing strong functional coupling to individual pyramidal cells.

    Science.gov (United States)

    Maurer, Andrew P; Cowen, Stephen L; Burke, Sara N; Barnes, Carol A; McNaughton, Bruce L

    2006-12-27

    Although hippocampal interneurons typically do not show discrete regions of elevated firing in an environment, such as seen in pyramidal cell place fields, they do exhibit significant spatial modulation (McNaughton et al., 1983a). Strong monosynaptic coupling between pyramidal neurons and nearby interneurons in the CA1 stratum pyramidale has been strongly implicated on the basis of significant, short-latency peaks in cross-correlogram plots (Csicsvari et al., 1998). Furthermore, interneurons receiving a putative monosynaptic connection from a simultaneously recorded pyramidal cell appear to inherit the spatial modulation of the latter (Marshall et al., 2002). Buzsaki and colleagues hypothesize that interneurons may also adopt the firing phase dynamics of their afferent place cells, which show a phase shift relative to the hippocampal theta rhythm as a rat passes through the place field ("phase precession"). This study confirms and extends the previous reports by showing that interneurons in the dorsal and middle hippocampus with putative monosynaptic connections with place cells recorded on the same tetrode share other properties with their pyramidal cell afferents, including the spatial scale of the place field of pyramidal cell, a characteristic of the septotemporal level of the hippocampus from which the cells are recorded, and the rate of phase precession, which is slower in middle regions. Furthermore, variations in pyramidal cell place field scale within each septotemporal level attributable to task variations are similarly associated with variations in interneuron place field scale. The available data strongly suggest that spatial selectivity of CA1 stratum pyramidale interneurons is inherited from a small cluster of local pyramidal cells and is not a consequence of spatially selective synaptic input from CA3 or other sources.

  11. Culturing rat hippocampal neurons.

    Science.gov (United States)

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  12. A threshold sodium current in pyramidal cells in rat hippocampus.

    Science.gov (United States)

    French, C R; Gage, P W

    1985-05-23

    Maintained, inward currents were activated by small depolarizations from the resting membrane potential (-50 to -60 mV) in voltage-clamped, pyramidal neurons in rat hippocampal slices. The currents were apparently Na currents as they were blocked by tetrodotoxin or removal of extracellular Na and were not affected by Cd. They showed little decrease in amplitude during prolonged depolarizations. The increase in Na conductance with depolarization was sigmoidal, with half-maximum conductance at about -50 mV, and saturated at -20 to -30 mV. This 'threshold' Na current may be involved in setting patterns of repetitive firing of action potentials.

  13. Intracellular calcium elevation during plateau potentials mediated by extrasynaptic NMDA receptor activation in rat hippocampal CA1 pyramidal neurons is primarily due to calcium entry through voltage-gated calcium channels.

    Science.gov (United States)

    Oda, Yoshiaki; Kodama, Satoshi; Tsuchiya, Sadahiro; Inoue, Masashi; Miyakawa, Hiroyoshi

    2014-05-01

    We reported previously that plateau potentials mediated by extrasynaptic N-methyl-d-aspartate receptors (NMDARs) can be induced either by synaptic stimulation in the presence of glutamate transporter antagonist or by iontophoresis of NMDA in rat hippocampal CA1 pyramidal neurons. To examine whether the plateau potentials are accompanied by an elevation of intracellular Ca2+ and to determine the source of Ca2+ elevation, we performed Ca2+ imaging during the plateau potential. Neurons were loaded with Ca2+ indicator fluo-4, and the plateau potentials were generated either synaptically in the presence of glutamate transporter antagonist or by iontophoretically applying NMDA. We have found that a transient elevation in intracellular Ca2+ accompanies the plateau potential. The synaptically induced plateau potential and the Ca2+ elevation were blocked by 5,7-dichlorokynurenic acid (5,7-dCK), an antagonist for the glycine-binding sites of NMDAR. A mixture of Cd2+ and tetrodotoxin did not block NMDA-induced plateau potentials, but completely abolished the accompanying Ca2+ elevation in both the presence and absence of Mg2+ ions in the bathing solution. The NMDA-induced plateau potential was blocked by further adding 5,7-dCK. Our results show that the NMDAR-mediated plateau potential is accompanied by elevation of intracellular Ca2+ that is primarily caused by the influx of Ca2+ through voltage-gated Ca2+ channels. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Frequency-dependent signal processing in apical dendrites of hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Watanabe, H; Tsubokawa, H; Tsukada, M; Aihara, T

    2014-10-10

    Depending on an animal's behavioral state, hippocampal CA1 pyramidal cells receive distinct patterns of excitatory and inhibitory synaptic inputs. The time-dependent changes in the frequencies of these inputs and the nonuniform distribution of voltage-gated channels lead to dynamic fluctuations in membrane conductance. In this study, using a whole-cell patch-clamp method, we attempted to record and analyze the frequency dependencies of membrane responsiveness in Wistar rat hippocampal CA1 pyramidal cells following noise current injection directly into dendrites and somata under pharmacological blockade of all synaptic inputs. To estimate the frequency-dependent properties of membrane potential, membrane impedance was determined from the voltage response divided by the input current in the frequency domain. The cell membrane of most neurons showed low-pass filtering properties in all regions. In particular, the properties were strongly expressed in the somata or proximal dendrites. Moreover, the data revealed nonuniform distribution of dendritic impedance, which was high in the intermediate segment of the apical dendritic shaft (∼220-260μm from the soma). The low-pass filtering properties in the apical dendrites were more enhanced by membrane depolarization than those in the somata. Coherence spectral analysis revealed high coherence between the input signal and the output voltage response in the theta-gamma frequency range, and large lags emerged in the distal dendrites in the gamma frequency range. Our results suggest that apical dendrites of hippocampal CA1 pyramidal cells integrate synaptic inputs according to the frequency components of the input signal along the dendritic segments receiving the inputs.

  15. Extracellular calcium modulates persistent sodium current-dependent burst-firing in hippocampal pyramidal neurons.

    Science.gov (United States)

    Su, H; Alroy, G; Kirson, E D; Yaari, Y

    2001-06-15

    The generation of high-frequency spike bursts ("complex spikes"), either spontaneously or in response to depolarizing stimuli applied to the soma, is a notable feature in intracellular recordings from hippocampal CA1 pyramidal cells (PCs) in vivo. There is compelling evidence that the bursts are intrinsically generated by summation of large spike afterdepolarizations (ADPs). Using intracellular recordings in adult rat hippocampal slices, we show that intrinsic burst-firing in CA1 PCs is strongly dependent on the extracellular concentration of Ca(2+) ([Ca(2+)](o)). Thus, lowering [Ca(2+)](o) (by equimolar substitution with Mn(2+) or Mg(2+)) induced intrinsic bursting in nonbursters, whereas raising [Ca(2+)](o) suppressed intrinsic bursting in native bursters. The induction of intrinsic bursting by low [Ca(2+)](o) was associated with enlargement of the spike ADP. Low [Ca(2+)](o)-induced intrinsic bursts and their underlying ADPs were suppressed by drugs that reduce the persistent Na(+) current (I(NaP)), indicating that this current mediates the slow burst depolarization. Blocking Ca(2+)-activated K(+) currents with extracellular Ni(2+) or intracellular chelation of Ca(2+) did not induce intrinsic bursting. This and other evidence suggest that lowering [Ca(2+)](o) may induce intrinsic bursting by augmenting I(NaP). Because repetitive neuronal activity in the hippocampus is associated with marked decreases in [Ca(2+)](o), the regulation of intrinsic bursting by extracellular Ca(2+) may provide a mechanism for preferential recruitment of this firing mode during certain forms of hippocampal activation.

  16. Dendritic development of hippocampal CA1 pyramidal cells in a neonatal hypoxia-ischemia injury model.

    Science.gov (United States)

    Zhao, Yan Dong; Ou, Shan; Cheng, Sai Yu; Xiao, Zhi; He, Wen Juan; Zhang, Jin Hai; Ruan, Huai Zhen

    2013-09-01

    It is believed that neonatal hypoxia-ischemia (HI) brain injury causes neuron loss and brain functional defects. However, the effect of HI brain injury on dendritic development of the remaining pyramidal cells of the hippocampus and the reaction of contralateral hippocampal neurons require further studies. The Morris water maze and Golgi-Cox staining were used to evaluate the learning and memory and dendritic morphology of pyramidal cells. The results of Golgi-Cox staining showed CA1 pyramidal neurons of HI injury models with fewer bifurcations and shorter dendrite length than the naive control group. The density of dendritic spines of hippocampal CA1 pyramidal neurons was significantly lower in the HI brain injury group than in controls. With respect to hippocampal function, the HI brain injury group presented cognitive deficits in the reference memory task and probe trail. In the HI group, the pyramidal cells of left hippocampus that did not experienced ischemia but did experience hypoxia had more complex dendrites and higher density of spine than the HI injury side and control. The functional implementation of injured hippocampus might depend mainly on the hypertrophy of contralateral hippocampus after HI brain injury. Corticosterone can partially prevent the hippocampal pyramidal cells from HI injury and reduce the difference of the bilateral hippocampus pyramidal cells, but there was no improvement in learning and memory.

  17. Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

    Science.gov (United States)

    Storm, J F

    1987-03-20

    Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

  18. Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.

    Science.gov (United States)

    Izumi, Y; Svrakic, N; O'Dell, K; Zorumski, C F

    2013-03-13

    Neurosteroids are a class of endogenous steroids synthesized in the brain that are believed to be involved in the pathogenesis of neuropsychiatric disorders and memory impairment. Ammonia impairs long-term potentiation (LTP), a synaptic model of learning, in the hippocampus, a brain region involved in memory acquisition. Although mechanisms underlying ammonia-mediated LTP inhibition are not fully understood, we previously found that the activation of N-methyl-d-aspartate receptors (NMDARs) is important. Based on this, we hypothesize that metabolic stressors, including hyperammonemia, promote untimely NMDAR activation and result in neural adaptations that include the synthesis of allopregnanolone (alloP) and other GABA-potentiating neurosteroids that dampen neuronal activity and impair LTP and memory formation. Using an antibody against 5α-reduced neurosteroids, we found that 100 μM ammonia acutely enhanced neurosteroid immunostaining in pyramidal neurons in the CA1 region of rat hippocampal slices. The enhanced staining was blocked by finasteride, a selective inhibitor of 5α-reductase, a key enzyme required for alloP synthesis. Finasteride also overcame LTP inhibition by 100 μM ammonia, as did picrotoxin, an inhibitor of GABA-A receptors. These results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction. These results suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia.

  19. The changes of brain-derived neurotrophic factor positive neurons and the morphology of pyramidal cells in hippocampal in sodium valproate induced autism rats%丙戊酸钠孤独症模型鼠海马脑源性神经营养因子阳性神经元表达及锥体细胞形态学的变化

    Institute of Scientific and Technical Information of China (English)

    衣明纪; 马小旭; 李音

    2013-01-01

    目的 观察丙戊酸钠(VPA)孤独症模型鼠海马脑源性神经营养因子(BDNF)阳性神经元表达及锥体细胞形态学改变.方法 按Schneider方法制作VPA孤独症动物模型,采用免疫组化和图像分析技术检测模型鼠海马CA1区BDNF阳性神经元表达水平及海马CA1区锥体细胞形态学的改变.结果 孤独症模型组与正常对照组比较,海马CA1区锥体细胞BDNF阳性神经元表达水平增强,孤独症模型组与正常对照组阳性细胞数分别为(5.00±1.60)/视野和(3.00±1.04)/视野,差异有统计学意义(t=3.63,P=0.0015);海马CA1区锥体细胞形态学显示,孤独症模型鼠海马CA1区锥体神经元发生凋亡增加.结论 孤独症的发病可能与海马CA1区锥体细胞BDNF表达水平以及锥体神经细胞的凋亡有关.%Objective To explore the pathogenesis of autism by observation of changes of brain-derived neurotrophic factor(BDNF) positive neurons and the morphology of pyramidal cells in hippocampal CA1 region,and provide theoretical evidence for the therapeutic schedule.Methods Animal model of autism was obtained by Schneider method.Using the immunohistochemistry methods and image analysis,the number of BDNF positive neurons was examined in hippocampal CA1 region of the autism model rats and the normal rats,and the changes of pyramidal cell were observed in hippocampal CA1 region after HE staining.Results The numbers of BDNF positive neurons in the hippocampal CA1 region of the autism model rats were more than those of the normal rats (5.00 ±1.60 vs 3.00 ± 1.04,t =3.63,P =0.0015).The morphology of pyramidal cells showed that the pyramidal cells of the autism model rats in hippocampal CA1 region had apoptosis.Conclusion The occurrence of autism may be related to the changes of BDNF and the morphology of pyramidal cells in hippocampal CA1 region.

  20. Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

    Directory of Open Access Journals (Sweden)

    Atsushi Takeda

    Full Text Available The translocation of synaptic Zn(2+ to the cytosolic compartment has been studied to understand Zn(2+ neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+ in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+ in the hippocampus was induced with clioquinol (CQ, a zinc ionophore. Zn(2+ delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+ levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2 into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+ in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+ and/or the preferential vulnerability to Zn(2+ in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+ in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+. The present study indicates that the transient increase in cytosolic Zn(2+ in CA1 pyramidal neurons reversibly impairs object recognition memory.

  1. Low Concentrations of Alcohol Inhibit BDNF-Dependent GABAergic Plasticity via L-type Ca2+ channel Inhibition in Developing CA3 Hippocampal Pyramidal Neurons

    OpenAIRE

    Zucca, Stefano; Valenzuela, C. Fernando

    2010-01-01

    Fetal Alcohol Spectrum Disorder (FASD) is associated with learning and memory alterations that could be, in part, a consequence of hippocampal damage. The CA3 hippocampal subfield is one of the regions affected by ethanol (EtOH), including exposure during the 3rd trimester-equivalent (i.e. neonatal period in rats). However, the mechanism of action of EtOH is poorly understood. In CA3 pyramidal neurons from neonatal rats, dendritic BDNF release causes long-term potentiation of the frequency of...

  2. Electrophysiological effects of SKF83959 on hippocampal CA1 pyramidal neurons: potential mechanisms for the drug's neuroprotective effects.

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    Hong-Yuan Chu

    Full Text Available Although the potent anti-parkinsonian action of the atypical D₁-like receptor agonist SKF83959 has been attributed to the selective activation of phosphoinositol(PI-linked D₁ receptor, whereas the mechanism underlying its potent neuroprotective effect is not fully understood. In the present study, the actions of SKF83959 on neuronal membrane potential and neuronal excitability were investigated in CA1 pyramidal neurons of rat hippocampal slices. SKF83959 (10-100 µM caused a concentration-dependent depolarization, associated with a reduction of input resistance in CA1 pyramidal neurons. The depolarization was blocked neither by antagonists for D₁, D₂, 5-HT(2A/2C receptors and α₁-adrenoceptor, nor by intracellular dialysis of GDP-β-S. However, the specific HCN channel blocker ZD7288 (10 µM antagonized both the depolarization and reduction of input resistance caused by SKF83959. In voltage-clamp experiments, SKF83959 (10-100 µM caused a concentration-dependent increase of Ih current in CA1 pyramidal neurons, which was independent of D₁ receptor activation. Moreover, SKF83959 (50 µM caused a 6 mV positive shift in the activation curve of Ih and significantly accelerated the activation of Ih current. In addition, SKF83959 also reduced the neuronal excitability of CA1 pyramidal neurons, which was manifested by the decrease in the number and amplitude of action potentials evoked by depolarizing currents, and by the increase of firing threshold and rhoebase current. The above results suggest that SKF83959 increased Ih current through a D₁ receptor-independent mechanism, which led to the depolarization of hippocampal CA1 pyramidal neurons. These findings provide a novel mechanism for the drug's neuroprotective effects, which may contributes to its therapeutic benefits in Parkinson's disease.

  3. Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

    Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  4. Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

    Science.gov (United States)

    Bhat, M Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2007-03-01

    The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  5. Effects of lithium chloride on outward potassium currents in acutely isolated hippocampal CA1 pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chaofeng; DU Huizhi; YANG Pin

    2006-01-01

    Although lithium possesses neuroprotective functions, the molecular mechanism underlying its actions has not been fully elucidated. In the present paper, the effects of lithium chloride on voltage-dependent potassium currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied using the whole-cell patch-clamp technique. Depolarizing test pulses activated two components of outward potassium currents: a rapidly activating and inactivating component, IA and a delayed component, IK. Results showed that lithium chloride increased the amplitude of IA in a concentration-dependent manner. Half enhancement concentration (EC50) was 22.80±5.45 μmol·L-1. Lithium chloride of 25 μmol·L-1 shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the activation kinetics. The amplitude and the activation processes of IK were not affected by lithium chloride. The effects of lithium chloride on potassium channel appear to possess neuroprotective properties by Ca2+-lowing effects modulate neuronal excitability by activating IA in rat hippocampal neurons.

  6. Whole-cell recordings of voltage-gated Calcium, Potassium and Sodium currents in acutely isolated hippocampal pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    Shuyun Huang; Qing Cai; Weitian Liu; Xiaoling Wang; Tao Wang

    2009-01-01

    Objective:To record Calcium, Potassium and Sodium currents in acutely isolated hippocampal pyramidal neurons. Methods:Hip-pocampal CA3 neurons were freshly isolated by 1 mg protease/3 ml SES and mechanical trituration with polished pipettes of progressively smaller tip diameters. Patch clamp technique in whole-cell mode was employed to record voltage-gated channel currents. Results:The procedure dissociated hippocampal neurons, preserving apical dendrites and several basal dendrites, without impairing the electrical characteristics of the neurons. Whole-cell patch clamp configuration was successfully used to record voltage-gated Ca2+ currents, delayed rectifier K+ current and voltage-gated Na+ currents. Conclusion:Protease combined with mechanical trituration may be used for the dissociation of neurons from rat hippocampus. Voltage-gated channels currents could be recorded using a patch clamp technique.

  7. Modelling the Somatic Electrical Response of Hippocampal Pyramidal Neurons

    Science.gov (United States)

    1989-09-01

    non-linear, time-varying conductances in the soma, including those that underly three putative sodium currents , (IN.-tr,, INa-tail, and INa-rep), a...for excitation and propagation of the nerve impulse. Biophysics Journal. 6:, 1966. [12] C. French and P. Gage. A threshold sodium current in pyramidal

  8. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Directory of Open Access Journals (Sweden)

    Bopanna I Kalappa

    Full Text Available BACKGROUND: The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596. METHODOLOGY/PRINCIPAL FINDINGS: An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the

  9. Effects of organophosphates on rabbit pyramidal cells firing pattern and hippocampal theta rhythm.

    Science.gov (United States)

    Nio, J; Breton, P

    1994-01-01

    The effects of the irreversible acetylcholinesterase (AChE) antagonist paraoxon (Px) on hippocampal neurophysiology were investigated and compared to those of physostigmine in urethane-anaesthetized rabbits. Hippocampal CA1 EEG signals were analyzed by power spectra. Following intracarotid administration, the two drugs induced a similar fundamental low-frequency theta power peak while the appearance of a second theta harmonic was commonly found under Px. Again, inhibition of CA1 pyramidal cells firing was significantly more pronounced after Px injection than after physostigmine. A potent inhibitory action was also described following local Px iontophoretic application. However, a discrepancy appeared between the effects of Px and the classical cholinergic drugs (acetylcholine, physostigmine). The results indicate that Px and physostigmine have a rather similar influence on the septo-hippocampal pathway and support suggestions that Px could act within local hippocampal circuitry through other systems than the cholinergic system exclusively.

  10. Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels.

    Science.gov (United States)

    Leuner, Kristina; Li, Wei; Amaral, Michelle D; Rudolph, Stephanie; Calfa, Gaston; Schuwald, Anita M; Harteneck, Christian; Inoue, Takafumi; Pozzo-Miller, Lucas

    2013-01-01

    The standardized extract of the St. John's wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na(+) concentration through the activation of nonselective cationic TRPC6 channels. TRPC6 channels are also Ca(2+) -permeable, resulting in intracellular Ca(2+) elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca(2+) transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of nerve growth factor. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca(2+) transients and depolarizing inward currents sensitive to the TRPC channel blocker La(3+) , thus resembling the actions of the neurotrophin brain-derived neurotrophic factor (BDNF) in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John's wort are mediated by a mechanism similar to that engaged by BDNF.

  11. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Science.gov (United States)

    Wu, You Kure; Fujishima, Kazuto; Kengaku, Mineko

    2015-01-01

    Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s) from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  12. The electrical activity of hippocampal pyramidal neuron is subjected to descending control by the brain orexin/hypocretin system.

    Science.gov (United States)

    Riahi, Esmail; Arezoomandan, Reza; Fatahi, Zahra; Haghparast, Abbas

    2015-03-01

    The hippocampus receives sparse orexinergic innervation from the lateral hypothalamus and expresses a high level of orexin receptor. The function of orexin receptor in the regulation of hippocampal neural activity has never been investigated. In this study, in vivo single unit recording was performed in urethane-anesthetized rats. After 15 min of baseline recording from pyramidal neuron within the CA1 region of the dorsal hippocampus, i.c.v. injection of orexin-A 0.5 nmol, SB334867 400 nmol, a selective orexin receptor 1 antagonist, saline, or DMSO, or microinjection of carbachol 250 nmol or saline into the ipsilateral lateral hypothalamus were performed using a Hamilton microsyringe, and the spontaneous firing activity continued to be recorded for 25 min. Results showed that orexin administration into the lateral cerebral ventricle excited 6 out of 8 neurons and inhibited 1 neuron. Chemical stimulation of the lateral hypothalamus by carbachol excited 9 out of 13 hippocampal neurons and inhibited 3 neurons. On the other hand, i.c.v. injection of the SB334867, caused reductions in the firing activity of 6 out of 10 neurons and increases in 4 additional neurons. It seems that orexin neurotransmission in the hippocampus mostly elicits an excitatory response, whereas blockade of orexin receptor has an inhibitory effect. Further studies need to be done to elucidate the underlying mechanism of orexin action on hippocampal neurons.

  13. Thrombin modulates persistent sodium current in CA1 pyramidal neurons of young and adult rat hippocampus.

    Science.gov (United States)

    Lunko, O O; Isaev, D S; Krishtal, O O; Isaeva, E V

    2015-01-01

    Serine protease thrombin, a key factor of blood coagulation, participates in many neuronal processes important for normal brain functioning and during pathological conditions involving abnormal neuronal synchronization, neurodegeneration and inflammation. Our previous study on CA3 pyramidal neurons showed that application ofthrombin through the activation of specific protease-activated receptor 1 (PAR1) produces a significant hyperpolarizing shift of the activation of the TTX-sensitive persistent voltage-gated Na+ current (I(Nap)) thereby affecting membrane potential and seizure threshold at the network level. It was shown that PAR1 is also expressed in CA1 area of hippocampus and can be implicated in neuronal damage in this area after status epilepticus. The aim of the present study was to evaluate the effect of thrombin on I(NaP) in CA1 pyramidal neurons from adult and young rats. Using whole cell patch-clamp technique we demonstrate that thrombin application results in the hyperpolarization shift of I(NaP) activation as well as increase in the I(NaP) amplitude in both age groups. We have found that I(NaP) in pyramidal neurons of hippocampal CA 1 region is more vulnerable to the thrombin action than I(NaP) in pyramidal neurons of hippocampal CA3 region. We have also found that the immature hippocampus is more sensitive to thrombin action which emphasizes the contribution of thrombin-dependent pathway to the regulation of neuronal activity in immature brain.

  14. Postsynaptic blockade of inhibitory postsynaptic currents by plasmin in CA1 pyramidal cells of rat hippocampus.

    Science.gov (United States)

    Mizutani, A; Tanaka, T; Saito, H; Matsuki, N

    1997-06-27

    We have shown previously that plasmin facilitated the generation of long-term potentiation (LTP) in CA1 and dentate region of rat hippocampus. In the present study, we investigated the effects of plasmin on postsynaptic currents in CA1 pyramidal neurons of rat hippocampal slices. Plasmin (100 nM) had no effect on NMDA nor on non-NMDA receptor-mediated excitatory postsynaptic currents. However, plasmin significantly decreased GABA(A) receptor-mediated inhibitory postsynaptic currents. This effect of plasmin disappeared when intracellular Ca2+ was strongly chelated with BAPTA. Furthermore, plasmin attenuated the GABA-induced currents in CA1 pyramidal cells. These results suggest that the STP-enhancing effect of plasmin is due to a blockade of postsynaptic GABA(A) responses and that an increase in intracellular Ca2+ by plasmin may be involved in its mechanism.

  15. AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons.

    Science.gov (United States)

    Xia, Y-F; Arai, A C

    2005-01-01

    Positive modulators of AMPA receptors enhance synaptic plasticity and memory encoding. Facilitation of AMPA receptor currents not only results in enhanced activation of excitatory neurons but also increases the activity of inhibitory interneurons by up-modulating their excitatory input. However, little is known about the effects of these modulators on cells other than pyramidal neurons and about their impact on local microcircuits. This study examined the effects of members from three subfamilies of modulators (mainly CX516, CX546 and cyclothiazide) on excitatory synaptic responses in four classes of hippocampal CA1 neurons and on excitatory and disynaptically induced inhibitory field potentials in hippocampal slices. Effects on excitatory postsynaptic currents (EPSCs) were examined in pyramidal cells, in two types of inhibitory interneurons located in stratum radiatum and oriens, and in stratum radiatum giant cells, a novel type of excitatory neuron. With CX516, increases in EPSC amplitude in pyramidal cells were two to three times larger than in interneurons and six times larger than in radiatum giant cells. The effects of CX546 on response duration similarly were largest in pyramidal cells. However, this drug also strongly differentiated between stratum oriens and radiatum interneurons with increases being four times larger in the latter. In contrast, cyclothiazide had similar effects on response duration in all cell types. In field recordings, CX516 was several times more potent in enhancing excitatory postsynaptic potentials (EPSPs) than feedback or feedforward circuits, as expected from its larger influence on pyramidal cells. In contrast, BDP-20, a CX546 analog, was more potent in enhancing feedforward inhibition than either EPSPs or feedback inhibition. This preference for feedforward over feedback circuits is probably related to its higher potency in stratum radiatum versus oriens interneurons. Taken together, AMPA receptor modulators differ substantially

  16. Low concentrations of alcohol inhibit BDNF-dependent GABAergic plasticity via L-type Ca2+ channel inhibition in developing CA3 hippocampal pyramidal neurons.

    Science.gov (United States)

    Zucca, Stefano; Valenzuela, C Fernando

    2010-05-12

    Fetal alcohol spectrum disorder (FASD) is associated with learning and memory alterations that could be, in part, a consequence of hippocampal damage. The CA3 hippocampal subfield is one of the regions affected by ethanol (EtOH), including exposure during the third trimester-equivalent (i.e., neonatal period in rats). However, the mechanism of action of EtOH is poorly understood. In CA3 pyramidal neurons from neonatal rats, dendritic BDNF release causes long-term potentiation of the frequency of GABAA receptor-mediated spontaneous postsynaptic currents (LTP-GABAA) and this mechanism is thought to play a role in GABAergic synapse maturation. Here, we show that short- and long-term exposure of neonatal male rats to low EtOH concentrations abolishes LTP-GABAA by inhibiting L-type voltage-gated Ca2+ channels. These findings support the recommendation that even light drinking should be avoided during pregnancy.

  17. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    Science.gov (United States)

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

  18. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Directory of Open Access Journals (Sweden)

    You Kure Wu

    Full Text Available Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  19. Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing responses in hippocampal pyramidal cells.

    Science.gov (United States)

    Jackson, M F; Esplin, B; Capek, R

    1999-03-01

    Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant activity. GABA uptake inhibitors are believed to produce their anticonvulsant effects by prolonging the postsynaptic actions of GABA, released during episodes of neuronal hyperexcitability. However, tiagabine has recently been reported to facilitate the depolarizing actions of GABA in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity. In the present study, we performed extracellular and whole cell recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the functional consequences of tiagabine-augmented GABA-mediated depolarizing responses. Orthodromic population spikes (PSs), elicited from the stratum radiatum, were inhibited following the activation of recurrent inhibitory pathways by antidromic conditioning stimulation of the alveus, which consisted of either a single stimulus or a train of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which was always of much greater strength and duration than that produced by a single conditioning stimulus, was greatly enhanced following the bath application of tiagabine (2-100 microM). Thus, in the presence of tiagabine (20 microM), orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 +/- 2.6% (mean +/- SE) and 34.4 +/- 18.5% of their unconditioned amplitudes compared with only 35.4 +/- 12.7% and 98.8 +/- 12.4% in control. Whole cell recordings revealed that the bath application of tiagabine (20 microM) either caused the appearance or greatly enhanced the amplitude of GABA-mediated depolarizing responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum radiatum at time points that coincided with the DR were inhibited to below the threshold for action-potential firing

  20. Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells.

    Science.gov (United States)

    Gerber, U; Lüthi, A; Gähwiler, B H

    1993-11-22

    The effects of a novel antagonist of metabotropic glutamate receptors were investigated in CA3 pyramidal cells in hippocampal slice cultures of the rat. Earlier experiments showed that selective activation of metabotropic glutamate receptors with low concentrations of an agonist, 1S, 3R-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD), induced an inward current associated with a decrease in membrane conductance and inhibition of the slow calcium-dependent potassium current. These responses were strongly and reversibly reduced by the antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mM). In the presence of antagonists of ionotropic glutamate receptors, stimulation of the afferent mossy fibres evoked postsynaptic responses in CA3 pyramidal cells which paralleled those observed with exogenously applied metabotropic glutamate receptor agonists, i.e. a slow inward current and a reduction of calcium-dependent potassium current. Both responses were greatly reduced by bath-applied MCPG (1 mM). These results show that MCPG acts as an effective antagonist at metabotropic glutamate receptors coupled to potassium conductances in the hippocampus. Furthermore, they confirm that glutamate release from presynaptic terminals can modulate postsynaptic properties by activation of metabotropic glutamate receptors.

  1. 慢性脑缺血大鼠海马CA1区锥体细胞树突形态及树突棘密度的变化%Changes of dendritic morphology and spine density in hippocampal CA1 pyramidal cells of chronic cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    贾贺; 张博爱; 刘宇; 张小敏; 姬亚杰; 李星; 刘荣丽

    2012-01-01

    目的:研究慢性脑缺血大鼠海马CA1区锥体细胞树突形态及树突棘密度的变化.方法:对大鼠进行双侧颈总动脉永久性结扎(2VO)制备慢性脑缺血模型,分别于2周、4周、8周通过Morris水迷宫对各组大鼠进行行为学评价,筛选造模成功大鼠,进行Golgi染色,光镜下观察海马CA1区锥体细胞树突的分支、长度及树突棘密度的变化.结果:与对照组相比,4周、8周模型组树突的分支及长度显著减少(P<0.01),各周模型组树突棘的密度均有显著减少(P<0.01);模型组内随着缺血时间延长,树突的分支及长度、树突棘密度均显著减少(P<0.05).结论:慢性脑缺血可导致海马CA1区锥体细胞树突及树突棘损伤性变化,从而构成进展性认知功能障碍的病理生理学基础.%AIM:To investigate the changes of dendritic morphology and spine density in hippocampal CA1 pyramidal cells of the chronic cerebral ischemic rats. METHODS:The model of chronic cerebral ischemia was established by permanent occlusion of the bilateral common carotid arteries ( 2VO ) in rats. Two weeks, 4 weeks or 8 weeks later, the behavior of the rats in each group was evaluated through the Morris water maze to select the successful modeling, and the brains were collected for processing Golgi staining. The changes in dendritic branch and length, and spine density in hippocampal CA1 pyramidal cells were observed under optical microscope. RESULTS: Compared with sham - operated group, dendritic branch and length in model group was significantly reduced in 4 -week group and 8 -week group ( P <0. 01 ), and spine density in model group were significantly reduced in 2 -week, 4 -week and 8 -week groups ( P <0. 01 ). With prolonged ischemia, dendritic branch and length, and spine density in model group were all significantly reduced ( P < 0. 05 ). CONCLUSION: Chronic cerebral ischemia leads to traumatic changes in dendrites and spines in hippocampal CA1 pyramidal cells, which

  2. Delayed effects of corticosterone on slow after-hyperpolarization potentials in mouse hippocampal versus prefrontal cortical pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Anup G Pillai

    Full Text Available The rodent stress hormone corticosterone changes neuronal activity in a slow and persistent manner through transcriptional regulation. In the rat dorsal hippocampus, corticosterone enhances the amplitude of calcium-dependent potassium currents that cause a lingering slow after-hyperpolarization (sAHP at the end of depolarizing events. In this study we compared the putative region-dependency of the delayed effects of corticosterone (approximately 5 hrs after treatment on sAHP as well as other active and passive properties of layer 2/3 pyramidal neurons from three prefrontal areas, i.e. the lateral orbitofrontal, prelimbic and infralimbic cortex, with the hippocampus of adult mice. In agreement with previous studies, corticosterone increased sAHP amplitude in the dorsal hippocampus with depolarizing steps of increasing amplitude. However, in the lateral orbitofrontal, prelimbic and infralimbic cortices we did not observe any modifications of sAHP amplitude after corticosterone treatment. Properties of single action potentials or % ratio of the last spike interval with respect to the first spike interval, an indicator of accommodation in an action potential train, were not significantly affected by corticosterone in all brain regions examined. Lastly, corticosterone treatment did not induce any lasting changes in passive membrane properties of hippocampal or cortical neurons. Overall, the data indicate that corticosterone slowly and very persistently increases the sAHP amplitude in hippocampal pyramidal neurons, while this is not the case in the cortical regions examined. This implies that changes in excitability across brain regions reached by corticosterone may vary over a prolonged period of time after stress.

  3. Intracellular activities related to in vitro hippocampal sharp waves are altered in CA3 pyramidal neurons of aged mice.

    Science.gov (United States)

    Moradi-Chameh, H; Peng, J; Wu, C; Zhang, L

    2014-09-26

    Pyramidal neurons in the hippocampal CA3 area interconnect intensively via recurrent axonal collaterals, and such CA3-to-CA3 recurrent circuitry plays important roles in the generation of hippocampal network activities. In particular, the CA3 circuitry is able to generate spontaneous sharp waves (SPWs) when examined in vitro. These in vitro SPWs are thought to result from the network activity of GABAergic inhibitory interneurons as SPW-correlating intracellular activities are featured with strong IPSPs in pyramidal neurons and EPSPs or spikes in GABAergic interneurons. In view of accumulating evidence indicating a decrease in subgroups of hippocampal GABAergic interneurons in aged animals, we test the hypothesis that the intracellular activities related to in vitro SPWs are altered in CA3 pyramidal neurons of aged mice. Hippocampal slices were prepared from adult and aged C57 black mice (ages 3-6 and 24-28months respectively). Population and single-cell activities were examined via extracellular and whole-cell patch-clamp recordings. CA3 SPW frequencies were not significantly different between the slices of adult and aged mice but SPW-correlating intracellular activities featured weaker IPSC components in aged CA3 pyramidal neurons compared to adult neurons. It was unlikely that this latter phenomenon was due to general impairments of GABAergic synapses in the aged CA3 circuitry as evoked IPSC responses and pharmacologically isolated IPSCs were observed in aged CA3 pyramidal neurons. In addition, aged CA3 pyramidal neurons displayed more positive resting potentials and had a higher propensity of burst firing than adult neurons. We postulate that alterations of GABAergic network activity may explain the reduced IPCS contributions to in vitro SPWs in aged CA3 pyramidal neurons. Overall, our present observations are supportive of the notion that excitability of hippocampal CA3 circuitry is increased in aged mice.

  4. Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons

    Institute of Scientific and Technical Information of China (English)

    Jia-Qiang Zhang; Wan-Ying Xu; Chang-Qing Xu

    2016-01-01

    Background:Propofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission.However,their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear.We investigated the long-term GABAergic neurotransmission alterations,following neonatal propofol and etomidate administration.Methods:Sprague-Dawley rat pups at postnatal days 4 6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia.We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80-90 days.Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured.The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined.Results:Neonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz,P < 0.05) and did not affect the amplitude of mIPSCs and sIPSCs.Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs.68.18 ± 12.43 ms;P < 0.05).Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms).Conclusions:Neonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission.Propofol might act at pre-and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses;etomidate might act at the postsynaptic site.

  5. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Alonso, Mariana; Medina, Jorge H.; Pozzo-Miller, Lucas

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

  6. Membrane Potential Dynamics of CA1 Pyramidal Neurons during Hippocampal Ripples in Awake Mice.

    Science.gov (United States)

    Hulse, Brad K; Moreaux, Laurent C; Lubenov, Evgueniy V; Siapas, Athanassios G

    2016-02-17

    Ripples are high-frequency oscillations associated with population bursts in area CA1 of the hippocampus that play a prominent role in theories of memory consolidation. While spiking during ripples has been extensively studied, our understanding of the subthreshold behavior of hippocampal neurons during these events remains incomplete. Here, we combine in vivo whole-cell and multisite extracellular recordings to characterize the membrane potential dynamics of identified CA1 pyramidal neurons during ripples. We find that the subthreshold depolarization during ripples is uncorrelated with the net excitatory input to CA1, while the post-ripple hyperpolarization varies proportionately. This clarifies the circuit mechanism keeping most neurons silent during ripples. On a finer timescale, the phase delay between intracellular and extracellular ripple oscillations varies systematically with membrane potential. Such smoothly varying delays are inconsistent with models of intracellular ripple generation involving perisomatic inhibition alone. Instead, they suggest that ripple-frequency excitation leading inhibition shapes intracellular ripple oscillations.

  7. 5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation.

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    Johnston, April; McBain, Chris J; Fisahn, André

    2014-10-01

    Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease.In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin(5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations.Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3.Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

  8. Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons.

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    Sung-Cherl Jung

    Full Text Available Since its original description, the induction of synaptic long-term potentiation (LTP has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K(+ channels. In the present manuscript, we examined the role of A-type K(+ channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K(+ channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+ channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

  9. Glutamic acid decarboxylase-67-positive hippocampal interneurons undergo a permanent reduction in number following kainic acid-induced degeneration of ca3 pyramidal neurons.

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    Shetty, A K; Turner, D A

    2001-06-01

    Kainic acid (KA)-induced degeneration of CA3 pyramidal neurons leads to synaptic reorganization and hyperexcitability in both dentate gyrus and CA1 region of the hippocampus. We hypothesize that the substrate for hippocampal inhibitory circuitry incurs significant and permanent alterations following degeneration of CA3 pyramidal neurons. We quantified changes in interneuron density (N(v)) in all strata of the dentate gyrus and the CA1 and CA3 subfields of adult rats at 1, 4, and 6 months following intracerebroventricular (icv) KA administration, using glutamic acid decarboxylase-67 (GAD-67) immunocytochemistry. At 1 month postlesion, GAD-67-positive interneuron density was significantly reduced in all strata of every hippocampal region except stratum pyramidale of CA1. The reduction in GAD-67-positive interneuron density either persisted or exacerbated at 4 and 6 months postlesion in every stratum of all hippocampal regions. Further, the soma of remaining GAD-67-positive interneurons in dentate gyrus and CA3 subfield showed significant hypertrophy. Thus, both permanent reductions in the density of GAD-67-positive interneurons in all hippocampal regions and somatic hypertrophy of remaining GAD-67-positive interneurons in dentate gyrus and CA3 subfield occur following icv KA. In contrast, the density of interneurons visualized with Nissl in CA1 and CA3 regions was nearly equivalent to that in the intact hippocampus at all postlesion time points. Collectively, these results suggest that persistent reductions in GAD-67-positive interneuron density observed throughout the hippocampus following CA3 lesion are largely due to a permanent loss of GAD-67 expression in a significant fraction of interneurons, rather than widespread degeneration of interneurons. Nevertheless, a persistent decrease in interneuron activity, as evidenced by permanent down-regulation of GAD-67 in a major fraction of interneurons, would likely enhance the degree of hyperexcitability in the CA3

  10. Corticotropin-Releasing Hormone (CRH)-Containing Neurons in the Immature Rat Hippocampal Formation: Light and Electron Microscopic Features and Colocalization With Glutamate Decarboxylase and Parvalbumin

    OpenAIRE

    Yan, Xiao-Xin; Toth, Zsolt; Schultz, Linda; Ribak, Charles E; Tallie Z. Baram

    1998-01-01

    Corticotropin-releasing hormone (CRH) excites hippocampal neurons and induces death of selected CA3 pyramidal cells in immature rats. These actions of CRH require activation of specific receptors that are abundant in CA3 during early postnatal development. Given the dramatic effects of CRH on hippocampal neurons and the absence of CRH-containing afferents to this region, we hypothesized that a significant population of CRHergic neurons exists in developing rat hippocampus. This study defined ...

  11. Elevated potassium elicits recurrent surges of large GABAA-receptor-mediated post-synaptic currents in hippocampal CA3 pyramidal neurons.

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    Shin, Damian Seung-Ho; Yu, Wilson; Sutton, Alex; Calos, Megan; Carlen, Peter Louis

    2011-03-01

    Previously, we found that rat hippocampal CA3 interneurons become hyperactive with increasing concentrations of extracellular K(+) up to 10 mM. However, it is unclear how this enhanced interneuronal activity affects pyramidal neurons. Here we voltage-clamped rat hippocampal CA3 pyramidal neurons in vitro at 0 mV to isolate γ-aminobutyric acid (GABA)-activated inhibitory post-synaptic currents (IPSCs) and measured these in artificial cerebrospinal fluid (aCSF) and with 10 mM K(+) bath perfusion. In aCSF, small IPSCs were present with amplitudes of 0.053 ± 0.007 nA and a frequency of 0.27 ± 0.14 Hz. With 10 mM K(+) perfusion, IPSCs increased greatly in frequency and amplitude, culminating in surge events with peak amplitudes of 0.56 ± 0.08 nA, that appeared and disappeared cyclically with durations lasting 2.02 ± 0.37 min repeatedly, up to 10 times over a 30-min bath perfusion of elevated K(+). These large IPSCs were GABA(A)-receptor mediated and did not involve significant desensitization of this receptor. Perfusion of a GABA transporter inhibitor (NO-711), glutamate receptor inhibitors CNQX and APV, or a gap junctional blocker (carbenoxolone) prevented the resurgence of large IPSCs. Pressure ejected sucrose resulted in the abolishment of subsequent surges. No elevated K(+)-mediated surges were observed in CA3 interneurons from the stratum oriens layer. In conclusion, these cyclic large IPSC events observable in CA3 pyramidal neurons in 10 mM KCl may be due to transient GABA depletion from continuously active interneuronal afferents.

  12. Hippocampal pyramidal neurons switch from a multipolar migration mode to a novel "climbing" migration mode during development.

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    Kitazawa, Ayako; Kubo, Ken-ichiro; Hayashi, Kanehiro; Matsunaga, Yuki; Ishii, Kazuhiro; Nakajima, Kazunori

    2014-01-22

    The hippocampus plays important roles in brain functions. Despite the importance of hippocampal functions, recent analyses of neuronal migration have mainly been performed on the cerebral neocortex, and the cellular mechanisms responsible for the formation of the hippocampus are not yet completely understood. Moreover, why a prolonged time is required for hippocampal neurons to complete their migration has been unexplainable for several decades. We analyzed the migratory profile of neurons in the developing mouse hippocampal CA1 region and found that the hippocampal pyramidal neurons generated near the ventricle became postmitotic multipolar cells and accumulated in the multipolar cell accumulation zone (MAZ) in the late stage of development. The hippocampal neurons passed through the pyramidal layer by a unique mode of migration. Their leading processes were highly branched and made contact with many radial fibers. Time-lapse imaging revealed that the migrating cells changed their scaffolds from the original radial fibers to other radial fibers, and as a result they proceed in a zigzag manner, with long intervals. The migrating cells in the hippocampus reminded us of "rock climbers" that instead of using their hands to pull up their bodies were using their leading processes to pull up their cell bodies. Because this mode of migration had never been described, we called it the "climbing" mode. The change from the "climbing" mode in the hippocampus to the "locomotion" mode in the neocortex may have contributed to the brain expansion during evolution.

  13. 常压高氧处理对丙戊酸钠孤独症模型鼠学习记忆能力及海马CA1区锥体细胞形态学的影响%Effects of normobaric hyperoxia on the learning and memory abilities of valproic acid autism model rats and the morphology of pyramidal cells in hippocampal CA1 region

    Institute of Scientific and Technical Information of China (English)

    马遥; 衣明纪; 李音; 付伟伟; 万金娥

    2012-01-01

    test at the 28th day after birth,40 male VPA autism model rats were randomly selected 20 only and divided into normobaric hyperoxia model group (group A,n =10),atmospheric air model group (group B,n =10).Normal control groups were obtained in male offspring of Wistar rats that received intraperitoneal injection of equivalent physiological saline at the same period pregnancy.(group C,n =10).Rats in group A were treated with oxygen for 1 h per day and lasted 1 week;group B and C were treated with normal air.The learning and memory abilities of three groups were assessed at the 35th day after birth.The immunohistochemistry methods and image analysis were used to observe the pyramidal cells of autism model rats in hippocampal CA1 region.The effect of normobaric hyperoxia therapy on pyramidal cell of autism model rats in hippocampal CA1 region were evaluated by HE staining technique.Results The trying times of group A after treatment were less than those before treatment (31.15 ± 0.99 vs 31.54 ± 0.97,t =2.739,P =0.018).The memory times were more than those before treatment (3.00± 0.58 vs 2.69 ± 0.48,t =-2.309,P =0.040).The trying times of group A after treatment were less than those in group B after treatment (P =0.016).The memory times of group A were not different from that in group B after treatment(P=0.810).The morphology of pyramidal cells in hippocampal CA1 region showed that the pyramidal cells of the autism model rats had apoptosised.The number of apoptotic cells reduced and the number of normal form cells increased after the normobaric hyperoxia intervention compared with the autism model rats.Conclusion Normobaric hyperoxia intervention can improve the learning and memory abilities of the autism model rats.The apoptosis of the pyramidal neurons in hippocampal CA1 might be reduced after the normobaric hyperoxia intervention.

  14. Effects of droperidol on persistent sodium channel currents of pyramidal cell in hippocampal CA1 area of rats with cerebral ischemia%氟哌利多对大鼠脑缺血海马CA1区锥体细胞持续钠通道电流的影响

    Institute of Scientific and Technical Information of China (English)

    焦志华; 庄心良; 王士雷; 张一

    2005-01-01

    流.②脑缺血时海马CA1区神经元持续性钠电流的记录:缺血对照组缺血3 min时持续钠电流增加为正常情况的(1.60±0.21)倍,缺血5 min时持续钠电流增加为正常情况的(2.87±0.45)倍,差异显著(P<0.05).③不同浓度氟哌利多对脑缺血时持续性钠电流的影响:缺血对照组、氟哌利多3,10,30 μmol/L组持续钠电流的基础值分别是(77.42±15.17)pA,(87.44±21.56)pA,(84.13±20.06)pA,(80.22±19.30)pA,组间比较差异无显著性意义.缺血5min后氟哌利多3,10,30μmol/L组持续性钠电流分别为(105.36±17.16)pA,(94.74±18.88)pA,(84.88±13.94)pA,明显低于缺血对照组(218.31±29.34)pA.结论:在钳制电压-105mV、刺激电压-30mV条件下,脑缺血损伤时持续性钠电流增加,氟哌利多可能通过抑制持续性钠电流的增强而发挥神经元保护作用.%BACKGROUND: Both abnormal permeability of ionic channel and disturbance of ionic balance between inside and outside nerve cell are key factors for ischemic brain injury after ischemia. Depolarization induced by activation of sodium channel is starting link for cerebral ischemic injury.OBJECTIVE: To study the effects of droperidol on persistent sodium channel currents of pyramidal cell in hippocampal CA1 area of rats with cerebral ischemia with patch clamp technique so as to analyze whether droperidol can protect cerebral ischemic injury.DESIGN: Randomized controlled animal study.SETTING: Department of Anesthesiology of the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and Department of Anesthesiology of the First People's Hospital Affiliated to Shanghai Jiaotong University.MATERIALS: The experiment was carried out at the Department of Anesthesiology of the First People's Hospital Affiliated to Shanghai Jiaotong University from April 2002 to April 2003. Totally 14 SD rats, aging 10-14days, without ablactation, were selected. Two cells in hippocampal CA1area of each rat were collected, totally 28 cells were divided into 4 groups

  15. Cholinergic modulation differs between basal and apical dendritic excitation of hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Leung, L Stan; Péloquin, Pascal

    2010-08-01

    We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink-PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX-116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.

  16. Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus.

    Science.gov (United States)

    Williams, Tanya J; Torres-Reveron, Annelyn; Chapleau, Jeanette D; Milner, Teresa A

    2011-02-01

    Clinical and preclinical studies indicate that women and men differ in relapse vulnerability to drug-seeking behavior during abstinence periods. As relapse is frequently triggered by exposure of the recovered addict to objects previously associated with drug use and the formation of these associations requires memory systems engaged by the hippocampal formation (HF), studies exploring ovarian hormone modulation of hippocampal function are warranted. Previous studies revealed that ovarian steroids alter endogenous opioid peptide levels and trafficking of mu opioid receptors in the HF, suggesting cooperative interaction between opioids and estrogens in modulating hippocampal excitability. However, whether ovarian steroids affect the levels or trafficking of delta opioid receptors (DORs) in the HF is unknown. Here, hippocampal sections of adult male and normal cycling female Sprague-Dawley rats were processed for quantitative immunoperoxidase light microscopy and dual label fluorescence or immunoelectron microscopy using antisera directed against the DOR and neuropeptide Y (NPY). Consistent with previous studies in males, DOR-immunoreactivity (-ir) localized to select interneurons and principal cells in the female HF. In comparison to males, females, regardless of estrous cycle phase, show reduced DOR-ir in the granule cell layer of the dentate gyrus and proestrus (high estrogen) females, in particular, display reduced DOR-ir in the CA1 pyramidal cell layer. Ultrastructural analysis of DOR-labeled profiles in CA1 revealed that while females generally show fewer DORs in the distal apical dendrites of pyramidal cells, proestrus females, in particular, exhibit DOR internalization and trafficking towards the soma. Dual label studies revealed that DORs are found in NPY-labeled interneurons in the hilus, CA3, and CA1. While DOR colocalization frequency in NPY-labeled neuron somata was similar between animals in the hilus, proestrus females had fewer NPY-labeled neurons that

  17. Novel bio-spectroscopic imaging reveals disturbed protein homeostasis and thiol redox with protein aggregation prior to hippocampal CA1 pyramidal neuron death induced by global brain ischemia in the rat.

    Science.gov (United States)

    Hackett, Mark J; Smith, Shari E; Caine, Sally; Nichol, Helen; George, Graham N; Pickering, Ingrid J; Paterson, Phyllis G

    2015-12-01

    occur in the same CA1 pyramidal neurons 1 day after global ischemia. Further, analysis of serial tissue sections using X-ray absorption spectroscopy at the sulfur K-edge has revealed that CA1 pyramidal neurons have increased disulfide levels, a direct indicator of oxidative stress, at this time point. These changes at 1 day after ischemia precede a massive increase in aggregated protein and disulfide levels concomitant with loss of neuron integrity 2 days after ischemia. Therefore, this study has provided direct support for a correlative mechanistic link in both spatial and temporal domains between oxidative stress, protein aggregation and altered protein homeostasis prior to irreparable neuron damage following global ischemia.

  18. Lead exposure impairs NMDA agonist-induced no production in pyramidal hippocampal cells

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    Seyed Nasser Ostad

    2006-03-01

    Full Text Available Chronic exposure to Lead (Pb affects neural functions in central nervous system (CNS particularly the learning and memory. On the other hand, alteration of calcium level in the CNS results in activation of NOS where it is expected to increase nitric oxide level in hippocampus. In this study the role of Lead exposure in NMDA induced NO production in pyramidal hippocampal cells (CA1HP was investigated. The NO level was determined by measurement of concentration of nitrite and nitrate as NO products using the metHb production at 401 nm. The ACBD (NMDA agonist-induced NO level was almost reduced to the control level (2.5 nM in the presence of 10 and 100 nM of Lead acetate. Lead acetate at concentrations which normally results in chronic toxicity did not increase the nitric oxide (NO production by CA1HP. One reason for this finding could be the interaction of Lead with NMDA receptors due to similarity of Pb2+ to Zn2+ ion. Another reason may be related to direct interaction of Lead with NMDA receptors that inhibit the stimulated NO production.

  19. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    Science.gov (United States)

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  20. Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats

    Directory of Open Access Journals (Sweden)

    Valentina eCorvino

    2015-11-01

    Full Text Available Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2 administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT administration (8mg/kg, characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg i.p. or vehicle, and were sacrificed 48h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48h upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, Cadherin and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad 67, neuropeptide Y (Npy, parvalbumin , Pgc-1α and Sirtuin 1genes, the latter involved in parvalbumin (PV synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain.

  1. Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress.

    Science.gov (United States)

    Gavilán, Elena; Pintado, Cristina; Gavilan, Maria P; Daza, Paula; Sánchez-Aguayo, Inmaculada; Castaño, Angélica; Ruano, Diego

    2015-05-01

    Autophagy plays a key role in the maintenance of cellular homeostasis, and autophagy deregulation gives rise to severe disorders. Many of the signaling pathways regulating autophagy under stress conditions are still poorly understood. Using a model of proteasome stress in rat hippocampus, we have characterized the functional crosstalk between the ubiquitin proteasome system and the autophagy-lysosome pathway, identifying also age-related modifications in the crosstalk between both proteolytic systems. Under proteasome inhibition, both autophagy activation and resolution were efficiently induced in young but not in aged rats, leading to restoration of protein homeostasis only in young pyramidal neurons. Importantly, proteasome stress inhibited glycogen synthase kinase-3β in young but activated in aged rats. This age-related difference could be because of a dysfunction in the signaling pathway of the insulin growth factor-1 under stress situations. Present data highlight the potential role of glycogen synthase kinase-3β in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.

  2. Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Kerti, Katalin; Lorincz, Andrea; Nusser, Zoltan

    2012-01-01

    A-type K(+) current (I(A)) plays a critical role in controlling the excitability of pyramidal cell (PC) dendrites. In vitro dendritic patch-pipette recordings have demonstrated a prominent, sixfold increase in I(A) density along the main apical dendrites of rat hippocampal CA1 PCs. In these cells, I(A) is mediated by Kv4.2 subunits, whose precise subcellular distribution and densities in small-diameter oblique dendrites and dendritic spines are still unknown. Here we examined the densities of the Kv4.2 subunit in 13 axo-somato-dendritic compartments of CA1 PCs using a highly sensitive, high-resolution quantitative immunogold localization method (sodium dodecyl sulphate-digested freeze-fracture replica-labelling). Only an approximately 70% increase in Kv4.2 immunogold density was observed along the proximo-distal axis of main apical dendrites in the stratum radiatum with a slight decrease in density in stratum lacunosum-moleculare. A similar pattern was detected for all dendritic compartments, including main apical dendrites, small-diameter oblique dendrites and dendritic spines. The specificity of the somato-dendritic labelling was confirmed in Kv4.2(-/-) tissue. No specific immunolabelling for the Kv4.2 subunit was found in SNAP-25-containing presynaptic axons. Our results demonstrate a novel distribution pattern of a voltage-gated ion channel along the somato-dendritic surface of CA1 PCs, and suggest that the increase in the I(A) along the proximo-distal axis of PC dendrites cannot be solely explained by a corresponding increase in Kv4.2 channel number.

  3. Hippocampal network dynamics constrain the time lag between pyramidal cells across modified environments

    Science.gov (United States)

    Diba, Kamran; Buzsáki, György

    2008-01-01

    The hippocampus provides a spatial map of the environment. Changes in the environment alter the firing patterns of hippocampal neurons, but are presumably constrained by elements of the network dynamics. We compared the neural activity in CA1 and CA3 regions of the hippocampus in rats running for water reward on a linear track, before and after the track length was shortened. A fraction of cells lost their place-fields and new sets of cells with fields emerged, indicating distinct representation of the two tracks. Cells active in both environments shifted their place-fields in a location dependent manner, most notably at the beginning and the end of the track. Furthermore, peak firing rates and place-field sizes decreased, while place-field overlap and co-activity increased. Power in the theta-frequency band of the local field potentials also decreased in both CA1 and CA3, along with the coherence between the two structures. In contrast, the theta-scale (0–150 ms) time lags between cell pairs, representing distances on the tracks, were conserved, and the activity of the inhibitory neuron population was maintained across environments. We interpret these observations as reflecting the freedoms and constraints of the hippocampal network dynamics. The freedoms permit the necessary flexibility for the network to distinctly represent unique patterns, while the dynamics constrain the speed at which activity propagates between the cell assemblies representing the patterns. PMID:19074018

  4. Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment.

    Science.gov (United States)

    Shen, Ying; Kishimoto, Koji; Linden, David J; Sapirstein, Adam

    2007-04-03

    The arachidonic acid-generating enzyme cytosolic phospholipase A(2) alpha (cPLA(2)alpha) has been implicated in the progression of excitotoxic neuronal injury. However, the mechanisms of cPLA(2)alpha toxicity have yet to be determined. Here, we used a model system exposing mouse hippocampal slices to NMDA as an excitotoxic injury, in combination with simultaneous patch-clamp recording and confocal Ca(2+) imaging of CA1 pyramidal neurons. NMDA treatment caused significantly greater injury in wild-type (WT) than in cPLA(2)alpha null CA1 neurons. Bath application of NMDA evoked a slow inward current in voltage-clamped neurons (composed of both NMDA receptor-mediated and other conductances) that was smaller in cPLA(2)alpha null than in WT slices. This was not due to down-regulation of NMDA receptor function because NMDA receptor-mediated currents were equivalent in each genotype following brief photolysis of caged glutamate. Current-clamp recordings were made during and following NMDA exposure by eliciting a single action potential with a brief current injection. After NMDA exposure, WT CA1 neurons developed a spike-evoked plateau potential and an increased spike-evoked dendritic Ca(2+) transient. These effects were absent in CA1 neurons from cPLA(2)alpha null mice and WT neurons treated with a cPLA(2)alpha inhibitor. The Ca-sensitive K-channel toxins, apamin and paxilline, caused spike broadening and Ca(2+) enhancement in WT and cPLA(2)alpha null slices. NMDA application in WT and arachidonate applied to cPLA(2)alpha null cells occluded the effects of apamin/paxilline. These results indicate that cPLA(2)alpha activity is required for development of aberrant electrophysiologic events triggered by NMDA receptor activation, in part through attenuation of K-channel function.

  5. Distinct axo-somato-dendritic distributions of three potassium channels in CA1 hippocampal pyramidal cells.

    Science.gov (United States)

    Kirizs, Tekla; Kerti-Szigeti, Katalin; Lorincz, Andrea; Nusser, Zoltan

    2014-06-01

    Potassium channels comprise the most diverse family of ion channels and play critical roles in a large variety of physiological and pathological processes. In addition to their molecular diversity, variations in their distributions and densities on the axo-somato-dendritic surface of neurons are key parameters in determining their functional impact. Despite extensive electrophysiological and anatomical investigations, the exact location and densities of most K(+) channels in small subcellular compartments are still unknown. Here we aimed at providing a quantitative surface map of two delayed-rectifier (Kv1.1 and Kv2.1) and one G-protein-gated inwardly rectifying (Kir3.2) K(+) channel subunits on hippocampal CA1 pyramidal cells (PCs). Freeze-fracture replica immunogold labelling was employed to determine the relative densities of these K(+) channel subunits in 18 axo-somato-dendritic compartments. Significant densities of the Kv1.1 subunit were detected on axon initial segments (AISs) and axon terminals, with an approximately eight-fold lower density in the latter compartment. The Kv2.1 subunit was found in somatic, proximal dendritic and AIS plasma membranes at approximately the same densities. This subunit has a non-uniform plasma membrane distribution; Kv2.1 clusters are frequently adjacent to, but never overlap with, GABAergic synapses. A quasi-linear increase in the Kir3.2 subunit density along the dendrites of PCs was detected, showing no significant difference between apical dendritic shafts, oblique dendrites or dendritic spines at the same distance from the soma. Our results demonstrate that each subunit has a unique cell-surface distribution pattern, and predict their differential involvement in synaptic integration and output generation at distinct subcellular compartments.

  6. Adenosine A1 Receptor Suppresses Tonic GABAA Receptor Currents in Hippocampal Pyramidal Cells and in a Defined Subpopulation of Interneurons.

    Science.gov (United States)

    Rombo, Diogo M; Dias, Raquel B; Duarte, Sofia T; Ribeiro, Joaquim A; Lamsa, Karri P; Sebastião, Ana M

    2016-03-01

    Adenosine is an endogenous neuromodulator that decreases excitability of hippocampal circuits activating membrane-bound metabotropic A1 receptor (A1R). The presynaptic inhibitory action of adenosine A1R in glutamatergic synapses is well documented, but its influence on inhibitory GABAergic transmission is poorly known. We report that GABAA receptor (GABAAR)-mediated tonic, but not phasic, transmission is suppressed by A1R in hippocampal neurons. Adenosine A1R activation strongly inhibits GABAAR agonist (muscimol)-evoked currents in Cornu Ammonis 1 (CA1) pyramidal neurons and in a specific subpopulation of interneurons expressing axonal cannabinoid receptor type 1. In addition, A1R suppresses tonic GABAAR currents measured in the presence of elevated ambient GABA as well as in naïve slices. The inhibition of GABAergic currents involves both protein kinase A (PKA) and protein kinase C (PKC) signaling pathways and decreases GABAAR δ-subunit expression. On the contrary, no A1R-mediated modulation was detected in phasic inhibitory postsynaptic currents evoked either by afferent electrical stimulation or by spontaneous quantal release. The results show that A1R modulates extrasynaptic rather than synaptic GABAAR-mediated signaling, and that this modulation selectively occurs in hippocampal pyramidal neurons and in a specific subpopulation of inhibitory interneurons. We conclude that modulation of tonic GABAAR signaling by adenosine A1R in specific neuron types may regulate neuronal gain and excitability in the hippocampus.

  7. 磷脂酰肌醇-3-激酶/蛋白激酶B信号转导通路与针刺保护癫痫继发海马神经元损伤的关系%PI 3 K/Akt Signaling Pathway Contributed to the Protective Effect of Acupuncture Intervention on Epileptic Seizure-induced Injury of Hippocampal Pyramidal Cells in Epilepsy Rats

    Institute of Scientific and Technical Information of China (English)

    杨帆; 昂文平; 沈德凯; 刘向国; 杨永清; 马允

    2013-01-01

    Objective To observe the protective effect of acupuncture stimulation on pyramidal cells in hippocampal CA 1 and CA 3 regions and to analyze the involvement of phosphatidy linositol-3-kinase (PI 3 K) /protein kinase B(PKB or Akt) signaling pathway in the acupuncture effect in epilepsy rats. Methods A total of 120 SD rats were randomly divided into normal control group, model group, LY 294002 (a specific antagonist for PI 3 K/Akt signaling) group, acupuncture + LY 294002 group and acupuncture group (n = 24 in each group, 12 for H. E. staining, and 12 for electron microscope observation). Epilepsy model was established by intraperitoneal injection of pentylenetetrazol (PTZ, 5 μL). Manual acupuncture stimulation was applied to "Baihui" (GV20) and "Dazhui" (GV 14) once daily for 5 days. Dimethyl Sulfoxide (DMSO, 5 μL, a control solvent) was given to rats of the normal, model and acupuncture groups, and LY 294002 (5 μL, dissolved in DMSO) given to rats of the LY 294002 and acupuncture+LY 294002 groups by lateral ventricular injection. Four hours and 24 h after modeling, the hippocampus tissues were sampled for observing pathological changes of CA 1 and CA 3 regions after H. E. staining under light microscope and for checking ultrastructural changes of the pyramidal cells under transmission electron microscope. Results In comparison with the normal control group, the numbers of pyramidal cells of hippocampal CA3 region in the model group were decreased significantly 4 h and 24 h after epileptic seizure (P0. 05). Findings of the light microscope and electron microscope showed that the injury severity of pyramidal cells of hippocampal CA 1 and CA 3 regions was moderate 4 h after epileptic seizure and even worse 24 h after seizure in the model group, LY 294002 group and acupuncture + LY 294002 group, but relatively lighter in the acupuncture group. These results suggested an elimination of the acupuncture effect after blocking the PI 3 K/Akt signaling pathway by lateral

  8. Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons

    Directory of Open Access Journals (Sweden)

    Belrose Jillian C

    2012-04-01

    Full Text Available Abstract Background Glutathione (GSH plays an important role in neuronal oxidant defence. Depletion of cellular GSH is observed in neurodegenerative diseases and thereby contributes to the associated oxidative stress and Ca2+ dysregulation. Whether depletion of cellular GSH, associated with neuronal senescence, directly influences Ca2+ permeation pathways is not known. Transient receptor potential melastatin type 2 (TRPM2 is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. Importantly, GSH has been reported to inhibit TRPM2 channels, suggesting they may directly contribute to Ca2+ dysregulation associated with neuronal senescence. Herein, we explore the relation between cellular GSH and TRPM2 channel activity in long-term cultures of hippocampal neurons. Results In whole-cell voltage-clamp recordings, we observe that TRPM2 current density increases in cultured pyramidal neurons over time in vitro. The observed increase in current density was prevented by treatment with NAC, a precursor to GSH synthesis. Conversely, treatment of cultures maintained for 2 weeks in vitro with L-BSO, which depletes GSH by inhibiting its synthesis, augments TRPM2 currents. Additionally, we demonstrate that GSH inhibits TRPM2 currents through a thiol-independent mechanism, and produces a 3.5-fold shift in the dose-response curve generated by ADPR, the intracellular agonist for TRPM2. Conclusion These results indicate that GSH plays a physiologically relevant role in the regulation of TRPM2 currents in hippocampal pyramidal neurons. This interaction may play an important role in aging and neurological diseases associated with depletion of GSH.

  9. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.

    Science.gov (United States)

    Yang, Bo; Rajput, Padmesh S; Kumar, Ujendra; Sastry, Bhagavatula R

    2015-01-01

    The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.

  10. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.

    Directory of Open Access Journals (Sweden)

    Bo Yang

    Full Text Available The equilibrium potential for GABA-A receptor mediated currents (EGABA in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2 but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1. Theta-burst stimulation (TBS in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS-a-Methyl-4-carboxyphenylglycine (MCPG, a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.

  11. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.

    OpenAIRE

    Colmers, W. F.; Klapstein, G. J.; A. Fournier; St-Pierre, S.; Treherne, K. A.

    1991-01-01

    1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynapti...

  12. Effects of electromagnetic radiation on spatial memory and synapses in rat hippocampal CA1

    Institute of Scientific and Technical Information of China (English)

    Yuhong Li; Changhua Shi; Guobing Lu; Qian Xu; Shaochen Liu

    2012-01-01

    In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation (0.52-1.08 W/kg) was delivered to 8-week-old Wistar rats 2 hours per day for 1 month, behavioral changes were examined using the Morris water maze. Compared with the sham-irradiated rats, the irradiated rats exhibited impaired performance. Morphological changes were investigated by examining synaptic ultrastructural changes in the hippocampus. Using the physical dissector technique, the number of pyramidal neurons, the synaptic profiles, and the length of postsynaptic densities in the CA1 region were quantified stereologically. The morphological changes included mitochondrial degenerations, fewer synapses, and shorter postsynaptic densities in the radiated rats. These findings indicate that mobile phone radiation can significantly impair spatial learning and reference memory and induce morphological changes in the hippocampal CA1 region.

  13. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses

    Science.gov (United States)

    Vyleta, Nicholas P; Borges-Merjane, Carolina; Jonas, Peter

    2016-01-01

    Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network. DOI: http://dx.doi.org/10.7554/eLife.17977.001 PMID:27780032

  14. Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats.

    Science.gov (United States)

    Kowalski, Janina; Gan, Jian; Jonas, Peter; Pernía-Andrade, Alejandro J

    2016-05-01

    The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3-6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.

  15. Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC.

    Science.gov (United States)

    Hoffman, D A; Johnston, D

    1998-05-15

    We have reported recently a high density of transient A-type K+ channels located in the distal dendrites of CA1 hippocampal pyramidal neurons and shown that these channels shape EPSPs, limit the back-propagation of action potentials, and prevent dendritic action potential initiation (). Because of the importance of these channels in dendritic signal propagation, their modulation by protein kinases would be of significant interest. We investigated the effects of activators of cAMP-dependent protein kinase (PKA) and the Ca2+-dependent phospholipid-sensitive protein kinase (PKC) on K+ channels in cell-attached patches from the distal dendrites of hippocampal CA1 pyramidal neurons. Inclusion of the membrane-permeant PKA activators 8-bromo-cAMP (8-br-cAMP) or forskolin in the dendritic patch pipette resulted in a depolarizing shift in the activation curve for the transient channels of approximately 15 mV. Activation of PKC by either of two phorbol esters also resulted in a 15 mV depolarizing shift of the activation curve. Neither PKA nor PKC activation affected the sustained or slowly inactivating component of the total outward current. This downregulation of transient K+ channels in the distal dendrites may be responsible for some of the frequently reported increases in cell excitability found after PKA and PKC activation. In support of this hypothesis, we found that activation of either PKA or PKC significantly increased the amplitude of back-propagating action potentials in distal dendrites.

  16. Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

    Science.gov (United States)

    Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

    2015-05-22

    The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)hippocampal pyramidal neurons. Not all neuron types studied here expressed MG channel currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed no detectable MG channel activity. Moreover their robust rhythmic spike activity was resistant to mechanical modulation. Our observation that a single MG channel current can trigger spiking predicates the need for reassessment of the long held view that the impulse output of central neurons depends only upon their intrinsic voltage-gated channels and/or their integrated synaptic input.

  17. Three-dimensional structure of CA1 pyramidal cells in rat hippocampus——Optical recording of LSM and computer simulation of fractal structure

    Institute of Scientific and Technical Information of China (English)

    冯春华; 刘力; 刘守忠; 宁红; 孙海坚; 郭爱克

    1995-01-01

    The optical recording of three-dimensional(3-D)reconstruction of CA1 pyramidal cells wasderived from the studies on the CA1 region of the hippocampus in adult male Wistar rats.The recordingwas produced by the Confocal Laser Scan Microscope(LSM-10).The attemption was to outline themorphological neural network of CA1 pyramidal cells organization,following the trail of axo-dendritic connec-tions in 3-D spatial distributions among neurons.The fractal structure of neurons with their dendritic andaxonal trees using fractal algorithm was noticed,and 2—18 simulated cells were obtained using PC-486 comput-er.The simulational cells are similar in morphology to the natural CA1 hippocampal pyramidal cells.There-fore,the exploitation of an advanced neurohistological research technique combining optical recording of theLSM-10 and computer simulation of fractal structure can provide the quantitative fractal structural basis forchaosic dynamics of brain.

  18. Age-Related Deficits in Spatial Memory and Hippocampal Spines in Virgin, Female Fischer 344 Rats

    Directory of Open Access Journals (Sweden)

    Victoria N. Luine

    2011-01-01

    Full Text Available Effects of aging on memory and brain morphology were examined in aged, 21-month-old, and young, 4-month-old, Fischer 344 female rats. Spatial memory was assessed using the object placement task, and dendritic spine density was determined on pyramidal neurons in the hippocampus following Golgi impregnation. Consistent with previous studies, aged females showed poorer object placement performance than young subjects. Young subjects significantly discriminated the location of objects with a 1.5-hour intertrial delay while aged subjects did not. Spine density of basal dendrites on CA1 pyramidal cells was 16% lower in the aged subjects as compared to the young subjects. No differences in spine density were found between young and aged subjects in basal dendrites of CA1 or in either dendritic field of CA3 pyramidal neurons. Thus, decreased hippocampal CA1 dendritic spine density in aged rats may contribute to poorer spatial memory as compared to young rats. The possibility that the neuroplastic changes observed in this study may pertain only to female subjects having had a specific set of life experiences is discussed. Different factors, such as reproductive status, diet, and handling may contribute to neuroplasticity of the brain during aging; however, this view requires further examination.

  19. Proteolytic degradation of glutamate decarboxylase mediates disinhibition of hippocampal CA3 pyramidal cells in cathepsin D-deficient mice.

    Science.gov (United States)

    Shimizu, Tokiko; Hayashi, Yoshinori; Yamasaki, Ryo; Yamada, Jun; Zhang, Jian; Ukai, Kiyoharu; Koike, Masato; Mine, Kazunori; von Figura, Kurt; Peters, Christoph; Saftig, Paul; Fukuda, Takaichi; Uchiyama, Yasuo; Nakanishi, Hiroshi

    2005-08-01

    Although of clinical importance, little is known about the mechanism of seizure in neuronal ceroid lipofuscinosis (NCL). In the present study, we have attempted to elucidate the mechanism underlying the seizure of cathepsin D-deficient (CD-/-) mice that show a novel type of lysosomal storage disease with a phenotype resembling late infantile NCL. In hippocampal slices prepared from CD-/- mice at post-natal day (P)24, spontaneous burst discharges were recorded from CA3 pyramidal cells. At P24, the mean amplitude of IPSPs after stimulation of the mossy fibres was significantly smaller than that of wild-type mice, which was substantiated by the decreased level of gamma-aminobutyric acid (GABA) contents in the hippocampus measured by high-performance liquid chromatography (HPLC). At this stage, activated microglia were found to accumulate in the pyramidal cell layer of the hippocampal CA3 subfield of CD-/- mice. However, there was no significant change in the numerical density of GABAergic interneurons in the CA3 subfield of CD-/- mice at P24, estimated by counting the number of glutamate decarboxylase (GAD) 67-immunoreactive somata. In the hippocampus and the cortex of CD-/- mice at P24, some GABAergic interneurons displayed extremely high somatic granular immunoreactivites for GAD67, suggesting the lysosomal accumulation of GAD67. GAD67 levels in axon terminals abutting on to perisomatic regions of hippocampal CA3 pyramidal cells was not significantly changed in CD-/- mice even at P24, whereas the total protein levels of GAD67 in both the hippocampus and the cortex of CD-/- mice after P24 were significantly decreased as a result of degradation. Furthermore, the recombinant human GAD65/67 was rapidly digested by the lysosomal fraction prepared from the whole brain of wild-type and CD-/- mice. These observations strongly suggest that the reduction of GABA contents, presumably because of lysosomal degradation of GAD67 and lysosomal accumulation of its degraded forms

  20. Elevation of naloxone-sensitive /sup 3/H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D.D.; Mills, S.A.; Jobe, P.C.; Reigel, C.E.

    1988-01-01

    /sup 3/H-Dihydromorphine (DHM) binding sites were measured in the brain of non-epileptic control and GEPR rats using in vitro autoradiographic techniques. The number of naloxone-sensitive /sup 3/H-DHM binding sites was increased 38-57% in the pyramidal cell layer of ventral hippocampal CA/sub 3/ and CA/sub 1/ of GEPR-3 and GEPR-9 rats compared to non-epileptic controls. No significant differences in /sup 3/H-DHM binding were observed in dorsal hippocampal formation, lateral entorhinal cortex, lateral geniculate or cerebellum. The results suggest that an increase in the number of opioid receptors in ventral hippocampus of GEPR rats may be one factor contributing to the enhanced sensitivity of GEPR-9 rats to the proconvulsant effects of morphine.

  1. Potential Synaptic Connectivity of Different Neurons onto Pyramidal Cells in a 3D Reconstruction of the Rat Hippocampus

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    Deepak eRopireddy

    2011-07-01

    Full Text Available Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g. with electron microscopy or on regional connectivity (tract tracing. An individual pyramidal cell extends thousands of synapses over macroscopic distances (~cm. The contrasting requirements of high resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these ‘potential synapses’ functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto pyramidal cell dendrites from the axons of a dentate granule cell, three CA3 pyramidal cells, one CA2 pyramidal cell, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g. CA3 vs. CA1, layer (e.g. oriens vs. radiatum, and septo-temporal location (e.g. dorsal vs. ventral. The overall ratio between the numbers of actual and potential synapses was ~0.20 for the granule and CA3 pyramidal cells. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post

  2. Atorvastatin enhances kainate-induced gamma oscillations in rat hippocampal slices.

    Science.gov (United States)

    Li, Chengzhang; Wang, Jiangang; Zhao, Jianhua; Wang, Yali; Liu, Zhihua; Guo, Fang Li; Wang, Xiao Fang; Vreugdenhil, Martin; Lu, Cheng Biao

    2016-09-01

    Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post-synaptic currents, but did not affect the frequency of spontaneous excitatory post-synaptic currents. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.

  3. Synaptic conductances during interictal discharges in pyramidal neurons of rat entorhinal cortex

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    Dmitry V. Amakhin

    2016-10-01

    Full Text Available In epilepsy, the balance of excitation and inhibition underlying the basis of neural network activity shifts, resulting in neuronal network hyperexcitability and recurrent seizure-associated discharges. Mechanisms involved in ictal and interictal events are not fully understood, in particular, because of controversial data regarding the dynamics of excitatory and inhibitory synaptic conductances. In the present study, we estimated AMPAR-, NMDAR-, and GABAAR-mediated conductances during two distinct types of interictal discharge (IID in pyramidal neurons of rat entorhinal cortex in cortico-hippocampal slices. Repetitively emerging seizure-like events and IIDs were recorded in high extracellular potassium, 4-aminopyridine, and reduced magnesium-containing solution. An original procedure for estimating synaptic conductance during IIDs was based on the differences among the current-voltage characteristics of the synaptic components. The synaptic conductance dynamics obtained revealed that the first type of IID is determined by activity of GABAAR channels with depolarized reversal potential. The second type of IID is determined by the interplay between excitation and inhibition, with prominent early AMPAR and prolonged depolarized GABAAR and NMDAR-mediated components. The study then validated the contribution of these components to IIDs by intracellular pharmacological isolation. These data provide new insights into the mechanisms of seizures generation, development, and cessation.

  4. Selective pharmacological modulation of pyramidal neurons and interneurons in the CA1 region of the rat hippocampus

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    Marzia eMartina

    2013-03-01

    Full Text Available The hippocampus is a complex network tightly regulated by interactions between excitatory and inhibitory neurons. In neurodegenerative disorders where cognitive functions such as learning and memory are impaired this excitation-inhibition balance may be altered. Interestingly, the uncompetitive NMDAR antagonist memantine, currently in clinical use for the treatment of Alzheimer’s disease (AD, may alter the excitation-inhibition balance in the hippocampus. However, the specific mechanism by which memantine exerts this action is not clear. To better elucidate the effect of memantine on hippocampal circuitry, we studied its pharmacology on NMDAR currents in both pyramidal cells (PCs and interneurons (Ints in the CA1 region of the hippocampus. Applying whole-cell patch-clamp methodology to acute rat hippocampal slices, we report that memantine antagonism is more robust in PCs than in Ints. Using specific NMDAR subunit antagonists, we determined that this selective antagonism of memantine is attributable to specific differences in the molecular make up of the NMDARs in excitatory and inhibitory neurons. These findings offer new insight into the mechanism of action and therapeutic potential of NMDA receptor pharmacology in modulating hippocampal excitability.

  5. Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

    OpenAIRE

    Lushnikova, Irina; Skibo, Galina; Muller, Dominique; Nikonenko, Iryna

    2011-01-01

    Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic i...

  6. Tonic GABAA conductance decreases membrane time constant and increases EPSP-spike precision in hippocampal pyramidal neurons

    Directory of Open Access Journals (Sweden)

    Agnieszka I Wlodarczyk

    2013-12-01

    Full Text Available Because of a complex dendritic structure, pyramidal neurons have a large membrane surface relative to other cells and so a large electrical capacitance and a large membrane time constant (τm. This results in slow depolarizations in response to excitatory synaptic inputs, and consequently increased and variable action potential latencies, which may be computationally undesirable. Tonic activation of GABAA receptors increases membrane conductance and thus regulates neuronal excitability by shunting inhibition. In addition, tonic increases in membrane conductance decrease the membrane time constant (τm, and improve the temporal fidelity of neuronal firing. Here we performed whole-cell current clamp recordings from hippocampal CA1 pyramidal neurons and found that bath application of 10 µM GABA indeed decreases τm in these cells. GABA also decreased first spike latency and jitter (standard deviation of the latency produced by current injection of 2 rheobases (500 ms. However, when larger current injections (3-6 rheobases were used, GABA produced no significant effect on spike jitter, which was low. Using mathematical modelling we demonstrate that the tonic GABAA conductance decreases rise time, decay time and half-width of EPSPs in pyramidal neurons. A similar effect was observed on EPSP/IPSP pairs produced by stimulation of Schaffer collaterals: the EPSP part of the response became shorter after application of GABA. Consistent with the current injection data, a significant decrease in spike latency and jitter was obtained in cell attached recordings only at near-threshold stimulation (50% success rate, S50. When stimulation was increased to 2- or 3- times S50, GABA significantly affected neither spike latency nor spike jitter. Our results suggest that a decrease in τm associated with elevations in ambient GABA can improve EPSP-spike precision at near-threshold synaptic inputs.

  7. Tonic GABAA conductance decreases membrane time constant and increases EPSP-spike precision in hippocampal pyramidal neurons.

    Science.gov (United States)

    Wlodarczyk, Agnieszka I; Xu, Chun; Song, Inseon; Doronin, Maxim; Wu, Yu-Wei; Walker, Matthew C; Semyanov, Alexey

    2013-01-01

    Because of a complex dendritic structure, pyramidal neurons have a large membrane surface relative to other cells and so a large electrical capacitance and a large membrane time constant (τm). This results in slow depolarizations in response to excitatory synaptic inputs, and consequently increased and variable action potential latencies, which may be computationally undesirable. Tonic activation of GABAA receptors increases membrane conductance and thus regulates neuronal excitability by shunting inhibition. In addition, tonic increases in membrane conductance decrease the membrane time constant (τm), and improve the temporal fidelity of neuronal firing. Here we performed whole-cell current clamp recordings from hippocampal CA1 pyramidal neurons and found that bath application of 10μM GABA indeed decreases τm in these cells. GABA also decreased first spike latency and jitter (standard deviation of the latency) produced by current injection of 2 rheobases (500 ms). However, when larger current injections (3-6 rheobases) were used, GABA produced no significant effect on spike jitter, which was low. Using mathematical modeling we demonstrate that the tonic GABAA conductance decreases rise time, decay time and half-width of EPSPs in pyramidal neurons. A similar effect was observed on EPSP/IPSP pairs produced by stimulation of Schaffer collaterals: the EPSP part of the response became shorter after application of GABA. Consistent with the current injection data, a significant decrease in spike latency and jitter was obtained in cell attached recordings only at near-threshold stimulation (50% success rate, S50). When stimulation was increased to 2- or 3- times S50, GABA significantly affected neither spike latency nor spike jitter. Our results suggest that a decrease in τm associated with elevations in ambient GABA can improve EPSP-spike precision at near-threshold synaptic inputs.

  8. Persistent changes in action potential broadening and the slow afterhyperpolarization in rat CA1 pyramidal cells after febrile seizures.

    Science.gov (United States)

    Kamal, Amer; Notenboom, Robbert G E; de Graan, Pierre N E; Ramakers, Geert M J

    2006-04-01

    Febrile (fever-induced) seizures (FS) are the most common form of seizures during childhood and have been associated with an increased risk of epilepsy later in life. The relationship of FS to subsequent epilepsy is, however, still controversial. Insights from animal models do indicate that especially complex FS are harmful to the developing brain and contribute to a hyperexcitable state that may persist for life. Here, we determined long-lasting changes in neuronal excitability of rat hippocampal CA1 pyramidal cells after prolonged (complex) FS induced by hyperthermia on postnatal day 10. We show that hyperthermia-induced seizures at postnatal day 10 induce a long-lasting increase in the hyperpolarization-activated current I(h). Furthermore, we show that a reduction in the amount of spike broadening and in the amplitude of the slow afterhyperpolarization following FS are also likely to contribute to the hyperexcitability of the hippocampus long term.

  9. Enduring Effects of Early Life Stress on Firing Patterns of Hippocampal and Thalamocortical Neurons in Rats: Implications for Limbic Epilepsy.

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    Idrish Ali

    Full Text Available Early life stress results in an enduring vulnerability to kindling-induced epileptogenesis in rats, but the underlying mechanisms are not well understood. Recent studies indicate the involvement of thalamocortical neuronal circuits in the progression of kindling epileptogenesis. Therefore, we sought to determine in vivo the effects of early life stress and amygdala kindling on the firing pattern of hippocampus as well as thalamic and cortical neurons. Eight week old male Wistar rats, previously exposed to maternal separation (MS early life stress or early handling (EH, underwent amygdala kindling (or sham kindling. Once fully kindled, in vivo juxtacellular recordings in hippocampal, thalamic and cortical regions were performed under neuroleptic analgesia. In the thalamic reticular nucleus cells both kindling and MS independently lowered firing frequency and enhanced burst firing. Further, burst firing in the thalamic reticular nucleus was significantly increased in kindled MS rats compared to kindled EH rats (p<0.05. In addition, MS enhanced burst firing of hippocampal pyramidal neurons. Following a stimulation-induced seizure, somatosensory cortical neurons exhibited a more pronounced increase in burst firing in MS rats than in EH rats. These data demonstrate changes in firing patterns in thalamocortical and hippocampal regions resulting from both MS and amygdala kindling, which may reflect cellular changes underlying the enhanced vulnerability to kindling in rats that have been exposed to early life stress.

  10. Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells

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    Zsolt K. Bali

    2017-09-01

    Full Text Available The aim of the present study was to identify in vivo electrophysiological correlates of the interaction between cholinergic and glutamatergic neurotransmission underlying memory. Extracellular spike recordings were performed in the hippocampal CA1 region of anesthetized rats in combination with local microiontophoretic administration of N-methyl-D-aspartate (NMDA and acetylcholine (ACh. Both NMDA and ACh increased the firing rate of the neurons. Furthermore, the simultaneous delivery of NMDA and ACh resulted in a more pronounced excitatory effect that was superadditive over the sum of the two mono-treatment effects and that was explained by cholinergic potentiation of glutamatergic neurotransmission. Next, animals were systemically treated with scopolamine or methyllycaconitine (MLA to assess the contribution of muscarinic ACh receptor (mAChR or α7 nicotinic ACh receptor (nAChR receptor-mediated mechanisms to the observed effects. Scopolamine totally inhibited ACh-evoked firing, and attenuated the firing rate increase evoked by simultaneous application of NMDA and ACh. However, the superadditive nature of the combined effect was preserved. The α7 nAChR antagonist MLA robustly decreased the firing response to simultaneous application of NMDA and ACh, suspending their superadditive effect, without modifying the tonic firing rate increasing effect of ACh. These results provide the first in vivo electrophysiological evidence that, in the hippocampal CA1 region, α7 nAChRs contribute to pyramidal cell activity mainly through potentiation of glutamatergic signaling, while the direct cholinergic modulation of tonic firing is notably mediated by mAChRs. Furthermore, the present findings also reveal cellular physiological correlates of the interplay between cholinergic and glutamatergic agents in behavioral pharmacological models of cognitive decline.

  11. Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress

    NARCIS (Netherlands)

    Kole, MHP; Czeh, B; Fuchs, E

    2004-01-01

    The experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well un

  12. Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

    Science.gov (United States)

    Tong, Jian-Bin; Wong, Richard; Ching, Yick-Pang; Qiu, Guang; Tang, Siu-Wa; Lee, Tatia M. C.; So, Kwok-Fai

    2011-01-01

    Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress. PMID:21935393

  13. Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats.

    Directory of Open Access Journals (Sweden)

    Suk-Yu Yau

    Full Text Available Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg of corticosterone (CORT for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog /doublecortin (immature neuronal marker showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract

  14. Age-dependent variations in potassium sensitivity of A-currents in rat hippocampal neurons.

    Science.gov (United States)

    Klee, R; Eder, C; Ficker, E; Heinemann, U

    1997-09-01

    Hippocampal pyramidal neurons were either cultured from prenatal rats or acutely isolated from the brain of newborn and juvenile rats. The influence of lowering the concentration of the extracellular potassium concentration ([K+]o) on isolated fast transient outward K+ currents (I(A)) was studied in these neurons using the patch clamp technique in the whole cell configuration. With respect to the response of I(A) to lowering [K+]o, three types of cells were observed. The first subpopulation of neurons was characterized by a complete suppression of I(A) over the whole voltage range under potassium-free solutions (type A neurons). A second proportion of cells showed an increase of I(A) at test pulses below -0 mV and a decrease of I(A) at voltages above -0 mV (type B neurons). In a third group of neurons, amplitudes of I(A) increased at all potentials tested during omission of potassium ions from the extracellular superfusate (type C neurons). Whereas type A and type B neurons were preferentially found in freshly plated cultures and newborn rats, the majority of type C cells was detected in long-term cultures and in animals of older ages. Thus, hippocampal A-currents lose their sensitivity to extracellular potassium ions during early ontogenesis.

  15. Effect of low frequency repetitive transcranial magnetic stimulation on kindling-induced changes in electrophysiological properties of rat CA1 pyramidal neurons.

    Science.gov (United States)

    Moradi Chameh, Homeira; Janahmadi, Mahyar; Semnanian, Saeed; Shojaei, Amir; Mirnajafi-Zadeh, Javad

    2015-05-01

    In this study, the effect of repetitive transcranial magnetic stimulation (rTMS) on the kindling induced changes in electrophysiological firing properties of hippocampal CA1 pyramidal neurons was investigated. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (240 pulses at 1 Hz) at 5 min after termination of daily kindling stimulations. Twenty-four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using a whole-cell patch clamp technique, under current clamp condition. Amygdala kindling significantly decreased the adaptation index, post-afterhyperpolarization, rheobase current, utilization time, and delay to the first rebound spike. It also caused an increase in the voltage sag, number of rebound spikes and number of evoked action potential. Results of the present study revealed that application of rTMS following kindling stimulations had antiepileptogenic effects. In addition, application of rTMS prevented hyperexcitability of CA1 pyramidal neurons induced by kindling and conserved the normal neuronal firing.

  16. The rostral migratory stream generates hippocampal CA1 pyramidal-like neurons in a novel organotypic slice co-culture model

    Directory of Open Access Journals (Sweden)

    Ilyas Singec

    2015-10-01

    Full Text Available The mouse subventricular zone (SVZ generates large numbers of neuroblasts, which migrate in a distinct pathway, the rostral migratory stream (RMS, and replace specific interneurons in the olfactory bulb (OB. Here, we introduce an organotypic slice culture model that directly connects the RMS to the hippocampus as a new destination. RMS neuroblasts widely populate the hippocampus and undergo cellular differentiation. We demonstrate that RMS cells give rise to various neuronal subtypes and, surprisingly, to CA1 pyramidal neurons. Pyramidal neurons are typically generated before birth and are lost in various neurological disorders. Hence, this unique slice culture model enables us to investigate their postnatal genesis under defined in vitro conditions from the RMS, an unanticipated source for hippocampal pyramidal neurons.

  17. Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Poolos, N P; Johnston, D

    1999-07-01

    Evidence is accumulating that voltage-gated channels are distributed nonuniformly throughout neurons and that this nonuniformity underlies regional differences in excitability within the single neuron. Previous reports have shown that Ca2+, Na+, A-type K+, and hyperpolarization-activated, mixed cation conductances have varying distributions in hippocampal CA1 pyramidal neurons, with significantly different densities in the apical dendrites compared with the soma. Another important channel mediates the large-conductance Ca2+-activated K+ current (IC), which is responsible in part for repolarization of the action potential (AP) and generation of the afterhyperpolarization that follows the AP recorded at the soma. We have investigated whether this current is activated by APs retrogradely propagating in the dendrites of hippocampal pyramidal neurons using whole-cell dendritic patch-clamp recording techniques. We found no IC activation by back-propagating APs in distal dendritic recordings. Dendritic APs activated IC only in the proximal dendrites, and this activation decayed within the first 100-150 micrometer of distance from the soma. The decay of IC in the proximal dendrites occurred despite AP amplitude, plus presumably AP-induced Ca2+ influx, that was comparable with that at the soma. Thus we conclude that IC activation by action potentials is nonuniform in the hippocampal pyramidal neuron, which may represent a further example of regional differences in neuronal excitability that are determined by the nonuniform distribution of voltage-gated channels in dendrites.

  18. VIP enhances both pre- and postsynaptic GABAergic transmission to hippocampal interneurones leading to increased excitatory synaptic transmission to CA1 pyramidal cells.

    Science.gov (United States)

    Cunha-Reis, Diana; Sebastião, Ana M; Wirkner, Kerstin; Illes, Peter; Ribeiro, Joaquim Alexandre

    2004-11-01

    Vasoactive intestinal peptide (VIP) is present in the hippocampus in three subtypes of GABAergic interneurones, two of which innervate preferentially other interneurones, responsible for pyramidal cell inhibition. We investigated how pre- and postsynaptic modulation of GABAergic transmission (to both pyramidal cells and interneurones) by VIP could influence excitatory synaptic transmission in the CA1 area of the hippocampus. VIP (0.1-100 nM) increased [(3)H]GABA release from hippocampal synaptosomes (maximum effect at 1 nM VIP; 63.8 +/- 4.0%) but did not change [(3)H]glutamate release. VIP (0.3-30 nM) enhanced synaptic transmission in hippocampal slices (maximum effect at 1 nM VIP; field excitatory postsynaptic potentials (epsp) slope: 23.7 +/- 1.1%; population spike amplitude: 20.3 +/- 1.7%). The action on field epsp slope was fully dependent on GABAergic transmission since it was absent in the presence of picrotoxin (50 microM) plus CGP55845 (1 microM). VIP (1 nM) did not change paired-pulse facilitation but increased paired-pulse inhibition in CA1 pyramidal cells (16.0 +/- 0.9%), reinforcing the involvement of GABAergic transmission in the action of VIP. VIP (1 nM) increased muscimol-evoked inhibitory currents by 36.4 +/- 8.7% in eight out of ten CA1 interneurones in the stratum radiatum. This suggests that VIP promotes increased inhibition of interneurones that control pyramidal cells, leading to disinhibition of synaptic transmission to pyramidal cell dendrites. In conclusion, concerted pre- and postsynaptic actions of VIP lead to disinhibition of pyramidal cell dendrites causing an enhancement of synaptic transmission.

  19. Damage of hippocampal neurons in rats with chronic alcoholism

    Institute of Scientific and Technical Information of China (English)

    Ailin Du; Hongbo Jiang; Lei Xu; Na An; Hui Liu; Yinsheng Li; Ruiling Zhang

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deifcits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6%alcohol for 42 days. Endog-enous hydrogen sulifde content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were signiifcantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear mem-brane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  20. Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startle.

    Science.gov (United States)

    Greene, J R; Kerkhoff, J E; Guiver, L; Totterdell, S

    2001-01-01

    The effects of social isolation on prepulse inhibition of acoustic startle (PPI), electrophysiology and morphology of subicular pyramidal neurons and the densities of interneuronal sub-types in the hippocampal formation were examined. Wistar rats (male weanlings) were housed socially (socials, n=8) or individually (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats then received terminal anaesthesia before slices of hippocampal formation were made in which the electrophysiological properties of a total of 108 subicular neurons were characterized. There were no differences in neuronal sub-types recorded in socials compared with isolates. Intrinsically burst-firing and regular spiking pyramidal neurons were examined in detail. There were no differences in resting membrane potential or input resistance in isolates compared with socials but action potential height was reduced and action potential threshold raised in isolates. A limited morphological examination of Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences in cell-body area or in number of primary dendrites. Sections from the contralateral hemispheres of the same rats were stained with antibodies to calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS). In isolates, the density of calretinin positive neurons was increased in the dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS positive neuronal densities were unchanged. Hence in rats with environmentally induced reductions in PPI there are structural and functional abnormalities in the hippocampal formation. If the reduction in PPI stems from these abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs that correct the reported electrophysiological changes might have antipsychotic effects.

  1. Postnatal morphine administration alters hippocampal development in rats.

    Science.gov (United States)

    Traudt, Christopher M; Tkac, Ivan; Ennis, Kathleen M; Sutton, Leah M; Mammel, Daniel M; Rao, Raghavendra

    2012-01-01

    Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.

  2. Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron.

    Science.gov (United States)

    Ishikawa, Yasuyuki; Tamura, Hideki; Shiosaka, Sadao

    2011-07-15

    Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer collateral pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging.

  3. Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Liu, Pin W; Bean, Bruce P

    2014-04-02

    Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60-80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from -70 mV, but not -80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at -70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation.

  4. Effect of prenatal exposure to ethanol on the pyramidal tract in developing rats.

    Science.gov (United States)

    Miller, Michael W

    2017-10-01

    Prenatal exposure to ethanol induces a relative increase in the numbers of pyramidal tract axons relative to the number of corticospinal projection neurons in somatosensory/motor cortices in the adult rat. The present study examines the effects of ethanol on the numbers of axons in the developing caudal pyramidal tract, i.e., corticospinal axons. Electron microscopic analyses of the pyramidal tracts of the offspring of pregnant rat dams fed a control diet ad libitum, pair-fed a liquid control diet, or fed an ethanol-containing diet ad libitum were performed. The pups were 5-, 15-, 30- and 90-days-old. The numbers of axons in control rats fell precipitously after postnatal day (P) 15 and the frequency of myelinated axons rose dramatically between P15 and P90. Ethanol exposure had no significant effect on the numbers of pyramidal tract axons at any age. Moreover, no ethanol-induced differences in the numbers of axons in different stages of myelination, i.e., axons that were "free" of glial associations, glia-engulfed, invested by 1-2 layers of myelin, or myelinated by 3+ layers of myelin, were detected on P15. Thus, it appears that (a) pyramidal tract axons are lost or pruned during the first two postnatal weeks and (b) postnatal development of pyramidal tract axons (e.g., pruning and myelination) is not affected by ethanol. The implications are that the ethanol-induced increase in the number of axons relative to the number of somata of corticospinal neurons detected in pups and adults results from the effects of ethanol on early stages (initiation) of axogenesis. Copyright © 2017. Published by Elsevier B.V.

  5. Dopamine Inhibits High-Frequency Stimulation-Induced Long-Term Potentiation of Intrinsic Excitability in CA1 Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Chun-ling Wei

    2012-09-01

    Full Text Available The efficiency of neural circuits is modified by changes not only in synaptic strength, but also in intrinsic excitability of neurons. In CA1 hippocampal pyramidal neurons, bidirectional changes in the intrinsic excitability are often presented after induction of synaptic long-term potentiation or depression. This plasticity of intrinsic excitability has been identified as a cellular correlate of learning. Besides, behavioral learning often involves action of reinforcement or rewarding mediated by dopamine (DA. Here, we examined how DA influences the intrinsic plasticity of CA1 hippocampal pyramidal neurons when high-frequency stimulation (HFS was applied to Schaffer collaterals. The results showed that DA inhibits the decrease in rheobase and increase in mean firing rate of pyramidal neurons induced by HFS, and that this inhibition was abolished by the D1-like receptor antagonist SCH23390 but not by the D2-like receptor antagonist sulpiride. The results suggest that DA inhibits the potentiation of excitability induced by presynaptic HFS, and that this inhibition depends on the activation of D1-like receptors.

  6. Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse☆

    Science.gov (United States)

    Kerrigan, T.L.; Brown, J.T.; Randall, A.D.

    2014-01-01

    Transgenic mice that accumulate Aβ peptides in the CNS are commonly used to interrogate functional consequences of Alzheimer's disease-associated amyloidopathy. In addition to changes to synaptic function, there is also growing evidence that changes to intrinsic excitability of neurones can arise in these models of amyloidopathy. Furthermore, some of these alterations to intrinsic properties may occur relatively early within the age-related progression of experimental amyloidopathy. Here we report a detailed comparison between the intrinsic excitability properties of hippocampal CA1 pyramidal neurones in wild-type (WT) and PDAPP mice. The latter is a well-established model of Aβ accumulation which expresses human APP harbouring the Indiana (V717F) mutation. At the age employed in this study (9–10 months) CNS Abeta was elevated in PDAPP mice but significant plaque pathology was absent. PDAPP mice exhibited no differences in subthreshold intrinsic properties including resting potential, input resistance, membrane time constant and sag. When CA1 cells of PDAPP mice were given depolarizing stimuli of various amplitudes they initially fired at a higher frequency than WT cells. Commensurate with this, PDAPP cells exhibited a larger fast afterdepolarizing potential. PDAPP mice had narrower spikes but action potential threshold, rate of rise and peak were not different. Thus not all changes seen in our previous studies of amyloidopathy models were present in PDAPP mice; however, narrower spikes, larger ADPs and the propensity to fire at higher frequencies were consistent with our prior work and thus may represent robust, cross-model, indices of amyloidopathy. This article is part of a Special Issue entitled ‘Neurodevelopment Disorder’. PMID:24055500

  7. Intrinsic Ca2+-dependent theta oscillations in apical dendrites of hippocampal CA1 pyramidal cells in vitro.

    Science.gov (United States)

    Hansen, Allan Kjeldsen; Nedergaard, Steen; Andreasen, Mogens

    2014-08-01

    Behavior-associated theta-frequency oscillation in the hippocampal network involves a patterned activation of place cells in the CA1, which can be accounted for by a somatic-dendritic interference model predicting the existence of an intrinsic dendritic oscillator. Here we describe an intrinsic oscillatory mechanism in apical dendrites of in vitro CA1 pyramidal cells, which is induced by suprathreshold depolarization and consists of rhythmic firing of slow spikes in the theta-frequency band. The incidence of slow spiking (29%) increased to 78% and 100% in the presence of the β-adrenergic agonist isoproterenol (2 μM) or 4-aminopyridine (2 mM), respectively. Prior depolarization facilitated the induction of slow spiking. Applied electrical field polarization revealed a distal dendritic origin of slow spikes. The oscillations were largely insensitive to tetrodotoxin, but blocked by nimodipine (10 μM), indicating that they depend on activation of L-type Ca2+ channels. Antagonists of T-, R-, N-, and P/Q-type Ca2+ channels had no detectable effect. The slow spike dimension and frequency was sensitive to 4-aminopyridine (0.1-2 mM) and TEA (10 mM), suggesting the contribution from voltage-dependent K+ channels to the oscillation mechanism. α-Dendrotoxin (10 μM), stromatoxin (2 μM), iberiotoxin (0.2 μM), apamin (0.5 μM), linorpidine (30 μM), and ZD7288 (20 μM) were without effect. Oscillations induced by sine-wave current injection or theta-burst synaptic stimulation were voltage-dependently attenuated by nimodipine, indicating an amplifying function of L-type Ca2+ channels on imposed signals. These results show that the apical dendrites have intrinsic oscillatory properties capable of generating rhythmic voltage fluctuations in the theta-frequency band.

  8. GluN2D-containing NMDA receptors-mediate synaptic currents in hippocampal interneurons and pyramidal cells in juvenile mice

    Directory of Open Access Journals (Sweden)

    Jakob evon Engelhardt

    2015-03-01

    Full Text Available The differential regulation of the two major N-methyl-D-aspartate receptor (NMDAR subunits GluN2A and GluN2B during development in forebrain pyramidal cells has been thoroughly investigated. In contrast, much less is known about the role of GluN2D, which is expressed at low levels and is downregulated following the second postnatal week. However, it appears that few cells, presumably interneurons, continue to express GluN2D also in juvenile mice. To investigate which hippocampal cell types express this subunit, we generated transgenic mice with EGFP-tagged GluN2D receptors. The expression of the transgene was confined to hippocampal interneurons, most of which were parvalbumin- and/or somatostatin-positive. Electrophysiological and morphological analyses showed that GluN2D was present mainly in fast spiking basket and axo-axonic cells. Based on pharmacological evidence and electrophysiological analysis of GluN2D knockout mice, we conclude that GluN2D-containing NMDARs mediate synaptic currents in hippocampal interneurons of young and juvenile mice and in CA1 pyramidal neurons of newborn mice.

  9. Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number.

    Science.gov (United States)

    Akdogan, Ilgaz; Adiguzel, Esat; Yilmaz, Ismail; Ozdemir, M Bulent; Sahiner, Melike; Tufan, A Cevik

    2008-10-22

    This study was designed to evaluate the penicillin-induced epilepsy model in terms of dose-response relationship of penicillin used to induce epilepsy seizure on hippocampal neuron number and hippocampal volume in Sprague-Dawley rats. Seizures were induced with 300, 500, 1500 and 2000IU of penicillin-G injected intracortically in rats divided in four experimental groups, respectively. Control group was injected intracortically with saline. Animals were decapitated on day 7 of treatment and brains were removed. The total neuron number of pyramidal cell layer from rat hippocampus was estimated using the optical fractionator method. The volume of same hippocampal areas was estimated using the Cavalieri method. Dose-dependent decrease in hippocampal neuron number was observed in three experimental groups (300, 500 and 1500IU of penicillin-G), and the effects were statistically significant when compared to the control group (P<0.009). Dose-dependent decrease in hippocampal volume, on the other hand, was observed in all three of these groups; however, the difference compared to the control group was only statistically significant in 1500IU of penicillin-G injected group (P<0.009). At the dose of 2000IU penicillin-G, all animals died due to status seizures. These results suggest that the appropriate dose of penicillin has to be selected for a given experimental epilepsy study in order to demonstrate the relevant epileptic seizure and its effects. Intracortical 1500IU penicillin-induced epilepsy model may be a good choice to practice studies that investigate neuroprotective mechanisms of the anti-epileptic drugs.

  10. Subregional Expression of Hippocampal Glutamatergic and GABAergic Genes in F344 Rats with Social Isolation after Weaning.

    Science.gov (United States)

    Iwata, Hisaya; Yamamuro, Yutaka

    2016-02-01

    Many studies have shown that postweaning social isolation (pwSI) alters various behavioral phenotypes, including hippocampusdependent tasks. Here, we report the comprehensive analysis of the expression of glutamatergic and GABAergic neurotransmissionrelated genes in the distinct hippocampal subregions of pwSI rats. Male F344 rats (age, 4 wk) experienced either pwSI or group housing (controls). At 7 wk of age, the hippocampus of each rat was removed and laser-microdissected into the CA1 and CA3 layers of pyramidal cells and the granule cell layer of the dentate gyrus. Subsequently, the expression of glutamatergic- and GABAergic- related genes was analyzed by quantitative RT-PCR. In the CA1 and CA3 pyramidal cell layers, 18 of 24 glutamate receptor subunit genes were at least 1.5-fold increased in expression after pwSI. In particular, the expression of several N-methyl-D-aspartate and kainate receptors (for example, Grin2a in CA1, Grik4 in CA3) was significantly increased after pwSI. In contrast, pwSI tended to decrease the expression of GABAA receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the group-housed rats. These results indicate a subregion- specific increase of glutamate receptors and reduction of GABAA receptors, suggesting that the hippocampal circuits of pwSI rats may be in more excitable states than those of group-housed rats.

  11. Activity-based anorexia during adolescence disrupts normal development of the CA1 pyramidal cells in the ventral hippocampus of female rats.

    Science.gov (United States)

    Chowdhury, Tara G; Ríos, Mariel B; Chan, Thomas E; Cassataro, Daniela S; Barbarich-Marsteller, Nicole C; Aoki, Chiye

    2014-12-01

    Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and irrational fears of gaining weight. There is no accepted pharmacological treatment for AN, and AN has the highest mortality rate among psychiatric illnesses. Anorexia nervosa most commonly affects females during adolescence, suggesting an effect of sex and hormones on vulnerability to the disease. Activity-based anorexia (ABA) is a rodent model of AN that shares symptoms with AN, including over-exercise, elevation of stress hormones, and genetic links to anxiety traits. We previously reported that ABA in adolescent female rats results in increased apical dendritic branching in CA1 pyramidal cells of the ventral hippocampus at postnatal day 44 (P44). To examine the long-term effects of adolescent ABA (P44) in female rats, we compared the apical branching in the ventral hippocampal CA1 after recovery from ABA (P51) and after a relapse of ABA (P55) with age-matched controls. To examine the age-dependence of the hippocampal plasticity, we examined the effect of ABA during adulthood (P67). We found that while ABA at P44 resulted in increased branching of ventral hippocampal pyramidal cells, relapse of ABA at P55 resulted in decreased branching. ABA induced during adulthood did not have an effect on dendritic branching, suggesting an age-dependence of the vulnerability to structural plasticity. Cells from control animals were found to exhibit a dramatic increase in branching, more than doubling from P44 to P51, followed by pruning from P51 to P55. The proportion of mature spines on dendrites from the P44-ABA animals is similar to that on dendrites from P55-CON animals. These results suggest that the experience of ABA may cause precocious anatomical development of the ventral hippocampus. Importantly, we found that adolescence is a period of continued development of the hippocampus, and increased vulnerability to mental disorders during adolescence may be due to insults during this

  12. Effects of Stress and Hippocampal NMDA Receptor Antagonism on Recognition Memory in Rats

    OpenAIRE

    Kevin B Baker; Kim, Jeansok J

    2002-01-01

    Exposures to uncontrollable stress have been shown to alter ensuing synaptic plasticity in the hippocampus and interfere with hippocampal-dependent spatial memory in rats. The present study examined whether stress, which impairs hippocampal long-term potentiation (LTP), also affects (nonspatial) hippocampal-dependent object-recognition memory, as tested on the visual paired comparison task (VPC) in rats. After undergoing an inescapable restraint–tailshock stress experience, rats exhibited mar...

  13. Complete axon arborization of a single CA3 pyramidal cell in the rat hippocampus, and its relationship with postsynaptic parvalbumin-containing interneurons.

    Science.gov (United States)

    Sik, A; Tamamaki, N; Freund, T F

    1993-12-01

    The complete axon arborization of a single CA3 pyramidal cell has been reconstructed from 32 (60 microns thick) sections from the rat hippocampus following in vivo intracellular injection of neurobiotin. The same sections were double-immunostained for parvalbumin--a calcium-binding protein selectively present in two types of GABAergic interneurons, the basket and chandelier cells--in order to map boutons of the pyramidal cell in contact with dendrites and somata of these specific subsets of interneurons visualized in a Golgi-like manner. The axon of the pyramidal cell formed 15,295 boutons, 63.8% of which were in stratum oriens, 15.4% in stratum pyramidale and 20.8% in stratum radiatum. Only 2.1% of the axon terminals contacted parvalbumin-positive neurons. Most of these were single contacts (84.7%), but double or triple contacts (15.3%) were also found. The majority of the boutons terminated on dendrites (84.1%) of parvalbumin-positive cells, less frequently on cell bodies (15.9%). In order to estimate the proportion of contacts representing synapses, 16 light microscopically identified contacts between boutons of the filled pyramidal cell axon and the parvalbumin-positive targets were examined by correlated electron microscopy. Thirteen of them were found to be asymmetrical synapses, and in the remaining three cases synapses between the labelled profiles could not be confirmed. We conclude that the physiologically effective excitatory connections between single pyramidal cells and postsynaptic inhibitory neurons are mediated by a small number of contacts, mostly by a single synapse. This results in a high degree of convergence and divergence in hippocampal networks.

  14. Morphology of CA3 non-pyramidal cells in the developing rat hippocampus.

    OpenAIRE

    Gaïarsa, Jean-Luc; Khalilov, Ilgam; Gozlan, Henri; Ben-Ari, Yehezkel

    2001-01-01

    International audience; Although several investigations have shown that the local GABAergic circuit in the rat hippocampus is functional very early in development, this result has not been yet completed by the investigation of the full dendritic and axonal arborization of the neonatal interneurones. In the present study, intracellular injection of biocytin was used to assess the branching pattern of interneurones in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their...

  15. Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats.

    Science.gov (United States)

    Ju, Ling-sha; Jia, Min; Sun, Jie; Sun, Xiao-ru; Zhang, Hui; Ji, Mu-huo; Yang, Jian-jun; Wang, Zhong-yun

    2016-02-01

    General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments.

  16. Superstitious bar pressing in hippocampal and septal rats.

    Science.gov (United States)

    Devenport, L D

    1979-08-17

    Unlike normal animals or those with sham lesions, rats with hippocampal and septal lesions behaved in an operant chamber as if a dependency existed between pellet delivery and their behavior, despite the fact that reinforcement was based on time, not behavior, and was therefore free. This superstitious behavior did not result from a general inability to inhibit responding, as responding rapidly ceased when the pellets were discontinued. These findings suggest that the hippocampus integrates information regarding response-reinforcer relations, which in the normal rat permits superfluous operant behavior to be eliminated.

  17. Selective shunting of the NMDA EPSP component by the slow afterhyperpolarization in rat CA1 pyramidal neurons.

    Science.gov (United States)

    Fernández de Sevilla, David; Fuenzalida, Marco; Porto Pazos, Ana B; Buño, Washington

    2007-05-01

    Pyramidal neuron dendrites express voltage-gated conductances that control synaptic integration and plasticity, but the contribution of the Ca(2+)-activated K(+)-mediated currents to dendritic function is not well understood. Using dendritic and somatic recordings in rat hippocampal CA1 pyramidal neurons in vitro, we analyzed the changes induced by the slow Ca(2+)-activated K(+)-mediated afterhyperpolarization (sAHP) generated by bursts of action potentials on excitatory postsynaptic potentials (EPSPs) evoked at the apical dendrites by perforant path-Schaffer collateral stimulation. Both the amplitude and decay time constants of EPSPs (tau(EPSP)) were reduced by the sAHP in somatic recordings. In contrast, the dendritic EPSP amplitude remained unchanged, whereas tau(EPSP) was reduced. Temporal summation was reduced and spatial summation linearized by the sAHP. The amplitude of the isolated N-methyl-D-aspartate component of EPSPs (EPSP(NMDA)) was reduced, whereas tau(NMDA) was unaffected by the sAHP. In contrast, the sAHP did not modify the amplitude of the isolated EPSP(AMPA) but reduced tau(AMPA) both in dendritic and somatic recordings. These changes are attributable to a conductance increase that acted mainly via a selective "shunt" of EPSP(NMDA) because they were absent under voltage clamp, not present with imposed hyperpolarization simulating the sAHP, missing when the sAHP was inhibited with isoproterenol, and reduced under block of EPSP(NMDA). EPSPs generated at the basal dendrites were similarly modified by the sAHP, suggesting both a somatic and apical dendritic location of the sAHP channels. Therefore the sAHP may play a decisive role in the dendrites by regulating synaptic efficacy and temporal and spatial summation.

  18. Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

    Science.gov (United States)

    Potier, B; Krzywkowski, P; Lamour, Y; Dutar, P

    1994-10-24

    Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

  19. Multi-walled carbon nanotube inhibits CA1 glutamatergic synaptic transmission in rat's hippocampal slices.

    Science.gov (United States)

    Chen, Ting; Yang, Jiajia; Zhang, Hui; Ren, Guogang; Yang, Zhuo; Zhang, Tao

    2014-09-17

    The purpose of the study was to investigate the neurotoxic effect of multi-walled carbon nanotubes (MWCNTs) on the properties of glutamatergic synaptic transmission in rat's hippocampal slices using whole-cell patch clamp technique. The amplitude and frequency of excitatory postsynaptic current (EPSC) were accessed on the hippocampal pyramidal neurons. The alterations of glutamatergic synaptic transmission in CA3-CA1 were examined by measuring both the amplitude of evoked excitatory postsynaptic current (eEPSC) and paired-pulse ratio (PPR). The data showed that the amplitude of either spontaneous excitatory postsynaptic current (sEPSC) or miniature excitatory postsynaptic current (mEPSC) was significantly inhibited by 1 μg/mL MWCNTs. However, it was found that there was a trend of different change on the frequency index. When 1 μg/mL MWCNTs was applied, there were a decreased frequency of mEPSC and an increased frequency of sEPSC, which might be due to the effect of action potential. Furthermore, the amplitudes of eEPSC at CA3-CA1 synapses were remarkably decreased. And the mean amplitude of AMPAR-mediated eEPSC was significantly reduced as well. Meanwhile, a majority of PPRs data were greater than one. There were no significant differences of PPRs between control and MWCNTs states, but an increased trend of paired-pulse facilitation was found. These results suggested that MWCNT markedly inhibited hippocampal CA1 glutamatergic synaptic transmission in vitro, which provided new insights into the MWCNT toxicology on CNS at cellular level.

  20. Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal slices: Role of astrocytes and extracellular matrix proteins.

    Science.gov (United States)

    Giordano, Gennaro; Guizzetti, Marina; Dao, Khoi; Mattison, Hayley A; Costa, Lucio G

    2011-12-01

    In an in vitro co-culture system of astrocytes and neurons, stimulation of cholinergic muscarinic receptors in astrocytes had been shown to cause neuritogenesis in hippocampal neurons, and this effect was inhibited by ethanol. The present study sought to confirm these earlier findings in a more complex system, in vitro rat hippocampal slices in culture. Exposure of hippocampal slices to the cholinergic agonist carbachol (1mM for 24h) induced neurite outgrowth in hippocampal pyramidal neurons, which was mediated by activation of muscarinic M3 receptors. Specifically, carbachol induced a >4-fold increase in the length of the longest neurite, and a 4-fold increase in the length of minor neurites and in the number of branches. Co-incubation of carbachol with ethanol (50mM) resulted in significant inhibition of the effects induced by carbachol on all parameters measured. Neurite outgrowth in CNS neurons is dependent on various permissive factors that are produced and released by glial cells. In hippocampal slices carbachol increased the levels of two extracellular matrix protein, fibronectin and laminin-1, by 1.6-fold, as measured by Western blot. Co-incubation of carbachol with ethanol significantly inhibited these increases. Carbachol-induced increases in levels of extracellular matrix proteins were antagonized by a M3 muscarinic receptor antagonist. Furthermore, function-blocking fibronectin or laminin-1 antibodies antagonized the effect of carbachol on neurite outgrowth. These results indicate that in hippocampal slices stimulation of muscarinic M3 receptors induces neurite outgrowth, which is mediated by fibronectin and laminin-1, two extracellular matrix proteins released by astrocytes. By decreasing fibronectin and laminin levels ethanol prevents carbachol-induced neuritogenesis. These findings highlight the importance of glial-neuronal interactions as important targets in the developmental neurotoxicity of alcohol.

  1. Age- and location-dependent differences in store depletion-induced h-channel plasticity in hippocampal pyramidal neurons.

    Science.gov (United States)

    Clemens, Ann M; Johnston, Daniel

    2014-03-01

    Disruptions of endoplasmic reticulum (ER) Ca(2+) homeostasis are heavily linked to neuronal pathology. Depletion of ER Ca(2+) stores can result in cellular dysfunction and potentially cell death, although adaptive processes exist to aid in survival. We examined the age and region dependence of one postulated, adaptive response to ER store-depletion (SD), hyperpolarization-activated cation-nonspecific (h)-channel plasticity in neurons of the dorsal and ventral hippocampus (DHC and VHC, respectively) from adolescent and adult rats. With the use of whole-cell patch-clamp recordings from the soma and dendrites of CA1 pyramidal neurons, we observed a change in h-sensitive measurements in response to SD, induced by treatment with cyclopiazonic acid, a sarcoplasmic reticulum/ER Ca(2+)-ATPase blocker. We found that whereas DHC and VHC neurons in adolescent animals respond to SD with a perisomatic expression of SD h plasticity, adult animals express SD h plasticity with a dendritic and somatodendritic locus of plasticity in DHC and VHC neurons, respectively. Furthermore, SD h plasticity in adults was dependent on membrane potential and on the activation of L-type voltage-gated Ca(2+) channels. These results suggest that cellular responses to the impairment of ER function, or ER stress, are dependent on brain region and age and that the differential expression of SD h plasticity could provide a neural basis for region- and age-dependent disease vulnerabilities.

  2. The effect of Lead Acetate on the Nitric Oxide system in the rat Hippocampal cells: An in-vitro study

    Directory of Open Access Journals (Sweden)

    "Ghane T

    2001-05-01

    Full Text Available The mechanism by which lead may cause a perturbotion in the nevous system is through the nitric oxide synthase. In this study the effect of lead acetate on the hippocampal constitutive nitric oxide production was studied. The variation in the nitric oxide production may contribute to physiological lead neurotoxicity in vivo. Different concentrations of lead acetate (10-9 to 10-6 M, wre added to cultures of hippocampal pyramidal cell obtained from one-day newborn rats. Sodium acetate was used as control. In this range of stuy viability of cells did not alter when it was compared to control (P<0.05. In another part of study, cells were obtained from one day dams whose mothers were chronically intoxicated by lead acetate. The resuts showed that neither direct exposure of normal cells mor cells obtained from latter group could show andy increase in the amount of nitric oxide. Administration of lead to the cells 10 minute before measurement showed same results.These results showed that how concentration of lead acetate can not induce nitric oxide production in the pyramidal cells

  3. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico......The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model...... for neurotoxicological studies, including further studies of neurotoxic mechanisms of TMT. Four-week-old cultures, derived from 7-day-old donor rats and grown in serum-free medium, were exposed to TMT (0.5-100 microM) for 24 h followed by 24 h in normal medium. TMT-induced neurodegeneration was then monitored by (a...... of TMT neurotoxicity....

  4. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  5. The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.

    Science.gov (United States)

    Fabene, P F; Correia, L; Carvalho, R A; Cavalheiro, E A; Bentivoglio, M

    2001-01-01

    At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

  6. Effects of deprivation of oxygen or glucose on the neural activity in the guinea pig hippocampal slice--intracellular recording study of pyramidal neurons.

    Science.gov (United States)

    Takata, T; Okada, Y

    1995-06-12

    The block of synaptic transmission and neural activity during deprivation of oxygen or glucose has been simply attributed to the lack of energy due to the disorder of energy production. To clarify the interrelation between neural activity and energy metabolism during hypoxia or glucose deprivation, we studied the changes in ATP levels and electrical events of pyramidal neurons in the CA3 region and [Ca2+]i mobilization of the dendritic and cellular region of CA3 area, using guinea pig hippocampal slices. The studies of field potentials and intracellular recording from the pyramidal cell of CA3 area during hypoxia or glucose deprivation revealed that the cessation of synaptic activity and the depolarization of resting potential occurred earlier than during glucose deprivation while the increase of [Ca2+]i was slow during hypoxia but rapid during glucose deprivation although the ATP level of CA3 area was maintained at its original level for 20 min during both conditions. When glucose was replaced by lactate, ATP concentration was not reduced but the electrical activity decayed and [Ca2+]i increased with the similar time course as observed during lack of glucose, only. These results suggest that different mechanisms underlie the block of synaptic transmission in the CA3 pyramidal neurons during hypoxia and glucose deprivation and that lactate cannot substitute for glucose in the maintenance of neural activity.

  7. Different patterns of synaptic transmission revealed between hippocampal CA3 stratum oriens and stratum lucidum interneurons and their pyramidal cell targets.

    Science.gov (United States)

    Aaron, G B; Wilcox, K S; Dichter, M A

    2003-01-01

    Stratum lucidum (SL) interneurons likely mediate feedforward inhibition between the dentate gyrus mossy fibers and CA3 pyramidal cells, while stratum oriens (SO) interneurons likely provide both feedforward and feedback inhibition within the CA3 commissural/associational network. Using dual whole-cell patch-clamp recordings between interneurons and CA3 pyramidal cells, we have examined SL and SO interneurons and their synapses within organotypic hippocampal slice cultures. Biocytin staining revealed different morphologies between these interneuron groups, both being very similar to those found previously in acute slices. The kinetics of IPSCs were similar between the two groups, but the reliability of synaptic transmission of SL interneuron (SL-INT) IPSCs was significantly lower than the virtually 100% reliability (non-existent failure rates) of SO-INT IPSCs. The SL-INT IPSCs also had a lower quantal content than the SO-INT IPSCs. In addition, SL-INTs were less likely than SO-INTs to innervate or to be innervated by nearby CA3 pyramidal cells. Paired-pulse stimulation at 100 ms interstimulus intervals produced similar paired-pulse depression in both interneuron synapses, despite the significantly higher failure rate of IPSCs produced by the SL-INTs compared with SO-INTs. CV analysis supported the hypothesis that paired-pulse depression was presynaptic. During repetitive, high frequency stimulation (>10 Hz for 500 ms) the two different synapses exhibited distinctly different forms of short-term plasticity: all SL interneurons displayed significant short-term facilitation (mean 113% facilitation, n=4), while, by contrast, SO interneuron synapses displayed either short-term depression (mean 42% depression, n=5 of 8) or no net facilitation or depression (n=3 of 8). These results indicate that the synaptic properties of interneurons can be quite different for interneurons in different hippocampal circuits.

  8. Enhanced intrinsic excitability and EPSP-spike coupling accompany enriched environment-induced facilitation of LTP in hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Malik, Ruchi; Chattarji, Sumantra

    2012-03-01

    Environmental enrichment (EE) is a well-established paradigm for studying naturally occurring changes in synaptic efficacy in the hippocampus that underlie experience-induced modulation of learning and memory in rodents. Earlier research on the effects of EE on hippocampal plasticity focused on long-term potentiation (LTP). Whereas many of these studies investigated changes in synaptic weight, little is known about potential contributions of neuronal excitability to EE-induced plasticity. Here, using whole-cell recordings in hippocampal slices, we address this gap by analyzing the impact of EE on both synaptic plasticity and intrinsic excitability of hippocampal CA1 pyramidal neurons. Consistent with earlier reports, EE increased contextual fear memory and dendritic spine density on CA1 cells. Furthermore, EE facilitated LTP at Schaffer collateral inputs to CA1 pyramidal neurons. Analysis of the underlying causes for enhanced LTP shows EE to increase the frequency but not amplitude of miniature excitatory postsynaptic currents. However, presynaptic release probability, assayed using paired-pulse ratios and use-dependent block of N-methyl-d-aspartate receptor currents, was not affected. Furthermore, CA1 neurons fired more action potentials (APs) in response to somatic depolarization, as well as during the induction of LTP. EE also reduced spiking threshold and after-hyperpolarization amplitude. Strikingly, this EE-induced increase in excitability caused the same-sized excitatory postsynaptic potential to fire more APs. Together, these findings suggest that EE may enhance the capacity for plasticity in CA1 neurons, not only by strengthening synapses but also by enhancing their efficacy to fire spikes-and the two combine to act as an effective substrate for amplifying LTP.

  9. Hippocampal and Cerebellar Single-Unit Activity During Delay and Trace Eyeblink Conditioning in the Rat

    Science.gov (United States)

    Green, John T.; Arenos, Jeremy D.

    2007-01-01

    In delay eyeblink conditioning, the CS overlaps with the US and only a brainstem-cerebellar circuit is necessary for learning. In trace eyeblink conditioning, the CS ends before the US is delivered and several forebrain structures, including the hippocampus, are required for learning, in addition to a brainstem-cerebellar circuit. The interstimulus interval (ISI) between CS onset and US onset is perhaps the most important factor in classical conditioning, but studies comparing delay and trace conditioning have typically not matched these procedures in this crucial factor, so it is often difficult to determine whether results are due to differences between delay and trace or to differences in ISI. In the current study, we employed a 580-ms CS-US interval for both delay and trace conditioning and compared hippocampal CA1 activity and cerebellar interpositus nucleus activity in order to determine whether a unique signature of trace conditioning exists in patterns of single-unit activity in either structure. Long-Evans rats were chronically implanted in either CA1 or interpositus with microwire electrodes and underwent either delay eyeblink conditioning, or trace eyeblink conditioning with a 300-ms trace period between CS offset and US onset. On trials with a CR in delay conditioning, CA1 pyramidal cells showed increases in activation (relative to a pre-CS baseline) during the CS-US period in sessions 1-4 that was attenuated by sessions 5-6. In contrast, on trials with a CR in trace conditioning, CA1 pyramidal cells did not show increases in activation during the CS-US period until sessions 5-6. In sessions 5-6, increases in activation were present only to the CS and not during the trace period. For rats with interpositus electrodes, activation of interpositus neurons on CR trials was present in all sessions in both delay and trace conditioning. However, activation was greater in trace compared to delay conditioning in the first half of the CS-US interval (during the

  10. Calretinin is present in non-pyramidal cells of the rat hippocampus--III. Their inputs from the median raphe and medial septal nuclei.

    Science.gov (United States)

    Acsády, L; Halasy, K; Freund, T F

    1993-02-01

    The subcortical innervation of a recently described subpopulation of non-pyramidal neurons, containing the calcium binding protein, calretinin, was investigated in the rat hippocampus using the anterograde tracer Phaseolus vulgaris-leucoagglutinin and double immunocytochemistry for calretinin and serotonin at the light and electron microscopic levels. Our results show that the GABAergic component of the septohippocampal pathway and the serotonergic raphe afferents establish multiple synaptic contacts with the calretinin-immunoreactive interneurons. The majority of the targets of both pathways were spine-free calretinin neurons known to innervate the dendritic region of the principal cells, but the GABAergic septal pathway was found to terminate also on the spiny neurons of stratum lucidum of the CA3 region and in the dentate hilus. The present results demonstrate that the serotonergic raphe-hippocampal and the GABAergic septohippocampal pathways are able to modulate dendritic inhibition of principal cells via calretinin-containing GABAergic interneurons.

  11. Taste aversion learning and aging: a comparison with the effect of dorsal hippocampal lesions in rats.

    Science.gov (United States)

    Moron, I; Ballesteros, M A; Candido, A; Gallo, M

    2002-01-01

    The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning.

  12. Differential dendritic targeting of AMPA receptor subunit mRNAs in adult rat hippocampal principal neurons and interneurons.

    Science.gov (United States)

    Cox, David J; Racca, Claudia

    2013-06-15

    In hippocampal neurons, AMPA receptors (AMPARs) mediate fast excitatory postsynaptic responses at glutamatergic synapses, and are involved in various forms of synaptic plasticity. Dendritic local protein synthesis of selected AMPAR subunit mRNAs is considered an additional mechanism to independently and rapidly control the strength of individual synapses. We have used fluorescent in situ hybridization and immunocytochemistry to analyze the localization of AMPAR subunit (GluA1-4) mRNAs and their relationship with the translation machinery in principal cells and interneurons of the adult rat hippocampus. The mRNAs encoding all four AMPAR subunits were detected in the somata and dendrites of CA3 and CA1 pyramidal cells and those of six classes of CA1 γ-aminobutyric acid (GABA)ergic interneurons. GluA1-4 subunit mRNAs were highly localized to the apical dendrites of pyramidal cells, whereas in interneurons they were present in multiple dendrites. In contrast, in the dentate gyrus, GluA1-4 subunit mRNAs were virtually restricted to the somata and were absent from the dendrites of granule cells. These different regional and cell type-specific labeling patterns also correlated with the localization of markers for components of the protein synthesis machinery. Our results support the local translation of GluA1-4 mRNAs in dendrites of hippocampal pyramidal cells and CA1 interneurons but not in granule cells of the dentate gyrus. Furthermore, the regional and cell type-specific differences we observed suggest that each cell type uses distinct ways of regulating the local translation of AMPAR subunits.

  13. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  14. Temperature- and concentration-dependence of kainate-induced y oscillation in rat hippocampal slices under submerged condition

    Institute of Scientific and Technical Information of China (English)

    Cheng-biao LU; Zhi-hua WANG; Yan-hong ZHOU; Martin VREUGDENHIL

    2012-01-01

    Aim:Fast neuronal network oscillation at the y frequency band (y oscillation:30-80 Hz) has been studied extensively in hippocampal slices under interface recording condition.The aim of this study is to establish a method for recording Y oscillation in submerged hippocampal slices that allows simultaneously monitoring Y oscillation and the oscillation-related intracellular events,such as intracellular Ca2+ concentration or mitochondrial membrane potentials.Methods:Horizontal hippocampal slices (thickness:300 pm) of adult rats were prepared and placed in a submerged or an interface chamber.Extracellular field recordings Were made in the CA3c pyramidal layer of the slices.Kainate,an AMPA/kainate receptor agonist,was applied via perfusion.Data analysis was performed off-line.Results:Addition of kainate (25-1000 nmol/L) induced Y oscillation in both the submerged and interface slices.Kainate increased the Y power in a concentration-dependent manner,but the duration of steady state oscillation was reduced at higher concentrations of kainate.Long-lasting Y oscillation was maintained at the concentrations of 100-300 nmol/L.Under submerged condition,Y oscillation was temperature-dependent,with the maximum power achieved at 29℃.The induction of Y oscillation under submerged condition also required a fast rate of perfusion (5-7 mL/min) and showed a fast dynamic during development and after the washout.Conclusion:The kainite-induced Y oscillation recorded in submerged rat hippocampal slices is useful for studying the intracellular events related to neuronal network activities and may represent a model to reveal the mechanisms underlying the normal neuronal synchronizations and diseased conditions.

  15. Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

    Science.gov (United States)

    Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

    2017-10-01

    Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons

  16. Corticotropin-releasing hormone (CRH)-containing neurons in the immature rat hippocampal formation: light and electron microscopic features and colocalization with glutamate decarboxylase and parvalbumin.

    Science.gov (United States)

    Yan, X X; Toth, Z; Schultz, L; Ribak, C E; Baram, T Z

    1998-01-01

    Corticotropin-releasing hormone (CRH) excites hippocampal neurons and induces death of selected CA3 pyramidal cells in immature rats. These actions of CRH require activation of specific receptors that are abundant in CA3 during early postnatal development. Given the dramatic effects of CRH on hippocampal neurons and the absence of CRH-containing afferents to this region, we hypothesized that a significant population of CRHergic neurons exists in developing rat hippocampus. This study defined and characterized hippocampal CRH-containing cells by using immunocytochemistry, ultrastructural examination, and colocalization with gamma-aminobutyric acid (GABA)-synthesizing enzyme and calcium-binding proteins. Numerous, large CRH-immunoreactive (ir) neurons were demonstrated in CA3 strata pyramidale and oriens, fewer were observed in the corresponding layers of CA1, and smaller CRH-ir cells were found in stratum lacunosum-moleculare of Ammon's horn. In the dentate gyrus, CRH-ir somata resided in the granule cell layer and hilus. Ultrastructurally, CRH-ir neurons had aspiny dendrites and were postsynaptic to both asymmetric and symmetric synapses. CRH-ir axon terminals formed axosomatic and axodendritic symmetric synapses with pyramidal and granule cells. Other CRH-ir terminals synapsed on axon initial segments of principal neurons. Most CRH-ir neurons were coimmunolabeled for glutamate decarboxylase (GAD)-65 and GAD-67 and the majority also contained parvalbumin, but none were labeled for calbindin. These results confirm the identity of hippocampal CRH-ir cells as GABAergic interneurons. Further, a subpopulation of neurons immunoreactive for both CRH and parvalbumin and located within and adjacent to the principal cell layers consists of basket and chandelier cells. Thus, axon terminals of CRH-ir interneurons are strategically positioned to influence the excitability of the principal hippocampal neurons via release of both CRH and GABA.

  17. Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Lushnikova, Irina; Skibo, Galina; Muller, Dominique; Nikonenko, Irina

    2011-04-01

    Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygen-glucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Three-dimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatory-inhibitory balance. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  18. Synchrotron FTIR micro-spectroscopy study of the rat hippocampal formation after pilocarpine-evoked seizures.

    Science.gov (United States)

    Chwiej, J; Dulinska, J; Janeczko, K; Dumas, P; Eichert, D; Dudala, J; Setkowicz, Z

    2010-10-01

    In the present work, synchrotron radiation Fourier transform infrared (SRFTIR) micro-spectroscopy and imaging were used for topographic and semi-quantitative biochemical analysis of rat brain tissue in cases of pilocarpine-induced epilepsy. The tissue samples were analyzed with a beam defined by small apertures and spatial resolution steps of 10 microm which allowed us to probe the selected cellular layers of hippocampal formation. Raster scanning of the samples has generated 2D chemical cartographies revealing the distribution of proteins, lipids and nucleic acids. Spectral analysis has shown changes in the saturation level of phospholipids and relative secondary structure of proteins. Special interest was put in the analysis of two areas of the hippocampal formation (sector 3 of the Ammon's horn, CA3 and dentate gyrus, DG) in which elemental abnormalities were observed during our previous studies. Statistically significant increase in the saturation level of phospholipids (increased ratio of the absorption intensities at around 2921 and 2958 cm(-1)) as well as conformational changes of proteins (beta-type structure discrepancies as shown by the increased ratio of the absorbance intensities at around 1631 and 1657 cm(-1) as well as the ratio of the absorbance at 1548 and 1657 cm(-1)) were detected in pyramidal cells of CA3 area as well as in the multiform and molecular layers of DG. The findings presented here suggest that abnormalities in the protein secondary structure and increases in the level of phospholipid saturation could be involved in mechanisms of neurodegenerative changes following the oxidative stress evoked in brain areas affected by pilocarpine-induced seizures.

  19. Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat.

    Science.gov (United States)

    Hori, Nobuaki; Kadota, Tomoko; Akaike, Norio

    2015-01-01

    Chronic treatment of rats with methamphetamine (MAP) causes a range of functional changes to the central nervous system (CNS), including a toxicity that is widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In this report, we examined the effect of chronic MAP treatment on pyramidal neurons of the rat piriform cortex, an area involved in sensory processing, associative learning and a model system for studies on synaptic plasticity. MAP treatment significantly depolarized the membrane potential and decreased neuronal input resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses was disturbed by chronic MAP treatment, and the extent of long-term potentiation (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons were observed as blebbing of the dendrite trees. The changes we observed represent detrimental effects on the function of piriform cortical neurons further illustrating deficits in synaptic plasticity extend beyond the hippocampus. These changes may contribute to behavioural deficits in chronic MAP-treated animals.

  20. The effect of two lipophilic gamma-aminobutyric acid uptake blockers in CA1 of the rat hippocampal slice

    DEFF Research Database (Denmark)

    Rekling, J C; Jahnsen, H; Mosfeldt Laursen, A

    1990-01-01

    the blood. 2. We have investigated the effect of these two uptake inhibitors on the responses to exogenous GABA and on GABA-mediated inhibitory synaptic potentials in pyramidal neurones of the CA1 region in the rat hippocampal slice. 3. We found that both drugs increased the amplitude and duration...... of responses to exogenous GABA. Furthermore, the inhibitory synaptic potentials increased in amplitude. This increase was seen in both early and late phases of the synaptic potentials. We conclude that NO-05-0328 and NO-05-0329, at least in vitro, are more effective than older GABA uptake inhibitors...... such as nipecotic acid and they therefore deserve consideration for clinical use....

  1. Role of the amygdala in the hippocampal kindling effect of rats.

    Science.gov (United States)

    Araki, H; Aihara, H; Watanabe, S; Yamamoto, T; Ueki, S

    1985-02-01

    In the present experiment, the role of the amygdala in the formation of the hippocampal kindling effect was investigated in rats with chronic electrode implants. The number of trials required for the establishment of hippocampal kindling was significantly shortened by either ipsilateral or bilateral amygdaloid lesions. The high amplitude spike waves in the frontal cortex and reticular formation appeared earlier in the amygdaloid lesioned rats than in the sham lesioned rats. It is suggested that the amygdala has an inhibitory effect on the development of the hippocampal kindling effect. On the other hand, either the ipsilateral or bilateral amygdaloid lesions after the establishment of hippocampal kindling inhibited the induction of generalized convulsion by hippocampal stimulation. Three and 8 repeated daily stimulations were needed to reestablish the hippocampal kindling effect after the ipsilateral and bilateral amygdaloid lesions, respectively. These results do not coincide with the above-mentioned results indicating that the amygdala has an inhibitory role in the formation of hippocampal kindling. It is suggested that the neuronal circuits involved in the formation of hippocampal kindling in the amygdaloid lesioned rats are different from those in the intact rats.

  2. Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer's disease (AD).

    Science.gov (United States)

    Alldred, Melissa J; Lee, Sang Han; Petkova, Eva; Ginsberg, Stephen D

    2015-09-01

    Down syndrome (DS) is caused by the triplication of human chromosome 21 (HSA21) and is the most common genetic cause of intellectual disability, with individuals having deficits in cognitive function including hippocampal learning and memory and neurodegeneration of cholinergic basal forebrain neurons, a pathological hallmark of Alzheimer's disease (AD). To date, the molecular underpinnings driving this pathology have not been elucidated. The Ts65Dn mouse is a segmental trisomy model of DS and like DS/AD pathology, displays age-related cognitive dysfunction and basal forebrain cholinergic neuron (BFCN) degeneration. To determine molecular and cellular changes important for elucidating mechanisms of neurodegeneration in DS/AD pathology, expression profiling studies were performed. Molecular fingerprinting of homogeneous populations of Cornu Ammonis 1 (CA1) pyramidal neurons was performed via laser capture microdissection followed by Terminal Continuation RNA amplification combined with custom-designed microarray analysis and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting. Significant alterations were observed within CA1 pyramidal neurons of aged Ts65Dn mice compared to normal disomic (2N) littermates, notably in excitatory and inhibitory neurotransmission receptor families and neurotrophins, including brain-derived neurotrophic factor as well as several cognate neurotrophin receptors. Examining gene and protein expression levels after the onset of BFCN degeneration elucidated transcriptional and translational changes in neurons within a vulnerable circuit that may cause the AD-like pathology seen in DS as these individuals age, and provide rational targets for therapeutic interventions.

  3. Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons.

    Science.gov (United States)

    Yin, Hong Z; Sensi, Stefano L; Ogoshi, Fumio; Weiss, John H

    2002-02-15

    Synaptic release of Zn2+ and its translocation into postsynaptic neurons probably contribute to neuronal injury after ischemia or epilepsy. Studies in cultured neurons have revealed that of the three major routes of divalent cation entry, NMDA channels, voltage-sensitive Ca2+ channels (VSCCs), and Ca2+-permeable AMPA/kainate (Ca-A/K) channels, Ca-A/K channels exhibit the highest permeability to exogenously applied Zn2+. However, routes through which synaptically released Zn2+ gains entry to postsynaptic neurons have not been characterized in vivo. To model ischemia-induced Zn2+ movement in a system approximating the in vivo situation, we subjected mouse hippocampal slice preparations to controlled periods of oxygen and glucose deprivation (OGD). Timm's staining revealed little reactive Zn2+ in CA1 and CA3 pyramidal neurons of slices exposed in the presence of O2 and glucose. However, 15 min of OGD resulted in marked labeling in both regions. Whereas strong Zn2+ labeling persisted if both the NMDA antagonist MK-801 and the VSCC blocker Gd3+ were present during OGD, the presence of either the Ca-A/K channel blocker 1-naphthyl acetyl spermine (NAS) or the extracellular Zn2+ chelator Ca2+ EDTA substantially decreased Zn2+ accumulation in pyramidal neurons of both subregions. In parallel experiments, slices were subjected to 5 min OGD exposures as described above, followed 4 hr later by staining with the cell-death marker propidium iodide. As in the Timm's staining experiments, substantial CA1 or CA3 pyramidal neuronal damage occurred despite the presence of MK-801 and Gd3+, whereas injury was decreased by NAS or by Ca2+ EDTA (in CA1).

  4. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane.

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn(2+))-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p<0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn(2+)-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

  5. Electrical coupling between hippocampal astrocytes in rat brain slices.

    Science.gov (United States)

    Meme, William; Vandecasteele, Marie; Giaume, Christian; Venance, Laurent

    2009-04-01

    Gap junctions in astrocytes play a crucial role in intercellular communication by supporting both biochemical and electrical coupling between adjacent cells. Despite the critical role of electrical coupling in the network organization of these glial cells, the electrophysiological properties of gap junctions have been characterized in cultures while no direct evidence has been sought in situ. In the present study, gap-junctional currents were investigated using simultaneous dual whole-cell patch-clamp recordings between astrocytes from rat hippocampal slices. Bidirectional electrotonic coupling was observed in 82% of the cell pairs with an average coupling coefficient of 5.1%. Double patch-clamp analysis indicated that junctional currents were independent of the transjunctional voltage over a range from -100 to +110 mV. Interestingly, astrocytic electrical coupling displayed weak low-pass filtering properties compared to neuronal electrical synapses. Finally, during uncoupling processes triggered by either the gap-junction inhibitor carbenoxolone or endothelin-1, an increase in the input resistance in the injected cell paralleled the decrease in the coupling coefficient. Altogether, these results demonstrate that hippocampal astrocytes are electrically coupled through gap-junction channels characterized by properties that are distinct from those of electrical synapses between neurons. In addition, gap-junctional communication is efficiently regulated by endogenous compounds. This is taken to represent a mode of communication that may have important implications for the functional role of astrocyte networks in situ.

  6. Treadmill Exercise Induces Hippocampal Astroglial Alterations in Rats

    Directory of Open Access Journals (Sweden)

    Caren Bernardi

    2013-01-01

    Full Text Available Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP, glutamate uptake and glutamine synthetase (GS activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.

  7. Rat hippocampal GABAergic molecular markers are differentially affected by ageing.

    Science.gov (United States)

    Vela, José; Gutierrez, Antonia; Vitorica, Javier; Ruano, Diego

    2003-04-01

    We previously reported that the pharmacological properties of the hippocampal GABAA receptor and the expression of several subunits are modified during normal ageing. However, correlation between these post-synaptic modifications and pre-synaptic deficits were not determined. To address this issue, we have analysed the mRNA levels of several GABAergic molecular markers in young and old rat hippocampus, including glutamic acid decarboxylase enzymes, parvalbumin, calretinin, somatostatin, neuropeptide Y and vasoactive intestinal peptide (VIP). There was a differential age-related decrease in these interneuronal mRNAs that was inversely correlated with up-regulation of the alpha1 GABA receptor subunit. Somatostatin and neuropeptide Y mRNAs were most frequently affected (75% of the animals), then calretinin and VIP mRNAs (50% of the animals), and parvalbumin mRNA (25% of the animals) in the aged hippocampus. This selective vulnerability was well correlated at the protein/cellular level as analysed by immunocytochemistry. Somatostatin interneurones, which mostly innervate principal cell distal dendrites, were more vulnerable than calretinin interneurones, which target other interneurones. Parvalbumin interneurones, which mostly innervate perisomatic domains of principal cells, were preserved. This age-dependent differential reduction of specific hippocampal inteneuronal subpopulations might produce functional alterations in the GABAergic tone which might be compensated, at the post-synaptic level, by up-regulation of the expression of the alpha1 GABAA receptor subunit.

  8. Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures.

    Science.gov (United States)

    Fan, Rong; Tenner, Andrea J

    2004-02-01

    Amyloid beta peptide (Abeta) is a major component of senile plaques, one of the principle pathological features in Alzheimer's disease (AD) brains. Fibrillar Abeta has been shown to bind C1 via C1q, the recognition component of the classical complement pathway, resulting in the activation of the complement pathway, thereby initiating an inflammatory cascade in the brain. C1q has also been shown to enhance phagocytic activities of microglia, which could benefit in clearance of apoptotic cells or cellular debris. To begin to define the role of C1q in tissue injury mediated by Abeta, we assessed the appearance of C1q in hippocampal slice cultures treated with freshly solubilized or fibrillar Abeta 1-42. Here we demonstrate a dose- and time-dependent uptake of exogenously applied Abeta by pyramidal neurons in organotypic slice cultures from rat hippocampus. Importantly, when slices were immunostained with antibody against rat C1q, a distinct reactivity for C1q in cells within the neuronal cell layer of cornu ammonis (CA) of hippocampus, primarily the CA1/CA2, was observed in the Abeta-treated slices. No such immunoreactivity was detected in untreated cultures or upon addition of control peptides. ELISA assays also showed an increase in C1q in tissue extracts from slices of the treated group. Similarly, the mRNA level of C1q in slices was increased within 24 h after Abeta treatment. These data demonstrate that upon exposure to Abeta, C1q is expressed in neurons in this organotypic system. The induction of C1q may be an early, perhaps beneficial, tissue or cellular response to injury triggered by particular pathogenic stimuli.

  9. Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 1; Postnatal maturation of hippocampal cells

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    Represa, A.; Dessi, F.; Beaudoin, M.; Ben-Ari, Y. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France))

    1991-01-01

    The axons of dentate granule cells, the mossy fibres, establish synaptic contacts with the thorny excrescences of the apical dendrite of CA3 pyramidal neurons. Dentate granule cells develop postnatally in rats, whereas the CA3 pyramidal cells are generated before birth. In the present studies, using unilateral neonatal {gamma}-ray irradiation to destroy the granule cells in one hemisphere, we have studied the effect of mossy fibre deprivation on the development of their targets. We show that such ''degranulation'' prevents the normal development of giant thorny excrescences, suggesting that the development of thorny excrescences in CA3 pyramidal neurons is under the control of mossy fibres. In contrast, irradiation of the hippocampus of the neonatal rat does not affect the development of the dendritic arborization of CA3 pyramidal cells and their non-mossy dendritic spines. (author).

  10. Scorpion toxin prolongs an inactivation phase of the voltage-dependent sodium current in rat isolated single hippocampal neurons.

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    Kaneda, M; Oyama, Y; Ikemoto, Y; Akaike, N

    1989-05-15

    The effects of scorpion toxin on the voltage-dependent sodium current (INa) of CA1 pyramidal neurons isolated from rat hippocampus were studied under the single-electrode voltage-clamp condition using a 'concentration-clamp' technique. The toxin increased the peak amplitude of INa and prolonged its inactivation phase in a time- and dose-dependent manner. Inactivation phase of INa proceeded with two exponential components in the absence (control) and presence of the toxin. In the toxin-treated neurons, both the time constant of slow component and its fractional contribution to the total current increased dose-dependently while the fractional contribution of the fast one decreased in a dose-dependent fashion without changing its time constant. Actions of scorpion toxin on the sodium channels of hippocampal pyramidal neurons were essentially similar to those of peripheral preparations. Therefore, it can be concluded that the sodium channels of mammalian brain neurons have structures and functions similar to peripheral channels.

  11. Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

    Science.gov (United States)

    Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

    2017-02-18

    There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the expression of Kv3.1b in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labelled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. This article is protected by copyright. All rights reserved.

  12. Phasic and tonic type A γ-Aminobutryic acid receptor mediated effect of Withania somnifera on mice hippocampal CA1 pyramidal Neurons

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    Janardhan Prasad Bhattarai

    2014-01-01

    Full Text Available Background: In Nepali and Indian system of traditional medicine, Withania somnifera (WS is considered as a rejuvenative medicine to maintain physical and mental health and has also been shown to improve memory consolidation. Objective: In this study, a methanolic extract of WS (mWS was applied on mice hippocampal CA1 neurons to identify the receptors activated by the WS. Materials and Methods: The whole cell patch clamp recordings were performed on CA1 pyramidal neurons from immature mice (7-20 postnatal days. The cells were voltage clamped at -60 mV. Extract of WS root were applied to identify the effect of mWS. Results: The application of mWS (400 ng/μl induced remarkable inward currents (-158.1 ± 28.08 pA, n = 26 on the CA1 pyramidal neurons. These inward currents were not only reproducible but also concentration dependent. mWS-induced inward currents remained persistent in the presence of amino acid receptor blocking cocktail (AARBC containing blockers for the ionotropic glutamate receptors, glycine receptors and voltage-gated Na + channel (Control: -200.3 ± 55.42 pA, AARBC: -151.5 ± 40.58 pA, P > 0.05 suggesting that most of the responses by mWS are postsynaptic events. Interestingly, these inward currents were almost completely blocked by broad GABA A receptor antagonist, bicuculline- 20 μM (BIC (BIC: -1.46 ± 1.4 pA, P < 0.001, but only partially by synaptic GABA A receptor blocker gabazine (1 μM (GBZ: -18.26 ± 4.70 pA, P < 0.01. Conclusion: These results suggest that WS acts on synaptic/extrasynaptic GABA A receptors and may play an important role in the process of memory and neuroprotection via activation of synaptic and extrasynaptic GABA A receptors.

  13. Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hippocampal CA1 pyramidal neurons: Ca(2+)-dependent activation by blocking A1 adenosine receptors.

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    Klishin, A; Tsintsadze, T; Lozovaya, N; Krishtal, O

    1995-01-01

    When performed at increased external [Ca2+]/[Mg2+] ratio (2.5 mM/0.5 mM), temporary block of A1 adenosine receptors in hippocampus [by 8-cyclopentyltheophylline (CPT)] leads to a dramatic and irreversible change in the excitatory postsynaptic current (EPSC) evoked by Schaffer collateral/commissural (SCC) stimulation and recorded by in situ patch clamp in CA1 pyramidal neurons. The duration of the EPSC becomes stimulus dependent, increasing with increase in stimulus strength. The later occurring component of the EPSC is carried through N-methyl-D-aspartate (NMDA) receptor-operated channels but disappears under either the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These findings indicate that the late component of the SCC-evoked EPSC is polysynaptic: predominantly non-NMDA receptor-mediated SCC inputs excite CA1 neurons that recurrently excite each other by predominantly NDMA receptor-mediated synapses. These recurrent connections are normally silent but become active after CPT treatment, leading to enhancement of the late component of the EPSC. The activity of these connections is maintained for at least 2 hr after CPT removal. When all functional NMDA receptors are blocked by dizocilpine maleate (MK-801), subsequent application of CPT leads to a partial reappearance of NMDA receptor-mediated EPSCs evoked by SCC stimulation, indicating that latent NMDA receptors are recruited. Altogether, these findings indicate the existence of a powerful system of NMDA receptor-mediated synaptic contacts in SCC input to hippocampal CA1 pyramidal neurons and probably also in reciprocal connections between these neurons, which in the usual preparation are kept latent by activity of A1 receptors. PMID:8618915

  14. The effects of realistic synaptic distribution and 3D geometry on signal integration and extracellular field generation of hippocampal pyramidal cells and inhibitory neurons

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    Attila I Gulyas

    2016-11-01

    Full Text Available In vivo and in vitro multichannel field and somatic intracellular recordings are frequently used to study mechanisms of network pattern generation. When interpreting these data, neurons are often implicitly considered as electrotonically compact cylinders with a homogeneous distribution of excitatory and inhibitory inputs. However, the actual distributions of dendritic length, diameter, and the densities of excitatory and inhibitory input are non-uniform and cell type-specific. We first review quantitative data on the dendritic structure and synaptic input and output distribution of pyramidal cells and interneurons in the hippocampal CA1 area. Second, using multicompartmental passive models of four different types of neurons, we quantitatively explore the effect of differences in dendritic structure and synaptic distribution on the errors and biases of voltage clamp measurements of inhibitory and excitatory postsynaptic currents. Finally, using the 3-dimensional distribution of dendrites and synaptic inputs we calculate how different inhibitory and excitatory inputs contribute to the generation of local field potential in the hippocampus. We analyze these effects at different realistic background activity levels as synaptic bombardment influences neuronal conductance and thus the propagation of signals in the dendritic tree.We conclude that, since dendrites are electrotonically long and entangled in 3D, somatic intracellular and field potential recordings miss the majority of dendritic events in some cell types, and thus overemphasize the importance of perisomatic inhibitory inputs and belittle the importance of complex dendritic processing. Modeling results also suggest that pyramidal cells and inhibitory neurons probably use different input integration strategies. In pyramidal cells, second- and higher-order thin dendrites are relatively well-isolated from each other, which may support branch-specific local processing as suggested by studies

  15. Commissurally projecting inhibitory interneurons of the rat hippocampal dentate gyrus: a colocalization study of neuronal markers and the retrograde tracer Fluoro-gold.

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    Zappone, C A; Sloviter, R S

    2001-12-24

    Improved methods for detecting neuronal markers and the retrograde tracer Fluoro-Gold (FG) were used to identify commissurally projecting neurons of the rat hippocampus. In addition to the dentate hilar mossy cells and CA3 pyramidal cells shown previously to transport retrograde tracers after injection into the dorsal hippocampus, FG-positive interneurons of the dentate granule cell layer and hilus were detected in numbers greater than previously reported. FG labeling of interneurons was variable among animals, but was as high as 96% of hilar somatostatin-positive interneurons, 84% of parvalbumin-positive cells of the granule cell layer and hilus combined, and 33% of hilar calretinin-positive cells. By comparison, interneurons of the dentate molecular layer and all hippocampal subregions were conspicuously FG-negative. Whereas hilar mossy cells and CA3 pyramidal cells were FG-labeled throughout the longitudinal axis, FG-positive interneurons exhibited a relatively homotopic distribution. "Control" injections of FG into the neocortex, septum, and ventral hippocampus demonstrated that the homotopic labeling of dentate interneurons was injection site-specific, and that the CA1-CA3 interneurons unlabeled by contralateral hippocampal FG injection were nonetheless able to transport FG from the septum. These data suggest a hippocampal organizing principle according to which virtually all commissurally projecting hippocampal neurons share the property of being monosynaptic targets of dentate granule cells. Because granule cells innervate their exclusively ipsilateral target cells in a highly lamellar pattern, these results suggest that focal granule cell excitation may result in commissural inhibition of the corresponding "twin" granule cell lamella, thereby lateralizing and amplifying the influence of the initiating discharge.

  16. Low-frequency electrical stimulation enhances the effectiveness of phenobarbital on GABAergic currents in hippocampal slices of kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi-Chameh, Homeira; Ghafouri, Samireh; Sheibani, Vahid; Mirnajafi-Zadeh, Javad

    2016-08-25

    Low frequency stimulation (LFS) has been proposed as a new approach in the treatment of epilepsy. The anticonvulsant mechanism of LFS may be through its effect on GABAA receptors, which are the main target of phenobarbital anticonvulsant action. We supposed that co-application of LFS and phenobarbital may increase the efficacy of phenobarbital. Therefore, the interaction of LFS and phenobarbital on GABAergic inhibitory post-synaptic currents (IPSCs) in kindled and control rats was investigated. Animals were kindled by electrical stimulation of basolateral amygdala in a semi rapid manner (12 stimulations/day). The effect of phenobarbital, LFS and phenobarbital+LFS was investigated on GABAA-mediated evoked and miniature IPSCs in the hippocampal brain slices in control and fully kindled animals. Phenobarbital and LFS had positive interaction on GABAergic currents. In vitro co-application of an ineffective pattern of LFS (100 pulses at afterdischarge threshold intensity) and a sub-threshold dose of phenobarbital (100μM) which had no significant effect on GABAergic currents alone, increased the amplitude and area under curve of GABAergic currents in CA1 pyramidal neurons of hippocampal slices significantly. Interestingly, the sub-threshold dose of phenobarbital potentiated the GABAergic currents when applied on the hippocampal slices of kindled animals which received LFS in vivo. Post-synaptic mechanisms may be involved in observed interactions. Obtained results implied a positive interaction between LFS and phenobarbital through GABAA currents. It may be suggested that a combined therapy of phenobarbital and LFS may be a useful manner for reinforcing the anticonvulsant action of phenobarbital. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

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    Huaqiu Zhang

    Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

  18. Low concentrations of the solvent dimethyl sulphoxide alter intrinsic excitability properties of cortical and hippocampal pyramidal cells.

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    Francesco Tamagnini

    Full Text Available Dimethylsulfoxide (DMSO is a widely used solvent in biology. It has many applications perhaps the most common of which is in aiding the preparation of drug solutions from hydrophobic chemical entities. Recent studies have suggested that this molecule may be able to induce apoptosis in neural tissues urging caution regarding its introduction into humans, for example as part of stem cell transplants. Here we have used in vitro electrophysiological methods applied to murine brain slices to examine whether a few hours treatment with 0.05% DMSO (a concentration regarded by many as innocuous alters intrinsic excitability properties of neurones. We investigated pyramidal neurones in two distinct brain regions, namely area CA1 of the hippocampus and layer 2 of perirhinal cortex. In the former there was no effect on resting potential but input resistance was decreased by DMSO pre-treatment. In line with this action potential count for any level of depolarizing current stimulus was reduced by ∼25% following DMSO treatment. Ih-mediated "sag" was also increased in CA1 pyramids and action potential waveform analysis demonstrated that DMSO treatment moved action potential threshold towards resting potential. In perirhinal cortex a decreased action potential output for various depolarizing current stimuli was also seen. In these cells action potential threshold was unaltered by DMSO but a significant increase in action potential width was apparent. These data indicate that pre-treatment with this widely employed solvent can elicit multifaceted neurophysiological changes in mammalian neurones at concentrations below those frequently encountered in the published literature.

  19. Activity-dependent induction of multitransmitter signaling onto pyramidal cells and interneurons of hippocampal area CA3.

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    Romo-Parra, Héctor; Vivar, Carmen; Maqueda, Jasmín; Morales, Miguel A; Gutiérrez, Rafael

    2003-06-01

    The granule cells of the dentate gyrus (DG) are considered to be glutamatergic, but they contain glutamic acid decarboxylase, gamma-amino butyric acid (GABA), and the vesicular GABA transporter mRNA. Their expression is regulated in an activity-dependent manner and coincides with the appearance of GABAergic transmission from the mossy fibers (MF) to pyramidal cells in area CA3. These data support the hypothesis that MF are able to release glutamate and GABA. Following the principle that a given neuron releases the same neurotransmitter(s) onto all its targets, we here demonstrate the emergence, after a generalized convulsive seizure, of MF GABAergic signaling sensitive to activation mGluR-III onto pyramidal cells and interneurons of CA3. Despite this, excitation overrides inhibition in interneurons, preventing disinhibition. Furthermore, on blockade of GABA and glutamate ionotropic receptors, an M1-cholinergic depolarizing signal is also revealed in both targets, which postsynaptically modulates the glutamatergic and GABAergic fast neurotransmission. The emergence of these nonglutamatergic signals depends on protein synthesis. In contrast to cholinergic responses evoked by associational/commissural fibers activation, cholinergic transmission evoked by DG stimulation is only observed after seizures and is strongly depressed by the activation of mGluR-II, whereas both are depressed by M2-AChR activation. With immunohistological experiments, we show that this cholinergic pathway runs parallel to the MF. Thus seizures compromise a delicate balance of excitation and inhibition, on which a complex interaction of different neurotransmitters emerges to counteract excitation at pre- and postsynaptic sites. Particularly, MF GABAergic inhibition emerges to exert an overall inhibitory action on CA3.

  20. Impaired effect of activation of rat hippocampal 5-HT7 receptors, induced by treatment with the 5-HT7 receptor antagonist SB 269970.

    Science.gov (United States)

    Kusek, M; Sowa, J; Tokarski, K; Hess, G

    2015-04-01

    Effects of the 5-HT(7) receptor antagonist SB 269970, administered for 14 days (1.25 mg/kg), were studied in ex vivo slices of rat hippocampus. To activate the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT, 200 nM) was applied in the presence of WAY 100635 (2 μM), a 5-HT(1A) receptor antagonist. In contrast to control preparations, no 5-HT(7) receptor-mediated increase in excitability nor depolarization and an increase in the input resistance of CA1 and CA3 pyramidal neurons were present in slices prepared from rats treated with SB 269970. The treatment also abolished the stimulatory effect of 5-HT(7) receptor activation on spontaneous excitatory postsynaptic currents recorded from CA1 stratum radiatum/lacunosum-moleculare interneurons. These data demonstrate that repeated administration of SB 269970 impairs the reactivity of the CA1 hippocampal neuronal network to 5-HT(7) receptor activation.

  1. [The effects of SO2 on electric activity learning and memory of rat hippocampal neurons].

    Science.gov (United States)

    Liu, Xiaoli; Yang, Dongsheng; Meng, Ziqiang

    2008-11-01

    To study the toxicological mechanism of SO2 on central neural system by electrophysiological method. Male SD rats were housed in exposure chambers and treated at the concentration of 28 mg/m3 SO2 for 7 days (6h/d), while control rats were treated with filtered air in the same condition. Using glass micro-electrodes recording in vivo, the frequencies and numbers of spontaneous discharge in hippocampal CAI neurons were measured. Influences of the learning and memory functions were measured by setting up passive avoidance behavior reflex. SO2 decreased significantly the neurons spontaneous discharge frequency and prolonged the neurons spontaneous period in hippocampal CAl. SO2 significantly decreased the learning and memory function of rats. The results indicated that SO2 could be a neurotoxin. It could inhibit the hippocampal neurons excitability and affect the learning and memory function of rats.

  2. DIFFERENT EFFECTS OF MUSCARINIC AGONISTS IN RAT SUPERIOR CERVICAL-GANGLION AND HIPPOCAMPAL SLICES

    NARCIS (Netherlands)

    BODDEKE, HWGM

    1991-01-01

    In this study the effects of muscarinic antagonists and agonists on M1 muscarinic receptors in the isolated rat superior cervical ganglion and the rat hippocampal slice were investigated. Oxotremorine and APE but not pilocarpine, McN-A-343 or 4-Cl-McN-A-343 induced small M2 muscarinic

  3. Water maze learning and hippocampal synaptic plasticity in streptozotocin diabetic rats: effects of insulin treatment

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Kamal, A.; Urban, I.J.A.; Spruijt, B.M.; Erkelens, D.W.

    1998-01-01

    Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characteriz

  4. A protein phosphatase is involved in the cholinergic suppression of the Ca(2+)-activated K(+) current sI(AHP) in hippocampal pyramidal neurons.

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    Krause, M; Pedarzani, P

    2000-04-27

    The slow calcium-activated potassium current sI(AHP) underlies spike-frequency adaptation and has a substantial impact on the excitability of hippocampal CA1 pyramidal neurons. Among other neuromodulatory substances, sI(AHP) is modulated by acetylcholine acting via muscarinic receptors. The second-messenger systems mediating the suppression of sI(AHP) by muscarinic agonists are largely unknown. Both protein kinase C and A do not seem to be involved, whereas calcium calmodulin kinase II has been shown to take part in the muscarinic action on sI(AHP). We re-examined the mechanism of action of muscarinic agonists on sI(AHP) combining whole-cell recordings with the use of specific inhibitors or activators of putative constituents of the muscarinic pathway. Our results suggest that activation of muscarinic receptors reduces sI(AHP) in a G-protein-mediated and phospholipase C-independent manner. Furthermore, we obtained evidence for the involvement of the cGMP-cGK pathway and of a protein phosphatase in the cholinergic suppression of sI(AHP), whereas release of Ca(2+) from IP(3)-sensitive stores seems to be relevant neither for maintenance nor for modulation of sI(AHP).

  5. Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide.

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    Nicola J Corbett

    Full Text Available Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature of Alzheimer's disease. FG-Loop (FGL, a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. In the present study impairments in social recognition memory were seen 24 days after a 5 mg/15 µl amyloid-beta(25-35 injection into the right lateral ventricle of the young adult rat brain. This impairment was prevented if the animal was given a systemic treatment of FGL. Unbiased stereology was used to investigate the ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the amyloid-beta(25-35 injection. NeuN, a neuronal marker (for nuclear staining was used to identify pyramidal cells, and immunocytochemistry was also used to identify inactive glycogen synthase kinase 3beta (GSK3β and to determine the effects of amyloid-beta(25-35 and FGL on the activation state of GSK3β, since active GSK3β has been shown to cause a range of AD pathologies. The cognitive deficits were not due to hippocampal atrophy as volume estimations of the entire hippocampus and its regions showed no significant loss, but amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by FGL. However, FGL treatment without amyloid-beta was also found to cause a 40% decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of GSK3β, as an increased proportion of CA1 pyramidal neurons contained inactive GSK3β after FGL treatment. These data suggest that FGL, although potentially disruptive in non-pathological conditions, can be neuroprotective in disease-like conditions.

  6. Chronic exercise dampens hippocampal glutamate overflow induced by kainic acid in rats.

    Science.gov (United States)

    Holmes, Philip V; Reiss, Jenny I; Murray, Patrick S; Dishman, Rod K; Spradley, Jessica M

    2015-05-01

    Our laboratory has previously reported that chronic, voluntary exercise diminishes seizure-related behaviors induced by convulsant doses of kainic acid. The present experiments tested the hypothesis that exercise exerts this protective effect through a mechanism involving suppression of glutamate release in the hippocampal formation. Following three weeks of voluntary wheel running or sedentary conditions, rats were injected with 10 mg/kg of kainic acid, and hippocampal glutamate was measured in real time using a telemetric, in vivo voltammetry system. A separate experiment measured electroencephalographic (EEG) activity following kainic acid treatment. Results of the voltammetry experiment revealed that the rise in hippocampal glutamate induced by kainic acid is attenuated in exercising rats compared to sedentary controls, indicating that the exercise-induced protection against seizures involves regulation of hippocampal glutamate release. The findings reveal the potential benefit of regular exercise in the treatment and prevention of seizure disorders and suggest a possible neurobiological mechanism underlying this effect.

  7. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

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    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1989-08-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

  8. GABAB and adenosine receptors mediate enhancement of the K+ current, IAHP, by reducing adenylyl cyclase activity in rat CA3 hippocampal neurons.

    Science.gov (United States)

    Gerber, U; Gähwiler, B H

    1994-11-01

    1. Gamma-aminobuturic acid-B (GABAB) and adenosine A1 receptors, which are expressed in hippocampal pyramidal cells, are linked to pertussis toxin-sensitive G-proteins known to be coupled negatively to the enzyme adenylyl cyclase. This study investigates the electrophysiological consequences of adenylyl cyclase inhibition in response to stimulation of these receptors. 2. Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal slice cultures in presence of tetrodotoxin. The calcium-dependent potassium current (IAHP), which is very sensitive to intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP), was used as an electrophysiological indicator of adenylyl cyclase activity. 3. Application of baclofen (10 microM), a selective agonist at GABAB receptors, or adenosine (50 microM) each resulted in a transient decrease followed by a significant enhancement in the amplitude of evoked IAHP. The initial reduction in amplitude of IAHP probably reflects inadequacies in voltage clamp of electronically distant dendritic sites, due to the shunting caused by concomitant activation of potassium conductance by baclofen/adenosine. Comparable increases in membrane conductance in response to the GABAA agonist, muscimol, caused a similar reduction in IAHP. The enhancement of IAHP is consistent with an inhibition of constitutively active adenylyl cyclase. 4. The receptor mediating the responses to adenosine was identified as belonging to the A1 subtype on the basis of its sensitivity to the selective antagonist 8-cyclopentyl-1,3-dipropylxanthine.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Simultaneous activation of gamma and theta network oscillations in rat hippocampal slice cultures.

    Science.gov (United States)

    Fischer, Yacov; Wittner, Lucia; Freund, Tamas F; Gähwiler, Beat H

    2002-03-15

    Hippocampal activity in vivo is characterized by concurrent oscillations at theta (4-15 Hz) and gamma (20-80 Hz) frequencies. Here we show that cholinergic receptor activation (methacholine 10-20 nm) in hippocampal slice cultures induces an oscillatory mode of activity, in which the intrinsic network oscillator (located in the CA3 area) expresses simultaneous theta and gamma network oscillations. Pyramidal cells display synaptic theta oscillations, characterized by cycles consisting of population EPSP-IPSP sequences that are dominated by population IPSPs. These rhythmic IPSPs most probably result from theta-modulated spiking activity of several interneurons. At the same time, the majority of interneurons consistently display synaptic gamma oscillations. These oscillatory cycles consist of fast depolarizing rhythmic events that are likely to reflect excitatory input from CA3 pyramidal cells. Interneurons comprising this functional group were identified morphologically. They include four known types of interneurons (basket, O-LM, bistratified and str. lucidum-specific cells) and one new type of CA3 interneuron (multi-subfield cell). The oscillatory activity of these interneurons is only weakly correlated between neighbouring cells, and in about half of these (44 %) is modulated by depolarizing theta rhythmicity. The overall characteristics of acetylcholine-induced oscillations in slice cultures closely resemble the rhythmicity observed in hippocampal field and single cell recordings in vivo. Both rhythmicities depend on intrinsic synaptic interactions, and are expressed by different cell types. The fact that these oscillations persist in a network lacking extra-hippocampal connections emphasizes the importance of intrinsic mechanisms in determining this form of hippocampal activity.

  10. Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Colbert, C M; Magee, J C; Hoffman, D A; Johnston, D

    1997-09-01

    Na+ action potentials propagate into the dendrites of pyramidal neurons driving an influx of Ca2+ that seems to be important for associative synaptic plasticity. During repetitive (10-50 Hz) firing, dendritic action potentials display a marked and prolonged voltage-dependent decrease in amplitude. Such a decrease is not apparent in somatic action potentials. We investigated the mechanisms of the different activity dependence of somatic and dendritic action potentials in CA1 pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp methods. There were three main findings. First, dendritic Na+ currents decreased in amplitude when repeatedly activated by brief (2 msec) depolarizations. Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less in somatic than in dendritic patches. Third, although K+ currents remained constant during trains, K+ currents were necessary for dendritic action potential amplitude to decrease in whole-cell experiments. These results suggest that regional differences in Na+ and K+ channels determine the differences in the activity dependence of somatic and dendritic action potential amplitudes.

  11. Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats.

    Science.gov (United States)

    Huang, He; Liu, Cun-Ming; Sun, Jie; Hao, Ting; Xu, Chun-Mei; Wang, Dan; Wu, Yu-Qing

    2016-08-01

    Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague-Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal

  12. Melanin concentrating hormone induces hippocampal acetylcholine release via the medial septum in rats.

    Science.gov (United States)

    Lu, Zhi-Hong; Fukuda, Satoru; Minakawa, Yoichi; Yasuda, Atsushi; Sakamoto, Hidetoshi; Sawamura, Shigehito; Takahashi, Hidenori; Ishii, Noriko

    2013-06-01

    Among various actions of melanin concentrating hormone (MCH), its memory function has been focused in animal studies. Although MCH neurons project to various areas in the brain, one main target site of MCH is hippocampal formation for memory consolidation. Recent immunohistochemical study shows that MCH neurons directly project to the hippocampal formation and may indirectly affect the hippocampus through the medial septum nucleus (MS). It has been reported that sleep is necessary for memory and that hippocampal acetylcholine (ACh) release is indispensable for memory consolidation. However, there is no report how MCH actually influences the hippocampal ACh effluxes in accordance with the sleep-wake cycle changes. Thus, we investigated the modulatory function of intracerebroventricular (icv) injection of MCH on the sleep-wake cycle and ACh release using microdialysis techniques. Icv injection of MCH significantly increased the rapid eye movement (REM) and non-REM episode time and the hippocampal, not cortical, ACh effluxes. There was a significant correlation between REM episode time and hippocampal ACh effluxes, but not between REM episode time and cortical ACh effluxes. Microinjection of MCH into the MS increased the hippocampal ACh effluxes with no influence on the REM episode time. It appears that the effect sites of icv MCH for prolongation of REM episode time may be other neuronal areas than the cholinergic neurons in the MS. We conclude that MCH actually increases the hippocampal ACh release at least in part through the MS in rats.

  13. Chronic prenatal exposure to the 900 megahertz electromagnetic field induces pyramidal cell loss in the hippocampus of newborn rats.

    Science.gov (United States)

    Bas, O; Odaci, E; Mollaoglu, H; Ucok, K; Kaplan, S

    2009-07-01

    Widespread use of mobile phones which are a major source of electromagnetic fields might affect living organisms. However, there has been no investigation concerning prenatal exposure to electromagnetic fields or their roles in the development of the pyramidal cells of the cornu ammonis in postnatal life. Two groups of pregnant rats, a control group and an experimental group, that were exposed to an electromagnetic field were used. For obtaining electromagnetic field offspring, the pregnant rats were exposed to 900 megahertz electromagnetic fields during the 1-19th gestation days. There were no actions performed on the control group during the same period. The offspring rats were spontaneously delivered--control group (n = 6) and electromagnetic field group (n = 6). Offspring were sacrificed for stereological analyses at the end of the 4th week. Pyramidal cell number in rat cornu ammonis was estimated using the optical fractionator technique. It was found that 900 megahertz of electromagnetic field significantly reduced the total pyramidal cell number in the cornu ammonis of the electromagnetic field group (P electromagnetic field exposure in the prenatal period.

  14. Electroacupuncture at Du channel and meridian of foot- Taiyang for hippocampal neurons in rats with depression

    Institute of Scientific and Technical Information of China (English)

    Min Pi; Wenshu Luo; Lihong Diao; Xiaodan Rao; Haibo Yu; Zhuoxin Yang

    2007-01-01

    BACKGROUND: Long-term anti-depression treatment can promote the regeneration of hippocampal regeneration. Up-regulation of hippocampal regeneration can reverse or prevent against the injury of stress to cerebrum, especially to hippocampal structure and function. Therefore, promoting hippocampal neuronal regeneration may be a new strategy for treating depression and anxiety.OBJECTIVE: To observe the effect of electro-acupuncture at Du channel and meridian of foot-Taiyang on hippocampal neurons from model rats of depression.DESIGN: A randomized controlled animal experiment.SETTING: Department of Acupuncture and Moxibustion, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine.MATERIALS: Twenty-four Wistar rats, of either gender, aged 2 months old, weighing 200 - 220 g, were provided by the Animal Experimental Center, Guangzhou University of Traditional Chinese Medicine.METHODS: This experiment was carried out in the Clinical Molecular Biochemical Laboratory, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine between October 2006 and April 2007.①The involved rats were randomized into 4 groups according to body mass: blank control group,model group, electroacupuncture A group and electroacupuncture B group, with 6 in each. Rats in the blank control group were free to access to water, and were not given any intervention. Rats in the latter 3 groups were developed into rat depression models by chronic stress combined with feeding alone, and received 21-day unpredictable various stresses. Rats in the model group were euthanized at 14 days after modeling,and their brain tissues were harvested. Rats in the electroacupuncture A group were modeled, then points "Baihui" and "Shenting" were chosen, and given electroacupuncture, once a day, 20 minutes once. Rats in the electroacupuncture B group were modeled, then points "Baihui", "Shenting", "Xinshu"and "Ganshu" were chosen, and frequency and therapeutic time were

  15. Effects of Dalteparin on Structure of Hippocampal Neurons of Rats in Chronic Stress

    OpenAIRE

    Mansoureh Soleimani; Arezo Nahavandi; Fereshteh Farajdokht

    2012-01-01

    Introduction: Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke rodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats.Methods : the study was carried out on 60 adult male wistar rats, weighing 200-250 gr. The rats were randomly divided into three groups: control, stress and stre...

  16. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis ?

    Directory of Open Access Journals (Sweden)

    Damien eBonhomme

    2014-02-01

    Full Text Available A disruption of the vitamin A signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using vitamin A deficiency (VAD, a nutritional model leading to a hyposignaling of the retinoid pathway, we have recently demonstrated that retinoic acid (RA, the active metabolite of vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs occurring with aging is known to strongly inhibit hippocampal plasticity and functions and few studies report on the counteracting effects of RA signaling pathway on GCs action. Here, we have addressed whether the modulation of brain GCs availability could be one of the biological mechanisms involved in the effects of vitamin A status on hippocampal plasticity and functions. Thus, we have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week vitamin A supplementation on plasma and hippocampal corticosterone (CORT levels in Wistar rats. We have also investigated corticosteroid binding globulin (CBG binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1 activity, both important modulators of CORT availability at the peripheral and hippocampal levels respectively. Interestingly, we show that the vitamin A status regulates levels of free plasma CORT and hippocampal CORT levels, by acting through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our results suggest that increased CORT levels in VAD rats could have some deleterious consequences on spatial memory, anxiety-like behavior and adult hippocampal neurogenesis whereas these effects could be corrected by a vitamin A supplementation. Thus, the modulation of GCs availability by vitamin A status is an important biological mechanism that should be taken into account in order to prevent age-related cognitive decline and hippocampal plasticity alterations.

  17. GABA mediated excitation in immature rat CA3 hippocampal neurons.

    Science.gov (United States)

    Cherubini, E; Rovira, C; Gaiarsa, J L; Corradetti, R; Ben Ari, Y

    1990-01-01

    Intracellular recordings from rat hippocampal neurons in vitro during the first postnatal week revealed the presence of spontaneous giant depolarizing potentials (GDPs). These were generated by the synchronous discharge of a population of neurons. GDPs reversed polarity at -27 and -51 mV when recorded with KCl or K-methylsulphate filled electrodes, respectively. GDPs were blocked by the GABAA receptor antagonist bicuculline (10 microM). Iontophoretic or bath applications of GABA (10-300 microM) in the presence of tetrodotoxin (1 microM), induced a membrane depolarization or in voltage clamp experiments an inward current which reversed polarity at the same potential as GDPs. The response to GABA was blocked in a non-competitive manner by bicuculline (10 microM) and did not desensitize. GABA mediated GDPs were presynaptically modulated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Their frequency was reduced or blocked by NMDA receptor antagonists and by the rather specific non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The frequency of GDPs was enhanced by glycine and D-serine (10-30 microM) in a strychnine insensitive manner. This effect was blocked by AP-5, suggesting that it was mediated by the allosteric modulatory site of the NMDA receptor. These observations suggest that most of the 'excitatory' drive in immature neurons is mediated by GABA acting on GABAA receptors; furthermore excitatory amino acids modulate the release of GABA by a presynaptic action on GABAergic interneurons.

  18. Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats.

    Science.gov (United States)

    Speisman, Rachel B; Kumar, Ashok; Rani, Asha; Foster, Thomas C; Ormerod, Brandi K

    2013-02-01

    We tested whether daily exercise modulates immune and neuroimmune cytokines, hippocampus-dependent behavior and hippocampal neurogenesis in aging male F344 rats (18mo upon arrival). Twelve weeks after conditioned running or control group assignment, the rats were trained and tested in a rapid water maze followed by an inhibitory avoidance task. The rats were BrdU-injected beginning 12days after behavioral testing and killed 3weeks later to quantify cytokines and neurogenesis. Daily exercise increased neurogenesis and improved immediate and 24h water maze discrimination index (DI) scores and 24h inhibitory avoidance retention latencies. Daily exercise decreased cortical VEGF, hippocampal IL-1β and serum MCP-1, GRO-KC and leptin levels but increased hippocampal GRO-KC and IL-18 concentrations. Serum leptin concentration correlated negatively with new neuron number and both DI scores while hippocampal IL-1β concentration correlated negatively with memory scores in both tasks. Cortical VEGF, serum GRO-KC and serum MCP-1 levels correlated negatively with immediate DI score and we found novel positive correlations between hippocampal IL-18 and GRO-KC levels and new neuron number. Pathway analyses revealed distinct serum, hippocampal and cortical compartment cytokine relationships. Our results suggest that daily exercise potentially improves cognition in aging rats by modulating hippocampal neurogenesis and immune and neuroimmune cytokine signaling. Our correlational data begin to provide a framework for systematically manipulating these immune and neuroimmune signaling molecules to test their effects on cognition and neurogenesis across lifespan in future experiments. Published by Elsevier Inc.

  19. Effects and wavelet spectral entropy analysis of rhubarb extracts rhein on synaptic transmission in rat hippocampal ca1 area in vitro

    Institute of Scientific and Technical Information of China (English)

    GU Jian-wen; ZHENG Chong-xun; ZHANG Ai-hua; Hiroshi Hasuo; Takashi Akasu; YANG Wen-tao; YANG li-bin; XIA Xun; MA Yuan

    2005-01-01

    Background 5-dihydroxyanthraquinone-2-carboxylic acid (rhein) inhibits oxidoreduction induced by reducing nicotingamide adenine dinucleotide in the mitochondria and reducing reactive oxygen species, it also suppresses lipid peroxidation in rat brain homogenates. This study was to assess the effects of anthraquinone derivatives, rhein on synaptic transmission in the rat hippocampal CA1 pyramidal cell layer by intracellular recording.Methods The excitatory postsynaptic potential (EPSP) evoked by stimulation of the Schaffer collaterals in the presence of bicuculline (15 μmol/L) was depressed by application of rhein (0.3-30 μmol/L). The amplitude of the EPSP was restored within 20 minutes after removal of rhein from the supernatant. At a concentration of 30 μmol/L, rhein reduced the amplitude of the EPSP to 42%±3.7% (n=24) of the control. Subsequently, wavelet spectral entropy was used to analyze the EPSP. Results A strong positive correlation was observed between the wavelet spectral entropy and other parameters such as amplitude, slope of rising phase and slope of descending phase of the EPSP. The paired-pulse facilitation (PPF) of the EPSP was significantly increased by rhein (30 μmol/L). The inhibitory postsynaptic potential (IPSP) recorded in the presence of CNQX (20 μmol/L) and APV (40 μmol/L) is not altered by rhein (30 μmol/L). Conclusions Rhein (30 μmol/L) can decrease the frequency but not the amplitude of the miniature EPSP (mEPSP). It is suggested that rhein inhibits excitatory synaptic transmission by decreasing the release of glutamate in rat hippocampal CA1 pyramidal neurons.

  20. Curcumin protects against interleukin-6-induced rapid Ca2+ influx in rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Qinying Deng; Tao Huang; Hongmei Tang; Xingming Zhong; Sujian Xia; Xiangcai Wei; Jun Dong

    2011-01-01

    The current study sought to investigate the potential protective action of curcumin against interleukin-6-induced injury in rat hippocampal neurons. The results revealed that interleukin-6 induced typical cellular injury, such as the swelling of cell bodies and increased Ca2+ concentration. After administration of curcumin, interleukin-6-induced neurons recovered to a normal state, and the fluorescence intensity of Ca2+ gradually returned to normal. These findings suggest that curcumin exerts a protective effect on hippocampal neurons of rats. In addition, our results suggest that the protective effect of curcumin involves prevention of the rapid Ca2+ influx induced by interleukin-6, which maintains Ca2+ homeostasis.

  1. Effects of chronic forced swim stress on hippocampal brain-derived neutrophic factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats.

    Science.gov (United States)

    Badowska-Szalewska, Ewa; Spodnik, Edyta; Klejbor, Ilona; Morys, Janusz

    2010-01-01

    A type of stress stimulation and age are claimed to affect the expression of brain-derived neurotrophic factor (BDNF) and its receptor - tyrosine kinase B (TrkB) in the hippocampal regions differentially. This study aimed to explore the influence of chronic (15 min daily for 21 days) forced swim stress (FS) exposure on the BDNF and TrkB containing neurons in the hippocampal CA1, CA3 pyramidal cell layers and dentate gyrus (DG) granule cell layer in juvenile (P28) and aged (P360) rats. An immunofluorescence (-ir) method was used to detect BDNF-ir and TrkB-ir cells. Under chronic FS exposure, in the group of juvenile rats a significant decrease in the density of BDNF immunoreactive neurons was observed in CA1 and DG (P less than CA3, where it remained unaltered just as the density of TrkB-ir cells in CA1 and DG, but in CA3 the number of TrkB-ir cells was found to grow (P less than 0.05) in comparison with control groups. After chronic FS exposure of aged (P360) rats, the density of BDNF-ir and TrkB-ir cells did not decline in any of the subregions of the hippocampus. In all subfields of the hippocampus, the denseness of BDNF-positive neurons was significantly higher in P360 stressed group, compared with P28 stressed group, but the density of TrkB-ir fell more markedly in P360 than in P28. In conclusion, chronic FS stress influenced the number of BDNF and TrkB immunoreactive neurons only in juvenile animals. The age of rats tested in the chronic forced swim test was a decisive factor determining changes in the density of BDNF-ir and TrkB-ir in the hippocampal structures.

  2. Characterization of voltage-gated Ca(2+ conductances in layer 5 neocortical pyramidal neurons from rats.

    Directory of Open Access Journals (Sweden)

    Mara Almog

    Full Text Available Neuronal voltage-gated Ca(2+ channels are involved in electrical signalling and in converting these signals into cytoplasmic calcium changes. One important function of voltage-gated Ca(2+ channels is generating regenerative dendritic Ca(2+ spikes. However, the Ca(2+ dependent mechanisms used to create these spikes are only partially understood. To start investigating this mechanism, we set out to kinetically and pharmacologically identify the sub-types of somatic voltage-gated Ca(2+ channels in pyramidal neurons from layer 5 of rat somatosensory cortex, using the nucleated configuration of the patch-clamp technique. The activation kinetics of the total Ba(2+ current revealed conductance activation only at medium and high voltages suggesting that T-type calcium channels were not present in the patches. Steady-state inactivation protocols in combination with pharmacology revealed the expression of R-type channels. Furthermore, pharmacological experiments identified 5 voltage-gated Ca(2+ channel sub-types - L-, N-, R- and P/Q-type. Finally, the activation of the Ca(2+ conductances was examined using physiologically derived voltage-clamp protocols including a calcium spike protocol and a mock back-propagating action potential (mBPAP protocol. These experiments enable us to suggest the possible contribution of the five Ca(2+ channel sub-types to Ca(2+ current flow during activation under physiological conditions.

  3. Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    Chunling Zhao; Yan Chen; Chunlai Zhang; Linya Lü; Qian Xu

    2011-01-01

    The present study established a rat model of chronic intermittent hypoxia (CIH) to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase (ChAT) and nicotinic acetylcholine receptor (nAChR) expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinergic activity may be involved in CIH-induced cognitive impairment in rats.

  4. Fractal dimension of apical dendritic arborization differs in the superficial and the deep pyramidal neurons of the rat cerebral neocortex.

    Science.gov (United States)

    Puškaš, Nela; Zaletel, Ivan; Stefanović, Bratislav D; Ristanović, Dušan

    2015-03-04

    Pyramidal neurons of the mammalian cerebral cortex have specific structure and pattern of organization that involves the presence of apical dendrite. Morphology of the apical dendrite is well-known, but quantification of its complexity still remains open. Fractal analysis has proved to be a valuable method for analyzing the complexity of dendrite morphology. The aim of this study was to establish the fractal dimension of apical dendrite arborization of pyramidal neurons in distinct neocortical laminae by using the modified box-counting method. A total of thirty, Golgi impregnated neurons from the rat brain were analyzed: 15 superficial (cell bodies located within lamina II-III), and 15 deep pyramidal neurons (cell bodies situated within lamina V-VI). Analysis of topological parameters of apical dendrite arborization showed no statistical differences except in total dendritic length (p=0.02), indicating considerable homogeneity between the two groups of neurons. On the other hand, average fractal dimension of apical dendrite was 1.33±0.06 for the superficial and 1.24±0.04 for the deep cortical neurons, showing statistically significant difference between these two groups (pfractal dimension values, apical dendrites of the superficial pyramidal neurons tend to show higher structural complexity compared to the deep ones.

  5. Ketamine prevents lidocaine-caused neurotoxicity in the CA3 hippocampal and basolateral amygdala regions of the brain in adult rats.

    Science.gov (United States)

    Lopez-Galindo, Gabriel Eduardo; Cano-Europa, Edgar; Ortiz-Butron, Rocio

    2008-01-01

    Our objective was to prove whether blocking the action of glutamate on N-methyl-D: -aspartate (NMDA) receptors could prevent the neuronal damage caused by the acute administration of lidocaine. Twenty male 2-month-old Wistar rats were randomly assigned to the following groups (n = 5 in each group): groups I and II received 0.9% saline i.p., and groups III and IV received 100 mg x kg(-1) of ketamine i.p. Thirty minutes later, groups I and III were again dosed with 0.9% saline i.p., and groups II and IV received 60 mg x kg(-1) of lidocaine i.p. During treatment, the rectal temperature of the animals was monitored and maintained at 37.5 +/- 0.5 degrees C. Ten days after administration of the agents, all rats were transcardially perfused, under pentobarbital anesthesia, with 10% formaldehyde. Their brains were removed and were embedded in paraffin. Coronal cuts of 7 microm were obtained from -2.3 to -3.8 mm from the bregma. Each brain section was stained with cresyl violet-eosin. The number of normal and abnormal pyramidal neurons in the CA3 hippocampal region and the number of large and medium neurons in the basolateral amygdala within an area of 10 000 microm2 were evaluated. We found that lidocaine significantly reduced the number of normal neurons in both the CA3 hippocampal region (F (3,16) = 225.8; P lidocaine-induced damage in the CA3 hippocampal region and the basolateral amygdala. These results demonstrate the participation of NMDA-receptor activation by lidocaine in the CA3 hippocampal and basolateral amygdala regions as a neurotoxic mechanism.

  6. Anterior Thalamic Lesions Alter Both Hippocampal-Dependent Behavior and Hippocampal Acetylcholine Release in the Rat

    Science.gov (United States)

    Savage, Lisa M.; Hall, Joseph M.; Vetreno, Ryan P.

    2011-01-01

    The anterior thalamic nuclei (ATN) are important for learning and memory as damage to this region produces a persistent amnestic syndrome. Dense connections between the ATN and the hippocampus exist, and importantly, damage to the ATN can impair hippocampal functioning. Acetylcholine (ACh) is a key neurotransmitter in the hippocampus, and in vivo…

  7. GABAA receptor-mediated feedforward and feedback inhibition differentially modulate the gain and the neural code transformation in hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Jang, Hyun Jae; Park, Kyerl; Lee, Jaedong; Kim, Hyuncheol; Han, Kyu Hun; Kwag, Jeehyun

    2015-12-01

    Diverse variety of hippocampal interneurons exists in the CA1 area, which provides either feedforward (FF) or feedback (FB) inhibition to CA1 pyramidal cell (PC). However, how the two different inhibitory network architectures modulate the computational mode of CA1 PC is unknown. By investigating the CA3 PC rate-driven input-output function of CA1 PC using in vitro electrophysiology, in vitro-simulation of inhibitory network, and in silico computational modeling, we demonstrated for the first time that GABAA receptor-mediated FF and FB inhibition differentially modulate the gain, the spike precision, the neural code transformation and the information capacity of CA1 PC. Recruitment of FF inhibition buffered the CA1 PC spikes to theta-frequency regardless of the input frequency, abolishing the gain and making CA1 PC insensitive to its inputs. Instead, temporal variability of the CA1 PC spikes was increased, promoting the rate-to-temporal code transformation to enhance the information capacity of CA1 PC. In contrast, the recruitment of FB inhibition sub-linearly transformed the input rate to spike output rate with high gain and low spike temporal variability, promoting the rate-to-rate code transformation. These results suggest that GABAA receptor-mediated FF and FB inhibitory circuits could serve as network mechanisms for differentially modulating the gain of CA1 PC, allowing CA1 PC to switch between different computational modes using rate and temporal codes ad hoc. Such switch will allow CA1 PC to efficiently respond to spatio-temporally dynamic inputs and expand its computational capacity during different behavioral and neuromodulatory states in vivo.

  8. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; Fernaud-Espinosa, Isabel; Rodriguez-Alvarez, Natalia; Reynolds, James; Reschke, Cristina R; Conroy, Ronan M; McKiernan, Ross C; deFelipe, Javier; Henshall, David C

    2015-07-01

    Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.

  9. Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats

    Directory of Open Access Journals (Sweden)

    Jena B. Hales

    2015-01-01

    Full Text Available Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP. However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF. In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion.

  10. Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats

    Science.gov (United States)

    Hales, Jena B.; Ocampo, Amber C.; Broadbent, Nicola J.; Clark, Robert E.

    2015-01-01

    Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. PMID:26380123

  11. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

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    Tomoko Inagaki

    Full Text Available BACKGROUND: Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after

  12. Batroxobin Against Anoxic Damage of Rat Hippocampal Neurons in Culture: Morphological Changes and Hsp70 Expression

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Batroxobin,the thrombin-like enzyme,is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied the neuroprotective effect of batroxobin on anoxic hippocampal neurons in vitro. The purpose of this study was to obtain further information on the mechanism of the batroxobin-induced neuroprotection and examine the neuroprotective effect on neurons exposed to anoxia. The effect of batroxobin on anoxic damages in cultured hippocampal neurons of neonatal rats was investigated by using morphological changes and heat shock protein 70Kd (Hsp70) immunoreactive expression as indicators. The results indicate that batroxobin, besides its defibrination, may have a direct neuroprotective effect on anoxic damage of hippocampal neurons.

  13. Gentianine protects hippocampal neurons in a rat model of recurrent febrile convulsion

    Institute of Scientific and Technical Information of China (English)

    Xuewei Liu; Shumin Liu; Na Wang; Fang Lu; Min Cao

    2011-01-01

    Gentianine has been shown to have a protective effect on hippocampal CA1 neurons in rats subjected to recurrent febrile convulsion (FC).The present study sought to explore the possible mechanism of gentianine by intraperitoneally injecting gentianine into rats with warm water-induced FC.The results revealed that neuronal organelle injury was slightly ameliorated in the hippocampal CA1 region.The level of glutamate was decreased,but the level of γ-aminobutyric acid was increased,as detected by ninhydrin staining.In addition,glutamate acid decarboxylase expression in hippocampal CA1 was increased,as determined by immunohistochemistry.The results demonstrated that gentianine can ameliorate FC-induced neuronal injury by enhancing glutamate acid decarboxylase activity,decreasing glutamate levels and increasing γ-aminobutyric acid levels.

  14. Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats.

    Science.gov (United States)

    Shetty, A K; Turner, D A

    1998-05-04

    Aging leads to alterations in the function and plasticity of hippocampal circuitry in addition to behavioral changes. To identify critical alterations in the substrate for inhibitory circuitry as a function of aging, we evaluated the numbers of hippocampal interneurons that were positive for glutamic acid decarboxylase and those that expressed calcium-binding proteins (parvalbumin, calbindin, and calretinin) in young adult (4-5 months old) and aged (23-25 months old) male Fischer 344 rats. Both the overall interneuron population and specific subpopulations of interneurons demonstrated a commensurate decline in numbers throughout the hippocampus with aging. Interneurons positive for glutamic acid decarboxylase were significantly depleted in the stratum radiatum of CA1, the strata oriens, radiatum and pyramidale of CA3, the dentate molecular layer, and the dentate hilus. Parvalbumin interneurons showed significant reductions in the strata oriens and pyramidale of CA1, the stratum pyramidale of CA3, and the dentate hilus. The reductions in calbindin interneurons were more pronounced than other calcium-binding protein-positive interneurons and were highly significant in the strata oriens and radiatum of both CA1 and CA3 subfields and in the dentate hilus. Calretinin interneurons were decreased significantly in the strata oriens and radiatum of CA3, in the dentate granule cell and molecular layers, and in the dentate hilus. However, the relative ratio of parvalbumin-, calbindin-, and calretinin-positive interneurons compared with glutamic acid decarboxylase-positive interneurons remained constant with aging, suggesting actual loss of interneurons expressing calcium-binding proteins with age. This loss contrasts with the reported preservation of pyramidal neurons with aging in the hippocampus. Functional decreases in inhibitory drive throughout the hippocampus may occur due to this loss, particularly alterations in the processing of feed-forward information through the

  15. Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5.

    Science.gov (United States)

    Wirth, Marcus J; Brun, Annika; Grabert, Jochen; Patz, Silke; Wahle, Petra

    2003-12-01

    Neurotrophins are candidate molecules for regulating dendritogenesis. We report here on dendritic growth of rat visual cortex pyramidal and interneurons overexpressing 'brain-derived neurotrophic factor' BDNF and 'neurotrophin 4/5' NT4/5. Neurons in organotypic cultures were transfected with plasmids encoding either 'enhanced green fluorescent protein' EGFP, BDNF/EGFP or NT4/5/EGFP either at the day of birth with analysis at 5 days in vitro, or at 5 days in vitro with analysis at 10 days in vitro. In pyramidal neurons, both TrkB ligands increased dendritic length and number of segments without affecting maximum branch order and number of primary dendrites. In the early time window, only infragranular neurons were responsive. Neurons in layers II/III became responsive to NT4/5, but not BDNF, during the later time window. BDNF and NT4/5 transfectants at 10 days in vitro had still significantly shorter dendrites than adult pyramidal neurons, suggesting a massive growth spurt after 10 days in vitro. However, segment numbers were already in the range of adult neurons. Although this suggested a role for BDNF, long-term activity-deprived, and thus BDNF-deprived, pyramidal cells developed a dendritic complexity not different from neurons in active cultures except for higher spine densities on neurons of layers II/III and VI. Neutralization of endogenous NT4/5 causes shorter and less branched dendrites at 10 days in vitro suggesting an essential role for NT4/5. Neutralization of BDNF had no effect. Transfected multipolar interneurons became identifiable during the second time window. Both TrkB ligands significantly increased number of segments and branch order towards the adult state with little effects on dendritic length. The results suggested that early in development BDNF and NT4/5 probably accelerate dendritogenesis in an autocrine fashion. In particular, branch formation was advanced towards the adult pattern in pyramidal cells and interneurons.

  16. Developmental hypothyroidism abolishes bilateral differences in sonic hedgehog gene control in the rat hippocampal dentate gyrus.

    Science.gov (United States)

    Tanaka, Takeshi; Wang, Liyun; Kimura, Masayuki; Abe, Hajime; Mizukami, Sayaka; Yoshida, Toshinori; Shibutani, Makoto

    2015-03-01

    Both developmental and adult-stage hypothyroidism disrupt rat hippocampal neurogenesis. We previously showed that exposing mouse offspring to manganese permanently disrupts hippocampal neurogenesis and abolishes the asymmetric distribution of cells expressing Mid1, a molecule regulated by sonic hedgehog (Shh) signaling. The present study examined the involvement of Shh signaling on the disruption of hippocampal neurogenesis in rats with hypothyroidism. Pregnant rats were treated with methimazole (MMI) at 0 or 200 ppm in the drinking water from gestation day 10-21 days after delivery (developmental hypothyroidism). Adult male rats were treated with MMI in the same manner from postnatal day (PND) 46 to PND 77 (adult-stage hypothyroidism). Developmental hypothyroidism reduced the number of Mid1(+) cells within the subgranular zone of the dentate gyrus of offspring on PND 21, and consequently abolished the normal asymmetric predominance of Mid1(+) cells on the right side through the adult stage. In control animals, Shh was expressed in a subpopulation of hilar neurons, showing asymmetric distribution with left side predominance on PND 21; however, this asymmetry did not continue through the adult stage. Developmental hypothyroidism increased Shh(+) neurons bilaterally and abolished the asymmetric distribution pattern on PND 21. Adult hypothyroidism also disrupted the asymmetric distribution of Mid1(+) cells but did not affect the distribution of Shh(+) hilar neurons. The results suggest that the hippocampal neurogenesis disruption seen in hypothyroidism involves changes in asymmetric Shh(+) neuron distribution in developmental hypothyroidism and altered Mid1 expression in both developmental and adult-stage hypothyroidism.

  17. Hippocampal testosterone relates to reference memory performance and synaptic plasticity in male rats

    Directory of Open Access Journals (Sweden)

    Kristina eSchulz

    2010-12-01

    Full Text Available Steroids are important neuromodulators influencing cognitive performance and synaptic plasticity. While the majority of literature concerns adrenal- and gonadectomized animals, very little is known about the natural endogenous release of hormones during learning. Therefore, we measured blood and brain (hippocampus, prefrontal cortex testosterone, estradiol, and corticosterone concentrations of intact male rats undergoing a spatial learning paradigm which is known to reinforce hippocampal plasticity. We found significant modulations of all investigated hormones over the training course. Corticosterone and testosterone were correlated manifold with behaviour, while estradiol expressed fewer correlations. In the recall session, testosterone was tightly coupled to reference memory performance, which is crucial for reinforcement of synaptic plasticity in the dentate gyrus. Intriguingly, prefrontal cortex and hippocampal levels related differentially to reference memory performance. Correlations of testosterone and corticosterone switched from unspecific activity to specific cognitive functions over training. Correspondingly, exogenous application of testosterone revealed different effects on synaptic and neuronal plasticity in trained versus untrained animals. While hippocampal long-term potentiation (LTP of the field excitatory postsynaptic potential (fEPSP was prolonged in untrained rats, both the fEPSP- and the population spike amplitude-LTP was impaired in trained rats. Behavioural performance was unaffected, but correlations of hippocampal field potentials with behaviour were decoupled in treated rats. The data provide important evidence that besides adrenal, also gonadal steroids play a mechanistic role in linking synaptic plasticity to cognitive performance.

  18. Hippocampal Testosterone Relates to Reference Memory Performance and Synaptic Plasticity in Male Rats

    Science.gov (United States)

    Schulz, Kristina; Korz, Volker

    2010-01-01

    Steroids are important neuromodulators influencing cognitive performance and synaptic plasticity. While the majority of literature concerns adrenal- and gonadectomized animals, very little is known about the “natural” endogenous release of hormones during learning. Therefore, we measured blood and brain (hippocampus, prefrontal cortex) testosterone, estradiol, and corticosterone concentrations of intact male rats undergoing a spatial learning paradigm which is known to reinforce hippocampal plasticity. We found significant modulations of all investigated hormones over the training course. Corticosterone and testosterone were correlated manifold with behavior, while estradiol expressed fewer correlations. In the recall session, testosterone was tightly coupled to reference memory (RM) performance, which is crucial for reinforcement of synaptic plasticity in the dentate gyrus. Intriguingly, prefrontal cortex and hippocampal levels related differentially to RM performance. Correlations of testosterone and corticosterone switched from unspecific activity to specific cognitive functions over training. Correspondingly, exogenous application of testosterone revealed different effects on synaptic and neuronal plasticity in trained versus untrained animals. While hippocampal long-term potentiation (LTP) of the field excitatory postsynaptic potential (fEPSP) was prolonged in untrained rats, both the fEPSP- and the population spike amplitude (PSA)-LTP was impaired in trained rats. Behavioral performance was unaffected, but correlations of hippocampal field potentials with behavior were decoupled in treated rats. The data provide important evidence that besides adrenal, also gonadal steroids play a mechanistic role in linking synaptic plasticity to cognitive performance. PMID:21188275

  19. Effects of intra-uterine and early extra-uterine malnutrition on seizure threshold and hippocampal morphometry of pup rats.

    Science.gov (United States)

    Florian, Mariana Lorenzet; Nunes, Magda Lahorgue

    2010-12-01

    We evaluate the influence of different malnutrition paradigms (intra-uterine × extra-uterine) in body and brain weight, in seizure threshold and in hippocampus morphometry, in developing rats. Intra-uterine malnutrition model consisted in reduction by half of the ration offered to pregnant female; extra-uterine malnutrition consisted of progressive limitation of lactation, from P2 to P15. Seizure induction was accomplished by exposure to flurothyl, at P15. At the same day animals were sacrificed. Morphometric analysis was based on hippocampal pyramidal and granular cells estimate number, through volume calculation and cellular density. Extra-uterine malnutrition significantly reduced pups body and brain weight, seizure threshold and neuronal number in CA4 region only. Intra-uterine malnutrition reduced neuronal number in CA2, CA4 and DG regions regarding well-nourished and extra-uterine malnourished animals. In CA3, CA4 and dentate gyrus, a significant cell increase was observed in groups exposed to seizures, regarding similar control groups.

  20. Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats.

    Science.gov (United States)

    Bealer, Steven L; Little, Jason G

    2013-07-01

    The prolonged seizures of status epilepticus produce chronic arrhythmogenic changes in cardiac function. This study was designed to determine if repeated, self-limiting seizures administered to kindled rats induce similar cardiac dysfunction. Multiple seizures administered to rats following hippocampal kindling resulted in cardiac QT interval prolongation and increased susceptibility to experimental arrhythmias. These data suggest that multiple, self-limiting seizures of intractable epilepsy may have cardiac effects that can contribute to sudden unexpected death in epilepsy (SUDEP).

  1. Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kamal, A; Artola, A; Biessels, G J; Gispen, W H; Ramakers, G M J

    2003-01-01

    Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca(2+) spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca(2+) influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging.

  2. Hippocampal distribution of IL-1β and IL-1RI following lithium-pilocarpine-induced status epilepticus in the developing rat

    Directory of Open Access Journals (Sweden)

    Dulce-Mariely Álvarez-Croda

    2016-01-01

    Full Text Available The contribution of Interleukin-1β (IL-1β to neuronal injury induced by status epilepticus (SE in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1β and its type 1 receptor (IL-1RI following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1β and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1β and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1β mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1β and IL-1RI immunoreactivity was not detected in control animals. IL-1β and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1β and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat.

  3. Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors.

    Science.gov (United States)

    Nalloor, Rebecca; Bunting, Kristopher M; Vazdarjanova, Almira

    2014-07-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after experiencing a traumatic event. Susceptibility to PTSD exists, as only some trauma-exposed individuals develop this condition. Investigating susceptibilities in animal models can contribute to understanding the etiology of the disorder. We previously reported an animal model which allows reliable pre-classification of rats as susceptible (Sus) or resistant (Res) to developing a PTSD-like phenotype after a later trauma. Here we report that Sus, compared to Res, rats have altered hippocampal function, along the septo-temporal axis, prior to experiencing a traumatic event. In Experiment I, Res and Sus rats explored a novel box twice. Using a cellular imaging method for assessing plasticity-related immediate-early gene expression in large neuronal ensembles, Arc/Homer1a catFISH, we show that Sus rats have smaller vCA3 ensembles during the second exploration. This suppressed vCA3 activation in Sus rats was not due to a difference in exploratory behavior, or to a difference in Arc/Homer1a expression in the basolateral amygdala (BLA). BLA is a main source of inputs to vCA3, but both the ensemble size and overlap of BLA ensembles activated during the two explorations was similar to that of Res rats. Additionally, Sus rats had significant 'infidelity' in their dorsal hippocampal representations of the second event: a lower overlap, compared to Res rats, of Arc/Homer1a-expressing ensembles activated during the two explorations (the size of the ensembles were similar to those of Res rats). These differences were revealed only in conditions of relatively low stress, because they were not observed when Sus and Res rats experienced fear conditioning (Experiment II). Combined, the findings show that altered hippocampal function exists before experiencing emotional trauma in susceptible rats and suggest that this is a risk factor for PTSD.

  4. Influence of endogenous ciliary neurotrophic factor on neural differentiation of adult rat hippocampal progenitors

    Institute of Scientific and Technical Information of China (English)

    Jun Ding; Zhili He; Juan Ruan; Ying Liu; Chengxin Gong; Shenggang Sun; Honghui Chen

    2013-01-01

    Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.

  5. Estrogen intervention in microvascular morphology and choline acetyltransferase expression in rat hippocampal neurons in chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhenjun Yang; Hongwei Yan; Guomin Zhang; Zhihong Chen; Jingfeng Xue

    2011-01-01

    We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia.

  6. [The postnatal development of the lamina V pyramidal cells in the temporal cortex of the albino rat].

    Science.gov (United States)

    Nicolai, B

    1981-01-01

    1. The development of layer V pyramidal neurons is analysed quantitatively in albino rat temporal ("auditory") cortex from the 1st to the 90th postnatal days (12 stages). The length of apical dendrites, the number of primary dendrites and the total amount of apical dendrite spines are registered in Golgi-Cox preparations (55 animals). The diameters of the nucleus, length and width of the perikaryon and the relation between nucleus and perikaryon are measured in Nissl-series (45 animals). 2. Two types of development can be recognised by the examined parameters: --Length of apical dendrites, number of primary dendrites and of apical dendrite spines aspire more or less continuously to a maximum value. --Sizes of nucleus and perikaryon show intermediately a higher value than the terminal one ("overshooting growth"). 3. The postnatal development of the parameters suggests that the dendritic growth (also after initiated phase) starts from the perikaryon and relates with dendritic neuroplasmic flow. 4. In order to give general statements about the evolution of layer V pyramidal neuron's rates of growth are counted and their degree of maturity is determined. The biggest rates of growth are reached up to the 12th day post partum. At this time the pyramidal neurons have a relatively high degree of maturity. 5. There are two periods with especially marked alterations of structure of the layer V pyramidal neurons. These alterations are regarded as morphokineses according to Scharf. I. The morphological changes between the 8th and the 12th day are regarded as "morphokinesis as a reaction to planned crises" (2.2., according to Scharf 1970). In this case the critical situation is the beginning of hearing of the young rats, which is to be prepared. II. The morphological changes between the 24th and 36th day take place in the critical period of primary socialization (Scott et al. 1974). This could be understood as "morphokinesis as a reaction to environmental influences" (2

  7. Classical Conditioning of Hippocampal Theta Patterns in the Rat.

    Science.gov (United States)

    1976-08-01

    associated with changes in performance of learned tasks , 1,4,5, 8,9 there have been very few studies of neurona l plasticity of the hippocampus It self...rapid development of a conditioned hippocampal theta response to a visual sti mulus demonstrates tha t there is considerable neurona l plasticity in the

  8. Reinforcement of Rat Hippocampal LTP by Holeboard Training

    Science.gov (United States)

    Frey, Julietta U.; Korz, Volker; Uzakov, Shukhrat

    2005-01-01

    Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4-5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be…

  9. The effect of excitotoxic hippocampal lesions on simple and conditional discrimination learning in the rat.

    Science.gov (United States)

    Murray, T K; Ridley, R M

    1999-02-15

    The effect of excitotoxic lesions of the hippocampus on acquisition and reversal of simple and conditional tasks was investigated using a Y-maze. Hippocampal-lesioned rats were severely impaired on acquisition and reversal of a conditional visuo-spatial task (where different pairs of visually distinctive choice arms indicated whether a left or right arm choice was correct on that trial) and were unable to acquire a visuo-visual conditional discrimination (where the appearance of the start arm indicated which of the visually distinctive choice arms was correct irrespective of their left/right position). They were not impaired on acquisition or reversal of a simple spatial left/right discrimination task (where all arms had the same visual appearance) nor on acquisition of a visual discrimination (where the correct, visually distinctive, choice arm varied in its left/right position). Hippocampal-lesioned rats were, however, impaired on reversal of this visual discrimination task and on acquisition and reversal of another visual discrimination task in which the visually distinctive choice arms were less different from each other than in the first version of this task. The degree of impairment in the lesioned rats was related to task difficulty for the sham-operated rats and was not specific to tasks requiring spatial choices, visual discrimination or conditional responding. The impairment on conditional tasks was greater than the impairment on those non-conditional tasks which happened to be matched for task difficulty for the sham-operated rats, suggesting that the conditional demand may target the function of the hippocampus rather closely. Statistically worse than chance performance by hippocampal-lesioned (and sham-operated) rats at the beginning of reversal testing, which was given 24 h after achieving criterion on acquisition of that task, indicated that hippocampal-lesioned rats simultaneously exhibited good memory but impaired learning for the type of

  10. 916 MHz electromagnetic field exposure affects rat behavior and hippocampal neuronal discharge

    Institute of Scientific and Technical Information of China (English)

    Dongmei Hao; Lei Yang; Su Chen; Yonghao Tian; Shuicai Wu

    2012-01-01

    Wistar rats were exposed to a 916 MHz,10 W/m2 mobile phone electromagnetic field for 6 hours a day,5 days a week.Average completion times in an eight-arm radial maze were longer in the exposed rats than control rats after 4-5 weeks of exposure.Error rates in the exposed rats were greater than the control rats at 6 weeks.Hippocampal neurons from the exposed rats showed irregular firing patterns during the experiment,and they exhibited decreased spiking activity 6-9 weeks compared with that after 2-5 weeks of exposure.These results indicate that 916 MHz electromagnetic fields influence learning and memory in rats during exposure,but long-term effects are not obvious.

  11. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats

    OpenAIRE

    Puebla Jiménez, Lilian; Rodríguez Martín, Eulalia; Arilla Ferreiro, Eduardo

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 ¿g) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal ...

  12. GnRH analogue attenuated apoptosis of rat hippocampal neuron after ischemia-reperfusion injury.

    Science.gov (United States)

    Chu, Chenyu; Xu, Bainan; Huang, Weiquan

    2010-12-01

    The expression and new functions of reproductive hormones in organs beyond hypothalamus-pituitary-gonad axis have been reported. So far, there is no report about the protective effects of GnRH analogue to hippocampal neurons suffering from ischemia-reperfusion injury. Middle cerebral artery occlusion model together with TUNEL staining were made in vivo and oxygen-glucose deprivation model together with double staining of Annexin V/PI with flow cytometer were made in vitro to observe the anti-apoptotic effects of GnRH analogue to hippocampal neurons after ischemia-reperfusion injury. The results found that the number of TUNEL positive pyramidal neurons in CA1 region in GnRH analogue experiment group was less than that in control group in vivo; the percentage of apoptotic neurons in GnRH analogue experiment group was less than that in control group in vitro. These findings suggested that pretreatment with certain concentration of GnRH analogue could attenuate apoptosis of hippocampal neurons. GnRH analogue has the protective effects to neurons.

  13. Time window characteristics of cultured rat hippocampal neurons subjected to ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    XU Zhong; XU Ru-xiang; LIU Bao-song; JIANG Xiao-dan; HUANG Tao; DING Lian-shu; YUAN Jun

    2005-01-01

    Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury.Methods: Hippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points (0.25 h to 3.0 h) and then the same recovery (24 h) were prepared. Annexin V-PI staining and flow cytometry examined neuron death and apoptosis at different time after injury. Results: After OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P0.05). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P<0.05). Apoptosis rate gradually increased with significant difference among those of different time points (P<0.05). However, 2 h after ischemia, apoptosis rate decreased markedly.Conclusions: Apoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.

  14. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    Science.gov (United States)

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  15. Characterization of single voltage-gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons.

    Science.gov (United States)

    Magee, J C; Johnston, D

    1995-08-15

    1. We have used dendrite-attached patch-clamp techniques to record single Na+ and Ca2+ channel activity from the apical dendrites (up to 350 microns away from soma) of CA1 pyramidal neurons in rat hippocampal slices (ages: 2-8 weeks). 2. Na+ channels were found in every patch examined (range: 2 to > 20 channels per patch). Channel openings, which had a slope conductance of 15 +/- 0.3 pS (mean +/- S.E.M.), began with test commands to around -50 mV and consisted of both early transient channel activity and also later occurring prolonged openings of 5-15 ms. All Na+ channel activity was suppressed by inclusion of TTX (1 microM) in the recording pipette. 3. Ca2+ channel activity was recorded in about 80% of the patches examined (range: 1 to > 10 channels per patch). Several types of channel behaviour were observed in these patches. Single channel recordings in 110 mM BaCl2, revealed an approximately 10 pS channel of small unitary current amplitude (-0.5 pA at -20 mV). These channels began activating at relatively hyperpolarized potentials (-50 mV) and ensemble averages of this low voltage-activated (LVA) channel activity showed rapid inactivation. 4. A somewhat heterogeneous population of high voltage-activated, moderate conductance (HVAm; approximately 17 pS), Ca2+ channel activity was also encountered. These channels exhibited a relatively large unitary amplitude (-0.8 pA at 0 mV) and ensemble averages demonstrated moderate inactivation. The HVAm population of channels could be tentatively subdivided into two separate groups based upon mean channel open times. 5. Less frequently, HVA, large conductance (27 pS) Ca2+ channel activity (HVA1) was also observed. This large unitary amplitude (-1.5 pA at 0 mV) channel activity began with steps to approximately 0 mV and ensemble averages did not show any time-dependent inactivation. The dihydropyridine Ca2+ channel agonist Bay K 8644 (0.5 or 1 microM) was found to characteristically prolong these channel openings. 6. omega

  16. Effects of clobazam on amygdaloid and hippocampal kindled seizures in rats.

    Science.gov (United States)

    Ichimaru, Y; Gomita, Y; Moriyama, M

    1987-05-01

    The effect of clobazam, a 1,5-benzodiazepine, on kindling seizures was compared with the effects of 1,4-benzodiazepines, diazepam and bromazepam, in amygdaloid and hippocampal kindled rats. After kindled seizures were established (stage 5 seizure), the test drugs were administered intraperitoneally. In amygdaloid kindled rats, clobazam significantly suppressed the motor seizures (MS) at doses of 20 and 50 mg/kg and significantly shortened the duration of after-discharge (AD) at doses of 10 to 50 mg/kg. Diazepam at doses of 2 to 10 mg/kg and bromazepam at 1 to 5 mg/kg also significantly suppressed the MS and significantly shortened the duration of AD. Similar suppressive effects by these three benzodiazepines were observed in hippocampal kindled rats. From these results, clobazam was found to have a qualitatively similar but weaker anticonvulsive effect than those of 1,4-benzodiazepines.

  17. Buyuan Congnao decoction decreases hippocampal beta-amyloid expression in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Min Chen; Jing Wang; Cairong Ming

    2012-01-01

    A mixture of ibotenic acid and β-amyloid 1-42 was injected into the hippocampus of a rat model of Alzheimer's disease, followed by intragastric administration of a traditional Chinese medicine Buyuan Congnao decoction (main components included radix astragali, radix polygoni multiflori preparata, rhizoma acori talarinowii, radix polygalae, fructus alpiniae oxyphyllae, and radix glycyrrhizae preparata) and a piracetam suspension.Following treatment with traditional Chinese medicine or western medicine, β-amyloid expression decreased and neuronal morphology was normal in the rat hippocampal CA1 region, in addition to significantly shortened average latency in the Morris water navigation task.These findings suggested that compound prescription of Buyuan Congnao decoction, similar to the curative effects of piracetam, decreased hippocampal β-amyloid expression in a rat model of Alzheimer's disease, as well as improved learning and memory.

  18. Hippocampal NMDA receptors are involved in rats' spontaneous object recognition only under high memory load condition.

    Science.gov (United States)

    Sugita, Manami; Yamada, Kazuo; Iguchi, Natsumi; Ichitani, Yukio

    2015-10-22

    The possible involvement of hippocampal N-methyl-D-aspartate (NMDA) receptors in spontaneous object recognition was investigated in rats under different memory load conditions. We first estimated rats' object memory span using 3-5 objects in "Different Objects Task (DOT)" in order to confirm the highest memory load condition in object recognition memory. Rats were allowed to explore a field in which 3 (3-DOT), 4 (4-DOT), or 5 (5-DOT) different objects were presented. After a delay period, they were placed again in the same field in which one of the sample objects was replaced by another object, and their object exploration behavior was analyzed. Rats could differentiate the novel object from the familiar ones in 3-DOT and 4-DOT but not in 5-DOT, suggesting that rats' object memory span was about 4. Then, we examined the effects of hippocampal AP5 infusion on performance in both 2-DOT (2 different objects were used) and 4-DOT. The drug treatment before the sample phase impaired performance only in 4-DOT. These results suggest that hippocampal NMDA receptors play a critical role in spontaneous object recognition only when the memory load is high.

  19. Giant synaptic potentials in immature rat CA3 hippocampal neurones.

    Science.gov (United States)

    Ben-Ari, Y; Cherubini, E; Corradetti, R; Gaiarsa, J L

    1989-09-01

    1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85% of neurones. They were less frequent between P9 and P12 (48%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at -51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5-phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells

  20. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species.

  1. GENE EXPRESSION CHANGES AFTER SEIZURE PRECONDITIONING IN THE THREE MAJOR HIPPOCAMPAL CELL LAYERS

    Science.gov (United States)

    Borges, Karin; Shaw, Renee; Dingledine, Raymond

    2008-01-01

    Rodents experience hippocampal damage after status epilepticus (SE) mainly in pyramidal cells while sparing the dentate granule cell layer (DGCL). Hippocampal damage was prevented in rats that had been preconditioned by brief seizures on two consecutive days before SE. To identify neuroprotective genes and biochemical pathways changed after preconditioning we compared the effect of preconditioning on gene expression in the CA1 and CA3 pyramidal and DGCLs, harvested by laser capture microscopy. In the DGCL the expression of 632 genes was altered, compared to only 151 and 58 genes in CA1 and CA3 pyramidal cell layers. Most of the differentially expressed genes regulate tissue structure and intra- and extracellular signaling, including neurotransmission. A selective upregulation of energy metabolism transcripts occurred in CA1 pyramidal cells relative to the DGCL. These results reveal a broad transcriptional response of the DGCL to preconditioning, and suggest several mechanisms underlying the neuroprotective effect of preconditioning seizures. PMID:17239605

  2. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... documented an initial 2.6-fold increase in neurogenesis following a clinical relevant schedule of ECS, a treatment also rescuing depression-like behavior in rats. However, these results gave no demonstration of the longevity of newly generated neurons. The present study is a direct continuation...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd...

  3. Expression of hippocampal adrenergic receptor mRNA in a rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Jianbin Zhang; Lingling Wang; Xinjun Wang; Jingfeng Jiang; Xiaoren Xiang; Tianjun Wang

    2011-01-01

    Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor (AR) subtypes α1-AR, α2-AR, and β1-AR in hippocampal subregions (CA1, CA3, dentate gyrus) using in situ hybridization in a depression model induced by chronic unpredictable mild stress and social isolation. α1-AR mRNA expression was significantly increased in the CA3 and dentate gyrus, β1-AR mRNA was significantly increased in the CA1, and α2-AR mRNA remained unchanged in all regions of depression rats compared with controls. Thus, different AR subtypes exhibit a differing pattern of mRNA expression in various hippocampal subregions following depression.

  4. Roles of HIF-1α, VEGF, and NF-κB in Ischemic Preconditioning-Mediated Neuroprotection of Hippocampal CA1 Pyramidal Neurons Against a Subsequent Transient Cerebral Ischemia.

    Science.gov (United States)

    Lee, Jae-Chul; Tae, Hyun-Jin; Kim, In Hye; Cho, Jeong Hwi; Lee, Tae-Kyeong; Park, Joon Ha; Ahn, Ji Hyeon; Choi, Soo Young; Bai, Hui Chen; Shin, Bich-Na; Cho, Geum-Sil; Kim, Dae Won; Kang, Il Jun; Kwon, Young-Guen; Kim, Young-Myeong; Won, Moo-Ho; Bae, Eun Joo

    2016-10-26

    Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic insults by specific mechanisms. We tested the hypothesis that IPC attenuates post-ischemic neuronal death in the gerbil hippocampal CA1 region (CA1) throughout hypoxia inducible factor-1α (HIF-1α) and its associated factors such as vascular endothelial growth factor (VEGF) and nuclear factor-kappa B (NF-κB). Lethal ischemia (LI) without IPC increased expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) in CA1 pyramidal neurons at 12 h and/or 1-day post-LI; thereafter, their expressions were decreased in the CA1 pyramidal neurons with time and newly expressed in non-pyramidal cells (pericytes), and the CA1 pyramidal neurons were dead at 5-day post-LI, and, at this point in time, their immunoreactivities were newly expressed in pericytes. In animals with IPC subjected to LI (IPC/LI)-group), CA1 pyramidal neurons were well protected, and expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) were significantly increased compared to the sham-group and maintained after LI. Whereas, treatment with 2ME2 (a HIF-1α inhibitor) into the IPC/LI-group did not preserve the IPC-mediated increases of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) expressions and did not show IPC-mediated neuroprotection. In brief, IPC protected CA1 pyramidal neurons from LI by upregulation of HIF-1α, VEGF, and p-IκB-α expressions. This study suggests that IPC increases HIF-1α expression in CA1 pyramidal neurons, which enhances VEGF expression and NF-κB activation and that IPC may be a strategy for a therapeutic intervention of cerebral ischemic injury.

  5. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Pham Serena

    2011-08-01

    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  6. Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

    Science.gov (United States)

    Jin, Hua; Teng, Yueqiu; Zhang, Xuexin; Yang, Chunxiao; Xu, Manying; Yang, Lizhuang

    2014-06-27

    Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

  7. Resistance to extinction after schedules of partial delay or partial reinforcement in rats with hippocampal lesions.

    Science.gov (United States)

    Rawlins, J N; Feldon, J; Ursin, H; Gray, J A

    1985-01-01

    Two experimental procedures were employed to establish the reason why hippocampal lesions apparently block the development of tolerance for aversive events in partial reinforcement experiments, but do not do so in partial punishment experiments. Rats were trained to run in a straight alley following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO), and resistance to extinction was assessed following differing acquisition conditions. In Experiment 1 a 4-8 min inter-trial interval (ITI) was used. Either every acquisition trial was rewarded immediately (Continuous Reinforcement, CR), or only a randomly selected half of the trials were immediately rewarded, the reward being delayed for thirty seconds on the other trials (Partial Delay, PD). This delay procedure produced increased resistance to extinction in rats in all lesion groups. In Experiment 2 the ITI was reduced to a few seconds, and rats were trained either on a CR schedule, or on a schedule in which only half the trials were rewarded (Partial Reinforcement, PR). This form of partial reinforcement procedure also produced increased resistance to extinction in rats in all lesion groups. It thus appears that hippocampal lesions only prevent the development of resistance to aversive events when the interval between aversive and subsequent appetitive events exceeds some minimum value.

  8. Neuronal injury and cytogenesis after simple febrile seizures in the hippocampal dentate gyrus of juvenile rat.

    Science.gov (United States)

    Nazem, Amir; Jafarian, Amir Hossein; Sadraie, Seyed Homayoon; Gorji, Ali; Kheradmand, Hamed; Radmard, Mahla; Haghir, Hossein

    2012-11-01

    Although simple febrile seizures are frequently described as harmless, there is evidence which suggests that hippocampal damage may occur after simple febrile seizures. This study aimed to investigate possible neuronal damages as well as alterations in cytogenesis in the hippocampal dentate gyrus following simple febrile seizures. Simple febrile seizure was modeled by hyperthermia-induced seizures in 22-day-old male rats. The brains were removed 2 or 15 days after hyperthermia in all rats with (n=20) and without (n=10) occurrence of seizures as well as in control animals (n=10). The sections were stained with hematoxylin and eosin to estimate the surface numerical density of dark neurons. Ki-67 immunohistochemistry was performed to evaluate changes of cytogenesis following simple febrile seizures. Hyperthermia induced behavioral seizure activities in 67 % of the rats. The numerical densities of dark neurons as well as the mean Ki-67 index (the fraction of Ki-67-positive cells) were significantly increased in dentate gyrus after induction of seizures by hyperthermia compared to both controls and rats without seizure after hyperthermia. Both the seizure duration and intensity were correlated significantly with numerical densities of dark neurons (but not with Ki-67 index). The data indicate that simple febrile seizures can cause neuronal damages and enhancement of cytogenesis in the hippocampal dentate gyrus, which were still visible for at least 2 weeks. These findings also suggest the correlation of febrile seizure intensity and duration with neuronal damage.

  9. Leptin-induced downregulation of the rat hippocampal somatostatinergic system may potentiate its anorexigenic effects.

    Science.gov (United States)

    Perianes-Cachero, Arancha; Burgos-Ramos, Emma; Puebla-Jiménez, Lilian; Canelles, Sandra; Viveros, María Paz; Mela, Virginia; Chowen, Julie A; Argente, Jesús; Arilla-Ferreiro, Eduardo; Barrios, Vicente

    2012-12-01

    The learning and memory mechanisms in the hippocampus translate hormonal signals of energy balance into behavioral outcomes involved in the regulation of food intake. As leptin and its receptors are expressed in the hippocampus and somatostatin (SRIF), an orexigenic neuropeptide, may inhibit leptin-mediated suppression of food intake in other brain areas, we asked whether chronic leptin infusion induces changes in the hippocampal somatostatinergic system and whether these modifications are involved in leptin-mediated effects. We studied 18 male Wistar rats divided into three groups: controls (C), treated intracerebroventricularly (icv) with leptin (12 μg/day) for 14 days (L) and a pair-fed group (PF) that received the same amount of food consumed by the L group. Food restriction increased whereas leptin decreased the hippocampal SRIF receptor density, due to changes in SRIF receptor 2 protein levels. These changes in the PF group were concurrent with an increase of hippocampal G protein-coupled receptor kinase 2 protein levels and activation of Akt and cyclic AMP response element binding protein. The inhibitory effect of SRIF on adenylyl cyclase (AC) activity, however, was decreased in L rats, coincident with lower G inhibitory α3 and higher AC-I levels as well as signal transducer and activator of transcription factor 3 activation. In addition, 20 male Wistar rats were included to analyze whether the leptin antagonist L39A/D40A/F41A and the SRIF receptor agonist SMS 201-995 modify SRIF signaling and food intake, respectively. Administration of L39A/D40A/F41A reversed changes in SRIF signaling, whereas SMS 201-995 ameliorated food consumption in L. Altogether, these results suggest that increased somatostatinergic tone in PF rats may be a mechanism to improve the hippocampal orexigenic effects in a situation of metabolic demand, whereas down-regulation of this system in L rats may represent a mechanism to enhance the anorexigenic effects of leptin.

  10. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

    Directory of Open Access Journals (Sweden)

    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

  11. Qualitatively different hippocampal subfield engagement emerges with mastery of a spatial memory task by rats.

    Science.gov (United States)

    Poirier, Guillaume L; Amin, Eman; Aggleton, John P

    2008-01-30

    The parallel, entorhinal cortex projections to different hippocampal regions potentially support separate mnemonic functions. To examine this possibility, rats were trained in a radial-arm maze task so that hippocampal activity could be compared after "early" (two sessions) or "late" (five sessions) learning. Induction of the immediate-early gene Zif268 was then measured, so revealing possible activity differences across hippocampal subfields and the parahippocampal cortices. Each rat in the two experimental groups (early, late) was also yoked to a control rat that obtained the same number of rewards, visited the same number of maze arms, and spent a comparable amount of time in the maze. Although overall Zif268 levels did not distinguish the four groups, significant correlations were found between spatial memory performance and levels of dentate gyrus Zif268 expression in the early but not the late training group. Conversely, hippocampal fields CA3 and CA1 Zif268 expression correlated with performance in the late but not the early training group. This reversal in the correlation pattern was echoed by structural equation modeling, which revealed dynamic changes in effective network connectivity. With early training, the dentate gyrus appeared to help determine CA1 activity, but by late training the dentate gyrus reduced its neural influence. Furthermore, CA1 was distinguished from CA3, each subfield developing opposite relations with task mastery. Thus, functional entorhinal cortex coupling with CA1 activity became more direct with additional training, so producing a trisynaptic circuit bypass. The present study reveals qualitatively different patterns of hippocampal subfield engagement dependent on task demands and mastery.

  12. Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Zhihong Chen; Yaqiang He; Chengjun Song; Zhijun Dong; Zhejun Su; Jingfeng Xue

    2012-01-01

    In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway.

  13. Puerarin Ameliorates D-Galactose Induced Enhanced Hippocampal Neurogenesis and Tau Hyperphosphorylation in Rat Brain.

    Science.gov (United States)

    Hong, Xiao-Ping; Chen, Tao; Yin, Ni-Na; Han, Yong-Ming; Yuan, Fang; Duan, Yan-Jun; Shen, Feng; Zhang, Yan-Hong; Chen, Ze-Bin

    2016-01-01

    Enhanced neurogenesis has been reported in the hippocampus of patients with Alzheimer's disease (AD), the most common neurodegenerative disorder characterized with amyloid-β (Aβ) aggregation, tau hyperphosphorylation, and progressive neuronal loss. Previously we reported that tau phosphorylation played an essential role in adult hippocampal neurogenesis, and activation of glycogen synthase kinase (GSK-3), a crucial tau kinase, could induce increased hippocampal neurogenesis. In the present study, we found that treatment of D-galactose rats with Puerarin could significantly improve behavioral performance and ameliorate the enhanced neurogenesis and microtubule-associated protein tau hyperphosphorylation in the hippocampus of D-galactose rat brains. FGF-2/GSK-3 signaling pathway might be involved in the effects of Puerarin on hippocampal neurogenesis and tau hyperphosphorylation. Our finding provides primary in vivo evidence that Puerarin can attenuate AD-like enhanced hippocampal neurogenesis and tau hyperphosphorylation. Our finding also suggests Puerarin can be served as a treatment for age-related neurodegenerative disorders, such as AD.

  14. Hippocampal ultrastructural changes and apoptotic cell death in rats following endurance training and acute exhaustive exercise

    Institute of Scientific and Technical Information of China (English)

    Jianjun Zhang

    2008-01-01

    BACKGROUND: Exhaustive exercise can lead to apoptosis of skeletal muscle cells and myocardial cells as a result of pathological changes in the corresponding cellular ultrastructure. It is hypothesized that such changes could also occur in neurons. OBJECTIVE: To observe brain cell apoptosis and ultrastmctural changes in hippocampal neurons in rats following endurance training and acute exhaustive exercise. DESIGN, TIME AND SETTING: A randomized, controlled, morphological analysis was performed at the Medical Laboratory Center of Zhengzhou University between July and November 2007. MATERIALS: Forty male, 8-week-old, Sprague Dawley rats were included in this study. METHODS: Endurance training consisted of treadmill running once a day, 6 days a week, for 4 weeks. For acute exhaustive exercise, graded treadmill running was conducted. Rats were exposed to exercise at an increasing speed (10 m/min, increasing to 20 and 36 m/min for moderate- and high-intensity exhaustive exercise, respectively, and then was continued until exhaustion). A total of 40 rats were evenly distributed into the following 4 groups: Group A-rats were not exercised; Group B- rats were not trained but sacrificed 24 hours after acute exhaustive treadmill running exercise; Group C rats were subjected to endurance training and sacrificed immediately after acute exhaustive treadmill running exercise; Group D-rats were subjected to endurance training and sacrificed 24 hours after acute exhaustive treadmill running exercise. MAIN OUTCOME MEASURES: Apoptotic cell death was detected by the TUNEL method and hippocampal neuronal ultrastructural change was observed through using transmission electron microscopy. RESULTS: All 40 rats were included in the final analysis. Subsequent to exhaustive exercise, rat cerebral cortex and hippocampal neurons appeared contracted and degenerated. In addition, high amount of lipofuscin was visible in the hippocampal region. Necrotic neurons encased by glial cells appeared in

  15. Localization of GABA(B) (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations.

    Science.gov (United States)

    Sloviter, R S; Ali-Akbarian, L; Elliott, R C; Bowery, B J; Bowery, N G

    1999-11-01

    Immunocytochemical and autoradiographic methods were used to localize the GABA(B) receptor in the normal rat hippocampus. GABA(B) receptor 1-like immunoreactivity (GBR1-LI) was most intense in presumed GABAergic interneurons of all hippocampal subregions. It was also present throughout the hippocampal neuropil, where it was most intense in the dendritic strata of the dentate gyrus, which are innervated by the perforant pathway and inhibitory dentate hilar cells, and in strata oriens and radiatum of area CA3. The dendritic regions of area CA1 exhibited less GBR1-LI than area CA3. GBR1-LI was detectable in the somata of CA1 pyramidal cells, but was minimal or undetectable within the somata of dentate granule cells and CA3 pyramidal cells. GBR1-LI was similarly minimal in the dentate hilar neuropil, and in stratum lucidum, the two regions that contain granule cell axons and terminals. Nor was GBR1-LI detectable in the inhibitory basket cell fiber systems that surround hippocampal principal cell somata. Fluorescence co-localization studies indicated that significant proportions of interneurons expressing somatostatin, neuropeptide Y, cholecystokinin, calbindin, or calretinin also expressed GBR1-LI constitutively. Conversely, parvalbumin-positive GABAergic basket cells of the dentate gyrus and hippocampus, which form GABA(A) receptor-mediated inhibitory axo-somatic synapses, rarely contained detectable GBR1-LI. High resolution autoradiography with the GABA(B) receptor antagonist CGP 62349 revealed a close correspondence between receptor ligand binding and GBR1-LI, with several notable exceptions. Ligand binding closely matched GBR1-LI throughout the hippocampal, cortical, thalamic, and cerebellar neuropil. However, the hippocampal interneuron somata and dendrites that exhibited the most intense GBR1-LI, and the GBR1-positive somata of CA1 pyramidal cells, did not exhibit a similar density of [3H]-CGP 62349 binding. These data clarify the relationship between

  16. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

    Science.gov (United States)

    Lensu, Sanna; Ahtiainen, Juha P.; Johansson, Petra P.; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

    2016-01-01

    Key points Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.Our results confirm that sustained aerobic exercise is key in improving AHN. Abstract Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength

  17. Hippocampal lesions facilitate instrumental learning with delayed reinforcement but induce impulsive choice in rats

    Directory of Open Access Journals (Sweden)

    Cheung Timothy HC

    2005-05-01

    Full Text Available Abstract Background Animals must frequently act to influence the world even when the reinforcing outcomes of their actions are delayed. Learning with action-outcome delays is a complex problem, and little is known of the neural mechanisms that bridge such delays. When outcomes are delayed, they may be attributed to (or associated with the action that caused them, or mistakenly attributed to other stimuli, such as the environmental context. Consequently, animals that are poor at forming context-outcome associations might learn action-outcome associations better with delayed reinforcement than normal animals. The hippocampus contributes to the representation of environmental context, being required for aspects of contextual conditioning. We therefore hypothesized that animals with hippocampal lesions would be better than normal animals at learning to act on the basis of delayed reinforcement. We tested the ability of hippocampal-lesioned rats to learn a free-operant instrumental response using delayed reinforcement, and what is potentially a related ability – the ability to exhibit self-controlled choice, or to sacrifice an immediate, small reward in order to obtain a delayed but larger reward. Results Rats with sham or excitotoxic hippocampal lesions acquired an instrumental response with different delays (0, 10, or 20 s between the response and reinforcer delivery. These delays retarded learning in normal rats. Hippocampal-lesioned rats responded slightly less than sham-operated controls in the absence of delays, but they became better at learning (relative to shams as the delays increased; delays impaired learning less in hippocampal-lesioned rats than in shams. In contrast, lesioned rats exhibited impulsive choice, preferring an immediate, small reward to a delayed, larger reward, even though they preferred the large reward when it was not delayed. Conclusion These results support the view that the hippocampus hinders action-outcome learning

  18. Susceptibility of Rat Hippocampal Neurons to Hypothermia during Development

    OpenAIRE

    Kyung Ah Seo; Sehhyun Kim; Na Mi Lee; Soo Ahn Chae

    2013-01-01

    Purpose: This study evaluated the extent of damage due to hypothermia in the mature and immature brain. Methods: Hippocampal tissue cultures at 7 and 14 days in vitro (DIV) were used to represent the immature and mature brain, respectively. The cultures were exposed at 25?#608;for 0, 10, 30, and 60 minutes (n=30 in each subgroup). Propidium iodide fluorescent images were captured 24 and 48 hours after hypothermic injury. Damaged areas of the cornu ammonis 1 (CA1), CA3, and dentate gyrus (...

  19. The effect of cul length and hippocampal lesions on maze learning in the rat.

    Science.gov (United States)

    Strong, P N

    1978-01-01

    Twenty-four rats, 8 with bilateral hippocampal lesions, 8 with cortical lesions and 8 unoperated rats, were tested on one of 2 mazes. Half of each group were run in a conventional 5 choice multiple Y maze. The other half were run in a symetrical, long cul maze in which distance and number of successive choice point were equal for a right or wrong choice before the animal reached an cul end or the goal box. The correct path in the long cul maze was identical to that of the short cul maze. S's were run one trial a day for 15 days. On the symetrical, long cul maze there were no differences between groups. On the short cul maze, hippocampals were significantly worse than control S's and looked similar to control S's on the long cul maze. The results are interpreted in terms of frustration theory.

  20. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat.

    Science.gov (United States)

    Ego-Stengel, Valérie; Wilson, Matthew A

    2010-01-01

    The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp-wave ripple events, characteristic of slow-wave sleep, has been proposed as a neural mechanism for sleep-dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1-hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep-wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning.

  1. Acupuncture effects on the hippocampal cholinergic system in a rat model of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Junying Wang; Junling Liu; Shuping Chen; Yonghui Gao; Fanying Meng; Lina Qiao

    2012-01-01

    The present study observed the effects of repeated electroacupuncture of Zusanli (ST36) and Yanglingquan (GB34) on expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA in chronic constrictive injury (neuropathic pain) and/or ovariotomy rats. Results demonstrated increased expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA, as well as decreased pain threshold, in a rat model of chronic neuropathic pain after electroacupuncture. The effects of electroacupuncture increased with prolonged time, but the above-mentioned effects decreased in memory-deficient animals. Results indicated that repeated electroacupuncture has a cumulative analgesic effect, which is closely associated with upregulation of acetylcholinesterase and vesicular acetylcholine transporter activity, as well as M1 receptor mRNA expression and memory.

  2. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

    Science.gov (United States)

    Ye, Li-Juan; Bian, Hui; Fan, Yao-Dong; Wang, Zheng-Bo; Yu, Hua-Lin; Ma, Yuan-Ye; Chen, Feng

    2016-09-01

    Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 10(5) cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  3. Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus.

    OpenAIRE

    Gage, P W; Robertson, B

    1985-01-01

    Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or rise time of the currents but current amplitude was depressed at 200 microM. The prolongation of currents increased with drug concentration within the range tested (50 to 200 mic...

  4. Effects of topiramate on hippocampal neuronal apoptosis in rats after kainic acid-evoked seizures

    Institute of Scientific and Technical Information of China (English)

    Yuan Wu; Jiarong Pang; Jinou Zheng; Xiaoqing Deng; Xiulin Liang; Jiaquan Li; Zhiying Chen

    2008-01-01

    BACKGROUND:Apoptosis plays an important role in brain injury after seizures and the formation of chronic epilepsy.It is important to investigate whether topiramate exhibits either antiepileptic and/or anti-apoptotic effects on hippocampal neurons.OBJECTIVE:To observe euronal apoptosis in hippocampus of rat seizure models,and to investigate the antagonizing effect of topiramate on neuronal apoptosis after seizures.DESIGN:An animal experiment of comparative observation.SETTING:First Affiliated Hospital of Guangxi Medical University.MATERIALS:Sixty healthy male Sprague Dawley(SD)rats,4-6 weeks old and weighing 160-220 g,were provided by the Experimental Animal Center of Guangxi Medical University.Main apparatus and reagents were as follows:Rat brain solid positioner(SR-6N,made in Japan); kainic acid by Sigma(USA);pathological image analyzer(DMR+550)by Leica(Germany); in situ apoptosis detection kit by Wuhan Boster Biological Technology Co.,Ltd; topiramate by Xi'an-Janssen Pharmaceutical,Ltd.The treatment on animals in the experiment was in accordance with the standards of animal ethics.METHODS:The experiments were performed at the Scientific Experimental Center of Guangxi Medical University from June to December 2006.The rats were randomly divided into a topiramate-treated group(n=30)and a model group(n=30).① After anesthesia,all rats were administered a kainic acid injection(0.2 μ L,2 g/L)into the right lateral ventricle.Grade Ⅲ and greater Racine standards were considered to be a successful model establishment.Thirty minutes after seizure ,rats in the topiramate-treated group were treated with an intraperitoneal(i.p.)injection of topiramate every day(40 mg/kg/d)for 2 weeks.The rats in the model group were treated with an equal volume of saline for 2 weeks.③Six rats in the topiramate-treated group were sacrificed at 1 day,and 1,2,3,and 4 weeks after treatment,respectively.The model group animals were sacrificed at corresponding time points.The brain

  5. Effect of acupuncture on hippocampal Ref-1 expression in cerebral multi-infarction rats.

    Science.gov (United States)

    Liu, Cun-Zhi; Li, Zu-Guang; Wang, De-Jin; Shi, Guang-Xia; Liu, Li-Ying; Li, Qian-Qian; Li, Chong

    2013-03-01

    Redox effector factor (Ref-1) is a sensitive marker for oxidative cellular injury. The aim of this study was to investigate the effects of acupuncture on hippocampal Ref-1 expression in cerebral multi-infarction rats. The rats with reference memory impairment were randomly allocated to three groups: impaired group, acupuncture group and placebo acupuncture group. Moreover, normal group and sham-operated group were set as control groups. Morris water maze test showed that cerebral multi-infarction rats did not present significant changes in spatial working memory performance. Further investigation by immunohistochemistry revealed that acupunctural treatment significantly increased the expression of Ref-1 in the hippocampus of the impaired rats. These findings suggested that the spatial working memory was unaffected in the cerebral multi-infarction rats although spatial reference memory deficits were detected in our previous study; in addition, acupuncture could increase the Ref-1 expression, consequently exerting the anti-oxidant effects.

  6. Input-to-output transformation in a model of the rat hippocampal CA1 network

    OpenAIRE

    Olypher, Andrey V; Lytton, William W; Prinz, Astrid A.

    2012-01-01

    Here we use computational modeling to gain new insights into the transformation of inputs in hippocampal field CA1. We considered input-output transformation in CA1 principal cells of the rat hippocampus, with activity synchronized by population gamma oscillations. Prior experiments have shown that such synchronization is especially strong for cells within one millimeter of each other. We therefore simulated a one-millimeter patch of CA1 with 23,500 principal cells. We used morphologically an...

  7. Erythropoietin improved cognitive function and decreased hippocampal caspase activity in rat pups after traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Requena, Daniela F; Block, Benjamin; Davis, Lizeth J; Rodesch, Christopher; Casper, T Charles; Juul, Sandra E; Kesner, Raymond P; Lane, Robert H

    2014-02-15

    Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a developmental TBI model. We hypothesized that EPO would improve cognitive outcome and increase neuron fraction in the hippocampus in 17-day-old (P17) rat pups after controlled cortical impact (CCI). EPO or vehicle was given at 1, 24, and 48 h after CCI and at post injury day (PID) 7. Cognitive outcome at PID14 was assessed using Novel Object Recognition (NOR). Hippocampal EPO levels, caspase activity, and mRNA levels of the apoptosis factors Bcl2, Bax, Bcl-xL, and Bad were measured during the first 14 days after injury. Neuron fraction and caspase activation in CA1, CA3, and DG were studied at PID2. EPO normalized recognition memory after CCI. EPO blunted the increased hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared low relative to endogenous. Timing of EPO administration was associated with temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors. Conclusion/Speculation: EPO improved recognition memory, increased regional hippocampal neuron fraction, and decreased caspase activity in P17 rats after CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a result of improved neuronal survival via inhibition of caspase-dependent apoptosis early after injury.

  8. Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy.

    NARCIS (Netherlands)

    G. Sun; T.R. Werkman; W.J. Wadman

    2006-01-01

    AIM: To study whether the functional properties of sodium channels, and subsequently the channel modulation by carbamazepine (CBZ) in hippocampal CA1 neurons can be changed after epileptic seizures. METHODS: We used the acutely dissociated hippocampal CA1 pyramidal cells from epilepsy model rats 3 w

  9. Delivery of epidermal neural crest stem cells (EPI-NCSC) to hippocamp in Alzheimer's disease rat model.

    Science.gov (United States)

    Esmaeilzade, Banafshe; Nobakht, Maliheh; Joghataei, Mohammad Taghi; Rahbar Roshandel, Nahid; Rasouli, Homa; Samadi Kuchaksaraei, Ali; Hosseini, Seyed Mohammad; Najafzade, Nowruz; Asalgoo, Sara; Hejazian, Leila Beygom; Moghani Ghoroghi, Fatima

    2012-01-01

    Alzheimer's disease (AD) is characterized by progressive neuronal loss in hippocamp. Epidermal neural crest stem cells (EPI-NCSC) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the effects of transplanting EPI-NCSC into AD rat model. Two weeks after induction of AD by injection of Amyloid-β1-40 into CA1 area of rat hippocamp, Y-maze and single-trial passive avoidance tests were used to show deficit of learning and memory abilities. EPI-NCSC were obtained from the vibrissa hair follicle of rat, cultured and labeled with bromodeoxyuridine. When Alzheimer was proved by behavioral tests, EPI-NCSC was transplanted into CA3 area of hippocamp in AD rat model. The staining of EPI-NCSC markers (nestin and SOX10) was done in vitro. Double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells. We showed that transplanted EPI-NCSC survive and produce many neurons and a few glial cells, presenting glial fibrillary acidic protein. Total number of granule cells in hippocamp was estimated to be more in the AD rat model with transplanted cells as compared to AD control group. We observed that rats with hippocampal damage made more errors than control rats on the Y-maze, when reward locations were reversed. Transplanted cells were migrated to all areas of hippocamp and the total number of granule cell in treatment group was equal compared to control group. Transplantation of EPI-NCSC into hippocamp might differentiate into cholinergic neurons and could cure impairment of memory in AD rat model.

  10. Centella asiatica Attenuates Diabetes Induced Hippocampal Changes in Experimental Diabetic Rats

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    Nelli Giribabu

    2014-01-01

    Full Text Available Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized that Centella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role of C. asiatica on the hippocampus in diabetes. Methods. Streptozotocin- (STZ- induced adult male diabetic rats received 100 and 200 mg/kg/day body weight (b.w C. asiatica leaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-α; interleukin, IL-6; and interleukin, IL-1β and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition.

  11. Ouabain Modulates the Lipid Composition of Hippocampal Plasma Membranes from Rats with LPS-induced Neuroinflammation.

    Science.gov (United States)

    Garcia, Israel José Pereira; Kinoshita, Paula Fernanda; Scavone, Cristoforo; Mignaco, Julio Alberto; Barbosa, Leandro Augusto de Oliveira; Santos, Hérica de Lima

    2015-12-01

    The effects of ouabain (OUA) and lipopolysaccharide (LPS) in vivo on hippocampal membranes (RHM) of Wistar male rats aged 3 months were analyzed. After intraperitoneal (i.p.) injection of OUA only, LPS only, OUA plus LPS, or saline, the content of proteins, phospholipids, cholesterol and gangliosides from RHM was analyzed. The total protein and cholesterol contents of RHM were not significantly affected by OUA or LPS for the experimentally paired groups. In contrast, total phospholipids and gangliosides were strongly modulated by either OUA or LPS treatments. LPS reduced the total phospholipids (roughly 23 %) and increased the total gangliosides (approximately 40 %). OUA alone increased the total phospholipids (around 23 %) and also the total gangliosides (nearly 34 %). OUA pretreatment compensated the LPS-induced changes, preserving the total phospholipids and gangliosides around the same levels of the control. Thus, an acute treatment with OUA not only modulated the composition of hippocampal membranes from 3-month-old rats, but also was apparently able to counteract membrane alterations resulting from LPS-induced neuroinflammation. This study demonstrates for the first time that the OUA capacity modulates the lipid composition of hippocampal plasma membranes from rats with LPS-induced neuroinflammation.

  12. Protective effects of astragalus extract against intermittent hypoxia-induced hippocampal neurons impairment in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiang; GAO Wen-yuan; ZHANG Yun; CHEN Bao-yun; CHEN Zhe; ZHANG Wei-san; MAN Shu-li

    2013-01-01

    Background Intermittent hypoxia is the main pathophysiological cause of the obstructive sleep apnea syndrome.Astragalus shows improvement of spatial learning and memory abilities under intermittent hypoxia.Our study aimed to investigate the protective effect of astragalus against intermittent hypoxia induced-hippocampal neurons impairment in rats and lay the theoretical foundation for the sleep apnea improvement in cognitive function by astragalus.Methods Male Wistar rats were divided into 4 groups:blank control group,normoxia group,intermittent hypoxia group and astragalus treated intermittent hypoxia group.After 6-week treatment,apoptosis of neurons was evaluated by terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) assay.Furthermore,the expression of HIF-1a was detected by real-time reverse transcription polymerase chain reaction (RT-PCR) at the mRNA level as well as by immunohistochemistry (IHC) and Western blotting at the protein level.Results HPLC analysis indicated that astragaloside Ⅳ,astragaloside Ⅱ and astragaloside Ⅰ were the main compounds in astragals extract.Astragalus extract reduced the apoptosis of hippocampal neurons (P <0.05) and decreased the expression of HIF-1a at both the mRNA and protein levels in hippocampus compared with non-treated groups (P <0.05).Conclusion Astragalus protects against intermittent hypoxia-induced hippocampal neurons impairment in rats.

  13. Protective effects of endoplasmic reticulum stress preconditioning on hippocampal neurons in rats with status epilepticus

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    Yi ZHANG

    2014-12-01

    Full Text Available Objective To evaluate the protective effects of endoplasmic reticulum stress preconditioning induced by 2-deoxyglucose (2-DG on hippocampal neurons of rats with status epilepticus (SE and the possible mechanism.  Methods Ninety Sprague-Dawley (SD rats were randomly enrolled into preconditioning group (N = 30, SE group (N = 30 and control group (N = 30. Each group was divided into 6 subsets (N = 5 according to six time points (before seizure, 6 h, 12 h, 1 d, 2 d and 7 d after seizure. The preconditioning group was administered 2-DG intraperitoneally with a dose of 150 mg/kg for 7 days, and the lithium-pilocarpine induced SE rat model was established on both preconditioning group and SE group. The rats were sacrificed at the above six time points, and the brains were removed to make paraffin sections. Nissl staining was performed by toluidine blue to evaluate the hippocampal neuronal damage after seizure, and the number of survival neurons in hippocampal CA1 and CA3 regions of the rats were counted. Immunohistochemical staining was performed to detect the expressions of glucose regulated protein 78 (GRP78 and X-box binding protein 1 (XBP-1 in hippocampal CA3 region of the rats.  Results The number of survival neurons in preconditioning group was much more than that in SE group at 7 d after seizure (t = 5.353, P = 0.000, and was more obvious in CA1 region. There was no significant hippocampal neuronal damage in control group. The expressions of GRP78 and XBP-1 in CA3 region of hippocampus in SE group at 6 h after seizure were significantly higher than that in control group (P = 0.000, and then kept increasing until reaching the peak at 2 d (P = 0.000, for all. The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in control group before seizure (P = 0.000, for all. The level of GRP78 maintained the highest at 24 h and 2 d after seizure (P = 0.000, for all, while the XBP-1 level

  14. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats.

    Science.gov (United States)

    Puebla, L; Rodríguez-Martín, E; Arilla, E

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 micrograms) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 micrograms of histamine (23% +/- 1% vs. 17% +/- 1% and 37% +/- 2% vs. 23% +/- 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (Gi protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of Gi proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 micrograms)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number with specific SS receptors (541 +/- 24 vs. 365 +/- 16 fmol/mg protein, P histamine (10 micrograms)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine, respectively, were administered 1 h before histamine injection. The pretreatment with mepyramine or cimetidine induced an increase in the

  15. Achyranthes bidentata Blume extract promotes neuronal growth in cultured embryonic rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Xin Tang; Yiren Chen; Xiaosong Gu; Fei Ding

    2009-01-01

    We have prepared an aqueous extract of Achyranthes bidentata Blume,a commonly prescribed Chinese medicinal herb,and reported,in previous studies,that A.bidentata extract benefits nerve growth and prevents neuron apoptosis.In this study,we investigated the actions of ,4.bidentata extract on survival and growth of primarily cultured rat hippocampal neurons.The morphological observation revealed that neurite growth from hippocampal neurons was significantly enhanced by A.bidentata extract with similar effects to those induced by nerve growth factor (NGF),and the greatest neurite growth appeared on treatment with A.bidentata extract at 1 ttg/ml for 24 h.DNA microarray analysis indicated that there were 25 upregulated genes and 47 downregulated genes exhibiting significantly differential expression in hippocampal neurons treated with A.bidentata extract at 1 μg/ml for 6 h when compared to those in untreated hippocampal neurons.Real-time quantitative RT-PCR and Western blot analysis demonstrated that the expression of growth-associated protein-43 in hippocampal neurons was upregulated at both mRNA and protein levels after treatment with A.bidentata extract,and the optimal dosage of the extract was also 1 μg/ml.These data confirm that A.bidentata extract could promote in vitro hippocampal neuronal growth in a dose- and time-dependent manner.(C) 2009 National Natural Science Foundation of China and Chinese Academy of Sciences.Published by Elsevier Limited and Science in China Press.All rights reserved.

  16. Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.

    Science.gov (United States)

    Simonyan, K V; Chavushyan, V A

    2016-10-24

    The hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency. In the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats. Tetanic potentiation or depression with posttetanic potentiation and depression was recorded extracellularly in response to ipsilateral entorhinal cortex high frequency stimulation. In morpho-histochemical study revealing of the activity of Ca(2+)-dependent acid phosphatase was observed. In all groups (sham-operated, sham + Teucrium polium, OVX, OVX + Teucrium polium), most recorded hippocampal neurons at HFS of entorhinal cortex showed TD-PTP responses. After 8 weeks in OVX group an anomalous evoked spike activity was detected (a high percentage of typical areactive units). In OVX + Teucrium polium group a synaptic activity was revealed, indicating prevention OVX-induced degenerative alterations: balance of types of responses was close to norm and areactive units were not recorded. All recorded neurons in sham + Teucrium polium group were characterized by the highest mean frequency background and poststimulus activity. In OVX+ Teucrium polium group the hippocampal cells had recovered their size and shape in CA1 and CA3 field compared with OVX group where hippocampal cells were characterized by a sharp drop in phosphatase activity and there was a complete lack of processes reaction. Thus, Teucrium polium reduced OVX-induce neurodegenerative alterations in entorhinal cortex-hippocamp circuitry and facilitated neuronal survival by modulating activity of neurotransmitters and

  17. Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats.

    Science.gov (United States)

    Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba

    2015-11-02

    Stress is a potent modulator of hippocampal-dependent memory formation. The aim of the present study was to assess the role of hippocampal signaling pathways in stress-induced memory impairment in male Wistar rats. The animals were exposed to acute elevated platform (EP) stress and memory formation was measured by a step-through type passive avoidance task. The results indicated that post-training or pre-test exposure to EP stress impaired memory consolidation or retrieval respectively. Using western blot analysis, it was found that memory retrieval was associated with the increase in the levels of phosphorylated cAMP-responsive element binding protein (P-CREB), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its downstream targets in the hippocampus. In contrast, the stress exposure decreased the hippocampal levels of these proteins. In addition, stress-induced impairment of memory consolidation or retrieval was associated with the decrease in the P-CREB/CREB ratio and the PGC-1α level in the hippocampus. On the other hand, the hippocampal level of nuclear factor E2-related factor 2 (Nrf2) and gamma-glutamylcysteine synthetase (γ-GCS) which are the master regulators of defense system were decreased by the stress exposure. The increased hippocampal levels of Nrf2 and it׳s downstream was observed during memory retrieval, while stress-induced impairment of memory consolidation or retrieval inhibited this hippocampal signaling pathway. Overall, these findings suggest that down-regulation of CREB/PGC-1α signaling cascade and Nrf2 antioxidant pathways in the hippocampus may be associated with memory impairment induced by stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Effect of chronic intracerebroventricular insulin administration in rats on the peripheral glucose metabolism and synaptic plasticity of CA1 hippocampal neurons.

    Science.gov (United States)

    Kamal, Amer; Ramakers, Geert M J; Gispen, Willem Hendrik; Biessels, Geert Jan

    2012-01-30

    In this study we examined the effects of sustained intracerebroventricular insulin infusion on hippocampal synaptic plasticity in rats. Insulin was infused intracerebroventricularly in male Wistar rats (n=12) for 3 months using osmotic minipumps. A control group (n=12) received a sham operation. Insulin infusion led to an initial reduction in food intake and body weight gain, but these differences attenuated over 12 weeks. Insulin infusion did not affect fasting or non-fasting blood glucose levels. Field synaptic potentials recording from the hippocampus demonstrated a defect in the expression of long-term potentiation. Sharp electrode current-clamp recording showed that CA1 pyramidal cells fire action potentials in response to prolonged depolarizing current injection and those action potentials showed progressive broadening. The action potential broadening in the insulin-perfused animals were significantly longer than the control. The amplitude of slow after hyperpolarization (sAHP) was measured after manually "clamping" the cells at -65 mV and injecting currents to evoke a train of four APs. The sAHP amplitude was significantly longer than in the control animals. We conclude that local insulin infusion into the brain of rats had significant effects on synaptic plasticity in the absence of marked effects on systemic glucose levels. These results indicate that long-term elevation of insulin levels can have adverse effects directly on the brain.

  19. Hippocampal corticosterone receptors and novelty-induced behavioral activity : effect of kainic acid lesion in the hippocampus

    NARCIS (Netherlands)

    Nyakas, C; De Kloet, E R; Veldhuis, H D; Bohus, B

    1983-01-01

    Rats were injected bilaterally in the dorsal and ventral hippocampus with kainic acid (KA) or with artificial CSF and their behavior and brain corticosterone (B) receptor systems were studied. The hippocampal KA injection destroyed part of the pyramidal neurons and of the dentate gyrus neurons. Thes

  20. Loss of sensory input increases the intrinsic excitability of layer 5 pyramidal neurons in rat barrel cortex.

    Science.gov (United States)

    Breton, Jean-Didier; Stuart, Greg J

    2009-11-01

    Development of the cortical map is experience dependent, with different critical periods in different cortical layers. Previous work in rodent barrel cortex indicates that sensory deprivation leads to changes in synaptic transmission and plasticity in layer 2/3 and 4. Here, we studied the impact of sensory deprivation on the intrinsic properties of layer 5 pyramidal neurons located in rat barrel cortex using simultaneous somatic and dendritic recording. Sensory deprivation was achieved by clipping all the whiskers on one side of the snout. Loss of sensory input did not change somatic active and resting membrane properties, and did not influence dendritic action potential (AP) backpropagation. In contrast, sensory deprivation led to an increase in the percentage of layer 5 pyramidal neurons showing burst firing. This was associated with a reduction in the threshold for generation of dendritic calcium spikes during high-frequency AP trains. Cell-attached recordings were used to assess changes in the properties and expression of dendritic HCN channels. These experiments indicated that sensory deprivation caused a decrease in HCN channel density in distal regions of the apical dendrite. To assess the contribution of HCN down-regulation on the observed increase in dendritic excitability following sensory deprivation, we investigated the impact of blocking HCN channels. Block of HCN channels removed differences in dendritic calcium electrogenesis between control and deprived neurons. In conclusion, these observations indicate that sensory loss leads to increased dendritic excitability of cortical layer 5 pyramidal neurons. Furthermore, they suggest that increased dendritic calcium electrogenesis following sensory deprivation is mediated in part via down-regulation of dendritic HCN channels.

  1. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  2. Memory and hippocampal architecture following short-term midazolam in western diet-treated rats.

    Science.gov (United States)

    Rosenberger, Dorothea S; Falangola, Maria F; Ledreux, Aurélie; Nie, Xingju; Suhre, Wendy M; Boger, Heather A; Granholm, Ann-Charlotte

    2016-05-16

    The impact of short-term benzodiazepine exposure on cognition in middle-aged or older patients is a highly debated topic among anesthesiologists, critical care physicians and public media. "Western diet" (WD) consumption is linked to impaired cognition as well. The combination of benzodiazepines with substantial exposure to WD might set the stage for increased hippocampal vulnerability for benzodiazepines leading to exaggerated cognitive impairment in the postoperative period. In this study, Fischer 344 rats were fed either WD or standard rodent diet from 5 to 10.5 months of age. Rats were exposed to midazolam or placebo two days prior to an MRI scan using Diffusional Kurtosis Imaging (DKI) to assess brain microstructural integrity, followed by behavioral testing using a water radial arm maze. Hippocampal tissue was collected to assess alterations in protein biochemistry in brain regions associated with learning and memory. Our results showed that rats exposed to the combination of midazolam and WD had significantly delayed time of learning and exhibited spatial memory impairment. Further, we observed an overall increase of kurtosis metrics in the hippocampus and increased expression of the mitochondrial protein VDAC2 in midazolam-treated rats. Our data suggest that both the short-acting benzodiazepine midazolam and WD contribute to negatively affect the brain in middle-aged rats. This study is the first application of DKI on the effects of midazolam and WD exposure, and the findings demonstrate that diffusion metrics are sensitive indicators of changes in the complexity of neurite architecture.

  3. Dissociation of dorsal hippocampal regional activation under the influence of stress in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Johannes ePassecker

    2011-10-01

    Full Text Available Stress has deleterious effects on brain, body and behaviour in humans and animals alike. The present work investigated how 30-minute acute photic stress exposure impacts on spatial information processing in the main subregions of the dorsal hippocampal formation (CA1, CA3 and Dentate Gyrus, a brain structure prominently implicated in memory and spatial representation. Recordings were performed from spatially tuned hippocampal and dentate gyrus cells in rats while animals foraged in a square arena for food. The stress procedure induced a decrease in firing frequencies in CA1 and CA3 place cells while sparing locational characteristics. In contrast to the CA1-CA3 network, acute stress failed to induce major changes in the DG neuronal population. These data demonstrate a clear dissociation of the effects of stress on the main hippocampal sub-regions. Our findings further support the notion of decreased hippocampal excitability arising from stress in areas CA1 and CA3, but not in dentate gyrus.

  4. Electron tomographic structure and protein composition of isolated rat cerebellar, hippocampal and cortical postsynaptic densities.

    Science.gov (United States)

    Farley, M M; Swulius, M T; Waxham, M N

    2015-09-24

    Electron tomography and immunogold labeling were used to analyze similarities and differences in the morphology and protein composition of postsynaptic densities (PSDs) isolated from adult rat cerebella, hippocampi, and cortices. There were similarities in physical dimensions and gross morphology between cortical, hippocampal and most cerebellar PSDs, although the morphology among cerebellar PSDs could be categorized into three distinct groups. The majority of cerebellar PSDs were composed of dense regions of protein, similar to cortical and hippocampal PSDs, while others were either composed of granular or lattice-like protein regions. Significant differences were found in protein composition and organization across PSDs from the different brain regions. The signaling protein, βCaMKII, was found to be a major component of each PSD type and was more abundant than αCaMKII in both hippocampal and cerebellar PSDs. The scaffold molecule PSD-95, a major component of cortical PSDs, was found absent in a fraction of cerebellar PSDs and when present was clustered in its distribution. In contrast, immunogold labeling for the proteasome was significantly more abundant in cerebellar and hippocampal PSDs than cortical PSDs. Together, these results indicate that PSDs exhibit remarkable diversity in their composition and morphology, presumably as a reflection of the unique functional demands placed on different synapses.

  5. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats.

    Directory of Open Access Journals (Sweden)

    Emilie Bonnet

    Full Text Available A dysfunction of retinoid hippocampal signaling pathway has been involved in the appearance of affective and cognitive disorders. However, the underlying neurobiological mechanisms remain unknown. Hippocampal granule neurons are generated throughout life and are involved in emotion and memory. Here, we investigated the effects of vitamin A deficiency (VAD on neurogenesis and memory and the ability of retinoic acid (RA treatment to prevent VAD-induced impairments. Adult retinoid-deficient rats were generated by a vitamin A-free diet from weaning in order to allow a normal development. The effects of VAD and/or RA administration were examined on hippocampal neurogenesis, retinoid target genes such as neurotrophin receptors and spatial reference memory measured in the water maze. Long-term VAD decreased neurogenesis and led to memory deficits. More importantly, these effects were reversed by 4 weeks of RA treatment. These beneficial effects may be in part related to an up-regulation of retinoid-mediated molecular events, such as the expression of the neurotrophin receptor TrkA. We have demonstrated for the first time that the effect of vitamin A deficient diet on the level of hippoccampal neurogenesis is reversible and that RA treatment is important for the maintenance of the hippocampal plasticity and function.

  6. Exposure to prenatal stress has deleterious effects on hippocampal function in a febrile seizure rat model.

    Science.gov (United States)

    Qulu, Lihle; Daniels, W M U; Mabandla, Musa V

    2015-10-22

    Prenatal stress has been shown to result in the development of a number of neurological disorders in the offspring. Most of these disorders are a result of an altered HPA axis resulting in higher than normal glucocorticoid levels in the affected neonate. This leaves the offspring prone to immune challenges. Therefore the aim of the present study was to investigate the effects of prenatal stress and febrile seizures on behavior and hippocampal function. Pregnant dams were exposed to restraint stress during the third trimester. Following birth, febrile seizures were induced in two week old pups using lipopolysaccharide and kainic acid. A week later, anxiety-like behavior and navigational ability was assessed. Trunk blood was used to measure basal corticosterone concentration and hippocampal tissue was collected and analyzed. Our results show that exposure to prenatal stress increased basal corticosterone concentration. Exposure to prenatal stress exacerbated anxiety-like behavior and impaired the rat's navigational ability. Exposure to prenatal stress resulted in reduced hippocampal mass that was exacerbated by febrile seizures. However, exposure to febrile seizures did not affect hippocampal mass in the absence of prenatal stress. This suggests that febrile seizures are exacerbated by exposure to early life stressors and this may lead to the development of neurological symptoms associated with a malfunctioning hippocampus. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory.

    Science.gov (United States)

    Bétry, Cécile; Etiévant, Adeline; Pehrson, Alan; Sánchez, Connie; Haddjeri, Nasser

    2015-04-03

    Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing. In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25%. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus. In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes.

  8. Comparison of the severity of injury of hippocampal neuron in rats induced by simulated push-pull maneuver at various degrees

    Institute of Scientific and Technical Information of China (English)

    Suhong Guo; Hui Zhang

    2006-01-01

    hippocampal CA1 area.RESULTS: A total of 40 rats were involved in the final analysis. ① Stroke index and neurological evaluation of rats in experimental groups: At 30 minutes and 6 hours after push-pull exposure, stroke index and neurological evaluation were higher in ±6Gz group and ±8 Gz group than those in control group (P < 0.01), especially at 6 hours after push-pull exposure,those in ±8 Gz group were the highest at each time points [(11.00±2.16), (5.75±1.70) points]. At 24 hours after exposure, those were decreased as compared with those within the former two time points, but the values were still higher than those in control group (P< 0.05-0.01). ② Results of HE staining: At 6 and 24 hours after exposure, partially neuronal degeneration was observed in pyramidal layer in ±6 Gz group and ±8 Gz group, including crenation of neurons, triangle or polygon, and karyopycnosis, especially the injury in ±8 Gz group was the most obvious at 6 hours after exposure. ③ Results of ultrastructure with electron microscope:Partially neuronal degeneration at various degrees was observed in hippocampal CA1 area in ±2 Gz group at 6 hours after exposure and in ±6 Gz group and ±8 Gz group at 6 and 24 hours after exposure. At 6 hours after exposure, nucleus of hippocampal neurons in ±8 Gz group was irregular and umbilication.Caryotin was aggregated,nuclear matrix was swelled and disorder, and vacuolation was also observed. Rough endoplasmic reticulum was expanded, mitochondrium was swelled, and crista was disappeared.CONCLUSION: ① Push-pull cannot damage hippocampal neurons of rats in ±2 Gz group. ② Exposure can cause injury of hippocampal neurons of rats in ±6Gz group and ±8 Gz group,especially the injury is the severest at 6 hours after exposure in ±8 Gz group and relieves gradually 24 hours later.

  9. Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro.

    Science.gov (United States)

    Behrens, C J; Ul Haq, R; Liotta, A; Anderson, M L; Heinemann, U

    2011-09-29

    It has been suggested that gap junctions are involved in the synchronization during high frequency oscillations as observed during sharp wave-ripple complexes (SPW-Rs) and during recurrent epileptiform discharges (REDs). Ripple oscillations during SPW-Rs, possibly involved in memory replay and memory consolidation, reach frequencies of up to 200 Hz while ripple oscillations during REDs display frequencies up to 500 Hz. These fast oscillations may be synchronized by intercellular interactions through gap junctions. In area CA3, connexin 36 (Cx36) proteins are present and potentially sensitive to mefloquine. Here, we used hippocampal slices of adult rats to investigate the effects of mefloquine, which blocks Cx36, Cx43 and Cx50 gap junctions on both SPW-Rs and REDs. SPW-Rs were induced by high frequency stimulation in the CA3 region while REDs were recorded in the presence of the GABA(A) receptor blocker bicuculline (5 μM). Both, SPW-Rs and REDs were blocked by the gap junction blocker carbenoxolone. Mefloquine (50 μM), which did not affect stimulus-induced responses in area CA3, neither changed SPW-Rs nor superimposed ripple oscillations. During REDs, 25 and 50 μM mefloquine exerted only minor effects on the expression of REDs but significantly reduced the amplitude of superimposed ripples by ∼17 and ∼54%, respectively. Intracellular recordings of CA3 pyramidal cells revealed that mefloquine did not change their resting membrane potential and input resistance but significantly increased the afterhyperpolarization following evoked action potentials (APs) resulting in reduced probability of AP firing during depolarizing current injection. Similarly, mefloquine caused a reduction in AP generation during REDs. Together, our data suggest that mefloquine depressed RED-related ripple oscillations by reducing high frequency discharges and not necessarily by blocking electrical coupling.

  10. Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

    Science.gov (United States)

    Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

    2010-08-18

    The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

  11. Intercellular adhesion molecule-1 expression in the hippocampal CA1 region of hyperlipidemic rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yingying Cheng; Ying Zhang; Hongmei Song; Jiachun Feng

    2012-01-01

    Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hyperlipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hyperlipidemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hyperlipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particularly in rats with hyperlipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region, which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-1.

  12. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    Science.gov (United States)

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

  13. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

    Science.gov (United States)

    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

  14. Establishment of a mechanical injury model of rat hippocampal neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-feng; CAO Fei; PAN De-sheng; LIU Wei-guo; HU Wei-wei; ZHENG Xiu-jue; ZHAO Xue-qun; L(U) Shi-ting

    2006-01-01

    Objective:To establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro.Methods: Hippocampal neurons isolated from1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide(PI) uptaking at different time points (0.5, 1, 6, 12 and24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points.Results: Pathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P <0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group,the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P <0.05).Conclusions: The established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury,which can be used in the future research of traumatic brain injury.

  15. Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats.

    Science.gov (United States)

    Kamei, C; Chen, Z; Nakamura, S; Sugimoto, Y

    1997-05-01

    The influence of bilateral hippocampal lesions on active avoidance response was studied in rats, as well as the effect of intracerebroventricular (i.c.v.) injection of histamine on memory deficits caused by hippocampectomy. Retardation of learning acquisition was produced by lesioning of the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured by open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior. I.c.v. injection of histamine and i.p. injection of histidine resulted in an improvement of memory deficits (not only learning acquisition but also memory retrieval) induced by hippocampal lesions in rats. Histamine contents of the hippocampus and hypothalamus decreased after hippocampectomy, and a decrease in histamine contents of both areas was restored by histamine (i.c.v.) and histidine (i.p.) injection. In addition, a close relationship was found between decrease in response latency of avoidance response and an increase in histamine content of the hippocampus and hypothalamus after histamine injection.

  16. Postnatal development of temporal integration, spike timing and spike threshold regulation by a dendrotoxin-sensitive K⁺ current in rat CA1 hippocampal cells.

    Science.gov (United States)

    Giglio, Anna M; Storm, Johan F

    2014-01-01

    Spike timing and network synchronization are important for plasticity, development and maturation of brain circuits. Spike delays and timing can be strongly modulated by a low-threshold, slowly inactivating, voltage-gated potassium current called D-current (ID ). ID can delay the onset of spiking, cause temporal integration of multiple inputs, and regulate spike threshold and network synchrony. Recent data indicate that ID can also undergo activity-dependent, homeostatic regulation. Therefore, we have studied the postnatal development of ID -dependent mechanisms in CA1 pyramidal cells in hippocampal slices from young rats (P7-27), using somatic whole-cell recordings. At P21-27, these neurons showed long spike delays and pronounced temporal integration in response to a series of brief depolarizing current pulses or a single long pulse, whereas younger cells (P7-20) showed shorter discharge delays and weak temporal integration, although the spike threshold became increasingly negative with maturation. Application of α-dendrotoxin (α-DTX), which blocks ID , reduced the spiking latency and temporal integration most strongly in mature cells, while shifting the spike threshold most strongly in a depolarizing direction in these cells. Voltage-clamp analysis revealed an α-DTX-sensitive outward current (ID ) that increased in amplitude during development. In contrast to P21-23, ID in the youngest group (P7-9) showed smaller peri-threshold amplitude. This may explain why long discharge delays and robust temporal integration only appear later, 3 weeks postnatally. We conclude that ID properties and ID -dependent functions develop postnatally in rat CA1 pyramidal cells, and ID may modulate network activity and plasticity through its effects on synaptic integration, spike threshold, timing and synchrony.

  17. Effects of lead exposure on dendrite and spine development in hippocampal dentate gyrus areas of rats.

    Science.gov (United States)

    Hu, Fan; Ge, Meng-Meng; Chen, Wei-Heng

    2016-03-01

    Lead exposure has been implicated in the impairment of synaptic plasticity in the hippocampal dentate gyrus (DG) areas of rats. However, whether the degradation of physiological properties is based on the morphological alteration of granule neurons in DG areas remains elusive. Here, we examined the dendritic branch extension and spine formation of granule neurons after lead exposure during development in rats. Dendritic morphology was studied using Golgi-Cox stain method, which was followed by Sholl analysis at postnatal days 14 and 21. Our results indicated that, for both ages, lead exposure significantly decreased the total dendritic length and spine density of granule neurons in the DG of the rat hippocampus. Further branch order analysis revealed that the decrease of dendritic length was observed only at the second branch order. Moreover, there were obvious deficits in the proportion and size of mushroom-type spines. These deficits in spine formation and maturity were accompanied by a decrease in Arc/Arg3.1 expression. Our present findings are the first to show that developmental lead exposure disturbs branch and spine formation in hippocampal DG areas. Arc/Arg3.1 may have a critical role in the disruption of neuronal morphology and synaptic plasticity in lead-exposed rats. © 2016 Wiley Periodicals, Inc.

  18. High-frequency electroacupuncture evidently reinforces hippocampal synaptic transmission in Alzheimer’s disease rats

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Li-hong Kong; Hui Wang; Feng Shen; Ya-wen Wang; Hua Zhou; Guo-jie Sun

    2016-01-01

    The frequency range of electroacupuncture in treatment of Alzheimer’s disease in rats is commonly 2–5 Hz (low frequency) and 50–100 Hz (high frequency). We established a rat model of Alzheimer’s disease by injectingβ-amyloid 1–42 (Aβ1–42) into the bilateral hippocam-pal dentate gyrus to verify which frequency may be better suited in treatment. Electroacupuncture at 2 Hz or 50 Hz was used to stimulate Baihui(DU20) andShenshu (BL23) acupoints. The water maze test and electrophysiological studies demonstrated that spatial memory ability was apparently improved, and the ranges of long-term potentiation and long-term depression were increased in Alzheimer’s disease rats after electroacupuncture treatment. Moreover, the effects of electroacupuncture at 50 Hz were better than that at 2 Hz. These ifndings suggest that high-frequency electroacupuncture may enhance hippocampal synaptic transmission and potentially improve memory disor-ders in Alzheimer’s disease rats.

  19. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

    Directory of Open Access Journals (Sweden)

    Aline Rideau Batista Novais

    Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  20. Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors.

    Science.gov (United States)

    Talani, Giuseppe; Licheri, Valentina; Biggio, Francesca; Locci, Valentina; Mostallino, Maria Cristina; Secci, Pietro Paolo; Melis, Valentina; Dazzi, Laura; Carta, Gianfranca; Banni, Sebastiano; Biggio, Giovanni; Sanna, Enrico

    2016-04-01

    The endogenous endocannabinoid system has a crucial role in regulating appetite and feeding behavior in mammals, as well as working memory and reward mechanisms. In order to elucidate the possible role of cannabinoid type-1 receptors (CB1Rs) in the regulation of hippocampal plasticity in animals exposed to food restriction (FR), we limited the availability of food to a 2-h daily period for 3 weeks in Sprague-Dawley rats. FR rats showed a higher long-term potentiation at hippocampal CA1 excitatory synapses with a parallel increase in glutamate release when compared with animals fed ad libitum. FR rats showed a significant increase in the long-term spatial memory determined by Barnes maze. FR was also associated with a decreased inhibitory effect of the CB1R agonist win55,212-2 on glutamatergic field excitatory postsynaptic potentials, together with a decrease in hippocampal CB1R protein expression. In addition, hippocampal brain-derived neurotrophic factor protein levels and mushroom dendritic spine density were significantly enhanced in FR rats. Altogether, our data suggest that alterations of hippocampal CB1R expression and function in FR rats are associated with dendritic spine remodeling and functional potentiation of CA1 excitatory synapses, and these findings are consistent with increasing evidence supporting the idea that FR may improve cognitive functions.

  1. Hippocampal Excitability Increases during the Estrous Cycle in the Rat: A Potential Role for Brain-Derived Neurotrophic Factor

    OpenAIRE

    SCHARFMAN, HELEN E.; Mercurio, Thomas C.; Goodman, Jeffrey H.; Wilson, Marlene A.; MacLusky, Neil J.

    2003-01-01

    To test the hypothesis that induction of BDNF may contribute to changes in hippocampal excitability occurring during the female reproductive cycle, we examined the distribution of BDNF immunoreactivity and changes in CA1 and CA3 electrophysiology across the estrous cycle in rats. Hippocampal BDNF immunoreactivity increased on the day of proestrus as well as on the following morning (estrus), relative to metestrus or ovariectomized animals. Changes in immunoreactivity were clearest in mossy fi...

  2. Identification of mRNA for endocannabinoid biosynthetic enzymes within hippocampal pyramidal cells and CA1 stratum radiatum interneuron subtypes using quantitative real-time polymerase chain reaction.

    Science.gov (United States)

    Merrill, C B; McNeil, M; Williamson, R C; Poole, B R; Nelson, B; Sudweeks, S; Edwards, J G

    2012-08-30

    The hippocampus is required for short-term memory and contains both excitatory pyramidal cells and inhibitory interneurons. These cells exhibit various forms of synaptic plasticity, the mechanism underlying learning and memory. More recently, endocannabinoids were identified to be involved in synaptic plasticity. Our goal was to describe the distribution of endocannabinoid biosynthetic enzymes within CA1 stratum radiatum interneurons and CA3/CA1 pyramidal cells. We extracted mRNA from single interneurons and pyramidal cells and used real-time quantitative polymerase chain reaction (RT-PCR) to detect the presence of 12-lipoxygenase, N-acyl-phosphatidylethanolamine-specific phospholipase D, diacylglycerol lipase α, and type I metabotropic glutamate receptors, all known to be involved in endocannabinoid production and plasticity. We observed that the expression of endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that it is coexpressed with type I metabotropic glutamate receptors, suggesting interneurons have the potential to produce endocannabinoids. We also identified that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme mRNA. Our data provide the first molecular biological evidence for putative endocannabinoid production in interneurons, suggesting their potential ability to regulate endocannabinoid-mediated processes, such as synaptic plasticity.

  3. Dorsal hippocampal lesions impair blocking but not latent inhibition of taste aversion learning in rats.

    Science.gov (United States)

    Gallo, M; Cándido, A

    1995-06-01

    The aim of the present experiments was to study the effect of nonselective electrolytic lesions of the rat dorsal hippocampus on 2 learning phenomena: the L.J. Kamin (1969) blocking effect and latent inhibition of taste aversion learning. Bilateral dorsal hippocampal lesions selectively impaired blocking induced by 1 saccharin-lithium chloride pairing previous to 1 serial compound (saccharin-cider vinegar)-lithium pairing, but lesions had no effect on latent inhibition of a saline aversion, induced by 6 saline preexposures, in the same group of animals. Moreover, dorsal hippocampal lesions did not affect latent inhibition of saccharin-conditioned aversion induced by 1 or 6 preexposures. It is argued that blocking and latent inhibition of taste aversion learning do not share a common neural mechanism.

  4. Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

    Science.gov (United States)

    Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

    2016-12-01

    Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

  5. Developmental changes in hippocampal associative coding.

    Science.gov (United States)

    Goldsberry, Mary E; Kim, Jangjin; Freeman, John H

    2015-03-11

    Behavioral analyses of the ontogeny of memory have shown that hippocampus-dependent learning emerges relatively late in postnatal development compared with simple associative learning. Maturation of hippocampal mnemonic mechanisms has been hypothesized to underlie the development of the later emerging learning processes. However, the role of hippocampal maturation in learning has not been examined directly. The goal of the present study was to examine developmental changes in hippocampal neuronal coding during acquisition of a hippocampus-dependent learning task. We recorded activity from CA1 pyramidal cells in rat pups while they were trained on trace eyeblink conditioning. Trace eyeblink conditioning is a Pavlovian conditioning task that involves the association of a conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free trace interval. The inclusion of the trace interval is what makes the task hippocampus dependent. In the present study, rats were trained at 21-23, 24-26, and 31-33 d of age. Previous research from our laboratory and others shows that trace conditioning begins to emerge during the third postnatal week. The results indicate that hippocampal neurons show a substantial increase in responsiveness to task-relevant events during development. Moreover, there is an age-related increase in the proportion of neurons that respond to a combination of trial events (e.g., CS and trace). Our findings indicate that the developmental emergence of hippocampally mediated learning is related to increases in the strength and complexity of CA1 associative coding.

  6. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Cheng; Li, Zhengqian; Qian, Min; Zhou, Yang; Wang, Jun; Guo, Xiangyang, E-mail: puthmzk@163.com

    2015-05-15

    Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.

  7. Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia.

    Science.gov (United States)

    Davis, H P; Tribuna, J; Pulsinelli, W A; Volpe, B T

    1986-01-01

    Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than controls (p less than 0.05). However, an analysis of the last 20 trials (75-95) showed that while PI rats and control rats had comparable reference memory (p greater than 0.8). PI rats tended to have a persistent working memory deficit compared to controls (p less than 0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.

  8. Brief RU 38486 Treatment Normalizes the Effects of Chronic Stress on Calcium Currents in Rat Hippocampal CA1 Neurons.

    NARCIS (Netherlands)

    Karst, H.; Joëls, M.

    2007-01-01

    Chronic stress alters many properties in rat brain, like serotonin responsiveness and dendritic morphology. In the present study, we examined (i) whether unpredictable stress during 21 days affects calcium (Ca) currents of CA1 pyramidal neurons recorded on day 22; and (ii) if so, whether this change

  9. 小鼠海马CA1区锥体神经元树突棘的发育%Dendritic spine development of mouse hippocampal CA1 pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    刘畅; 范文娟; 程维杰; 左曙光; 邓锦波

    2012-01-01

    Objective To investigate the developmental characteristics of dendritic spines in mouse hippocampal CA1 pyramidal neurons by analysing the spine density and morphological changes. Methods Fifty mice were collected at postnatal days ( P ) 0, 5, 10, 20 and 30, 10 mice for each age. Dil diolistic labeling with gene gun was performed to observe dendritic spines development in mouse hippocampal CA1 pyramidal neurons. High quality labeled neurons were examined and photographed under a confocal microscope, whereas the ultrastructure of spines was observed under a transmission electron microscope. Results Dendritic spines changed their morphology and density with mouse development in response to neuronal activity. The smooth endoplasmic reticulum and spine apparatus in dendritic spines of hippocampal CA1 were observed with electron microscopy analysis, which might be involved in the regulation of plasticity at individual synapses. Conclusion The development of dendritic spines may be closely related to synaptogenesis and the formation of synaptic plasticity.%目的 对小鼠海马CA1区锥体神经元正常发育中树突棘密度及各种形态变化进行分析测定,为深入研究突触发生及突触可塑性提供直接的形态学依据.方法 分别取出生后0、5、10、20及30d 5个年龄段的C57BL/6小鼠各10只,采用基因枪对小鼠海马CA1区锥体神经元树突棘进行亲脂性荧光染料DiI标记,通过激光共焦显微镜对其进行观察分析;同时利用透射电镜技术对树突棘的超微结构进行分析.结果 树突棘的形态、大小及其密度随小鼠发育而变化,成熟树突棘内部存在滑面内质网与棘器,可能参与了突触后膜结合蛋白及其转运体的合成.结论 树突棘的发育过程与突触连接的形成以及突触可塑性密切相关.

  10. Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury.

    Science.gov (United States)

    Cao, Lei; Bie, Xiaohua; Huo, Su; Du, Jubao; Liu, Lin; Song, Weiqun

    2014-11-01

    The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after fluid percussion injury. Diazepam can inhibit the hyperexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment significantly increased the slope of input-output curves in rat neurons after fluid percussion injury. Diazepam significantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the fluid percussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.

  11. Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Lei Cao; Xiaohua Bie; Su Huo; Jubao Du; Lin Liu; Weiqun Song

    2014-01-01

    The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.

  12. Prenatal exposure to betamethasone decreases anxiety in developing rats: hippocampal neuropeptide y as a target molecule.

    Science.gov (United States)

    Velísek, Libor

    2006-10-01

    Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

  13. Hippocampal plasticity after a vagus nerve injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Giulia Ronchi; Vitaly Ryu; ong ling; Krzysztof Czaja

    2012-01-01

    Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus

  14. Intra-hippocampal injection of lipopolysaccharide inhibits kindled seizures and retards kindling rate in adult rats.

    Science.gov (United States)

    Ahmadi, Amin; Sayyah, Mohammad; Khoshkholgh-Sima, Baharak; Choopani, Samira; Kazemi, Jafar; Sadegh, Mehdi; Moradpour, Farshad; Nahrevanian, Hossein

    2013-04-01

    Neuroinflammation facilitates seizure acquisition and epileptogenesis in developing brain. Yet, the studies on impact of neuroinflammation on mature brain epileptogenesis have led to inconsistent results. Hippocampus is particularly vulnerable to damage caused by ischemia, hypoxia and trauma, and the consequent neuroinflammation, which can lead in turn to epilepsy. Lipopolysaccharide (LPS) is extensively used in experimental studies to induce neuroinflammation. In this study, effect of acute and chronic intra-CA1 infusion of LPS on amygdala-kindled seizures and epileptogenesis was examined in mature rats. LPS (5 μg/rat) inhibited evoked amygdala afterdischarges and behavioral seizures. Anticonvulsant effect of LPS was observed 0.5 h after administration and continued up to 24 h. This effect was accompanied by intra-hippocampal elevation of nitric oxide (NO), interleukin1-β, and tumor necrosis factor-α and was prevented by microglia inhibitor, naloxone, NO synthase inhibitor, Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, piroxicam, and interleukin1-β receptor antagonist, interleukin1-ra. Moreover, daily intra-hippocampal injection of LPS significantly retarded kindling rate. In order to further elucidate the effect of LPS on synaptic transmission and short-term plasticity, changes in field excitatory postsynaptic potentials and population spikes were measured in stratum radiatum and stratum pyramidale of LPS-treated kindled rats. LPS impaired baseline synaptic transmission in hippocampal Schaffer collateral-CA1 synapse and reduced the magnitude of paired-pulse facilitation. Our results suggest that direct suppression of presynaptic mechanisms in Schaffer collateral-CA1 synapses, as well as the inflammatory mediators released by LPS in the hippocampus, is involved in antiepileptic effect of LPS.

  15. Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.

    Science.gov (United States)

    Wen, Di; Zang, Guoqing; Sun, DongLei; Yu, Feng; Mei, Dong; Ma, Chunling; Cong, Bin

    2014-01-24

    Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

  16. Aβ induces acute depression of excitatory glutamatergic synaptic transmission through distinct phosphatase-dependent mechanisms in rat CA1 pyramidal neurons.

    Science.gov (United States)

    Yao, Wen; Zou, Hao-Jun; Sun, Da; Ren, Si-Qiang

    2013-06-17

    Beta-amyloid peptide (Aβ) has a causal role in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that Aβ can disrupt excitatory glutamatergic synaptic function at synaptic level. However, the underlying mechanisms remain obscure. In this study, we recorded evoked and spontaneous EPSCs in hippocampal CA1 pyramidal neurons via whole-cell voltage-clamping methods and found that 1 μM Aβ can induce acute depression of basal glutamatergic synaptic transmission through both presynaptic and postsynaptic dysfunction. Moreover, we also found that Aβ-induced both presynaptic and postsynaptic dysfunction can be reversed by the inhibitor of protein phosphatase 2B (PP2B), FK506, whereas only postsynaptic disruption can be ameliorated by the inhibitor of PP1/PP2A, Okadaic acid (OA). These results indicate that PP1/PP2A and PP2B have overlapping but not identical functions in Aβ-induced acute depression of excitatory glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons.

  17. mRNA expression of Rho GTPase-related signaling molecules during rat hippocampal development

    Institute of Scientific and Technical Information of China (English)

    Guoqing Guo; Jifeng Zhang; Li Xin; Jing Chen; Weizai Shen; Lin Yuan; Shizhen Zhong

    2009-01-01

    BACKGROUND:Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton.However,there are very few reports of developmental roles of signaling molecules related to Rho GTPases.OBJECTIVE:To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases,including Rho-A,Rac-1,collapsin response mediator protein 1(CRMP-1),and tubulin β3 (Tub β3) during rat hippocampus development.DESIGN,TIME AND SETTING:A non-randomized,controlled,animal experiment,based on different developmental stages of the rat hippocampus,was performed at the Guangdong Key Laboratory of Tissue Construction and Detection,Institute of Clinical Anatomy,Southern Medical University between December 2005 and July 2007.MATERIALS:Trizol reagent was purchased from Invitrogen,USA.RNA PCR kit (AMV) Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa,Japan.Unless otherwise specified,all other reagents were purchased from Sigma-Aldrich,USA.METHODS:Twenty-five Sprague Dawley rats were assigned to five groups (n=5) according to developmental stages:embryonic (embryonic 15 days),neonatal (postnatal 5 days),juvenile (postnatal 1 month),adult (postnatal 3 months),and senile (postnatal 18 months).MAIN OUTCOME MEASURES:Detection of mRNA expression of Rho-A,Rac-1,CRMP-1,and Tub β3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction.RESULTS:Hippocampal mRNA expression of Rho-A,as well as Rac-1,reached peak levels at embryonic,juvenile,and senile stages,and was relatively less during neonatal and adult stages.mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage.CRMP-1 mRNA expression levels were as follows:embryonic>neonatal>juvenile>adult<senile,while Tub β3 mRNA expression was embryonic>neonatal>juvenile>adult=senile.CONCLUSION:Rho-A and Rac-1 shared similar expression profiles,which demonstrated similar

  18. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats.

    Science.gov (United States)

    Tian, Yonglu; Yang, Chaojuan; Shang, Shujiang; Cai, Yijun; Deng, Xiaofei; Zhang, Jian; Shao, Feng; Zhu, Desheng; Liu, Yunbo; Chen, Guiquan; Liang, Jing; Sun, Qiang; Qiu, Zilong; Zhang, Chen

    2017-01-01

    Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1(exon4-KO) ). Electrophysiological analysis revealed that the theta-burst stimulation (TBS)-induced long-term potentiation (LTP) and the low-frequency stimulus (LFS)-induced long-term depression (LTD) were decreased in the hippocampal Schaffer collateral pathway of the Fmr1(exon4-KO) rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was also impaired. Consistent with previous reports, the Fmr1(exon4-KO) rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG)-induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1(exon4-KO) rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1(exon4-KO) rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1(exon4-KO) rats constitute a novel rat model of FXS that complements existing mouse models.

  19. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2017-08-01

    Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  20. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

    Science.gov (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  1. Antibody to collapsin response mediator protein 1 promotes neurite outgrowth from rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongsheng Lin; Jing Chen; Wenbin Zhang; Xiaobing Gong; Biao Chen; Guoqing Guo

    2011-01-01

    This study examined the role of collapsin response mediator protein 1 (CRMP-1) on neurite outgrowth from rat hippocampal neurons by blocking its function using an antibody. Hippocampal neurons, cultured in vitro, were treated (blocked) using a polyclonal antibody to CRMP-1, and neurite outgrowth and cytoskeletal changes w ere captured using atomic force microscopy and laser confocal microscopy. Control cells, treated with normal rabbit IgG, established their characteristic morphology and had a large number of processes emerging from the soma, including numerous branches. Microtubules were clearly visible in the soma, formed an elaborate network, and were aligned in parallel arrays to form bundles which projected into neurites. After blocking with CRMP-1 antibody, the number of branches emerging from axons and dendrites significantly increased and were substantially longer, compared with control cells. However, the microtubule network nearly disappeared and only a few remnants were visible. When CRMP-1 antibody-blocked neurons were treated with the Rho inhibitor, Y27632, numerous neurites emerged from the soma, and branches were more abundant than in control neurons. Although the microtubules were not as clearly visible compared with neurons cultured in control medium, the microtubule network recovered in cells treated with Y27632, when compared with cells that were blocked by CRMP-1 antibody (but not treated with Y27632). These results demonstrate that neurite outgrowth from hippocampal neurons can be promoted by blocking CRMP-1 with a polyclonal antibody.

  2. Hippocampal state-dependent behavioral reflex to an identical sensory input in rats.

    Directory of Open Access Journals (Sweden)

    Keita Tokuda

    Full Text Available We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits.

  3. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone.

    Science.gov (United States)

    Shende, Vishvesh H; McArthur, Simon; Gillies, Glenda E; Opacka-Juffry, Jolanta

    2015-01-01

    The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  4. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone

    Directory of Open Access Journals (Sweden)

    Vishvesh H. Shende

    2015-01-01

    Full Text Available The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  5. Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats

    Science.gov (United States)

    Bachstetter, Adam D.; Morganti, Josh M.; Jernberg, Jennifer; Schlunk, Andrea; Mitchell, Staten H.; Brewster, Kaelin W.; Hudson, Charles E.; Cole, Michael J; Harrison, Jeffrey K.; Bickford, Paula C.; Gemma, Carmelina

    2010-01-01

    Microglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX3CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/ CX3CR1 signaling in young adult rodents decreased survival and proliferation of neural progenitor cells through IL-1β. Aged rats were found to have decreased levels of hippocampal FKN protein; moreover, interruption of CX3CR1 function in these animals did not affect neurogenesis. The age-related loss of FKN could be restored by exogenous FKN reversing the age-related decrease in hippocampal neurogenesis. There were no measureable changes in young animals by the addition of exogenous FKN. The results suggest that FKN/ CX3CR1 signaling has a regulatory role in modulating hippocampal neurogenesis via mechanisms that involve indirect modification of the niche environment. As elevated neuroinflammation is associated with many age-related neurodegenerative diseases, enhancing FKN/ CX3CR1 interactions could provide an alternative therapeutic approach to slow age-related neurodegeneration. PMID:20018408

  6. Parkia biglobosa Improves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

    Directory of Open Access Journals (Sweden)

    Kayode Komolafe

    2014-01-01

    Full Text Available Objective. Methanolic leaf extracts of Parkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria. Methods. Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL or catechin (1, 5, or 10 µg/mL for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2 for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm were also determined. Results. PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na+, K+-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of the ΔΨm by PBE was independent of catechin. Conclusion. The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

  7. Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats.

    Directory of Open Access Journals (Sweden)

    Timo Ruusuvirta

    Full Text Available Any change in the invariant aspects of the auditory environment is of potential importance. The human brain preattentively or automatically detects such changes. The mismatch negativity (MMN of event-related potentials (ERPs reflects this initial stage of auditory change detection. The origin of MMN is held to be cortical. The hippocampus is associated with a later generated P3a of ERPs reflecting involuntarily attention switches towards auditory changes that are high in magnitude. The evidence for this cortico-hippocampal dichotomy is scarce, however. To shed further light on this issue, auditory cortical and hippocampal-system (CA1, dentate gyrus, subiculum local-field potentials were recorded in urethane-anesthetized rats. A rare tone in duration (deviant was interspersed with a repeated tone (standard. Two standard-to-standard (SSI and standard-to-deviant (SDI intervals (200 ms vs. 500 ms were applied in different combinations to vary the observability of responses resembling MMN (mismatch responses. Mismatch responses were observed at 51.5-89 ms with the 500-ms SSI coupled with the 200-ms SDI but not with the three remaining combinations. Most importantly, the responses appeared in both the auditory-cortical and hippocampal locations. The findings suggest that the hippocampus may play a role in (cortical manifestation of MMN.

  8. Mechanisms underlying activation of the slow AHP in rat hippocampal neurons.

    Science.gov (United States)

    Lima, Pedro A; Marrion, Neil V

    2007-05-30

    The firing of a train of action potentials in hippocampal pyramidal neurons is terminated by an afterhyperpolarization (AHP) that displays two main components; the medium AHP (I(mAHP)), lasting a few hundred milliseconds and the slow AHP (I(sAHP)), that has a duration of several seconds. It is unclear how much of I(mAHP) is dependent on the entry of calcium ions (Ca(2+)), whereas it is accepted that I(sAHP) is caused by activation of Ca(2+)-activated potassium channels. There has been controversy regarding the subcellular localization and mechanism of activation of these channels. Whole-cell recordings from CA1 neurons in the hippocampal slice preparation showed that inhibition of L-type, but not N-, P/Q-, T- and R-type Ca(2+) channels, reduced both I(mAHP) and I(sAHP). Inhibition of both AHP components by L-type Ca(2+) channel antagonists was not complete, with I(sAHP) being significantly more sensitive than I(mAHP). Somatic extracellular ionophoresis of BAPTA during I(sAHP) caused a transient inhibition, but had no effect on I(mAHP). Cell-attached patch recordings from the soma of CA1 neurons within a slice displayed channels that produced an ensemble waveform reminiscent of I(sAHP) when the patch was subjected to a train of action potential waveforms. The channels were Ca(2+)-activated, exhibited a limiting slope conductance of 19 pS and were not observed in dendritic membrane patches. These data demonstrate that the I(sAHP) is somatic in origin and arises from continued Ca(2+) entry through functionally co-localized L-type channels.

  9. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

  10. Occurrence of complement protein C3 in dying pyramidal neurons in rat hippocampus after systemic administration of kainic acid.

    Science.gov (United States)

    Morita, Hiroyuki; Suzuki, Katsuaki; Mori, Norio; Yasuhara, Osamu

    2006-11-27

    To evaluate the roles of complement in kainic acid (KA)-induced neuronal damages, the immunohistochemical localization of the complement protein C3 was examined in rat hippocampus after systemic KA injection. The immunoreactivity for C3 was found in glial cells in control rats, and such glial cells were increased in number after KA injection. Our confocal study showed that C3-positive glial cells were microglia. Three to seven days after KA, C3 immunoreactivity appeared in CA1 and CA3 pyramidal neurons. Double staining for C3 combined with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling showed that occurrence of C3 immunoreactivity in neurons coincided well with that of DNA fragmentation. Western blot analysis and RT-PCR experiments suggested local synthesis of C3 by brain cells. Our results suggest that C3 contributes greatly to neuronal death after systemic KA administration, and that microglia and neurons are the local source of C3 in KA-induced brain injury.

  11. Atorvastatin increases dynamin 1 expression in hippocampal CA1 region in a rat model of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Qinghua Li; Wensheng Zhou

    2011-01-01

    The current study examined a rat model of vascular dementia. The model rats exhibited obvious morphological and ultrastructural changes in neurons in the brain, and significantly reduced dynamin 1 expression in hippocampal CA1 region along with decreased learning and memory performance. Following atorvastatin treatment, the morphology and ultrastructure of cells in the model rat brain were significantly improved, dynamin 1 expression in hippocampal CA1 region was significantly enhanced, and learning and memory ability was significantly improved. The results demonstrated that impaired learning and memory abilities in vascular dementia model rats were closely correlated with decreased dynamin 1 expression. These findings indicate that atorvastatin can protect model rats against cognitive impairment by increasing dynamin 1 expression.

  12. Effects of transient oxygen-glucose deprivation on G-proteins and G-protein-coupled receptors in rat CA3 pyramidal cells in vitro.

    Science.gov (United States)

    Tanabe, M; Gähwiler, B H; Gerber, U

    1998-06-01

    The role of guanosine triphosphate-binding proteins (G-proteins) in the generation of the outward current during transient oxygen-glucose deprivation (OGD) was investigated in CA3 pyramidal cells in rat hippocampal organotypic slice cultures using the single-electrode voltage-clamp technique with KMeSO4-filled microelectrodes. To simulate ischaemia, brief chemical OGD (2 mM 2-deoxyglucose and 3 mM NaN3 for 4-9 min) was used, which induced an outward K+ current associated with an increase in input conductance. OGD failed to induce the outward current under conditions where G-protein function was disrupted by loading cells with guanosine 5'-O-(2-thiodiphosphate) [GDPbetaS] or after prolonged injection of guanosine 5'-O(3-thiotdphosphate) [GTPgammaS]. However, in slices treated with pertussis toxin (PTX), OGD still elicited the outward current, indicating that PTX-insensitive G-proteins are involved. Consistent with this insensitivity to PTX, neither adenosine receptors nor GABA(B) (gamma-aminobutyric acid) receptors, which operate via PTX-sensitive G-proteins, mediate the OGD-induced outward current. When adenosine receptors or GABA(B) receptors were blocked with 1,3-dipropyl-8-psulphophenylxanthine (DPSPX, 5 microM) or CGP 52 432 (10 microM), respectively, the OGD-induced response was not modified. The response also persisted following pretreatment of slice cultures with tetanus toxin to prevent vesicular release of neurotransmitters and neuromodulators from presynaptic terminals. Both PTX-sensitive and PTX-insensitive G-protein-mediated responses were suppressed during OGD. The inward current induced by the metabotropic glutamate receptor agonist 1 S, 3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) and the outward current elicited by adenosine or baclofen were strongly or completely attenuated. In contrast, the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) response was not affected. These findings suggest that during OGD there is

  13. Effects of prolonged abstinence from METH on the hippocampal BDNF levels, neuronal numbers and apoptosis in methamphetamine-sensitized rats.

    Science.gov (United States)

    Hajheidari, Samira; Sameni, Hamid Reza; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

    2017-04-03

    Methamphetamine (METH) use is associated with neuronal damage in various regions of brain, while effects of prolonged abstinence on METH-induced damage are not quite clear. This study evaluated serum and hippocampal BDNF levels, neuronal numbers and apoptosis in METH-sensitized and abstinent rats. Rats were sensitized to METH (2mg/kg, daily/18 days, s.c.). All rats were evaluated for neuron counting, the TUNEL test and serum and hippocampal BDNF levels after 30 days of forced abstinence from METH. The results showed that increased BDNF levels in the hippocampus and serum of METH-sensitized rats returned to control level after 30 days of abstinence. The number of neurons in the DG and CA1 of hippocampus and also, the total hippocampal perimeter and area in METH-sensitized rats were significantly lower than the saline rats. While, the number of neurons was not significantly increased in the hippocampus after prolonged abstinence from METH. Also, METH-sensitized rats showed a significant increase in TUNEL-positive cells, whereas METH-abstinent rats showed a slight but significant decrease in TUNEL-positive cells in the DG and CA3 of hippocampus. These results suggest that despite the reduction in BDNF levels, reducing the number of neurons, perimeter and area of the hippocampus were stable after abstinence. Thus, the degenerative effects of METH have been sustained even after prolonged abstinence in the hippocampus.

  14. Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats.

    Science.gov (United States)

    Wang, Qian-Qian; Zhu, Li-Jun; Wang, Xian-Hong; Zuo, Jian; He, Hui-Yan; Tian, Miao-Miao; Wang, Lei; Liang, Gui-Ling; Wang, Yu

    2016-05-01

    Trigeminal nerve stimulation (TNS) has recently been demonstrated effective in the treatment of epilepsy and mood disorders. Here, we aim to determine the effects of TNS on epileptogenesis, cognitive function, and the associated hippocampal apoptosis and inflammatory responses. Rats were injected with pilocarpine to produce status epilepticus (SE) and the following chronic epilepsy. After SE induction, TNS treatment was conducted for 4 consecutive weeks. A pilocarpine re-injection was then used to induce a seizure in the epileptic rats. The hippocampal neuronal apoptosis induced by seizure was assessed by TUNEL staining and inflammatory responses by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). The spontaneous recurrent seizure (SRS) number was counted through video monitoring, and the cognitive function assessed through Morris Water Maze (MWM) test. TNS treatment attenuated the SRS attacks and improved the cognitive impairment in epileptic rats. A pilocarpine re-injection resulted in less hippocampal neuronal apoptosis and reduced level of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and microglial activation in epileptic rats with TNS treatment in comparison to the epileptic rats without TNS treatment. It is concluded that TNS treatment shortly after SE not only protected against the chronic spontaneous seizures but also improved cognitive impairments. These antiepileptic properties of TNS may be related to its attenuating effects on hippocampal apoptosis and pro-inflammatory responses.

  15. Early life inflammatory pain induces long-lasting deficits in hippocampal-dependent spatial memory in male and female rats.

    Science.gov (United States)

    Henderson, Yoko O; Victoria, Nicole C; Inoue, Kiyoshi; Murphy, Anne Z; Parent, Marise B

    2015-02-01

    The present experiment tested the hypothesis that neonatal injury disrupts adult hippocampal functioning and that normal aging or chronic stress during adulthood, which are known to have a negative impact on hippocampal function, exacerbate these effects. Male and female Sprague-Dawley rats were given an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth and their memory was tested in the hippocampal-dependent spatial water maze in adulthood and again in middle age. We found that neonatal injury impaired hippocampal-dependent memory in adulthood, that the effects of injury on memory were more pronounced in middle-aged male rats, and that chronic stress accelerated the onset of these memory deficits. Neonatal injury also decreased glucocorticoid receptor mRNA in the dorsal CA1 area of middle-aged rats, a brain region critical for spatial memory. Morphine administration at the time of injury completely reversed injury-induced memory deficits, but neonatal morphine treatments in the absence of injury produced significant memory impairments in adulthood. Collectively, these findings are consistent with our hypothesis that neonatal injury produces long-lasting disruption in adult hippocampal functioning.

  16. Flat pyramid

    OpenAIRE

    Doherty, Kevin Andrew

    2017-01-01

    'Flat pyramid' is a multi-channel video installation. The project employs appropriated promotional and instructional video from a defunct pyramid scheme as the source material for fictionalized reenactment. The footage primarily consists of presentation documentation, testimonial interviews, and product photography—throughout all of which cutting rarely occurs between takes. Perpetrators and victims are seen moving in and out of their promotional personas, inadvertently making their disquieti...

  17. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  18. Glucose deprivation activates diversity of potassium channels in cultured rat hippocampal neurons.

    Science.gov (United States)

    Velasco, Myrian; García, Esperanza; Onetti, Carlos G

    2006-05-01

    1. Glucose is one of the most important substrates for generating metabolic energy required for the maintenance of cellular functions. Glucose-mediated changes in neuronal firing pattern have been observed in the central nervous system of mammals. K(+) channels directly regulated by intracellular ATP have been postulated as a linkage between cellular energetic metabolism and excitability; the functional roles ascribed to these channels include glucose-sensing to regulate energy homeostasis and neuroprotection under energy depletion conditions. The hippocampus is highly sensitive to metabolic insults and is the brain region most sensitive to ischemic damage. Because the identity of metabolically regulated potassium channels present in hippocampal neurons is obscure, we decided to study the biophysical properties of glucose-sensitive potassium channels in hippocampal neurons. 2. The dependence of membrane potential and the sensitivity of potassium channels to glucose and ATP in rat hippocampal neurons were studied in cell-attached and excised inside-out membrane patches. 3. We found that under hypoglycemic conditions, at least three types of potassium channels were activated; their unitary conductance values were 37, 147, and 241 pS in symmetrical K(+), and they were sensitive to ATP. For K(+) channels with unitary conductance of 37 and 241, when the membrane potential was depolarized the longer closed time constant diminished and this produced an increase in the open-state probability; nevertheless, the 147-pS channels were not voltage-dependent. 4. We propose that neuronal glucose-sensitive K(+) channels in rat hippocampus include subtypes of ATP-sensitive channels with a potential role in neuroprotection during short-term or prolonged metabolic stress.

  19. Effect of forced exercise and exercise withdrawal on memory, serum and hippocampal corticosterone levels in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-10-01

    Evidence suggests that there are positive effects of exercise on learning and memory. Moreover, some studies have demonstrated that forced exercise plays the role of a stressor. This study was aimed at investigating the effects of different timing of exercise and exercise withdrawal on memory, and serum and hippocampal corticosterone (CORT) levels. Wistar rats were randomly divided into five groups: control, sham, exercise-rest (exercise withdrawal), rest-exercise (exercised group), and exercise-exercise (continuous exercise). Rats were forced to run on a treadmill for 1 h/day at a speed 20-21-m/min. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. Findings showed that after the exercise withdrawal, short-term and mid-term memories, had significant enhancement compared to the control group, while the long-term memory did not present this result. In addition, the serum and hippocampal CORT levels were at the basal levels after the rest period in the exercise-rest group. In the rest-exercise group, exercise improved mid- and long-term memories, whereas continuous exercise improved all types short-, mid- and long-term memories, particularly the mid-term memory. Twenty-one and forty-two days of exercise significantly decreased the serum and hippocampal CORT levels. It seems that exercise for at least 21 days with no rest could affect biochemical factors in the brain. Also, regular continuous exercise plays an important role in memory function. Hence, the duration and withdraw of exercise are important factors for the neurobiological aspects of the memory responses.

  20. Persistent reduction of hippocampal glutamine synthetase expression after status epilepticus in immature rats.

    Science.gov (United States)

    van der Hel, W Saskia; Hessel, Ellen V S; Bos, Ineke W M; Mulder, Sandra D; Verlinde, Suzanne A M W; van Eijsden, Pieter; de Graan, Pierre N E

    2014-12-01

    Mesiotemporal sclerosis (MTS), the most frequent form of drug-resistant temporal lobe epilepsy, often develops after an initial precipitating injury affecting the immature brain. To analyse early processes in epileptogenesis we used the juvenile pilocarpine model to study status epilepticus (SE)-induced changes in expression of key components in the glutamate-glutamine cycle, known to be affected in MTS patients. SE was induced by Li(+) /pilocarpine injection in 21-day-old rats. At 2-19 weeks after SE hippocampal protein expression was analysed by immunohistochemistry and neuron damage by FluoroJade staining. Spontaneous seizures occurred in at least 44% of animals 15-18 weeks after SE. As expected in this model, we did not observe loss of principal hippocampal neurons. Neuron damage was most pronounced in the hilus, where we also detected progressive loss of parvalbumin-positive GABAergic interneurons. Hilar neuron loss (or end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity from 2 (-15%) to 19 weeks (-33.5%) after SE. Immunoreactivity for excitatory amino-acid transporters, vesicular glutamate transporter 1 and glial fibrillary acidic protein was unaffected. Our data show that SE elicited in 21-day-old rats induces a progressive reduction in hilar GS expression without affecting other key components of the glutamate-glutamine cycle. Reduced expression of glial enzyme GS was first detected 2 weeks after SE, and thus clearly before spontaneous recurrent seizures occurred. These results support the hypothesis that reduced GS expression is an early event in the development of hippocampal sclerosis in MTS patients and emphasize the importance of astrocytes in early epileptogenesis.

  1. Hippocampal and thalamic neuronal metabolism in a putative rat model of schizophrenia○

    Institute of Scientific and Technical Information of China (English)

    Guolin Ma; Tianbin Song; Min Chen; Yuan Fu; Yong Xu; Ensen Ma; Wu Wang; Jiang Du; Mingxiong Huang

    2013-01-01

    The transcription factor early growth response protein 3 (EGR3) is involved in schizophrenia. We developed a putative rat model of schizophrenia by transfecting lentiviral particles carrying the Egr3 gene into bilateral hippocampal dentate gyrus. We assessed spatial working memory using the Morris water maze test, and neuronal metabolite levels in bilateral hippocampus and thalamus were determined by 3.0 T proton magnetic resonance spectroscopy. Choline content was significantly greater in the hippocampus after transfection, while N-acetylaspartate and the ratio of N-acetylaspartate to creatine/phosphocreatine in the thalamus were lower than in controls. This study is the first to report evaluation of brain metabolites using 3.0 T proton magnetic resonance spectroscopy in rats transfected with Egr3, and reveals metabolic abnormalities in the hippocampus and thalamus in this putative model of schizophrenia.

  2. Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie

    2012-01-01

    Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large......-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found...... to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release...

  3. Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism.

    Science.gov (United States)

    da Conceição, Rodrigo Rodrigues; Laureano-Melo, Roberto; Oliveira, Kelen Carneiro; de Carvalho Melo, Maria Clara; Kasamatsu, Tereza Sayoko; de Barros Maciel, Rui Monteiro; de Souza, Janaina Sena; Giannocco, Gisele

    2016-04-01

    Thyroidectomy is a surgical procedure indicated in cases of several maligned or benign thyroid diseases, thus, the aim of our study was to verify how the hypothyroidism induced by thyroidectomy influences behavioral parameters and its relation to thyroid hormones metabolism and neurogenesis at hippocampus. For this purpose, Adult male Wistar rats underwent to thyroidectomy to induce hypothyroidism. Behavioral tests, the thyroid profile and hippocampal gene expression were evaluated in control and in thyroidectomized animals. It was observed that thyroidectomized group had a significant increasing in serum thyroid-stimulating hormone (TSH) and a decreasing in thyroxine (T4) levels as well as in triiodothyronine (T3) serum level. It was also observed reduction of the monocarboxylate transporter 8 (Mct8), thyroid hormone receptor alfa (Trα1), deiodinase type 2 (Dio2), ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) and brain-derived neurotrophic factor (Bdnf) mRNA expression in hippocampus of thyroidectomized animals. In the forced swimming test, it was verified that thyroidectomy promotes a decrease in time of immobility and climbing when compared with the control group. In summary, we demonstrated that antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism. This effect could be associated to an impaired neuronal activity in acute stress response as it is observed in forced swimming paradigm.

  4. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Directory of Open Access Journals (Sweden)

    Jodi L. Pawluski

    2014-01-01

    Full Text Available Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1 cookie and (2 osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

  5. Effects of the alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampal slices.

    Science.gov (United States)

    Ameri, A

    1997-08-01

    Alkaloids of different Aconitum species are employed as analgesics in traditional Chinese folk medicine. The present study was designed in order to investigate the effects of the structurally related alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampus. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. 6-Benzoylheteratisine (0.01-10 microM) inhibited the ortho- and antidromic population spike as well as the field EPSP in a concentration- and frequency-dependent manner. Heteratisine (1-100 microM) was a less potent inhibitor. It exerted a depression of the orthodromic spike, but failed to affect the antidromic population spike. 6-Benzoylheteratisine (10 microM) diminished epileptiform activity induced by bicuculline. In hippocampal neurons, this compound reduced the peak amplitude of the sodium current. There was no effect of heteratisine on the sodium current in concentrations up to 100 microM. It is concluded that the frequency-dependent action of 6-benzoylheteratisine suggests an inhibition of neuronal activity which underlies epileptiform burst discharges. The predominant effect is a suppression of neuronal activity due to a blockade of sodium channels.

  6. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

    Directory of Open Access Journals (Sweden)

    Amit eRanjan

    2014-05-01

    Full Text Available Microgravity and sleep loss lead to cognitive and learning deficits. These behavioral alterations are likely to be associated with cytomorphological changes and loss of neurons. To understand the phenomenon, we exposed rats (225-275g to 14 days simulated microgravity (SMg and compared its effects on CA1 hippocampal neuronal plasticity, with that of normal cage control rats. We observed that the mean area, perimeter, synaptic cleft and length of active zone of CA1 hippocampal neurons significantly decreased while dendritic arborization and number of spines significantly increased in SMg group as compared with controls. The mean thickness of the post synaptic density and total dendritic length remained unaltered. The changes may be a compensatory effect induced by exposure to microgravity; however, the effects may be transient or permanent, which need further study. These findings may be useful for designing effective prevention for those, including the astronauts, exposed to microgravity. Further, subject to confirmation we propose that SMg exposure might be useful for recovery of stroke patients.

  7. Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Jian-quan ZHENG; Xie-chuan WENG; Xiao-dan GAI; Jin LI; Wen-bin XIAO

    2004-01-01

    AIM: To investigate whether agmatine could selectively block a given type of the voltage-gated calcium channels (VGCC) and whether related receptors are involved in the blocking effect of agmatine on VGCC. METHODS: The whole-cell patch recording technique was performed to record VGCC currents in the cultured neonatal rat hippocampal neurons. RESULTS: Verapamil (100 μmol/L), a selective blocker of L-type calcium channel, significantly inhibited VGCC current by 80 %± 7 %. Agmatine (100 μmol/L) could further depress the remained currents by 25 %±6 %. The α2-adrenoceptor antagonist yohimbine (10 μmol/L) and the I2 imidazoline receptor antagonist idazoxon (10 and 40 μmol/L) had no significant effect on VGCC currents when used respectively. When the mixture of yohimbine and agmatine was applied, VGCC currents were still depressed remarkably. However, the blocking effect of agmatine was decreased by 29 %± 8 % in the presence of idazoxon (10 μmol/L). The effect of idazoxon did not increase at a higher concentration (40 μmol/L). CONCLUSION: Agmatine could block the L- and other types of VGCC currents in the cultured rat hippocampal neurons. Blocking effect of agmatine on VGCC was partially related to I2 imidazoline receptor and had no relationship with α2-adrenoceptors.

  8. Subacute toxicity of exogenous manganese on rat hippocampal neurons Examination by MRI and optical microscopy

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Xu; Yun Xiang; Min Yang

    2008-01-01

    BACKGROUND: Manganism may cause learning and memory impairment by influencing the normal function of the hippocampus, however, this effect requires further examination.OBJECTIVE: To investigate the effects of manganism on the rat hippocampus using immunohistochemistry and MRI examination.DESIGN, TIME AND SETTING: A randomized controlled study, performed in the School of Medicine and Life Science, Jianghan University and the State Key Laboratory of Atomic & Molecular Physics and Spectroscopy, Chinese Academy of Science, from July to September 2005.MATERIALS: Fourteen healthy SD rats aged two months were selected for this study. MnCl2 4H2O (BIID, UK) (batch number: 9791325); glial fibrillary acidic protein (GFAP) staining kit (Beijing Zhongshan Biotechnology); Biospec 4.7T/30 animal MRI formatter (Bruker, Germany).METHODS: Fourteen rats were randomly divided into a control group (n=7) and a manganism group (n=7). Rats in the manganism group Received intraperitoneal injection of MnCl2·4H2O (50mg/kg), once a day, for four successive days. Rats in the control group were injected according to the manganism regimen, but using saline instead of manganese solution.MAIN OUTCOME MEASURES: Twenty-four hours after the last injection, rats were examined using MRI. Immunohistochemically stained GFAP and hematoxylin-eosin stained hippocampal sections were observed under optical microscopy.RESULTS: Fourteen rats were included in the final analysis. After manganese treatment, T1 weighted image and inversion recovery MRI demonstrated that the signal intensity was significantly enhanced in hippocampus, compared to controls. Neuronal necrosis was not observed in the hippocampus after HE staining. As compared to the control group, GFAP expression was markedly enhanced in the hippocampus of the manganism group.CONCLUSION: Within the rat brain, manganese preferentially localizes to the hippocampus and can induce astroctye activation.

  9. Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.

    Science.gov (United States)

    Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong

    2017-05-01

    One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT3 receptor in the development of PTSD, even though 5-HT3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.

  10. Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

    Science.gov (United States)

    Castañeda, Patricia; Muñoz, Mauricio; García-Rojo, Gonzalo; Ulloa, José L; Bravo, Javier A; Márquez, Ruth; García-Pérez, M Alexandra; Arancibia, Damaris; Araneda, Karina; Rojas, Paulina S; Mondaca-Ruff, David; Díaz-Véliz, Gabriela; Mora, Sergio; Aliaga, Esteban; Fiedler, Jenny L

    2015-10-01

    Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons. © 2015 Wiley Periodicals, Inc.

  11. Glycine receptor in rat hippocampal and spinal cord neurons as a molecular target for rapid actions of 17-β-estradiol

    Directory of Open Access Journals (Sweden)

    Liu Chun-Feng

    2009-01-01

    Full Text Available Abstract Glycine receptors (GlyRs play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP and spinal dorsal horn (SDH neurons, 17-β-estradiol (E2 rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (IGly. In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, the E2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the IGly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level.

  12. Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats.

    Science.gov (United States)

    Nabetani, M; Okada, Y; Kawai, S; Nakamura, H

    1995-02-01

    To investigate the relationship between neural activity and cerebral energy metabolism during anoxia or ischemia in neural tissue of different ages, hippocampal slices were prepared from four-, seven- and 10-day-old and adult rats. For the index of the neural activity, the population spikes were recorded in the pyramidal cell layer of the CA3 area. ATP and phosphocreatine levels in the slices were measured during oxygen and/or glucose deprivation. After deprivation of both oxygen and glucose, population spikes of the slices from four, seven- and 10-day-old and adult rats ceased completely in 14.2, 11.8, 9.4 and 5.3 min, respectively. The level of ATP at the time of cessation of population spike in four-, seven- and 10-day-old and adult rats was 37.4, 30.2, 28.5 and 56.4% of the original concentrations. After deprivation of glucose only, the decay time of the population spikes of the slices from four-, seven- and 10-day-old and adult rats was 17.8, 14.5, 9.0 and 10.0 min and at the time of population spikes cessation the level of ATP was 99.8, 84.2, 79.3 and 49%, respectively. After deprivation of oxygen only, population spikes of the slices from four, seven- and 10-day old and adult rats ceased completely in 257, 283, 109 and 8.5 min, respectively. The level of ATP at the time of population spikes cessation was 50, 40, 36.6 and 94.4% of the initial values, respectively. These results indicate that the immature rat is extremely resistant to oxygen deprivation from a functional and a metabolic view, whereas in the adult rat, preservation of neural activity depends much on both oxygen and glucose. During glucose deprivation, population spikes of the slices of immature and mature rats ceased rapidly although the level of ATP is preserved at high levels. This suggests that glucose plays an important role in the preservation of neural activity in addition to its major function as an energy substrate especially in immature animals.

  13. Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development.

    Science.gov (United States)

    de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Fernandes, Jansen; Peixinho-Pena, Luiz Fernando; Scorza, Fulvio Alexandre; Cavalheiro, Esper Abrão; Arida, Ricardo Mario

    2013-10-11

    It has been established that low intensities of exercise produce beneficial effects for the brain, while high intensities can cause some neuronal damage (e.g. exacerbated inflammatory response and cell death). Although these effects are documented in the mature brain, the influence of exercise intensities in the developing brain has been poorly explored. To investigate the impact of exercise intensity in developing rats, we evaluated the hippocampal level of brain derived neurotrophic factor (BDNF), inflammatory cytokines (TNFα, IL6 and IL10) and the occurrence of hippocampal cell degeneration and proliferation at different stages of postnatal brain development of rats submitted to two physical exercise intensities. To this point, male rats were divided into different age groups: P21, P31, P41 and P51. Each age group was submitted to two exercise intensities (low and high) on a treadmill over 10 consecutive days, except the control rats. We verified that the density of proliferating cells was significantly higher in the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30 compared with high-intensity exercise and control rats. A significant increase of proliferative cell density was found in rats submitted to high-intensity exercise from P31 to P40 when compared to low-intensity exercise and control rats. Elevated hippocampal levels of IL6 were detected in rats submitted to high-intensity exercise from P21 to P30 compared to control rats. From P41 to P50 period, higher levels of BDNF, TNFα and IL10 were found in the hippocampal formation of rats submitted to high-intensity exercise in relation to their control rats. Our data show that exercise-induced neuroplastic effects on BDNF levels and cellular proliferation in the hippocampal region are dependent on exercise intensity and developmental period. Thus, exercise intensity is an inflammation-inducing factor and exercise-induced inflammatory response during the postnatal brain development is

  14. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  15. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.

    Science.gov (United States)

    Smith, Catherine A; Holahan, Matthew R

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  16. Calsyntenin-1 regulates targeting of dendritic NMDA receptors and dendritic spine maturation in CA1 hippocampal pyramidal cells during postnatal development.

    Science.gov (United States)

    Ster, Jeanne; Steuble, Martin; Orlando, Clara; Diep, Tu-My; Akhmedov, Alexander; Raineteau, Olivier; Pernet, Vincent; Sonderegger, Peter; Gerber, Urs

    2014-06-25

    Calsyntenin-1 is a transmembrane cargo-docking protein important for kinesin-1-mediated fast transport of membrane-bound organelles that exhibits peak expression levels at postnatal day 7. However, its neuronal function during postnatal development remains unknown. We generated a knock-out mouse to characterize calsyntenin-1 function in juvenile mice. In the absence of calsyntenin-1, synaptic transmission was depressed. To address the mechanism, evoked EPSPs were analyzed revealing a greater proportion of synaptic GluN2B subunit-containing receptors typical for less mature synapses. This imbalance was due to a disruption in calsyntenin-1-mediated dendritic transport of NMDA receptor subunits. As a consequence of increased expression of GluN2B subunits, NMDA receptor-dependent LTP was enhanced at Schaffer collateral-CA1 pyramidal cell synapses. Interestingly, these defects were accompanied by a decrease in dendritic arborization and increased proportions of immature filopodia-like dendritic protrusions at the expense of thin-type dendritic spines in CA1 pyramidal cells. Thus, these results highlight a key role for calsyntenin-1 in the transport of NMDA receptors to synaptic targets, which is necessary for the maturation of neuronal circuits during early development.

  17. Transcriptome differentiation along the dorso-ventral axis in laser-captured microdissected rat hippocampal granular cell layer

    DEFF Research Database (Denmark)

    Christensen, T.; Bisgaard, C.F.; Nielsen, Henrik Bjørn

    2010-01-01

    -related behaviors. Based on such findings our aim was to investigate the molecular differentiation along the dorso-ventral axis of the hippocampal granular cell layer of the rat dentate gyrus. Homogeneous isolation of this specific area was performed by laser-capture microdissection and Illumina microarray chips...

  18. Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

    Science.gov (United States)

    Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

    2015-01-01

    Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

  19. The antidepressant tianeptine persistently modulates glutamate receptor currents of the hippocampal CA3 commissural associational synapse in chronically stressed rats

    NARCIS (Netherlands)

    Kole, MHP; Swan, L; Fuchs, E

    2002-01-01

    Recent hypotheses on the action of antidepressants imply a modulation of excitatory amino acid transmission. Here, the effects of long-term antidepressant application in rats with the drug tianeptine were examined at hippocampal CA3 commissural associational (c/a) glutamate receptor ion channels, em

  20. Nimodipine Prevents Early Loss of Hippocampal CA1 Parvalbumin Immunoreactivity After Focal Cerebral Ischemia in the Rat

    NARCIS (Netherlands)

    Benyó, Zoltán; de Jong, Giena; Luiten, Paul G.M.

    1995-01-01

    The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the l

  1. The Effects of a High-Energy Diet on Hippocampal Function and Blood-Brain Barrier Integrity in the Rat

    OpenAIRE

    Kanoski, Scott E.; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L.

    2010-01-01

    Cognitive impairment and Alzheimer’s Disease are linked with intake of a Western Diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selecti...

  2. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G;

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  3. Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

    Directory of Open Access Journals (Sweden)

    Guy eSandner

    2014-01-01

    Full Text Available Rats with a neonatal ventral hippocampal lesion (NVHL are used to model schizophrenia. They show enhanced locomotion and difficulties in learning after puberty. Such behavioural modifications are strengthened by dopaminergic psychostimulant drugs, which is also relevant for schizophrenia because illustrating its dopaminergic facet. But it remains questionable that only dopaminergic drugs elicit such effects. The behavioural effects could simply represent a non specific arousal, in which case NVHL rats should also be hyper-responsive to other vigilance enhancing drugs. We administered an adenosine (caffeine or an adrenaline receptor antagonist, (RX821002 at doses documented to modify alertness of rats, respectively 5 mg/Kg and 1 mg/Kg. Rats were selected prior to the experiments using MRI (magnetic resonance imaging. Each group contained typical and similar NVHL lesions. They were compared to sham lesioned rats. We evaluated locomotion in a new environment and the capacity to remember a visual or acoustic cue that announced the occurrence of food. Both Caffeine and RX82100 enhanced locomotion in the novel environment, particularly in NVHL rats. But, RX82100 had a biphasic effect on locomotion, consisting of an initial reduction preceding the enhancement. It was independent of the lesion. Caffeine did not modify the learning performance of NVHL rats. But, RX821002 was found to facilitate learning.Patients tend to intake much more caffeine than healthy people, which has been interpreted as a means to counter some cognitive deficits. This idea was not validated with the present results. But adrenergic drugs could be helpful for attenuating some of their cognitive deficits.

  4. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    Science.gov (United States)

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented

  5. Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo.

    Science.gov (United States)

    Viney, Tim J; Lasztoczi, Balint; Katona, Linda; Crump, Michael G; Tukker, John J; Klausberger, Thomas; Somogyi, Peter

    2013-12-01

    Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when pyramidal cells fire most. AACs fired strongly and rhythmically around the peak of theta oscillations, when pyramidal cells fire at low probability. Distinguishing AACs from other parvalbumin-expressing interneurons by their lack of detectable SATB1 transcription factor immunoreactivity, we discovered a somatic GABAergic input originating from the medial septum that preferentially targets AACs. We recorded septo-hippocampal GABAergic cells that were activated during hippocampal sharp waves and projected to CA3. We hypothesize that inhibition of AACs, and the resulting subcellular redistribution of inhibition from the axon initial segment to other pyramidal cell domains, is a necessary condition for the emergence of sharp waves promoting memory consolidation.

  6. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

    Science.gov (United States)

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  7. Short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents in pyramidal neurons of rat neocortex.

    Science.gov (United States)

    Sickmann, Thomas; Alzheimer, Christian

    2003-10-01

    Whole cell recordings from acutely isolated rat neocortical pyramidal cells were performed to study the kinetics and the mechanisms of short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents during prolonged application (5 min) of baclofen, adenosine, or serotonin. Most commonly, desensitization of GIRK currents was characterized by a biphasic time course with average time constants for fast and slow desensitization in the range of 8 and 120 s, respectively. The time constants were independent of the agonist used to evoke the current. The biphasic time course was preserved in perforated-patch recordings, indicating that neither component of desensitization is attributable to cell dialysis. Desensitization of GIRK currents displayed a strong heterologous component in that application of a second agonist substantially reduced the responsiveness to a test agonist. Fast desensitization, but not slow desensitization, was lost in cells loaded with GDP, suggesting that the hydrolysis cycle of G proteins might underlie the initial, rapid current decline. Hydrolysis of phosphatidylinositol biphosphate is an unlikely candidate underlying short-term desensitization, because both components of desensitization were preserved in the presence of the phospholipase C inhibitor U73122. We conclude that short-term desensitization does neither result from receptor downregulation nor from altered channel gating but might involve modifications of the G-protein-dependent pathway that serves to translate receptor activation into channel opening.

  8. A precision 3D conformal treatment technique in rats: application to whole brain radiotherapy with hippocampal avoidance.

    Science.gov (United States)

    Yoon, Suk W; Cramer, Christina K; Miles, Devin A; Reinsvold, Michael H; Joo, Kyeung M; Kirsch, David G; Oldham, Mark

    2017-08-24

    To develop and validate 3D conformal hippocampal sparing whole-brain radiation therapy (HA-WBRT) for Wistar rats utilizing precision 3D printed immobilization and micro-blocks. This technique paves the way for future pre-clinical studies investigating brain treatments that reduce neurotoxicity. A novel pre-clinical treatment planning and delivery process was developed to enable precision 3D conformal treatment and hippocampal avoidance capability for the Xrad 225cx small animal irradiator. A range of conformal avoidance plans were evaluated consisting of equi-angularly spaced co-planar axial beams, with plans containing 2, 4, 7, and 8 fields. The hippocampal sparing and coverage of these plans were investigated through Monte Carlo dose calculation (SmART-Plan Xrad 225cx planning system). Treatment delivery was implemented through a novel process where hippocampal block shapes were computer-generated from an MRI rat atlas which was registered to on-board cone-beam-CT of the rat in treatment position. The blocks were 3D-printed with a tungsten-doped filament at lateral resolution of 80μm. Precision immobilization was achieved utilizing a 3D-printed support system which enabled angled positioning of the rat head in supine position and bite-block to improve coverage of the central diencephalon. Treatment delivery was verified on rodent-morphic Presage(®) 3D dosimeters optically scanned at 0.2mm isotropic resolution. Biological verification of hippocampal avoidance was performed with immunohistologic staining. All simulated plans spared the hippocampus while delivering high dose to the brain (22.5-26.2Gy mean dose to brain at mean hippocampal dose of 7Gy). No significant improvement in hippocampal sparing was observed by adding beams beyond 4 fields. Dosimetric sparing of hippocampal region of the 4-field plan was verified with the Presage(®) dosimeter (mean dose = 9.6Gy, D100% = 7.1Gy). Simulation and dosimeter match at distance-to-agreement of 2mm and dose

  9. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  10. Changes in hippocampal histamine receptors in rats after treatment with Trimeresurus albolabris venom

    Institute of Scientific and Technical Information of China (English)

    Qiyi He; Min Deng; Xiaodong Yu; Hui Li; Yixin Lin; Xia Chen

    2008-01-01

    BACKGROUND:It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE:To investigate the expression levels of the histamine receptor gene and protein in the hippocampi of rats prior to and after administration of Trimeresurus albolabris venom using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot techniques.DESIGN,TIME AND SETTING:A controlled observation based on cellular protein level was performed in the College of Life Sciences,Chongqing Normal University between March 2005 and April 2007.MATERIALS:Eighty adult male Sprague-Dawley rats were provided bv the Laboratory AnimaI Center of the Third Military Medical University of Chinese PLA.Tlle lyophilized pewder of Trimeresurus albolabris venom was collected from Jin-Hu-Shan in Chongqing,China.METHODS:Twenty rats were randomly and evenly divided irite an experimental group and a control group.The experimental group was subcutaneously injected with 0.65 mg/mL Trimeresurus albolabris venom,0.5 mL for each rat.The centrel group was subcutaneously injected with an equal amount of 0.9% physiological saline.Prior to and after iniection,rats from these two groups were placed in the Morris Water Maze for recording of path length and escape latency.The remaining 60 rats were randomly allocated to another experimental group(n=50)and another control group(n=10).Rats were correspondingly injected as described above.At difierent time points(0.1,0.5,1,2,and 3 hours after injection),rats were decapitated and bilateral hippocampal tissues were dissociated(approximately 100 mg for each sample).Then,the acquired hippocampal tissue was immediately preserved at-70℃ for subsequent experiments.MAIN OUTCOME MEASURES:(1)The levels of histamine receptor(including H1R,H2R,and H3R)mRNA and protein in the hippocampi of rats were measured prior to and after injection of Trimeresurus albolabris venom using RT-PCR and Western Blot

  11. The intra-hippocampal leucine administration impairs memory consolidation and LTP generation in rats.

    Science.gov (United States)

    Glaser, Viviane; Carlini, Valeria P; Gabach, Laura; Ghersi, Marisa; de Barioglio, Susana Rubiales; Ramirez, Oscar A; Perez, Mariela F; Latini, Alexandra

    2010-10-01

    Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder, predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of individuals affected by this deficiency, the mechanisms underlying the neuropathology of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter, long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls) into the hippocampus immediately post-training in the behavioral task. Twenty-four hours after training in the step-down test, the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements. Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from leucine-administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious leucine effect on cognition.

  12. Effect of cardiac arrest on cognitive impairment and hippocampal plasticity in middle-aged rats.

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    Charles H Cohan

    Full Text Available Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1 establishing a model of CA in nine month old middle-aged rats; and 2 to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning and field recordings (long-term potentiation and paired-pulse facilitation were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction.

  13. Effects of social housing on hippocampal dendrites and behavior in ovariectomized rats.

    Science.gov (United States)

    Leedy, Gail M; Barrows, Lorraine F; Clark, Suzanne

    2013-03-01

    Social stress is both species and gender specific. For female rats, individual housing and social instability housing conditions are associated with behavioral indicators of stress and depression. The present study directly compared the effects of six weeks of individual housing, social instability and mixed sex, semi-crowded housing in a visible burrow system (VBS) on ovariectomized female rats. Paired, stable housing was used as the control. Behavioral tests were conducted two, four and six weeks into the housing manipulations and included sucrose consumption, social interest, and activity in the open field. Following a series of four behavioral tests, animals were sacrificed and brains were processed for Golgi impregnation. Basal dendrites of CA3 hippocampal neurons were measured. Results indicate that the individual housing and social instability groups were comparable to the control group for all measures. In contrast, the rats housed in the VBS exhibited reduced activity in open field testing, and alterations in social interest. Dendritic lengths were also reduced in those animals living in the VBS in comparison to the animals housed in pairs. To our knowledge, this is the first report of behavioral and neural effects of VBS housing on female rats. Further research is necessary to determine what facets of the VBS housing are responsible for the behavioral and neural changes. This article is part of a Special Issue entitled 'Animal Models'.

  14. Decoupling Actions from Consequences: Dorsal Hippocampal Lesions Facilitate Instrumental Performance, but Impair Behavioral Flexibility in Rats

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    Busse, Sebastian; Schwarting, Rainer K. W.

    2016-01-01

    The present study is part of a series of experiments, where we analyze why and how damage of the rat’s dorsal hippocampus (dHC) can enhance performance in a sequential reaction time task (SRTT). In this task, sequences of distinct visual stimulus presentations are food-rewarded in a fixed-ratio-13-schedule. Our previous study (Busse and Schwarting, 2016) had shown that rats with lesions of the dHC show substantially shorter session times and post-reinforcement pauses (PRPs) than controls, which allows for more practice when daily training is kept constant. Since sequential behavior is based on instrumental performance, a sequential benefit might be secondary to that. In order to test this hypothesis in the present study, we performed two experiments, where pseudorandom rather than sequential stimulus presentation was used in rats with excitotoxic dorsal hippocampal lesions. Again, we found enhanced performance in the lesion-group in terms of shorter session times and PRPs. During the sessions we found that the lesion-group spent less time with non-instrumental behavior (i.e., grooming, sniffing, and rearing) after prolonged instrumental training. Also, such rats showed moderate evidence for an extinction impairment under devalued food reward conditions and significant deficits in a response-outcome (R-O)-discrimination task in comparison to a control-group. These findings suggest that facilitatory effects on instrumental performance after dorsal hippocampal lesions may be primarily a result of complex behavioral changes, i.e., reductions of behavioral flexibility and/or alterations in motivation, which then result in enhanced instrumental learning. PMID:27375453

  15. Haloperidol-induced extra pyramidal symptoms attenuated by imipramine in rats.

    Science.gov (United States)

    Samad, Noreen; Haleem, Darakhshan Jabeen

    2014-09-01

    Effects of administration of imipramine (IMI) are determined on haloperidol-induced extrapyramidal symptoms (EPS). Haloperidol is administered orally at a dose of 0.2 mg/rat/day in rats for a period of 5 weeks, by this treatment rats developed vacuous chewing movements (VCMs) after 2 weeks, which increased in a time dependent manner as the treatment continued for 5 weeks. Motor coordination (assess on rota rod activity) impaired maximally after 3 weeks and tolerance was developed in the haloperidol induced motor impairment after 5 weeks of treatment. Motor activity in an open field or activity box was not altered. The administration of IMI (intraperitoneally, for 5 weeks) did not affect motor activity or motor coordination. Co-administration of IMI at a dose of 5 mg/ml/kg/day attenuated the induction of haloperidol elicited VCMs (Quantitative orofacial dyskinesia) as well impairment of motor coordination. Results are discussed in the context of the mechanism involved by which imipramine attenuated haloperidol-induced EPS.

  16. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

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    Rafael Rodríguez-Muñoz

    Full Text Available The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f, during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV. By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60% and multipolar Glutamatergic (≤40% neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC: dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively, in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  17. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

    Science.gov (United States)

    Rodríguez-Muñoz, Rafael; Cárdenas-Aguayo, María Del Carmen; Alemán, Víctor; Osorio, Beatriz; Chávez-González, Oscar; Rendon, Alvaro; Martínez-Rojas, Dalila; Meraz-Ríos, Marco Antonio

    2015-01-01

    The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f), during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV). By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60%) and multipolar Glutamatergic (≤40%) neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC): dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively), in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles) of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  18. 钾通道阻断剂4-氨基吡啶诱导海马CA1锥体神经元钙瞬变%Calcium transient of CA1 pyramidal neurons induced by potassium blocker 4-aminopyridine in acute hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    苏涛; 丛文东; 廖卫平

    2011-01-01

    Objective To investigate the calcium transient of CA1 pyramidal neurons induced by potassium blocker 4-aminopyridine (4-AP) in acute hippocampal slices to explore the relation between potassium channel function and calcium transient, and their mechanism. Methods Fluorescent probe was employed to mark the hippocampai neurons in acute brain slices of rats; confocal microscopy was used to perform calcium imaging to observe the influences of different concentrations of 4-AP and perfusate with/without calcium on calcium transient of CA1 pyramidal neurons. Results The response of [Ca2+]I to lower concentration of 4-AP (<15 mmol/L) was in a dose-dependent manner (r2=0.910, P=0.000); the higher the concentration of 4-AP (20-80 mmol/L), the lower the peak level of calcium transient. The latency and amplitude of calcium transient induced by 4-AP were obviously reduced when the extracellular condition was switched to an absence of calcium, which was significantly different as compared with that with calcium (P<0.05). Conclusion Blockade of potassium channels with 4-AP can increase [Ca2+]I in the hippocampal pyramidal neurons of acute slices. The increase of [Ca2+]1 to 4-AP could be ascribe to calcium release from intracellular stores and calcium influx from extracellular matrix.%目的 研究4-氨基吡啶(4-AP)诱导的急性脑片海马CA1锥体神经元钙瞬变现象,探讨钾通道功能与钙瞬变的关系及可能机制.方法 荧光探针标记正常大鼠急性脑片海马神经元.共聚焦显微镜技术进行钙成像,观察不同浓度4-AP及细胞灌流液条件对神经元钙瞬变的影响.结果 低浓度(<15 mmol/L)4-AP诱导的钙瞬变峰值与剂量呈线性相关(r2=0.910,P=0.000),高浓度(20~80 mmol/L)4-AP诱导的钙瞬变峰值随浓度增高而下降.在无钙灌流液条件下,4-AP诱导的钙瞬变峰值水平下降,达峰时间延长,与含钙灌流液比较差异有统计学意义(P<0.05).结论 4-AP可诱导急性脑片海马CA1锥体神经

  19. Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

    2009-01-01

    BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P<0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P<0.05). CONCLUSION: Superior cervical ganglionectomy

  20. Effects of estradiol on cognition and hippocampal pathology after lateral fluid percussion brain injury in female rats.

    Science.gov (United States)

    Lebesgue, Diane; LeBold, David G; Surles, Nathan O; Morales, Diego M; Etgen, Anne M; Zukin, R Suzanne; Saatman, Kathryn E

    2006-12-01

    Studies involving animal models of acute central nervous system (CNS) stroke and trauma strongly indicate that sex and/or hormonal status are important determinants of outcome after brain injury. The present study was undertaken to examine the ability of estradiol to protect hippocampal neurons from lateral fluid percussion brain injury. Sprague-Dawley female rats (211-285 g; n = 119) were ovariectomized, and a subset (n = 66) were implanted with 17beta-estradiol pellets to provide near physiological levels of estradiol. Animals were subjected to lateral fluid percussion brain injury or sham injury 1 week later. Activation of caspase-3 (n = 26) and TUNEL staining (n = 21) were assessed at 3 and 12 h after injury, respectively, in surviving control and estradiol-treated animals. Memory retention was examined using a Morris water maze test in a separate subset of animals (n = 43) at 8 days after injury. Activated caspase-3 and TUNEL staining were observed in the dentate hilus, granule cell layer, and CA3 regions in all injured rats, indicative of selective hippocampal cell apoptosis in the acute posttraumatic period. Estradiol did not significantly alter the number of hippocampal neurons exhibiting caspase-3 activity or TUNEL staining. Brain injury impaired cognitive ability, assessed at 1 week post-injury (p < 0.001). However, estradiol at physiological levels did not significantly alter injury-induced loss of memory. These data indicate that estradiol at physiological levels does not ameliorate trauma-induced hippocampal injury or cognitive deficits in ovariectomized female rats.

  1. [The effect of enzymatic treatment using proteases on properties of persistent sodium current in CA1 pyramidal neurons of rat hippocampus].

    Science.gov (United States)

    Lun'ko, O O; Isaiev, D S; Maxymiuk, O P; Kryshtal', O O; Isaieva, O V

    2014-01-01

    We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (I(NaP)) in hippocampal CA1 pyramidal neurons. Properties of I(NaP) were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We show that in neurons isolated with pronase E kinetic of activation and density of I(NaP) was unaltered. Enzymatic treatment with protease type XXIII did not alter I(NaP) activation but result in significant decrease in I(NaP) density. Our data indicates that enzymatic treatment using pronase E for neuron isolation is preferable for investigation of I(NaP).

  2. Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats

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    Jiro Kasahara

    2016-01-01

    Full Text Available Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine. The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.

  3. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

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    Tanara Vieira Peres

    2013-01-01

    Full Text Available The molecular mechanisms mediating manganese (Mn-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs and tyrosine hydroxylase (TH could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old. The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK 1/2, as well as c-Jun N-terminal kinase (JNK 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3 in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

  4. Circadian rhythm modulates long-term potentiation induced at CA1 in rat hippocampal slices.

    Science.gov (United States)

    Nakatsuka, Hiroki; Natsume, Kiyohisa

    2014-03-01

    Circadian rhythm affects neuronal plasticity. Consistent with this, some forms of synaptic long-term potentiation (LTP) are modulated by the light/dark cycle (LD cycle). For example, this type of modulation is observed in hippocampal slices. In rodents, which are nocturnal, LTP is usually facilitated in the dark phase, but the rat hippocampal CA1 is an exception. The reason why LTP in the dark phase is suppressed in CA1 remains unknown. Previously, LTP was induced with high-frequency stimulation. In this study, we found that in the dark phase, theta-burst stimulation-induced LTP is indeed facilitated in CA1, similar to other regions in the rodent brain. Population excitatory postsynaptic potentials (pEPSP)-LTP and population spikes (PS)-LTP were recorded at CA1. The magnitude of PS-LTP in dark-phase slices was significantly larger than in light-phase slices, while that of pEPSP-LTP was unchanged. Using antidromic-orthodromic stimulation, we found that recurrent inhibition is suppressed in the dark phase. Local gabazine-application to stratum pyramidale in light-phase slices mimicked this disinhibition and facilitated LTP in dark-phase slices. These results suggest that the disinhibition of a GABAA recurrent inhibitory network can be induced in the dark phase, thereby facilitating LTP.

  5. Input-to-output transformation in a model of the rat hippocampal CA1 network.

    Science.gov (United States)

    Olypher, Andrey V; Lytton, William W; Prinz, Astrid A

    2012-01-01

    Here we use computational modeling to gain new insights into the transformation of inputs in hippocampal field CA1. We considered input-output transformation in CA1 principal cells of the rat hippocampus, with activity synchronized by population gamma oscillations. Prior experiments have shown that such synchronization is especially strong for cells within one millimeter of each other. We therefore simulated a one-millimeter ıt patch of CA1 with 23,500 principal cells. We used morphologically and biophysically detailed neuronal models, each with more than 1000 compartments and thousands of synaptic inputs. Inputs came from binary patterns of spiking neurons from field CA3 and entorhinal cortex (EC). On average, each presynaptic pattern initiated action potentials in the same number of CA1 principal cells in the patch. We considered pairs of similar and pairs of distinct patterns. In all the cases CA1 strongly separated input patterns. However, CA1 cells were considerably more sensitive to small alterations in EC patterns compared to CA3 patterns. Our results can be used for comparison of input-to-output transformations in normal and pathological hippocampal networks.

  6. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

    Science.gov (United States)

    Peres, Tanara Vieira; Pedro, Daniela Zótico; de Cordova, Fabiano Mendes; Lopes, Mark William; Gonçalves, Filipe Marques; Mendes-de-Aguiar, Cláudia Beatriz Nedel; Walz, Roger; Farina, Marcelo; Aschner, Michael; Leal, Rodrigo Bainy

    2013-01-01

    The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old). The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM) caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain. PMID:24324973

  7. The Role of Monosialoganglioside GM1 in LTP-Induction in Rat Hippocampal Slices

    Institute of Scientific and Technical Information of China (English)

    李永新; 梅镇彤

    1994-01-01

    The effect of monosialoganglioside GM1 of different doses on the long-term potentiation (LTP) of synaptic transmission has been studied in the CA1 region of rat hippocampal slices, and the possible role that calcium ion and NMDA receptor play has also been investigated. The results reveal that larger magnitude of LTP is induced in hippocampal slices pre-incubated with GM1. The dose-response curve appears in diphase, and the largest magnitude of LTP has been obtained at the GM1 concentration of 50 mg/L in incubation ACSF. Moreover, the magnitude of LTP induced from the slices pre-incubated with GM1 at lower calcium ion concentration is similar to that obtained from the control slices at normal calcium ion concentration. Under higher calcium ion concentration, the enhancing effect of GM1 on LTP seems relatively feeble. After NMDA receptors were blocked, no enhancing effect of GM1 was observed. The mechanism of GM1 action on LTP is discussed.

  8. Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat Hippocampal CA1 Neurons

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    Wei Xie

    2013-01-01

    Full Text Available Saikosaponin a (SSa, a main constituent of the Chinese herb Bupleurum chinense DC., has been demonstrated to have antiepileptic activity. Recent studies have shown that SSa could inhibit NMDA receptor current and persistent sodium current. However, the effects of SSa on potassium (K+ currents remain unclear. In this study, we tested the effect of SSa on 4AP-induced epileptiform discharges and K+ currents in CA1 neurons of rat hippocampal slices. We found that SSa significantly inhibited epileptiform discharges frequency and duration in hippocampal CA1 neurons in the 4AP seizure model in a dose-dependent manner with an IC50 of 0.7 μM. SSa effectively increased the amplitude of ITotal and IA, significantly negative-shifted the activation curve, and positive-shifted steady-state curve of IA. However, SSa induced no significant changes in the amplitude and activation curve of IK. In addition, SSa significantly increased the amplitude of 4AP-sensitive K+ current, while there was no significant change in the amplitude of TEA-sensitive K+ current. Together, our data indicate that SSa inhibits epileptiform discharges induced by 4AP in a dose-dependent manner and that SSa exerts selectively enhancing effects on IA. These increases in IA may contribute to the anticonvulsant mechanisms of SSa.

  9. Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the freely moving rat.

    Science.gov (United States)

    Bland, Brian H; Bird, Jen; Jackson, Jesse; Natsume, Kiyohisa

    2006-01-01

    Rats implanted with hippocampal recording electrodes were tested in a wheel-running apparatus under three conditions: (1) independent electrical stimulation of the medial septal nucleus (MS); (2) independent electrical stimulation of the posterior hypothalamic nucleus (PH); and (3) combined electrical stimulation of the MS and PH using pairings of two stimulation conditions, 7 or 10 Hz stimulation of the MS, and a low- or high-intensity PH stimulation. Quantitative measures of running speed were taken, and hippocampal recordings were subjected to fast-Fourier transform analysis. Electrical stimulation of the PH induced wheel-running behavior; running speed and the accompanying hippocampus (HPC) theta frequency increased with increase in stimulation intensity. Electrical stimulation of the MS failed to induce wheel-running behavior despite the fact that HPC theta was induced at the frequency of the applied stimulation (7 and 10 Hz). Electrical stimulation of the MS reset the frequency of HPC theta induced by PH stimulation in both the upward and downward directions and increased theta power, while wheel-running speed was modulated in a downward direction only.

  10. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats.

    Science.gov (United States)

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2014-06-01

    Astrocytes are responsible for modulating neurotransmitter systems and synaptic information processing, ionic homeostasis, energy metabolism, maintenance of the blood-brain barrier, and antioxidant and inflammatory responses. Our group recently published a culture model of cortical astrocytes obtained from adult Wistar rats. In this study, we established an in vitro model for hippocampal astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats. Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and neuroprotective effects that modulate glial functions. Here, we evaluated the effects of resveratrol on GSH content, GS activity, TNF-α and IL-1β levels in hippocampal astrocytes from newborn, adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an increase in the inflammatory response in hippocampal astrocytes from adult and aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol prevented these effects. These findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with antioxidant and anti-inflammatory activities.

  11. An examination of early neural and cognitive alterations in hippocampal-spatial function of ghrelin receptor-deficient rats.

    Science.gov (United States)

    Cahill, Shaina P; Hatchard, Taylor; Abizaid, Alfonso; Holahan, Matthew R

    2014-05-01

    Ghrelin, a hormone implicated in the regulation of feeding and energy balance, has also been associated with neural function underlying learning and memory. These effects are thought to be mediated by ghrelin targeting receptors at extra hypothalamic sites such as the hippocampus. Exogenous ghrelin administration increases dendritic spine density in the hippocampal CA1 region and neurogenesis in the dentate gyrus (DG), while improving memory in rats. In the present study, we sought to determine whether rats lacking the ghrelin receptor would show early neural or cognitive decline measured via hippocampal integrity (spine density and neurogenesis) and spatial learning and memory. As such, we used young and middle-aged adult rats with mutations to the gene encoding for the ghrelin receptor (GHS-R KO) and wildtype (WT) littermates to determine differences in performance on hippocampal-dependent tasks (the water maze and radial arm maze). In addition, we examined the hippocampal dentate gyrus of these rats for differences in dendritic spine density and cell proliferation (doublecortin). Overall, results demonstrated that spine density and doublecortin staining in the dentate gyrus of the young GHS-R KO group was similar to that seen in middle-aged groups (both KO and WT) and lower than the young WT group. Middle-aged GHS-R KO and WT groups showed deficits on the radial arm maze food-motivated task but not the water maze task. These data suggest that impaired ghrelin signaling leads to an early onset decrement in hippocampal structural integrity that may manifest in non- spatial-related behavioral deficits.

  12. Effect of Fluoxetine on Neurogenesis in Hippocampal Dentate Gyrus after Global Transient Cerebral Ischemia in Rats.

    Science.gov (United States)

    Khodanovich, M Yu; Kisel', A A; Chernysheva, G A; Smol'yakova, V I; Savchenko, R R; Plotnikov, M B

    2016-07-01

    Changes in cerebral neurogenesis provoked by ischemia and the effect of fluoxetine on this process were studied using a three-vessel occlusion model of global transient cerebral ischemia. The global transient cerebral ischemia was modeled on male Wistar rats by transient occlusion of three major vessels originating from the aortic arch and supplying the brain (brachiocephalic trunk, left subclavian artery, and left common carotid artery). The cells expressing doublecortin (DCX, a marker of young neurons) were counted in the hippocampal dentate gyrus on day 31 after ischemia modeling. It was found that ischemia inhibited neurogenesis in the dentate gyrus in comparison with sham-operated controls (p<0.05), while fluoxetine (20 mg/kg/day) injected over 10 days after surgery restored neurogenesis to the control level (p<0.001).

  13. APPswe mutation increases the frequency of spontaneous Ca2+-oscillations in rat hippocampal neurons

    DEFF Research Database (Denmark)

    Kloskowska, Ewa; Malkiewicz, Katarzyna; Winblad, Bengt;

    2008-01-01

    Altered calcium homeostasis is implicated in the pathogenesis of Alzheimer's disease (AD). Much effort has been put into understanding the association between protein mutations causative of this devastating neurodegenerative disease and perturbed calcium signaling. Whereas the presenilin mutations...... have received most attention in the context of neuronal calcium signaling, we focused on the effects of APP with the so-called Swedish mutation (APPswe) on spontaneous neuronal activity. We observed that primary hippocampal neurons from an APPswe transgenic rat showed increased frequency and unaltered...... amplitude of spontaneous calcium oscillations as compared to wild-type neurons. We found that the altered calcium signaling of APPswe transgenic neurons was unlikely to be due to modulation of the NMDA or nicotinic neurotransmitter systems, and did not depend on secreted APP derivates. The implications...

  14. Effects of calcium channel on 3-morpholinosydnonimine-induced rat hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Quanzhong Chang; Shuling Zhang; Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Shining Cai

    2011-01-01

    Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus.The present study investigated the effects of the broad-spectrum calcium channel blocker CdC12 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis.The chloride channel blockers 4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulfonic acid (SITS) or 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) increased the survival rate of 3-morpholinosydnonimine (SIN-1)-treated neurons and suppressed SIN-1-induced neuronal apoptosis.The calcium channel blocker CdC12 did not increase the survival rate of neurons and did not affect SIN-1-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis.Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.

  15. Effect of Brain-Derived Neurotrophic Factor Haploinsufficiency on Stress-Induced Remodeling of Hippocampal Neurons

    OpenAIRE

    Magariños, A.M.; Li, C. J.; Toth, J. Gal; Bath, K.G.; Jing, D; Lee, F S; MCEWEN, B. S.

    2011-01-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the ...

  16. Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area

    OpenAIRE

    Lasztóczi, Bálint; Tukker, John J.; Somogyi, Peter; Klausberger, Thomas

    2011-01-01

    Hippocampal oscillations reflect coordinated neuronal activity on many timescales. Distinct types of GABAergic interneuron participate in the coordination of pyramidal cells over different oscillatory cycle phases. In the CA3 area, which generates sharp waves and gamma oscillations, the contribution of identified GABAergic neurons remains to be defined. We have examined the firing of a family of cholecystokinin-expressing interneurons during network oscillations in urethane-anesthetized rats ...

  17. Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.

    Science.gov (United States)

    McCormick, Cheryl M; Thomas, Catherine M; Sheridan, Cheryl S; Nixon, Feather; Flynn, Jennifer A; Mathews, Iva Z

    2012-06-01

    The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

  18. Diet-dependent modulation of hippocampal expression of endocannabinoid signaling-related proteins in cannabinoid antagonist-treated obese rats.

    Science.gov (United States)

    Rivera, Patricia; Luque-Rojas, María Jesús; Pastor, Antoni; Blanco, Eduardo; Pavón, Francisco J; Serrano, Antonia; Crespillo, Ana; Vida, Margarita; Grondona, Jesús M; Cifuentes, Manuel; Bermúdez-Silva, Francisco J; de la Torre, Rafael; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2013-01-01

    Diet-induced obesity produces changes in endocannabinoid signaling (ECS), influencing the regulation of energy homeostasis. Recently, we demonstrated that, in high-fat-diet-fed rats, blockade of CB1 receptor by AM251 not only reduced body weight but also increased adult neurogenesis in the hippocampus, suggesting an influence of diet on hippocampal cannabinoid function. To further explore the role of hippocampal ECS in high-fat-diet-induced obesity, we investigated whether the immunohistochemical expression of the enzymes that produce (diacylglycerol lipase alpha and N-acyl phosphatidylethanolamine phospholipase D) and degrade (monoacylglycerol lipase and fatty acid amino hydrolase) endocannabinoids may be altered in the hippocampus of AM251 (3 mg/kg)-treated rats fed three different diets: standard diet (normal chow), high-carbohydrate diet (70% carbohydrate) and high-fat diet (60% fat). Results indicated that AM251 reduced caloric intake and body weight gain, and induced a modulation of the expression of ECS-related proteins in the hippocampus of animals exposed to hypercaloric diets. These effects were differentially restricted to either the 2-arachinodoyl glycerol or anandamide signaling pathways, in a diet-dependent manner. AM251-treated rats fed the high-carbohydrate diet showed a reduction of the diacylglycerol lipase alpha : monoacylglycerol lipase ratio, whereas AM251-treated rats fed the high-fat diet showed a decrease of the N-acyl phosphatidylethanolamine phospholipase D : fatty acid amino hydrolase ratio. These results are consistent with the reduced levels of hippocampal endocannabinoids found after food restriction. Regarding the CB1 expression, AM251 induced specific changes focused in the CA1 stratum pyramidale of high-fat-diet-fed rats. These findings indicated that the cannabinoid antagonist AM251 modulates ECS-related proteins in the rat hippocampus in a diet-specific manner. Overall, these results suggest that the hippocampal ECS participates

  19. GABA B receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons.

    Science.gov (United States)

    Lei, Saobo; McBain, Chris J

    2003-01-15

    Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABA(B) receptor-mediated responses at both synapse types. Postsynaptic GABA(B) receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (> or =P30) suggesting developmental regulation. In young animals, the GABA(B) receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd(2+), implicating presynaptic voltage-gated Ca(2+) channels as a target for baclofen modulation. In contrast, although Cd(2+) prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca(2+) channels contributed equally to GABA(B) receptor-mediated inhibition of EPSCs, more P/Q-type Ca(2+) channels were involved in GABA(B) receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABA(B) receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types.

  20. Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats.

    Science.gov (United States)

    Amano, K; Takamatu, J; Kaneyama, H; Miyazaki, C; Deshimaru, M; Sumiyoshi, S; Ogata, A; Miyakawa, T

    1998-08-01

    We examined the anticonvulsant properties of dipotassium clorazepate (DC) against hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to kindling 1 week after the implantation of electrodes. After five stage 5 seizures were induced, the generalized convulsion triggering threshold (GST) was determined. Dipotassium clorazepate was administered intraperitoneally in rats that showed two stable stage 5 seizures induced at the GST current intensity. Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did not completely suppress after-discharges (AD) even at the highest dose, which was 5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an anticonvulsant. The results of the present study suggest that DC has a modest anticonvulsant potency. It is reasonable to assume that its anticonvulsant efficacy is primarily due to attenuation of AD propagation rather than the raising of the seizure triggering threshold at the kindling focus.

  1. Alterations of hippocampal place cells in foraging rats facing a "predatory" threat.

    Science.gov (United States)

    Kim, Eun Joo; Park, Mijeong; Kong, Mi-Seon; Park, Sang Geon; Cho, Jeiwon; Kim, Jeansok J

    2015-05-18

    Fear is an adaptive mechanism evolved to influence the primal decisions of foragers in "approach resource-avoid predator" conflicts. To survive and reproduce, animals must attain the basic needs (food, water, shelter, and mate) while avoiding the ultimate cost of predation. Consistent with this view, ecological studies have found that predatory threats cause animals to limit foraging to fewer places in their habitat and/or to restricted times. However, the neurophysiological basis through which animals alter their foraging boundaries when confronted with danger remains largely unknown. Here, we investigated place cells in the hippocampus, implicated in processing spatial information and memory, in male Long-Evans rats foraging for food under risky situations that would be common in nature. Specifically, place cells from dorsal cornu ammonis field 1 (CA1) were recorded while rats searched for food in a semi-naturalistic apparatus (consisting of a nest and a relatively large open area) before, during, and after encountering a "predatory" robot situated remotely from the nest. The looming robot induced remapping of place fields and increased the theta rhythm as the animals advanced toward the vicinity of threat, but not when they were around the safety of the nest. These neurophysiological effects on the hippocampus were prevented by lesioning of the amygdala. Based on these findings, we suggest that the amygdalar signaling of fear influences the stability of hippocampal place cells as a function of threat distance in rats foraging for food.

  2. Chronic nicotine improves working and reference memory performance and reduces hippocampal NGF in aged female rats.

    Science.gov (United States)

    French, Kristen L; Granholm, Ann-Charlotte E; Moore, Alfred B; Nelson, Matthew E; Bimonte-Nelson, Heather A

    2006-05-15

    The cholinergic system is involved in cognition and several forms of dementia, including Alzheimer's disease, and nicotine administration has been shown to improve cognitive performance in both humans and rodents. While experiments with humans have shown that nicotine improves the ability to handle an increasing working memory load, little work has been done in animal models evaluating nicotine effects on performance as working memory load increases. In this report, we demonstrate that in aged rats nicotine improved the ability to handle an increasing working memory load as well as enhanced performance on the reference memory component of the water radial arm maze task. The dose required to exert these effects (0.3mg/kg/day) was much lower than doses shown to be effective in young rats and appears to be a lower maintenance dose than is seen in light to moderate smokers. In addition, our study reports a nicotine-induced reduction in nerve growth factor (NGF) protein levels in the hippocampus of the aged rat. The effects of nicotine on hippocampal NGF levels are discussed as a potential mechanism of nicotine-induced improvements in working and reference memory.

  3. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Rats.

    Science.gov (United States)

    Smith, Catherine A; Farmer, Kyle; Lee, Hyunmin; Holahan, Matthew R; Smith, Jeffrey C

    2015-10-27

    Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  4. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl Phthalate in Rats

    Directory of Open Access Journals (Sweden)

    Catherine A. Smith

    2015-10-01

    Full Text Available Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl phthalate (DEHP disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  5. Methamphetamine modulates glutamatergic synaptic transmission in rat primary cultured hippocampal neurons.

    Science.gov (United States)

    Zhang, Shuzhuo; Jin, Yuelei; Liu, Xiaoyan; Yang, Lujia; Ge, Zhi juan; Wang, Hui; Li, Jin; Zheng, Jianquan

    2014-09-25

    Methamphetamine (METH) is a psychostimulant drug. Abuse of METH produces long-term behavioral changes including behavioral, sensitization, tolerance, and dependence. It induces neurotoxic effects in several areas of the brain via enhancing dopamine (DA) level abnormally, which may cause a secondary release of glutamate (GLU). However, repeated administration of METH still increases release of GLU even when dopamine content in tissue is significantly depleted. It implies that some other mechanisms are likely to involve in METH-induced GLU release. The goal of this study was to observe METH affected glutamatergic synaptic transmission in rat primary cultured hippocampal neurons and to explore the mechanism of METH modulated GLU release. Using whole-cell patch-clamp recordings, we found that METH (0.1-50.0μM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs). However, METH decreased the frequency of sEPSCs and mEPSCs at high concentration of 100μM. The postsynaptic NMDA receptor currents and P/Q-type calcium channel were not affected by the use of METH (10,100μM). METH did not present visible effect on N-type Ca(2+) channel current at the concentration lower than 50.0μM, but it was inhibited by use of METH at a 100μM. The effect of METH on glutamatergic synaptic transmission was not revered by pretreated with DA receptor antagonist SCH23390. These results suggest that METH directly modulated presynaptic GLU release at a different concentration, while dopaminergic system was not involved in METH modulated release of GLU in rat primary cultured hippocampal neurons.

  6. Recovery of network-driven glutamatergic activity in rat hippocampal neurons during chronic glutamate receptor blockade.

    Science.gov (United States)

    Leininger, Eric; Belousov, Andrei B

    2009-01-28

    Previous studies indicated that a long-term decrease in the activity of ionotropic glutamate receptors induces cholinergic activity in rat and mouse hypothalamic neuronal cultures. Here we studied whether a prolonged inactivation of ionotropic glutamate receptors also induces cholinergic activity in hippocampal neurons. Receptor activity was chronically suppressed in rat hippocampal primary neuronal cultures with two proportionally increasing sets of concentrations of NMDA plus non-NMDA receptor antagonists: 100 microM/10 microM AP5/CNQX (1X cultures) and 200 microM/20 microM AP5/CNQX (2X cultures). Using calcium imaging we demonstrate that cholinergic activity does not develop in these cultures. Instead, network-driven glutamate-dependent activity, that normally is detected in hyper-excitable conditions, reappears in each culture group in the presence of these antagonists and can be reversibly suppressed by higher concentrations of AP5/CNQX. This activity is mediated by non-NMDA receptors and is modulated by NMDA receptors. Further, non-NMDA receptors, the general level of glutamate receptor activity and CaMK-dependent signaling are critical for development of this network-driven glutamatergic activity in the presence of receptor antagonists. Using electrophysiology, western blotting and calcium imaging we show that some neuronal parameters are either reduced or not affected by chronic glutamate receptor blockade. However, other parameters (including neuronal excitability, mEPSC frequency, and expression of GluR1, NR1 and betaCaMKII) become up-regulated and, in some cases, proportionally between the non-treated, 1X and 2X cultures. Our data suggest recovery of the network-driven glutamatergic activity after chronic glutamate receptor blockade. This recovery may represent a form of neuronal plasticity that compensates for the prolonged suppression of the activity of glutamate receptors.

  7. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.

    Science.gov (United States)

    Mano, Yukio; Kotani, Tomomi; Ito, Mikako; Nagai, Taku; Ichinohashi, Yuko; Yamada, Kiyofumi; Ohno, Kinji; Kikkawa, Fumitaka; Toyokuni, Shinya

    2014-04-01

    Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2׳-deoxyguanosine- and 4-hydroxy-2-nonenal-modified proteins. Both oxidative stress markers were significantly increased in the IR group, which was again ameliorated by the H2 intake. Last, 8-week-old rats were subjected to a Morris water maze test. Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inorganic lead may inhibit neurite development in cultured rat hippocampal neurons through hyperphosphorylation.

    Science.gov (United States)

    Kern, M; Audesirk, G

    1995-09-01

    Inorganic lead inhibits neurite initiation in cultured rat hippocampal neurons at concentrations as low as 100 nM. Conflicting reports suggest that Pb2+ may stimulate or inhibit protein kinase C, adenylyl cyclase, phosphodiesterase, and calmodulin, or increase intracellular free Ca2+ concentrations. Therefore, Pb2+ may alter the activities of Ca2+/calmodulin-dependent protein kinase (CaM kinase) or protein kinases C or A. We cultured rat hippocampal neurons in 100 nM PbCI2 alone or in combination with kinase or calmodulin inhibitors. Inhibiting protein kinase C with calphostin C exacerbated the inhibition of neurite initiation caused by PbCI2, but inhibiting protein kinase A with KT5720, CaM kinase with KN62, or calmodulin with calmidazolium completely reversed the effects of PbCI2. These results indicate that Pb2+ may inhibit neurite initiation by inappropriately stimulating protein phosphorylation by CaM kinase or cyclic AMP-dependent protein kinase (PKA), possibly by stimulating calmodulin. This hypothesis is supported by findings that other treatments that should increase protein phosphorylation (okadaic acid, a protein phosphatase inhibitor, and Sp-cAMPS, a PKA activator) also reduced neurite initiation. Whole-cell intracellular free Ca2+ ion concentrations were not significantly altered by 100 nM PbCI2 at 4, 12, 24, or 48 hr. Therefore, the hypothesized stimulatory effects of Pb2+ exposure on calmodulin, CaM kinase, or PKA are probably not caused by increases in whole-cell intracellular free Ca2+, but may be attributable either to intracellular Pb2+ or to localized increases in [Ca2+]in that are not reflected in whole-cell measurements.

  9. Prenatal protein malnutrition alters the proportion but not numbers of parvalbumin-immunoreactive interneurons in the hippocampus of the adult Sprague-Dawley rat

    OpenAIRE

    Lister, James P.; Blatt, Gene J.; Kemper, Thomas L.; Tonkiss, John; DeBassio, William A; GALLER, JANINA R.; Rosene, Douglas L.

    2011-01-01

    Prenatal protein malnutrition alters the structure and function of the adult rat hippocampal formation. The current study examines the effect of prenatal protein malnutrition on numbers of parvalbumin-immunoreactive (PV-IR) GABAergic interneurons, which are important for perisomatic inhibition of hippocampal pyramidal neurons. Brain sections from prenatally protein malnourished and normally nourished rats were stained for parvalbumin and PV-IR neurons were quantified using s...

  10. Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus.

    Science.gov (United States)

    Martina, M; Schultz, J H; Ehmke, H; Monyer, H; Jonas, P

    1998-10-15

    We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.

  11. Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

    Science.gov (United States)

    Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Wei, Yuling; Ji, Chaonan; Yang, Junqing

    2016-01-01

    Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dose-dependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients. PMID:27033056

  12. Neural stem cell activation and glial proliferation in the hippocampal CA3 region of posttraumatic epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Yuanxiang Lin; Kun Lin; Dezhi Kang; Feng Wang

    2011-01-01

    The present study observed the dynamic expression of CD133, nuclear factor-κB and glial fibrillary acidic protein in the hippocampal CA3 area of the experimental posttraumatic epilepsy rats to investigate whether gliosis occurs after posttraumatic epilepsy. CD133 and nuclear factor-κB expression was increased at 1 day after posttraumatic epilepsy, peaked at 7 days, and gradually decreased up to 14 days, as seen by double-immunohistochemical staining. Glial fibrillary acidic protein/nuclear factor-κB double-labeled cells increased with time and peaked at 14 days after posttraumatic epilepsy. Results show that activation of hippocampal neural stem cells and glial proliferation after posttraumatic epilepsy-induced oxidative stress increases hippocampal glial cell density.

  13. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  14. Hippocampal formation

    NARCIS (Netherlands)

    Cappaert, N.L.M.; van Strien, N.M.; Witter, M.P.; Paxinos, G.

    2015-01-01

    The hippocampal formation and parahippocampal region are prominent components of the rat nervous system and play a crucial role in learning, memory, and spatial navigation. Many new details regarding the entorhinal cortex have been discovered since the previous edition, and the growing interest in t

  15. Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

    Institute of Scientific and Technical Information of China (English)

    Hai-ju ZHANG; Ruo-peng SUN; Ge-fei LEI; Lu YANG; Chun-xi LIU

    2008-01-01

    Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods:Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis wore analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABAA) receptors and mitogen-activated protein kinase/extracellular sig-nal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesuifonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

  16. Inhibition of GABA release by presynaptic ionotropic GABA receptors in hippocampal CA3.

    Science.gov (United States)

    Axmacher, Nikolai; Draguhn, Andreas

    2004-02-09

    Vesicular transmitter release can be regulated by transmitter-gated ion channels at presynaptic axon terminals. The central inhibitory transmitter GABA acts on such presynaptic ionotropic receptors in various cells, including inhibitory interneurons. Here we report that GABA-mediated postsynaptic inhibitory currents in CA3 pyramidal cells of rat hippocampal slices are suppressed by agonists of GABAA receptors. The effect is present for both stimulus-induced and miniature IPSCs, indicating a reduction in the probability of vesicular release by presynaptic, action-potential-independent mechanisms. We conclude that the release of GABA from hippocampal CA3 interneurons is regulated by a negative feedback via presynaptic ionotropic GABA autoreceptors.

  17. Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor.

    Science.gov (United States)

    Scharfman, Helen E; Mercurio, Thomas C; Goodman, Jeffrey H; Wilson, Marlene A; MacLusky, Neil J

    2003-12-17

    To test the hypothesis that induction of BDNF may contribute to changes in hippocampal excitability occurring during the female reproductive cycle, we examined the distribution of BDNF immunoreactivity and changes in CA1 and CA3 electrophysiology across the estrous cycle in rats. Hippocampal BDNF immunoreactivity increased on the day of proestrus as well as on the following morning (estrus), relative to metestrus or ovariectomized animals. Changes in immunoreactivity were clearest in mossy fiber axons of dentate gyrus granule cells, which contain the highest concentration of BDNF. Increased immunoreactivity was also apparent in the neuropil-containing dendrites of CA1 and CA3 neurons. Electrophysiological recordings in hippocampal slices showed robust cycle-dependent differences. Evoked responses of CA1 neurons to Schaffer collateral stimulation changed over the cycle, with larger maximum responses at both proestrus and estrus relative to metestrus. In area CA3, repetitive hilar stimuli frequently evoked multiple population spikes at proestrus and estrus but only rarely at other cycle stages, and never in slices of ovariectomized rats. Hyperexcitability in area CA3 at proestrus was blocked by exposure to the high-affinity neurotrophin receptor antagonist K252a, or an antagonist of the alpha7 nicotinic cholinergic receptor, whereas it was induced at metestrus by the addition of BDNF to hippocampal slices. These studies suggest that hippocampal BDNF levels change across the estrous cycle, accompanied by neurophysiological responses that resemble the effects of BDNF treatment. An estrogen-induced interaction of BDNF and alpha7 nicotinic receptors on mossy fibers seems responsible for estrous cycle changes in area CA3. Periovulatory changes in hippocampal function may, thus, involve estrogen-induced increases in BDNF expression.

  18. Reactive changes in astrocytes, and delayed neuronal death, in the rat hippocampal CA1 region following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Xiang Luo; Zhiyuan Yu; Chao Ma; Shabei Xu; Wei Wang

    2009-01-01

    BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion. OBJECTIVE: To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion. DESIGN, TIME AND SETTING: The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007. MATERIALS: Rabbit anti-glial fibrillary acidic protein (GFAP) (Neomarkers, USA), goat anti-rabbit IgG (Sigma, USA) and ApoAlert apoptosis detection kit (Biosciences Clontech, USA) were used in this study. METHODS: A total of 42 healthy adult male Wistar rats, aged 3-5 months, were randomly divided into a sham operation group (n = 6) and a cerebral ischemia/reperfusion group (n = 36). In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death (+) subgroup and a delayed neuronal death (-) subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia. MAIN OUTCOME MEASURES: Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL. RESULTS: After 3 days of ischemia

  19. Influence of environmental enrichment on hippocampal synapses in adolescent offspring of mothers exposed to prenatal stress

    Institute of Scientific and Technical Information of China (English)

    Yaojin Peng; Xiaohong Jian; Lihua Liu; Jianbin Tong; Deliang Lei

    2011-01-01

    Environmental enrichment attenuates hippocampal synaptic injury induced by prenatal stress in offspring.However, the influence of hippocampal synaptic changes and regional differences in prenatal stress remains poorly understood.The present study induced stress in Sprague Dawley rats, which were at gestational age 13 19 days.Following weaning, the offspring were raised in an enriched environment to establish models of stress+enriched environment.Dendritic spine density and synaptophysin expression were detected in hippocampal neurons using Golgi staining and western blot analysis, respectively.Results showed that enriched environment increased dendritic spine density of apical dendrites in CA1 pyramidal cells and basal dendrites of granular cells in the outer layer of the dentate gyrus.In addition, hippocampal synaptophysin expression increased and the effects of prenatal stress on neuronal dendritic spines were reversed in adolescence.

  20. Repeated Acute Oral Exposure to Cannabis sativa Impaired Neurocognitive Behaviours and Cortico-hippocampal Architectonics in Wistar Rats.

    Science.gov (United States)

    Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A

    2017-03-06

    The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive.  The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.

  1. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

    OpenAIRE

    Zhang, Huaqiu; Xie, Minjie; Gary P. Schools; Feustel, Paul F.; Wang, Wei; Lei, Ting; Kimelberg, Harold K.; Zhou, Min

    2008-01-01

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membr...

  2. The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition.

    Science.gov (United States)

    Gong, Neng; Zhang, Min; Zhang, Xiao-Bing; Chen, Lin; Sun, Guang-Chun; Xu, Tian-Le

    2008-02-01

    Salicylate is the major metabolite and active component of aspirin (acetylsalicylic acid), which is widely used in clinical medicine for treating inflammation, pain syndromes and cardiovascular disorders. The well-known mechanism underlying salicylate's action mainly involves the inhibition of cyclooxygenase and subsequent decrease in prostaglandin production. Recent evidence suggests that salicylate also affects neuronal function through interaction with specific membrane channels/receptors. However, the effect of salicylate on synaptic and neural network function remains largely unknown. In this study, we investigated the effect of sodium salicylate on the synaptic transmission and neuronal excitation in the hippocampal CA1 area of rats, a key structure for many complex brain functions. With electrophysiological recordings in hippocampal slices, we found that sodium salicylate significantly enhanced neuronal excitation through reducing inhibitory GABAergic transmission without affecting the basal excitatory synaptic transmission. Salicylate significantly inhibited the amplitudes of both evoked and miniature inhibitory postsynaptic currents, and directly reduced gamma-aminobutyric acid type A (GABA(A)) receptor-mediated responses in cultured rat hippocampal neurons. Together, our results suggest that the widely used aspirin might impair hippocampal synaptic and neural network functions through its actions on GABAergic neurotransmission. Given the capability of aspirin to penetrate the blood-brain barrier, the present data imply that aspirin intake may cause network hyperactivity and be potentially harmful in susceptible subpopulations.

  3. Hippocampal sharp waves: their origin and significance.

    Science.gov (United States)

    Buzsáki, G

    1986-11-29

    This study investigated the spatial distribution and cellular-synaptic generation of hippocampal sharp waves (SPW) in the dorsal hippocampus of the awake rat. Depth analyses of SPWs were performed by stepping the recording electrode in 82.5 microns increments. SPWs were present during slow wave sleep, awake immobility, drinking, grooming and eating (0.01-2/s). The largest negative SPWs were recorded from the middle part of the stratum radiatum of CA1, the stratum lucidum of CA3, the inner molecular layer of the dentate gyrus and from layer I of the subiculum, in that order. The polarity of the SPWs was positive in layers II-IV of the subiculum, in stratum oriens and stratum pyramidale of CA1 and CA3, and in the hilus of the dentate gyrus. The electrical gradients across the null zones of the field SPWs were as large as 8-14 mV/mm. SPWs were associated with population bursts of pyramidal cells and increased discharges of interneurons and granule cells. During the SPW the excitability of granule cells and pyramidal cells to afferent volleys increased considerably. Picrotoxin and atropine and aspiration lesion of the fimbria-fornix increased either the amplitude or the frequency of SPWs. Diazepam and Nembutal could completely abolish SPWs. It is suggested that: hippocampal SPWs are triggered by a population burst of CA3 pyramidal cells as a result of temporary disinhibition from afferent control; and field SPWs represent summed extracellular PSPs of CA1 and subicular pyramidal cells, and dentate granular cells induced by the Schaffer collaterals and the associational fibers of hilar cells, respectively. The relevance of the physiological SPWs to epileptic interictal spikes and long-term potentiation is discussed.

  4. [Effect of Qidan Granule on PMC Derived Peptide Content and Structure of Hippocampal CA1 Region in Microwave Radiated Rats].

    Science.gov (United States)

    Guan, Lan-fang; Li, Ya-wei; Xu, Jun-jie; Zhong, Xiu-hong; Zhang, Hong; Zhu, Wen-he; Lv, Shi-jie

    2016-04-01

    To explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats. Totally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope. Compared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.

  5. Hippocampal cell loss and propagation of abnormal discharges accompanied with the expression of tonic convulsion in the spontaneously epileptic rat.

    Science.gov (United States)

    Hanaya, Ryosuke; Sasa, Masashi; Sugata, Sei; Tokudome, Mai; Serikawa, Tadao; Kurisu, Kaoru; Arita, Kazunori

    2010-04-30

    Spontaneously epileptic rats (SER) are double mutants with both tonic convulsion and absence-like seizures from the age of 8 weeks. Hippocampal CA3 neurons in SER display a long-lasting depolarizing shift accompanied by repetitive firing (attributed to abnormalities of the Ca(2+) channels) with a single stimulation of the mossy fibers. In the present investigation, we examined if the seizure discharges of SER were correlated with the hippocampal abnormality of SER using electrophysiological and histological methods. In CA1 neurons of seizure-susceptible mature SER, higher-voltage (<8-11 V) stimulations induced a long depolarization shift (in 25% of neurons) with repetitive firing (in 12.5% of neurons). However, the tremor rat, one of the parent strains of SER, did not exhibit such abnormal firing in the CA3 region of the hippocampus. The number of CA3 neurons in SER was significantly (p<0.01) lower than that in tremor rats and Wistar rats, although no significant difference was established in the hilus. Sprouting of mossy fiber was observed in the dentate of mature SER; however, negligible staining was spotted in the dentate of both mature tremor and Wistar rats. Interestingly, expression of the brain-derived neurotrophic factor was higher in the hilus, CA3, and granular cell layer of dentate gyrus in SER than normal Wistar rats. The expression levels of TUNEL, bax, and Caspase-3 did not show significant changes between the SER and Wistar rats. SER exhibited hippocampal sclerosis-like changes which did not have enough potential for epileptogenesis. Repetitive tonic seizures and vulnerable CA3 neurons of SER could be involved in the induction of sclerosis-like changes in the hippocampus.

  6. Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats

    OpenAIRE

    Kowalski, Janina; Gan, Jian; Jonas, Peter; Pernía‐Andrade, Alejandro J.

    2015-01-01

    ABSTRACT The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high...

  7. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Toxicology, Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510-300 (China); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Takahashi, Masahide [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Wang, Yun [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Gaku, E-mail: gak@med.nagoya-u.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan)

    2011-11-15

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p < 0.05; fold change {>=} {+-} 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system. -- Highlights: Black-Right-Pointing-Pointer 1-BP modified hippocampal proteome in rat and 19 altered proteins were identified. Black-Right-Pointing-Pointer Expression of Ran, TPI, HSP60, PSMA1, ECH1, TPI, B-CK and DJ-1 was changed by 1-BP. Black

  8. Role of reuniens nucleus projections to the medial prefrontal cortex and to the hippocampal pyramidal CA1 area in associative learning.

    Directory of Open Access Journals (Sweden)

    Lyndell Eleore

    Full Text Available We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS and an electric shock to the trigeminal nerve as unconditioned stimulus (US. A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs. Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP.

  9. Histamine H1 and endothelin ETB receptors mediate phospholipase D stimulation in rat brain hippocampal slices.

    Science.gov (United States)

    Sarri, E; Picatoste, F; Claro, E

    1995-08-01

    Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans-(1S,3R)-aminocyclopentyl-1,3-dicarboxylic acid (trans-ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32P]Pi-prelabeled rat brain cortical and hippocampal slices. The accumulation of [32P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans-ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 microM) was inhibited by the H1 receptor antagonist mepyramine with a Ki constant of 0.7 nM and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 nM) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 nM, respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively.

  10. Modulation of neurite branching by protein phosphorylation in cultured rat hippocampal neurons.

    Science.gov (United States)

    Audesirk, G; Cabell, L; Kern, M

    1997-09-20

    The control of branching of axons and dendrites is poorly understood. It has been hypothesized that branching may be produced by changes in the cytoskeleton [F.J. Diez-Guerra, J. Avila, MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture, NeuroReport 4 (1993) 412-419; P. Friedrich, A. Aszodi, MAP2: a sensitive cross-linker and adjustable spacer in dendritic architecture, FEBS Lett. 295 (1991) 5-9]. The assembly and stability of microtubules, which are prominent cytoskeletal elements in both axons and dendrites, are regulated by microtubule-associated proteins, including tau (predominantly found in axons) and MAP2 (predominantly found in dendrites). The phosphorylation state of tau and MAP2 modulates their interactions with microtubules. In their low-phosphorylation states, tau and MAP2 bind to microtubules and increase microtubule assembly and/or stability. Increased phosphorylation decreases these effects. Diez-Guerra and Avila [F.J. Diez-Guerra, J. Avila, MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture, NeuroReport 4 (1993) 412-419] found that protein phosphorylation correlates with neurite branching in cultured rat hippocampal neurons, and hypothesized that increased protein phosphorylation stimulates neurite branching. To test this hypothesis, we cultured rat hippocampal neurons in the presence of specific modulators of serine-threonine protein kinases and phosphatases. Inhibitors of several protein kinases, which would be expected to decrease protein phosphorylation, reduced branching. KT5720, an inhibitor of cyclic AMP-dependent protein kinase, and KN62, an inhibitor of Ca(2+)-calmodulin-dependent protein kinases, inhibited branching of both axons and dendrites. Calphostin C and chelerythrine, inhibitors of protein kinase C, inhibited branching of axons but not dendrites. Treatments that would be expected to increase protein phosphorylation, including inhibitors of protein

  11. Neuropeptide Y and nestin expression in the hippocampal CA3 region following restrained and inverted stress in rats

    Institute of Scientific and Technical Information of China (English)

    Guogang Sun; Ailing Li; Bo Chen; Guangbi Fan; Hongwen Xiao; Yue Chen; Jie Xu; Ye Nie; Bing Zhang; Lin Gong

    2011-01-01

    Our preliminary study demonstrated that neuropeptide Y (NPY)/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits, as well as sustained cerebral injury in the adult hippocampus.

  12. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

    Science.gov (United States)

    Magariños, A M; Li, C J; Gal Toth, J; Bath, K G; Jing, D; Lee, F S; McEwen, B S

    2011-03-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.

  13. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    Science.gov (United States)

    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  14. Diurnal inhibition of NMDA-EPSCs at rat hippocampal mossy fibre synapses through orexin-2 receptors.

    Science.gov (United States)

    Perin, Martina; Longordo, Fabio; Massonnet, Christine; Welker, Egbert; Lüthi, Anita

    2014-10-01

    Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A- and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4-8, corresponding to 4-8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4-8, exogenous Ox-A (100 nm in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)-CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral-CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μm), but not by orexin-1 receptor inhibition (SB334867, 1 μm) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through i.p. injections of almorexant (100 mg kg(-1)), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep-wake cycle.

  15. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

    Science.gov (United States)

    Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast e