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Sample records for ca1 pyramidal neurons

  1. Activity-dependent Regulation of h Channel Distribution in Hippocampal CA1 Pyramidal Neurons

    National Research Council Canada - National Science Library

    Minyoung Shin; Dane M. Chetkovich

    2007-01-01

    ...) channel subunits, HCN1 and HCN2. Pyramidal neuron h channels within hippocampal area CA1 are remarkably enriched in distal apical dendrites, and this unique distribution pattern is critical for regulating dendritic excitability...

  2. Zbtb20-Induced CA1 Pyramidal Neuron Development and Area Enlargement in the Cerebral Midline Cortex of Mice

    DEFF Research Database (Denmark)

    Nielsen, Jakob V; Blom, Jonas B; Noraberg, Jens

    2010-01-01

    Expression of the transcriptional repressor Zbtb20 is confined to the hippocampal primordium of the developing dorsal midline cortex in mice. Here, we show that misexpression of Zbtb20 converts projection neurons of the subiculum and postsubiculum (dorsal presubiculum) to CA1 pyramidal neurons...... that are innervated by Schaffer collateral projections in ectopic strata oriens and radiatum. The Zbtb20-transformed neurons express Bcl11B, Satb2, and Calbindin-D28k, which are markers of adult CA1 pyramidal neurons. Downregulation of Zbtb20 expression by RNA interference impairs the normal maturation of CA1...... pyramidal neurons resulting in deficiencies in Calbindin-D28k expression and in reduced apical dendritic arborizations in stratum lacunosum moleculare. Overall, the results show that Zbtb20 is required for various aspects of CA1 pyramidal neuron development such as the postnatal extension of apical...

  3. Altered intrinsic excitability of hippocampal CA1 pyramidal neurons in aged PDAPP mice

    Directory of Open Access Journals (Sweden)

    Francesco eTamagnini

    2015-10-01

    Full Text Available Amyloidopathy involves the accumulation of insoluble amyloid β (Aβ species in the brain’s parenchyma and is a key histopathological hallmark of Alzheimer’s disease (AD. Work on transgenic mice that overexpress A suggests that elevated A levels in the brain are associated with aberrant epileptiform activity and increased intrinsic excitability of CA1 hippocampal neurons. In this study we examined if similar changes could be observed in hippocampal CA1 pyramidal neurons from aged PDAPP mice (20-23 month old, Indiana mutation: V717F on APP gene compared to their age-matched WT littermate controls. Whole-cell current clamp recordings revealed that sub-threshold intrinsic properties, such as input resistance, resting membrane potential and hyperpolarization activated sag were unaffected, but capacitance was significantly decreased in the transgenic animals. No differences between genotypes were observed in the overall number of action potentials (AP elicited by 500 ms supra-threshold current stimuli. PDAPP neurons, however, exhibited higher instantaneous firing frequencies after accommodation in response to high intensity current injections. The AP waveform was narrower and shorter in amplitude in PDAPP mice: these changes, according to our in silico model of a CA1/3 pyramidal neuron, depended on the respective reduction and increase of Na+ and K+ voltage-gated channels maximal conductances. Finally, the after-hyperpolarization (AHP, seen after the first AP evoked by a +300 pA current injection and after 50 Hz AP bursts, was more pronounced in PDAPP mice.These data show that Aβ-overexpression in aged mice altered the capacitance, the neuronal firing and the AP waveform of CA1 pyramidal neurons. Some of these findings are consistent with previous work on younger PDAPP, they also show important differences that can be potentially ascribed to the interaction between amyloidopathy and ageing. Such a change of IE properties over time

  4. Action-potential discharge in hippocampal CA1 pyramidal neurons: current source-density analysis.

    Science.gov (United States)

    Richardson, T L; Turner, R W; Miller, J J

    1987-11-01

    1. The site of origin of evoked action-potential discharge in hippocampal CA1 pyramidal neurons was investigated using the in vitro rat hippocampal slice preparation. 2. Action-potential discharge in pyramidal cells was evoked by stimulation of efferent pyramidal cell fibers in the alveus (antidromic) or afferent synaptic inputs in stratum oriens (SO) or stratum radiatum (SR). Laminar profiles of evoked extracellular field potentials were recorded at 25-micron intervals along the entire dendrosomatic axis of the pyramidal cell and a one-dimensional current source-density analysis was applied. 3. Suprathreshold stimulation of the alveus evoked an antidromic population spike response and current sink with the shortest peak latency in stratum pyramidale or proximal stratum oriens. A biphasic positive/negative potential associated with a current source/sink was recorded in dendritic regions, with both components increasing in peak latency with distance from the border of stratum pyramidale. 4. Suprathreshold stimulation of SO or SR evoked a population spike response superimposed upon the underlying synaptic depolarization at all levels of the dendrosomatic axis. The shortest latency population spike and current sink were recorded in stratum pyramidale or proximal stratum oriens. In dendritic regions, a biphasic positive/negative potential and current source/sink conducted with increasing latency from the border of stratum pyramidale. 5. A direct comparison of alvear- and SR-evoked responses revealed a basic similarity in population spike potentials and associated sink/source relationships at both the somatic and dendritic level and a similar shift in peak latency of spike components along the pyramidal cell axis. 6. It is concluded that the initial site for generation of a spike along the dendrosomatic axis of the pyramidal cell following antidromic or orthodromic stimulation is in the region of the cell body layer (soma or axon hillock). Action-potential discharge in

  5. Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing.

    Science.gov (United States)

    Yamada-Hanff, Jason; Bean, Bruce P

    2015-10-01

    We used dynamic clamp and action potential clamp techniques to explore how currents carried by tetrodotoxin-sensitive sodium channels and HCN channels (Ih) regulate the behavior of CA1 pyramidal neurons at resting and subthreshold voltages. Recording from rat CA1 pyramidal neurons in hippocampal slices, we found that the apparent input resistance and membrane time constant were strongly affected by both conductances, with Ih acting to decrease apparent input resistance and time constant and sodium current acting to increase both. We found that both Ih and sodium current were active during subthreshold summation of artificial excitatory postsynaptic potentials (EPSPs) generated by dynamic clamp, with Ih dominating at less depolarized voltages and sodium current at more depolarized voltages. Subthreshold sodium current-which amplifies EPSPs-was most effectively recruited by rapid voltage changes, while Ih-which blunts EPSPs-was maximal for slow voltage changes. The combined effect is to selectively amplify rapid EPSPs. We did similar experiments in mouse CA1 pyramidal neurons, doing voltage-clamp experiments using experimental records of action potential firing of CA1 neurons previously recorded in awake, behaving animals as command voltages to quantify flow of Ih and sodium current at subthreshold voltages. Subthreshold sodium current was larger and subthreshold Ih was smaller in mouse neurons than in rat neurons. Overall, the results show opposing effects of subthreshold sodium current and Ih in regulating subthreshold behavior of CA1 neurons, with subthreshold sodium current prominent in both rat and mouse CA1 pyramidal neurons and additional regulation by Ih in rat neurons. Copyright © 2015 the American Physiological Society.

  6. Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons.

    Science.gov (United States)

    Edelmann, Elke; Cepeda-Prado, Efrain; Leßmann, Volkmar

    2017-01-01

    Understanding learning and memory mechanisms is an important goal in neuroscience. To gain insights into the underlying cellular mechanisms for memory formation, synaptic plasticity processes are studied with various techniques in different brain regions. A valid model to scrutinize different ways to enhance or decrease synaptic transmission is recording of long-term potentiation (LTP) or long-term depression (LTD). At the single cell level, spike timing-dependent plasticity (STDP) protocols have emerged as a powerful tool to investigate synaptic plasticity with stimulation paradigms that also likely occur during memory formation in vivo . Such kind of plasticity can be induced by different STDP paradigms with multiple repeat numbers and stimulation patterns. They subsequently recruit or activate different molecular pathways and neuromodulators for induction and expression of STDP. Dopamine (DA) and brain-derived neurotrophic factor (BDNF) have been recently shown to be important modulators for hippocampal STDP at Schaffer collateral (SC)-CA1 synapses and are activated exclusively by distinguishable STDP paradigms. Distinct types of parallel synaptic plasticity in a given neuron depend on specific subcellular molecular prerequisites. Since the basal and apical dendrites of CA1 pyramidal neurons are known to be heterogeneous, and distance-dependent dendritic gradients for specific receptors and ion channels are described, the dendrites might provide domain specific locations for multiple types of synaptic plasticity in the same neuron. In addition to the distinct signaling and expression mechanisms of various types of LTP and LTD, activation of these different types of plasticity might depend on background brain activity states. In this article, we will discuss some ideas why multiple forms of synaptic plasticity can simultaneously and independently coexist and can contribute so effectively to increasing the efficacy of memory storage and processing capacity of the

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

    Directory of Open Access Journals (Sweden)

    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.

  8. ToF-SIMS cluster ion imaging of hippocampal CA1 pyramidal rat neurons

    Science.gov (United States)

    Francis, J. T.; Nie, H.-Y.; Taylor, A. R.; Walzak, M. J.; Chang, W. H.; MacFabe, D. F.; Lau, W. M.

    2008-12-01

    Recent studies have demonstrated the power of time-of-flight secondary ion mass spectrometry (ToF-SIMS) cluster ion imaging to characterize biological structures, such as that of the rat central nervous system. A large number of the studies to date have been carried out on the "structural scale" imaging several mm 2 using mounted thin sections. In this work, we present our ToF-SIMS cluster ion imaging results on hippocampal rat brain neurons, at the cellular and sub-cellular levels. As a part of an ongoing investigation to examine gut linked metabolic factors in autism spectrum disorders using a novel rat model, we have observed a possible variation in hippocampal Cornu ammonis 1 (CA1) pyramidal neuron geometry in thin, paraformaldehyde fixed brain sections. However, the fixation process alters the tissue matrix such that much biochemical information appears to be lost. In an effort to preserve as much as possible this original information, we have established a protocol using unfixed thin brain sections, along with low dose, 500 eV Cs + pre-sputtering that allows imaging down to the sub-cellular scale with minimal sample preparation.

  9. 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…

  10. Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Edelmann, Elke; Cepeda-Prado, Efrain; Leßmann, Volkmar

    2017-01-01

    Understanding learning and memory mechanisms is an important goal in neuroscience. To gain insights into the underlying cellular mechanisms for memory formation, synaptic plasticity processes are studied with various techniques in different brain regions. A valid model to scrutinize different ways to enhance or decrease synaptic transmission is recording of long-term potentiation (LTP) or long-term depression (LTD). At the single cell level, spike timing-dependent plasticity (STDP) protocols have emerged as a powerful tool to investigate synaptic plasticity with stimulation paradigms that also likely occur during memory formation in vivo. Such kind of plasticity can be induced by different STDP paradigms with multiple repeat numbers and stimulation patterns. They subsequently recruit or activate different molecular pathways and neuromodulators for induction and expression of STDP. Dopamine (DA) and brain-derived neurotrophic factor (BDNF) have been recently shown to be important modulators for hippocampal STDP at Schaffer collateral (SC)-CA1 synapses and are activated exclusively by distinguishable STDP paradigms. Distinct types of parallel synaptic plasticity in a given neuron depend on specific subcellular molecular prerequisites. Since the basal and apical dendrites of CA1 pyramidal neurons are known to be heterogeneous, and distance-dependent dendritic gradients for specific receptors and ion channels are described, the dendrites might provide domain specific locations for multiple types of synaptic plasticity in the same neuron. In addition to the distinct signaling and expression mechanisms of various types of LTP and LTD, activation of these different types of plasticity might depend on background brain activity states. In this article, we will discuss some ideas why multiple forms of synaptic plasticity can simultaneously and independently coexist and can contribute so effectively to increasing the efficacy of memory storage and processing capacity of the

  11. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons

    OpenAIRE

    Wang, Desheng; Schreurs, Bernard G.

    2010-01-01

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2% cholesterol or normal ...

  12. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Wang, Desheng; Schreurs, Bernard G

    2010-08-02

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2 percent cholesterol or normal chow for 8 weeks revealed changes including decreased after-hyperpolarization amplitudes (AHPs) - an index of membrane excitability shown to be important for rabbit eyeblink conditioning. This index was reversed by adding copper to drinking water - a dietary manipulation that can retard rabbit eyeblink conditioning. Evidence of cholesterol effects on membrane excitability was provided by application of methyl-beta-cyclodextrin, a compound that reduces membrane cholesterol, which increased the excitability of hippocampal CA1 neurons.

  13. The possible consequences for cognitive functions of external electric fields at power line frequency on hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Migliore, Rosanna; De Simone, Giada; Leinekugel, Xavier; Migliore, Michele

    2017-04-01

    The possible effects on cognitive processes of external electric fields, such as those generated by power line pillars and household appliances are of increasing public concern. They are difficult to study experimentally, and the relatively scarce and contradictory evidence make it difficult to clearly assess these effects. In this study, we investigate how, why and to what extent external perturbations of the intrinsic neuronal activity, such as those that can be caused by generation, transmission and use of electrical energy can affect neuronal activity during cognitive processes. For this purpose, we used a morphologically and biophysically realistic three-dimensional model of CA1 pyramidal neurons. The simulation findings suggest that an electric field oscillating at power lines frequency, and environmentally measured strength, can significantly alter both the average firing rate and temporal spike distribution properties of a hippocampal CA1 pyramidal neuron. This effect strongly depends on the specific and instantaneous relative spatial location of the neuron with respect to the field, and on the synaptic input properties. The model makes experimentally testable predictions on the possible functional consequences for normal hippocampal functions such as object recognition and spatial navigation. The results suggest that, although EF effects on cognitive processes may be difficult to occur in everyday life, their functional consequences deserve some consideration, especially when they constitute a systematic presence in living environments. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. 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

    2010-11-01

    Full Text Available 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.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 entire pyramidal neuron and occasionally

  15. Local diameter fully constrains dendritic size in basal but not apical trees of CA1 pyramidal neurons.

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    Donohue, Duncan E; Ascoli, Giorgio A

    2005-10-01

    Computational modeling of dendritic morphology is a powerful tool for quantitatively describing complex geometrical relationships, uncovering principles of dendritic development, and synthesizing virtual neurons to systematically investigate cellular biophysics and network dynamics. A feature common to many morphological models is a dependence of the branching probability on local diameter. Previous models of this type have been able to recreate a wide variety of dendritic morphologies. However, these diameter-dependent models have so far failed to properly constrain branching when applied to hippocampal CA1 pyramidal cells, leading to explosive growth. Here we present a simple modification of this basic approach, in which all parameter sampling, not just bifurcation probability, depends on branch diameter. This added constraint prevents explosive growth in both apical and basal trees of simulated CA1 neurons, yielding arborizations with average numbers and patterns of bifurcations extremely close to those observed in real cells. However, simulated apical trees are much more varied in size than the corresponding real dendrites. We show that, in this model, the excessive variability of simulated trees is a direct consequence of the natural variability of diameter changes at and between bifurcations observed in apical, but not basal, dendrites. Conversely, some aspects of branch distribution were better matched by virtual apical trees than by virtual basal trees. Dendritic morphometrics related to spatial position, such as path distance from the soma or branch order, may be necessary to fully constrain CA1 apical tree size and basal branching pattern.

  16. Expression profile analysis of vulnerable CA1 pyramidal neurons in young-middle aged Ts65Dn mice

    Science.gov (United States)

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

    2014-01-01

    Down syndrome (DS) is the most prevalent cause of intellectual disability (ID). Individuals with DS show a variety of cognitive deficits, most notably in hippocampal learning and memory, and display pathological hallmarks of Alzheimer's disease (AD), with neurodegeneration of cholinergic basal forebrain (CBF) neurons. Elucidation of the molecular and cellular underpinnings of neuropathology has been assessed via gene expression analysis in a relevant animal model, termed the Ts65Dn mouse. The Ts65Dn mouse is a segmental trisomy model of DS which mimics DS/AD pathology, notably age-related cognitive dysfunction and degeneration of basal forebrain cholinergic neurons (BFCNs). To determine expression level changes, molecular fingerprinting of Cornu Ammonis 1 (CA1) pyramidal neurons was performed in adult (4-9 month old) Ts65Dn mice, at the initiation of BFCN degeneration. To quantitate transcriptomic changes during this early time period, laser capture microdissection (LCM), terminal continuation (TC) RNA amplification, custom-designed microarray analysis, and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting was performed. Results indicate significant alterations within CA1 pyramidal neurons of Ts65Dn mice compared to normal disomic (2N) littermates, notably in the downregulation of neurotrophins and their cognate neurotrophin receptors among other classes of transcripts relevant to neurodegeneration. These results of this single population gene expression analysis at the time of septohippocampal deficits in a trisomic mouse model shed light on a vulnerable circuit that may cause the AD-like pathology invariably seen in DS that could help to identify mechanisms of degeneration, and provide novel gene targets for therapeutic interventions. PMID:25131634

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

    Science.gov (United States)

    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 (Plead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Repetitive magnetic stimulation induces plasticity of excitatory postsynapses on proximal dendrites of cultured mouse CA1 pyramidal neurons.

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    Lenz, Maximilian; Platschek, Steffen; Priesemann, Viola; Becker, Denise; Willems, Laurent M; Ziemann, Ulf; Deller, Thomas; Müller-Dahlhaus, Florian; Jedlicka, Peter; Vlachos, Andreas

    2015-11-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human brain can lead to long-lasting changes in cortical excitability. However, the cellular and molecular mechanisms which underlie rTMS-induced plasticity remain incompletely understood. Here, we used repetitive magnetic stimulation (rMS) of mouse entorhino-hippocampal slice cultures to study rMS-induced plasticity of excitatory postsynapses. By employing whole-cell patch-clamp recordings of CA1 pyramidal neurons, local electrical stimulations, immunostainings for the glutamate receptor subunit GluA1 and compartmental modeling, we found evidence for a preferential potentiation of excitatory synapses on proximal dendrites of CA1 neurons (2-4 h after stimulation). This rMS-induced synaptic potentiation required the activation of voltage-gated sodium channels, L-type voltage-gated calcium channels and N-methyl-D-aspartate-receptors. In view of these findings we propose a cellular model for the preferential strengthening of excitatory synapses on proximal dendrites following rMS in vitro, which is based on a cooperative effect of synaptic glutamatergic transmission and postsynaptic depolarization.

  19. Effects of low frequency electric fields on synaptic integration in hippocampal CA1 pyramidal neurons: implications for power line emissions

    Directory of Open Access Journals (Sweden)

    Francesco eCavarretta

    2014-10-01

    Full Text Available The possible cognitive effects of low frequency external electric fields, such as those generated by power lines, are poorly understood. Their functional consequences for mechanisms at the single neuron level are very difficult to study and identify experimentally, especially in vivo. The major open problem is that experimental investigations on humans have given inconsistent or contradictory results, making it difficult to estimate the possible effects of external low frequency electric fields on cognitive functions. Here we investigate this issue with a realistic model of hippocampal CA1 pyramidal neurons. The model suggests how and why external electric fields, with environmentally observed frequencies and intensities far lower than what is required for direct neural activation, can perturb dendritic signal processing and somatic firing of neurons that are crucially involved in cognitive tasks such as learning and memory. These results show that individual neuronal morphology, ion channel dendritic distribution, and alignment with the electric field are major determinants of overall effects, and provide a physiologically plausible explanation of why experimental findings can appear to be small and difficult to reproduce, yet deserve serious consideration.

  20. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

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    Liu, Pin W.

    2014-01-01

    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. PMID:24695716

  1. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

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    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

  2. MUSCARINIC LONG-TERM ENHANCEMENT OF TONIC AND PHASIC GABAA INHIBITION IN RAT CA1 PYRAMIDAL NEURONS

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    Soledad Dominguez

    2016-10-01

    Full Text Available ABSTRACTAcetylcholine (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 postsynaptic 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.

  3. Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia.

    Science.gov (United States)

    Kim, In Hye; Jeon, Yong Hwan; Lee, Tae-Kyeong; Cho, Jeong Hwi; Lee, Jae-Chul; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Bich-Na; Kim, Yang Hee; Hong, Seongkweon; Yan, Bing Chun; Won, Moo-Ho; Lee, Yun Lyul

    2017-06-01

    Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning (2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult (5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.

  4. Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release.

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    van de Vrede, Y; Fossier, P; Baux, G; Joels, M; Chameau, P

    2007-11-01

    In several neuronal preparations, the ryanodine-sensitive calcium store was reported to participate in the generation of slow afterhyperpolarization currents (IsAHP) involved in spike frequency adaptation. We show that calcium release from the ryanodine-sensitive calcium store is a major determinant of the triggering of IsAHP in mouse CA1 pyramidal neurons. Whole-cell patch clamp recordings in hippocampus slices show that the intracellular calcium stores depletion using an inhibitor of the endoplasmic reticulum Ca2+-ATPase (5 microM cyclopiazonic acid), as well as the specific blockade of ryanodine receptors (100 microM ryanodine) both reduced the IsAHP by about 70%. Immunohistology, using an anti-RyR3 specific antibody, indicates that RyR3 expression is particularly enriched in the CA1 apical dendrites (considered as the most important site for sAHP generation). We show that our anti-RyR3 antibody acts as a functional RyR3 antagonist and induced a reduction in IsAHP by about 70%. The additional ryanodine application (100 micro M) did not further affect IsAHP, thus excluding RyR2 in IsAHP activation. Our results argue in favor of a specialized function of RyR3 in CA1 pyramidal cells in triggering IsAHP due to their localization in the apical dendrite.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats.

    Science.gov (United States)

    Lâm, Thiên-Trí; Leranth, Csaba

    2003-05-01

    Oestrogen is known to influence pyramidal cell spine synapse plasticity in the CA1 subfield of the hippocampus. Apart from direct oestrogen action on the hippocampus, oestrogen effects mediated by subcortical structures are known to be important. The purpose of this study was to investigate whether the medial septum diagonal band of Broca (MSDB) takes part in mediating oestrogen effects to the hippocampus. Special attention was given to the role of cholinergic MSDB neurons that project to the hippocampus, as a rather large population of them contains oestrogen receptors and, consequently, may be sensitive to oestrogen signals. Adult female rats were ovariectomized. Oestradiol- and cholesterol-filled cannulae (control) were implanted into the MSDB. To selectively eliminate the cholinergic population of MSDB neurons of oestrogen-treated animals, a group of rats was injected with 192 IgG-saporin (SAP) into the lateral ventricle 1 week before the cannula implant. Immunostaining with anti-choline acetyltransferase and parvalbumin (PA) showed that cholinergic but not PA-containing GABAergic neurons were substantially reduced in the MSDB of SAP rats. Comparative electron microscopic unbiased stereological analysis on the spine synapse density of CA1 area pyramidal cells was performed between all animal groups. Rats that received oestradiol-filled cannulae showed a higher (30%) spine synapse density than control animals. Oestrogen-treated rats that had received SAP treatment showed no significant difference to controls. Thus, this observation indicates that septo-hippocampal cholinergic neurons are involved in mediating oestrogen effects to the hippocampus. The relevance of this observation to mnemonic functions and Alzheimer's disease is discussed.

  7. Dampening of hyperexcitability in CA1 pyramidal neurons by polyunsaturated fatty acids acting on voltage-gated ion channels.

    Directory of Open Access Journals (Sweden)

    Jenny Tigerholm

    Full Text Available A ketogenic diet is an alternative treatment of epilepsy in infants. The diet, rich in fat and low in carbohydrates, elevates the level of polyunsaturated fatty acids (PUFAs in plasma. These substances have therefore been suggested to contribute to the anticonvulsive effect of the diet. PUFAs modulate the properties of a range of ion channels, including K and Na channels, and it has been hypothesized that these changes may be part of a mechanistic explanation of the ketogenic diet. Using computational modelling, we here study how experimentally observed PUFA-induced changes of ion channel activity affect neuronal excitability in CA1, in particular responses to synaptic input of high synchronicity. The PUFA effects were studied in two pathological models of cellular hyperexcitability associated with epileptogenesis. We found that experimentally derived PUFA modulation of the A-type K (K(A channel, but not the delayed-rectifier K channel, restored healthy excitability by selectively reducing the response to inputs of high synchronicity. We also found that PUFA modulation of the transient Na channel was effective in this respect if the channel's steady-state inactivation was selectively affected. Furthermore, PUFA-induced hyperpolarization of the resting membrane potential was an effective approach to prevent hyperexcitability. When the combined effect of PUFA on the K(A channel, the Na channel, and the resting membrane potential, was simulated, a lower concentration of PUFA was needed to restore healthy excitability. We therefore propose that one explanation of the beneficial effect of PUFAs lies in its simultaneous action on a range of ion-channel targets. Furthermore, this work suggests that a pharmacological cocktail acting on the voltage dependence of the Na-channel inactivation, the voltage dependences of K(A channels, and the resting potential can be an effective treatment of epilepsy.

  8. Membrane voltage fluctuations reduce spike frequency adaptation and preserve output gain in CA1 pyramidal neurons in a high conductance state

    Science.gov (United States)

    Fernandez, Fernando R.; Broicher, Tilman; Truong, Alan; White, John A.

    2011-01-01

    Modulating the gain of the input-output function of neurons is critical for processing of stimuli and network dynamics. Previous gain control mechanisms have suggested that voltage fluctuations play a key role in determining neuronal gain in vivo. Here we show that, under increased membrane conductance, voltage fluctuations restore Na+ current and reduce spike frequency adaptation in rat hippocampal CA1 pyramidal neurons in vitro. As a consequence, membrane voltage fluctuations produce a leftward shift in the f-I relationship without a change in gain, relative to an increase in conductance alone. Furthermore, we show that these changes have important implications for the integration of inhibitory inputs. Due to the ability to restore Na+ current, hyperpolarizing membrane voltage fluctuations mediated by GABAA-like inputs can increase firing rate in a high conductance state. Finally, our data show that the effects on gain and synaptic integration are mediated by voltage fluctuations within a physiologically relevant range of frequencies (10–40 Hz). PMID:21389243

  9. Chronic Benzodiazepine-induced reduction in GABAA receptor-mediated synaptic currents in hippocampal CA1 pyramidal neurons prevented by prior nimodipine injection

    Science.gov (United States)

    Xiang, Kun; Tietz, Elizabeth I.

    2008-01-01

    One week oral flurazepam (FZP) administration in rats results in reduced GABAA receptor-mediated synaptic transmission in CA1 pyramidal neurons associated with benzodiazepine tolerance in vivo and in vitro. Since voltage-gated calcium channel (VGCC) current density is enhanced 2-fold during chronic FZP treatment, the role of L-type VGCCs in regulating benzodiazepine-induced changes in CA1 neuron GABAA receptor-mediated function was evaluated. Nimodipine (10 mg/kg, i.p.) or vehicle (0.5 % Tween 80, 2 ml/kg) was injected 1 day after ending FZP treatment and 24 hours prior to hippocampal slice preparation for measurement of mIPSC characteristics and in vitro tolerance to zolpidem. The reduction in GABAA receptor-mediated mIPSC amplitude and estimated unitary channel conductance measured 2 days after drug removal was no longer observed following prior nimodipine injection. However, the single nimodipine injection failed to prevent in vitro tolerance to zolpidem's ability to prolong mIPSC decay in FZP-treated neurons, suggesting multiple mechanisms may be involved in regulating GABAA receptor-mediated synaptic transmission following chronic FZP administration. As reported previously in recombinant receptors, nimodipine inhibited synaptic GABAA receptor currents only at high concentrations (>30 μM), significantly greater than attained in vivo (1 μM) 45 min after a single antagonist injection. Thus, the effects of nimodipine were unlikely to be related to direct effects on GABAA receptors. As with nimodipine injection, buffering intracellular free [Ca2+] with BAPTA similarly prevented the effects on GABAA receptor-mediated synaptic transmission, suggesting intracellular Ca2+ homeostasis is important to maintain GABAA receptor function. The findings further support a role for activation of L-type VGCCs, and perhaps other Ca2+-mediated signaling pathways, in the modulation of GABAA receptor synaptic function following chronic benzodiazepine administration, independent of

  10. 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.

  11. Evidence for Neuroprotective Effect of Sulbutiamine against Oxygen-Glucose Deprivation in Rat Hippocampal CA1 Pyramidal Neurons

    National Research Council Canada - National Science Library

    Jeehyun KWAGa; Aman Shah Abdul MAJIDb; c; Kui Dong KANGd

    2011-01-01

    .... Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD...

  12. Cell Type-Specific mRNA Dysregulation in Hippocampal CA1 Pyramidal Neurons of the Fragile X Syndrome Mouse Model

    Directory of Open Access Journals (Sweden)

    Laura Ceolin

    2017-10-01

    Full Text Available Fragile X syndrome (FXS is a genetic disorder due to the silencing of the Fmr1 gene, causing intellectual disability, seizures, hyperactivity, and social anxiety. All these symptoms result from the loss of expression of the RNA binding protein fragile X mental retardation protein (FMRP, which alters the neurodevelopmental program to abnormal wiring of specific circuits. Aberrant mRNAs translation associated with the loss of Fmr1 product is widely suspected to be in part the cause of FXS. However, precise gene expression changes involved in this disorder have yet to be defined. The objective of this study was to identify the set of mistranslated mRNAs that could contribute to neurological deficits in FXS. We used the RiboTag approach and RNA sequencing to provide an exhaustive listing of genes whose mRNAs are differentially translated in hippocampal CA1 pyramidal neurons as the integrative result of FMRP loss and subsequent neurodevelopmental adaptations. Among genes differentially regulated between adult WT and Fmr1−/y mice, we found enrichment in FMRP-binders but also a majority of non-FMRP-binders. Interestingly, both up- and down-regulation of specific gene expression is relevant to fully understand the molecular deficiencies triggering FXS. More importantly, functional genomic analysis highlighted the importance of genes involved in neuronal connectivity. Among them, we show that Klk8 altered expression participates in the abnormal hippocampal dendritic spine maturation observed in a mouse model of FXS.

  13. Enhanced sensitivity to ethanol-induced inhibition of LTP in CA1 pyramidal neurons of socially isolated C57BL/6J mice: role of neurosteroids

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    Giuseppe eTalani

    2011-10-01

    Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social

  14. Sulforhodamine 101 induces long-term potentiation of intrinsic excitability and synaptic efficacy in hippocampal CA1 pyramidal neurons

    DEFF Research Database (Denmark)

    Kang, J.; Kang, N.; Yu, Y.

    2010-01-01

    Sulforhodamine 101 (SR101) has been extensively used for investigation as a specific marker for astroglia in vivo and activity-dependent dye for monitoring regulated exocytosis. Here, we report that SR101 has bioactive effects on neuronal activity. Perfusion of slices with SR101 (1 microM) for 10...

  15. Spatial distributions of GABA receptors and local inhibition of Ca2+ transients studied with GABA uncaging in the dendrites of CA1 pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yuya Kanemoto

    Full Text Available GABA (γ-amino-butylic acid-mediated inhibition in the dendrites of CA1 pyramidal neurons was characterized by two-photon uncaging of a caged-GABA compound, BCMACM-GABA, and one-photon uncaging of RuBi-GABA in rat hippocampal slice preparations. Although we found that GABA(A-mediated currents were diffusely distributed along the dendrites, currents elicited at the branch points of the apical dendritic trunk were approximately two times larger than those elsewhere in the dendrite. We examined the inhibitory action of the GABA-induced currents on Ca(2+ transients evoked with a single back-propagating action potential (bAP in oblique dendrites. We found that GABA uncaging selectively inhibited the Ca(2+ transients in the region adjacent (20 µm. Our data indicate that GABA inhibition results in spatially confined inhibition of Ca(2+ transients shortly after bAP, and suggest that this effect is particularly potent at the dendritic branch points where GABA receptors cluster.

  16. Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

    OpenAIRE

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike Timing-Dependent Plasticity (STDP) is a cellular model of hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15-20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased l...

  17. Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release.

    NARCIS (Netherlands)

    Y. Vrede, van de; Fossier, P.; Baux, G.; Joëls, M.; Chameau, P.J.P.

    2007-01-01

    In several neuronal preparations, the ryanodine-sensitive calcium store was reported to participate in the generation of slow afterhyperpolarization currents (IsAHP) involved in spike frequency adaptation. We show that calcium release from the ryanodine-sensitive calcium store is a major determinant

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

    Science.gov (United States)

    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.

  19. CA1 pyramid-pyramid connections in rat hippocampus in vitro: dual intracellular recordings with biocytin filling.

    Science.gov (United States)

    Deuchars, J; Thomson, A M

    1996-10-01

    In adult rat hippocampus, simultaneous intracellular recordings from 989 pairs of CA1 pyramidal cells revealed nine monosynaptic, excitatory connections. Six of these pairs were sufficiently stable for electrophysiological analysis. Mean excitatory postsynaptic potential amplitude recorded at a postsynaptic membrane potential between -67 and -70 mV was 0.7 +/- 0.5 mV (0.17-1.5 mV), mean 10-90% rise time was 2.7 +/- 0.9 ms (1.5-3.8 ms) and mean width at half-amplitude was 16.8 +/- 4.1 ms (11.6-25 ms). Cells were labelled with biocytin and identified histologically. For one pair that was fully reconstructed morphologically, excitatory postsynaptic potential average amplitude was 1.5 mV, 10-90% rise time 2.8 ms and width at half-amplitude 11.6 ms (at -67 mV). In this pair, correlated light and electron microscopy revealed that the presynaptic axon formed two synaptic contacts with third-order basal dendrites of the postsynaptic pyramid, one with a dendritic spine, the other with a dendritic shaft. In the four pairs tested, postsynaptic depolarization increased excitatory postsynaptic potential amplitude and duration. In two, D-2-amino-5-phosphonovalerate (50 microM) reduced the amplitude and duration of the excitatory postsynaptic potential. The remainder of the excitatory postsynaptic potential now increased with postsynaptic hyperpolarization and was abolished by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (n = 1). Paired-pulse depression was evident in the four excitatory postsynaptic potentials tested. This depression decreased with increasing inter-spike interval. These results provide the first combined electrophysiological and morphological illustration of synaptic contacts between pyramidal neurons in the hippocampus and confirm that connections between CA1 pyramidal neurons are mediated by both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptors.

  20. Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat.

    Science.gov (United States)

    Hosseini-sharifabad, Mohammad; Esfandiari, Ebrahim

    2015-01-01

    Experimental evidence indicates that administration of Boswellia resin, known as olibanum or Frankincense, increases memory power. It is reported that beta boswellic acid, the major component of Boswellia serrata gum resin, could enhance neurite outgrowth and branching in hippocampal neurons. We therefore studied whether Boswellia treatment produces morphological changes in the superior region of cornu ammonis (CA1) in aged rats. Sixteen male Wistar rats, 24 months of age, were randomly divided in experimental and control groups. The experimental group was orally administered Boswellia serrata gum resin (100 mg/kg per day for 8 weeks) and the control group received a similar volume of water. The Cavalieri principle was employed to estimate the volumes of CA1 hippocampal field, and a quantitative Golgi study was used to analysis of dendritic arborizations of CA1 pyramidal cells. Comparisons revealed that Boswellia-treated aged rats had greater volumes than control animals in stratum pyramidale and stratum radiatum lacunosum-moleculare. The neurons of CA1 in experimental rats had more dendritic segments (40.25 ± 4.20) than controls (30.9 ± 4.55), P = 0.001. The total dendritic length of CA1 neurons was approximately 20 % larger in the experimental group compared to control. Results also indicated that the aged rats treated with Boswellia resin had more numerical branching density in the apical dendrites of CA1 pyramidal neurons. The results of the present study show that long-term administration of Boswellia resin can attenuate age-related dendritic regression in CA1 pyramidal cells in rat hippocampus.

  1. Structured Dendritic Inhibition Supports Branch-Selective Integration in CA1 Pyramidal Cells.

    Science.gov (United States)

    Bloss, Erik B; Cembrowski, Mark S; Karsh, Bill; Colonell, Jennifer; Fetter, Richard D; Spruston, Nelson

    2016-03-02

    Neuronal circuit function is governed by precise patterns of connectivity between specialized groups of neurons. The diversity of GABAergic interneurons is a hallmark of cortical circuits, yet little is known about their targeting to individual postsynaptic dendrites. We examined synaptic connectivity between molecularly defined inhibitory interneurons and CA1 pyramidal cell dendrites using correlative light-electron microscopy and large-volume array tomography. We show that interneurons can be highly selective in their connectivity to specific dendritic branch types and, furthermore, exhibit precisely targeted connectivity to the origin or end of individual branches. Computational simulations indicate that the observed subcellular targeting enables control over the nonlinear integration of synaptic input or the initiation and backpropagation of action potentials in a branch-selective manner. Our results demonstrate that connectivity between interneurons and pyramidal cell dendrites is more precise and spatially segregated than previously appreciated, which may be a critical determinant of how inhibition shapes dendritic computation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

    Science.gov (United States)

    Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

    2010-05-31

    Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Interplay between global and pathway-specific synaptic plasticity in CA1 pyramidal cells.

    Science.gov (United States)

    Berberich, Sven; Pohle, Jörg; Pollard, Marie; Barroso-Flores, Janet; Köhr, Georg

    2017-12-06

    Mechanisms underlying information storage have been depicted for global cell-wide and pathway-specific synaptic plasticity. Yet, little is known how these forms of plasticity interact to enhance synaptic competition and network stability. We examined synaptic interactions between apical and basal dendrites of CA1 pyramidal neurons in mouse hippocampal slices. Bursts (50 Hz) of three action potentials (AP-bursts) paired with preceding presynaptic stimulation in stratum radiatum specifically led to LTP of the paired pathway in adult mice (P75). At adolescence (P28), an increase in burst frequency (>50 Hz) was required to gain timing-dependent LTP. Surprisingly, paired radiatum and unpaired oriens pathway potentiated, unless the pre-post delay was shortened from 10 to 5 ms, which selectively potentiated paired radiatum pathway, since unpaired oriens pathway decreased back to baseline. Conversely, the exact same 5 ms pairing in stratum oriens potentiated both pathways, as did AP-bursts alone, which potentiated synaptic efficacy as well as current-evoked postsynaptic spiking. L-type voltage-gated Ca 2+ channels were involved in mediating synaptic potentiation in oriens, whereas NMDA and adenosine receptors counteracted unpaired stratum oriens potentiation following pairing in stratum radiatum. This asymmetric plasticity uncovers important insights into alterations of synaptic efficacy and intrinsic neuronal excitability for pathways that convey hippocampal and extra-hippocampal information.

  4. Stochastic resonance in hippocampal CA1 neurons

    Science.gov (United States)

    Stacey, William Charles

    Stochastic Resonance (SR) is a phenomenon observed in nonlinear systems whereby the introduction of noise enhances the detection of a subthreshold signal for a certain range of noise intensity. Many central neurons, such as hippocampal CAI cells, are good candidates for SR due to their function of signal detection in a noisy environment, but the role of SR in the CNS is unclear. Physiological levels of noise are able to improve signal detection through SR, as found in simulated CAI neurons and in vitro rat hippocampal slices. Further investigation, utilizing a novel method of in vitro noise modulation, shows that endogenous noise sources can generate SR activity. These results suggest SR may provide a means for the hippocampus to modulate detection of specific inputs through endogenous noise sources. The role of noise in signal detection for a network of CAI cells is tested with a network simulation. The network shows improved detection as the number of cells and coupling increase for noise with low variance. One cell receiving the signal cannot recruit the remaining cells unless the network is very active and tuned by the coupling and noise. Periodic oscillations at high noise amplitudes corrupt all outputs. These oscillations develop into synchronized, periodic bursts as a function of both noise and coupling. These findings are relevant for the analysis of the role of physiological noise in signal processing in the brain and in the synchronization of neural activity as in epilepsy.

  5. A sodium-pump-mediated afterhyperpolarization in pyramidal neurons.

    Science.gov (United States)

    Gulledge, Allan T; Dasari, Sameera; Onoue, Keita; Stephens, Emily K; Hasse, J Michael; Avesar, Daniel

    2013-08-07

    The sodium-potassium ATPase (i.e., the "sodium pump") plays a central role in maintaining ionic homeostasis in all cells. Although the sodium pump is intrinsically electrogenic and responsive to dynamic changes in intracellular sodium concentration, its role in regulating neuronal excitability remains unclear. Here we describe a physiological role for the sodium pump in regulating the excitability of mouse neocortical layer 5 and hippocampal CA1 pyramidal neurons. Trains of action potentials produced long-lasting (∼20 s) afterhyperpolarizations (AHPs) that were insensitive to blockade of voltage-gated calcium channels or chelation of intracellular calcium, but were blocked by tetrodotoxin, ouabain, or the removal of extracellular potassium. Correspondingly, the AHP time course was similar to the decay of activity-induced increases in intracellular sodium, whereas intracellular calcium decayed at much faster rates. To determine whether physiological patterns of activity engage the sodium pump, we replayed in vitro a place-specific burst of 15 action potentials recorded originally in vivo in a CA1 "place cell" as the animal traversed the associated place field. In both layer 5 and CA1 pyramidal neurons, this "place cell train" generated small, long-lasting AHPs capable of reducing neuronal excitability for many seconds. Place-cell-train-induced AHPs were blocked by ouabain or removal of extracellular potassium, but not by intracellular calcium chelation. Finally, we found calcium contributions to the AHP to be temperature dependent: prominent at room temperature, but largely absent at 35°C. Our results demonstrate a previously unappreciated role for the sodium-potassium ATPase in regulating the excitability of neocortical and hippocampal pyramidal neurons.

  6. Reverse stochastic resonance in a hippocampal CA1 neuron model.

    Science.gov (United States)

    Durand, Dominique M; Kawaguchi, Minato; Mino, Hiroyuki

    2013-01-01

    Stochastic resonance (SR) is a ubiquitous and counter- intuitive phenomenon whereby the addition of noise to a non-linear system can improve the detection of sub-threshold signals. The "signal" is normally periodic or deterministic whereas the "noise" is normally stochastic. However, in neural systems, signals are often stochastic. Moreover, periodic signals are applied near neurons to control neural excitability (i.e. deep brain stimulation). We therefore tested the hypothesis that a quasi-periodic signal applied to a neural network could enhance the detection of a stochastic neural signal (reverse stochastic resonance). Using computational methods, a CA1 hippocampal neuron was simulated and a Poisson distributed subthreshold synaptic input ("signal") was applied to the synaptic terminals. A periodic or quasi periodic pulse train at various frequencies ("noise") was applied to an extracellular electrode located near the neuron. The mutual information and information transfer rate between the output and input of the neuron were calculated. The results display the signature of stochastic resonance with information transfer reaching a maximum value for increasing power (or frequency) of the "noise". This result shows that periodic signals applied extracellularly can improve the detection of subthreshold stochastic neural signals. The optimum frequency (110 Hz) is similar to that used in patients with Parkinson's suggesting that this phenomenon could play a role in the therapeutic effect of high frequency stimulation.

  7. Plasticité de l'excitabilité des neurones de la région CA1 de rat

    OpenAIRE

    Campanac, Emilie

    2008-01-01

    It has been previously shown in pyramidal neurons of CA1 that in addition to long term synaptic plasticity, tetanus protocols (HFS/LFS) of afferent input induced a synergic plasticity of integration of synaptic potentials. In this context, we have addressed the following questions: 1) are changes on dendritic integration associated to STDP? 2) what are the mechanisms of facilitation of integration expression observed after LTP? and 3) does synaptic activity also induce persistent changes in e...

  8. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice

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    M Zamani

    2013-01-01

    Full Text Available Introduction: Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Oxidative Stress is considered to be involved in a number of human diseases including ischemia. Preliminary studies confirmed reduction of cell death in brain following treatment with antioxidants. Aim: According to this finding, we study the relationship between consumption of olive oil on cell death and memory disorder in brain ischemia. We studied the protective effect of olive oil against ischemia-reperfusion. Material and Methods: Experimental design includes three groups: Intact (n = 8, ischemic control (n = 8 and treatment groups with olive oil (n = 8. The mice treated with olive oil as pre-treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction of inflammation [a week after ischemia], the mice post-treated with olive oil. Nissl staining applied for counting necrotic cells in hippocampus CA1. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply y-maze and shuttle box tests and for detection the rate of apoptotic and treated cell, we used western blotting test for bax and bcl2 proteins. Results: High rate of apoptosis was seen in ischemic group that significantly associated with short-term memory loss. Cell death was significantly lower when mice treated with olive oil. The memory test results were adjusted with cell death results and bax and bcl2 expression in all groups′ comparison. Ischemia for 15 min induced cell death in hippocampus with more potent effect on CA1. Conclusion: Olive oil intake significantly reduced cell death and decreased memory loss.

  9. Supralinear dendritic Ca2+ signalling in young developing CA1 pyramidal cells

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    Pohle, Jörg; Bischofberger, Josef

    2014-01-01

    Although Ca2+ is critically important in activity-dependent neuronal development, not much is known about the regulation of dendritic Ca2+ signals in developing neurons. Here, we used ratiometric Ca2+ imaging to investigate dendritic Ca2+ signalling in rat hippocampal pyramidal cells during the first 1–4 weeks of postnatal development. We show that active dendritic backpropagation of Nav channel-dependent action potentials (APs) evoked already large dendritic Ca2+ transients in animals aged 1 week with amplitudes of ∼150 nm, similar to the amplitudes of ∼160 nM seen in animals aged 4 weeks. Although the AP-evoked dendritic Ca2+ load increased about four times during the first 4 weeks, the peak amplitude of free Ca2+ concentration was balanced by a four-fold increase in Ca2+ buffer capacity κs (∼70 vs. ∼280). Furthermore, Ca2+ extrusion rates increased with postnatal development, leading to a slower decay time course (∼0.2 s vs. ∼0.1 s) and more effective temporal summation of Ca2+ signals in young cells. Most importantly, during prolonged theta-burst stimulation dendritic Ca2+ signals were up to three times larger in cells at 1 week than at 4 weeks of age and much larger than predicted by linear summation, which is attributable to an activity-dependent slow-down of Ca2+ extrusion. As Ca2+ influx is four-fold smaller in young cells, the larger Ca2+ signals are generated using four times less ATP consumption. Taken together, the data suggest that active backpropagations regulate dendritic Ca2+ signals during early postnatal development. Remarkably, during prolonged AP firing, Ca2+ signals are several times larger in young than in mature cells as a result of activity-dependent regulation of Ca2+ extrusion rates. PMID:25239458

  10. Long term delivery of pulsed magnetic fields does not alter visual discrimination learning or dendritic spine density in the mouse CA1 pyramidal or dentate gyrus neurons [v2; ref status: indexed, http://f1000r.es/2gk

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    Matthew Sykes

    2013-12-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is thought to facilitate brain plasticity. However, few studies address anatomical changes following rTMS in relation to behaviour. We delivered 5 weeks of daily pulsed rTMS stimulation to adult ephrin-A2-/- and wildtype (C57BI/6j mice (n=10 per genotype undergoing a visual learning task and analysed learning performance, as well as spine density, in the dentate gyrus molecular and CA1 pyramidal cell layers in Golgi-stained brain sections. We found that neither learning behaviour, nor hippocampal spine density was affected by long term rTMS. Our negative results highlight the lack of deleterious side effects in normal subjects and are consistent with previous studies suggesting that rTMS has a bigger effect on abnormal or injured brain substrates than on normal/control structures.

  11. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

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    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  12. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

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    Patricia F Kao

    2010-10-01

    Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

  13. Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

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    Julien eDine

    2016-04-01

    Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  14. Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy

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    Zhang, Xuebin; Huang, Huiling; Wang, Jin; Wang, Yajing; Tong, Xiaoguang; Wang, Jinhuan; Wu, Jialing

    2015-01-01

    The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy. PMID:26325184

  15. Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.

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    Pierri, Joseph N; Volk, Christine L E; Auh, Sungyoung; Sampson, Allan; Lewis, David A

    2003-07-15

    Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in deep layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC deep layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of deep layer 3 pyramidal neurons. We estimated the mean somal volume of NNFP-IR neurons in deep layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all deep layer 3 pyramidal neurons identified in Nissl-stained material. In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC deep layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.

  16. Activation of extrasynaptic GABA(A) receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons.

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    Wan, Li; Liu, Xu; Wu, Zheng; Ren, Wanting; Kong, Shuzhen; Dargham, Raya Abou; Cheng, Longzhen; Wang, Yun

    2014-10-01

    Extrasynaptic GABA(A) receptors (GABA(A)Rs)-mediated tonic inhibition is reported to involve in the pathogenesis of epilepsy. In this study, we used cyclothiazide (CTZ)-induced in vitro brain slice seizure model to explore the effect of selective activation of extrasynaptic GABA(A)Rs by 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) on the CTZ-induced epileptiform activity in hippocampal neurons. Perfusion with CTZ dose-dependently induced multiple epileptiform peaks of evoked population spikes (PSs) in CA1 pyramidal neurons, and treatment with THIP (5 μmol/L) significantly reduced the multiple PS peaks induced by CTZ stimulation. Western blot showed that the δ-subunit of the GABA(A)R, an extrasynaptic specific GABA(A)R subunit, was also significantly down-regulated in the cell membrane 2 h after CTZ treatment. Our results suggest that the CTZ-induced epileptiform activity in hippocampal CA1 neurons is suppressed by the activation of extrasynaptic GABA(A)Rs, and further support the hypothesis that tonic inhibition mediated by extrasynaptic GABA(A)Rs plays a prominent role in seizure generation.

  17. Abelson tyrosine kinase links PDGFbeta receptor activation to cytoskeletal regulation of NMDA receptors in CA1 hippocampal neurons

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    Beazely Michael A

    2008-12-01

    Full Text Available Abstract Background We have previously demonstrated that PDGF receptor activation indirectly inhibits N-methyl-D-aspartate (NMDA currents by modifying the cytoskeleton. PDGF receptor ligand is also neuroprotective in hippocampal slices and cultured neurons. PDGF receptors are tyrosine kinases that control a variety of signal transduction pathways including those mediated by PLCγ. In fibroblasts Src and another non-receptor tyrosine kinase, Abelson kinase (Abl, control PDGF receptor regulation of cytoskeletal dynamics. The mechanism whereby PDGF receptor regulates cytoskeletal dynamics in central neurons remains poorly understood. Results Intracellular applications of active Abl, but not heat-inactivated Abl, decreased NMDA-evoked currents in isolated hippocampal neurons. This mimics the effects of PDGF receptor activation in these neurons. The Abl kinase inhibitor, STI571, blocked the inhibition of NMDA currents by Abl. We demonstrate that PDGF receptors can activate Abl kinase in hippocampal neurons via mechanisms similar to those observed previously in fibroblasts. Furthermore, PDGFβ receptor activation alters the subcellular localization of Abl. Abl kinase is linked to actin cytoskeletal dynamics in many systems. We show that the inhibition of NMDA receptor currents by Abl kinase is blocked by the inclusion of the Rho kinase inhibitor, Y-27632, and that activation of Abl correlates with an increase in ROCK tyrosine phosphorylation. Conclusion This study demonstrates that PDGFβ receptors act via an interaction with Abl kinase and Rho kinase to regulated cytoskeletal regulation of NMDA receptor channels in CA1 pyramidal neurons.

  18. Sodium-activated potassium conductance participates in the depolarizing afterpotential following a single action potential in rat hippocampal CA1 pyramidal cells.

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    Liu, Xinhuai; Stan Leung, L

    2004-10-15

    The depolarizing afterpotential (DAP) following an action potential increases the excitability of a neuron. Mechanisms related to the DAP following an antidromic or current-induced spike were studied in CA1 pyramidal cells by whole-cell recordings in hippocampal slices in vitro. In DAP-holding voltage curves, the DAP at 10 ms after the spike peak (DAP10) was extrapolated to reverse at about -50 mV. Increase of extracellular K(+) concentration increased DAP and neuronal bursting. DAP10 reversal potential shifted positively with an increase in [K(+)](o) and with the blockade of K(+) conductance using pipettes filled with Cs(+). Similarly, extracellular tetraethylammonium (TEA; 10 mM), 4-aminopyridine (3-10 mM) increased DAP and shifted the DAP10 reversal potential to a depolarizing direction. Decrease of [Ca(2+)](o) did not alter DAP significantly, suggesting a nonessential role of Ca(2+) in the DAP. Perfusion of tetrodotoxin (TTX; 0.1-1 microM) and replacement of extracellular Na(+) by choline(+) suppressed both spike height and DAP simultaneously. Replacement of extracellular Na(+) by Li(+) increased DAP and spike bursts, and caused a positive shift of the DAP10 reversal potential. It is suggested that Li(+) increased DAP by blocking an Na(+)-activated K(+) current. In summary, multiple K(+) conductances are normally active during the DAP following a single action potential.

  19. Integrative spike dynamics of rat CA1 neurons: a multineuronal imaging study.

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    Sasaki, Takuya; Kimura, Rie; Tsukamoto, Masako; Matsuki, Norio; Ikegaya, Yuji

    2006-07-01

    The brain operates through a coordinated interplay of numerous neurons, yet little is known about the collective behaviour of individual neurons embedded in a huge network. We used large-scale optical recordings to address synaptic integration in hundreds of neurons. In hippocampal slice cultures bolus-loaded with Ca2+ fluorophores, we stimulated the Schaffer collaterals and monitored the aggregate presynaptic activity from the stratum radiatum and individual postsynaptic spikes from the CA1 stratum pyramidale. Single neurons responded to varying synaptic inputs with unreliable spikes, but at the population level, the networks stably output a linear sum of synaptic inputs. Nonetheless, the network activity, even though given constant stimuli, varied from trial to trial. This variation emerged through time-varying recruitment of different neuron subsets, which were shaped by correlated background noise. We also mapped the input-frequency preference in spiking activity and found that the majority of CA1 neurons fired in response to a limited range of presynaptic firing rates (20-40 Hz), acting like a band-pass filter, although a few neurons had high pass-like or low pass-like characteristics. This frequency selectivity depended on phasic inhibitory transmission. Thus, our imaging approach enables the linking of single-cell behaviours to their communal dynamics, and we discovered that, even in a relatively simple CA1 circuit, neurons could be engaged in concordant information processing.

  20. Diabetes impairs learning performance and affects the mitochondrial function of hippocampal pyramidal neurons.

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    Ye, Lin; Wang, Feng; Yang, Rui-Hua

    2011-09-09

    Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. The present study investigated the effect of streptozotocin (STZ)-induced diabetes on spatial learning and memory using the Morris Water Maze. The effects of diabetes on CA1 pyramidal neurons in hippocampus were also examined. Diabetes impaired spatial learning and memory of rats. Diabetes induced the apoptosis of neurons and translocation of Bax from cytoplasm to mitochondria. On the contrary, diabetes induced cytochrome c release into the cytoplasm from mitochondria. Release of Cyt-c from mitochondria into cytoplasm may play a role in apoptosis of the CA1 pyramidal neurons, which resulted in a decrease of the number of neurons in hippocampus and impaired the performance function. These results partially explain the mechanism of the effect of diabetes on learning and memory. To protect mitochondrial function is possible candidate for preventing the impairments of diabetes on hippocampal function. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Scanning Ultrasound (SUS Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice.

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    Robert John Hatch

    Full Text Available Scanning ultrasound (SUS is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.

  2. Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.

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    Hanna B Laurén

    Full Text Available Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA-induced status epilepticus (SE in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed, and long-term potentiation (LTP; 18 genes changed. Also genes involved in Ca(2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP, apolipoprotein E (apo E, cannabinoid type 1 receptor (CB1, Purkinje cell protein 4 (PEP-19, and interleukin 8 receptor (CXCR1, with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE. However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the

  3. PyramidalExplorer: A New Interactive Tool to Explore Morpho-Functional Relations of Human Pyramidal Neurons.

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    Toharia, Pablo; Robles, Oscar D; Fernaud-Espinosa, Isabel; Makarova, Julia; Galindo, Sergio E; Rodriguez, Angel; Pastor, Luis; Herreras, Oscar; DeFelipe, Javier; Benavides-Piccione, Ruth

    2015-01-01

    This work presents PyramidalExplorer, a new tool to interactively explore and reveal the detailed organization of the microanatomy of pyramidal neurons with functionally related models. It consists of a set of functionalities that allow possible regional differences in the pyramidal cell architecture to be interactively discovered by combining quantitative morphological information about the structure of the cell with implemented functional models. The key contribution of this tool is the morpho-functional oriented design that allows the user to navigate within the 3D dataset, filter and perform Content-Based Retrieval operations. As a case study, we present a human pyramidal neuron with over 9000 dendritic spines in its apical and basal dendritic trees. Using PyramidalExplorer, we were able to find unexpected differential morphological attributes of dendritic spines in particular compartments of the neuron, revealing new aspects of the morpho-functional organization of the pyramidal neuron.

  4. [Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

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    Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

    2013-09-01

    In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending

  5. The analysis of hippocampus neuronal density (CA1 and CA3 after Ocimum sanctum ethanolic extract treatment on the young adulthood and middle age rat model

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    Dwi Liliek Kusindarta

    2018-02-01

    Full Text Available Aim: This study aimed to assess the changes in neuronal density in CA1 and CA3 regions in the hippocampus of young adulthood and middle age rat model after feeding by Ocimum sanctum ethanolic extract. Materials and Methods: In this research, 30 male Wistar rats consist of young to middle-aged rats were divided into three groups (3, 6, and 9 months old and treated with a different dosage of O. sanctum ethanolic extract (0, 50, and 100 mg/kg b.w. for 45 days. Furthermore, cresyl violet staining was performed to analyze hippocampus formation mainly in CA1 and CA3 area. The concentrations of acetylcholine (Ach in brain tissues were analyzed by enzyme-linked immunosorbent assay. Results: In our in vivo models using rat model, we found that the administration of O. sanctum ethanolic extract with a dosage of 100 mg/kg b.w. for 45 days induced the density of pyramidal cells significantly in CA1 and CA3 of the hippocampus. These results were supported by an increase of Ach concentrations on the brain tissue. Conclusion: The administration of O. sanctum ethanolic extract may promote the density of the pyramidal cells in the CA1 and CA3 mediated by the up-regulated concentration of Ach.

  6. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia

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    Seyedeh Farzaneh Moniri

    2018-01-01

    Full Text Available Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR, vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract. Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001. Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001. Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  7. Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons.

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    Losonczy, Attila; Zemelman, Boris V; Vaziri, Alipasha; Magee, Jeffrey C

    2010-08-01

    Although hippocampal theta oscillations represent a prime example of temporal coding in the mammalian brain, little is known about the specific biophysical mechanisms. Intracellular recordings support a particular abstract oscillatory interference model of hippocampal theta activity, the soma-dendrite interference model. To gain insight into the cellular and circuit level mechanisms of theta activity, we implemented a similar form of interference using the actual hippocampal network in mice in vitro. We found that pairing increasing levels of phasic dendritic excitation with phasic stimulation of perisomatic projecting inhibitory interneurons induced a somatic polarization and action potential timing profile that reproduced most common features. Alterations in the temporal profile of inhibition were required to fully capture all features. These data suggest that theta-related place cell activity is generated through an interaction between a phasic dendritic excitation and a phasic perisomatic shunting inhibition delivered by interneurons, a subset of which undergo activity-dependent presynaptic modulation.

  8. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia.

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    Moniri, Seyedeh Farzaneh; Hedayatpour, Azim; Hassanzadeh, Gholamreza; Vazirian, Mahdi; Karimian, Morteza; Belaran, Maryam; Ejtemaie Mehr, Shahram; Akbari, Mohamad

    2017-12-01

    Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks) used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (Pextract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  9. Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1.

    Science.gov (United States)

    Lee, Jae-Chul; Kim, In Hye; Park, Joon Ha; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Cho, Geum-Sil; Tae, Hyun-Jin; Chen, Bai Hui; Yan, Bing Chun; Yoo, Ki-Yeon; Choi, Jung Hoon; Lee, Choong Hyun; Hwang, In Koo; Cho, Jun Hwi; Kwon, Young-Guen; Kim, Young-Myeong; Won, Moo-Ho

    2015-02-01

    Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic injury by activating specific mechanisms. In this study, we tested the hypothesis that IPC attenuates postischemic neuronal death via heme oxygenase-1 (HO-1). Animals used in this study were randomly assigned to 4 groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group and IPC+ischemia-operated group. IPC was induced by subjecting gerbils to 2min of ischemia followed by 1 day of recovery. A significant loss of neurons was observed in pyramidal neurons of the hippocampal CA1 region (CA1) in the ischemia-operated groups at 5 days postischemia. In the IPC+ischemia-operated groups, CA1 pyramidal neurons were well protected. The level of HO-1 protein and its activity increased significantly in the CA1 of the IPC+sham-operated group, and the level and activity was maintained in all the time after ischemia-reperfusion compared with the ischemia-operated groups. HO-1 immunoreactivity was induced in the CA1 pyramidal neurons in both IPC+sham-operated- and IPC+ischemia-operated groups. We also found that levels or immunoreactivities of superoxide anion, 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal were significantly decreased in the CA1 of both IPC+sham-operated- and IPC+ischemia-operated groups. Whereas, treatment with zinc protoporphyrin IX (a HO-1 inhibitor) into the IPC+ischemia-operated groups did not preserve the IPC-mediated increase of HO-1 and lost beneficial effects of IPC by inhibiting ischemia-induced DNA damage and lipid peroxidation. In brief, IPC protects CA1 pyramidal neurons from ischemic injury by upregulating HO-1, and we suggest that the enhancement of HO-1 expression by IPC may be a legitimate strategy for a therapeutic intervention of cerebral ischemic damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

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    Nabi Shamsaei

    2015-01-01

    Full Text Available Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks. Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  11. Experimental study on the effect of controlled hypotension levels on rabbit CA1 neurons.

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    Liu, Bingbing; Zhou, Diawei; Huang, Hongyan; Xiao, Xiaoshan

    2013-06-01

    The present study investigated the effect of controlled hypotension (CH) levels regulated by nitroprusside on hippocampal CA1 neurons. All experimental rabbits were randomly divided into five groups to perform CH for recording their vital signs and survived for a certain time. The arterial blood was collected to measure the serum levels of interleukin 6 and tumor necrosis factor α and then the brain tissues were perfused and sectioned to carry out hematoxylin-eosin staining, TdT-mediated dUTP nick end labeling fluorescence, c-fos immunohistochemistry, and ultrastructural observation of hippocampal neuronal mitochondria. All data were analyzed with SPSS13.0 software, and P < 0.05 was indicated as statistically significant. Heart rate, mean arterial pressure, and the dosage of sodium nitroprusside were not statistically significant between groups, but at T2, heart rate levels in groups II-IV were lower than those in groups I and V. Simultaneously, interleukin 6 was remarkably overexpressed in group II than in other groups at T2, whereas tumor necrosis factor α was higher in groups I-III than in groups IV and V. At the light and electronic microscopic levels, the CA1 regional neurons of group IV were more seriously damaged and deranged compared with other groups so was the expression of c-fos. However, fluorescence from TdT-mediated dUTP nick end labeling assay was more intensive in groups II-IV than that in other groups. Results further showed that Flameng scores of mitochondria were the highest in group IV, but they were not statistically significant among the other groups. The different levels of CH remarkably affected the functional activities of hippocampal CA1 neurons; with the decrease of mean arterial pressure, neuronal apoptosis, and c-fos expression was gradually increased and reached the peak in 45% of basic values of blood pressure. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

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    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

    Science.gov (United States)

    Andjelic, Sofija; Gallopin, Thierry; Cauli, Bruno; Hill, Elisa L.; Roux, Lisa; Badr, Sammy; Hu, Emilie; Tamás, Gábor; Lambolez, Bertrand

    2009-01-01

    The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity. PMID:19052106

  14. The Effect of N-acetyl-cysteine on Memory Retrieval and the Number of Intact Neurons of Hippocampal CA1 Area in Streptozotocin-induced Alzheimeric Male Rats

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    Niloufar Darbandi

    2018-01-01

    Full Text Available Abstract Background: Alzheimer is a neurodegenerative disease wich caused memory impairment, reduced cognitive functions, intellectual ability and behavior changes. In this study, the effect of N-acetyl-cysteine (NAC as a strong antioxidant on memory deficiency and number of CA1 pyramidal neurons in Streptozotocine (STZ - induced Alzheimeric rats were studied. Materials and Methods: 32 Male Wistar rats were divided into four groups: sham group, streptozotocin group, treated group with streptozotocin plus N-acetyl-cysteine, and treated group with N-acetyl-cysteine alone. Intracerebroventricular (ICV administration of STZ was done in the first and the third day of surgery and i.p injection of N-acetyl-cysteine was done in the fourth of surgery. After the memory test, the animals were killed and their brains were fixed and density of intact neurons in the CA1 area of the hippocampus was investigated. Statistical analysis was performed with software SPSS, ANOVA and Prisme software. The level of statistical significance was set at p 0.05. Conclusion: N-acetyl-cysteine improved memory retrieval and hippocampal CA1 area intact neurons in streptozotocin-induced Alzheimeric male rats.

  15. Enhancement of information transmission with stochastic resonance in hippocampal CA1 neuron models.

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    Mino, Hiroyuki; Durand, Dominique M; Kawaguchi, Minato

    2006-01-01

    Stochastic resonance (SR) has been shown to enhance the signal to noise ratio or detection of signals in neurons. It is not yet clear how this effect of SR on the signal to noise ratio affects signal processing in neural networks. In this paper, we test the hypothesis that SR can improve information transmission in the hippocampus. From spike firing times recorded at the soma, the inter spike intervals were generated and then "total" and "noise" entropies were estimated to obtain the mutual information and information rate of the spike trains. The results show that the information rate reached a maximum value at a specific amplitude of the background noise, implying that the stochastic resonance can improve the information transmission in the CA1 neuron model. Furthermore, the results also show that the effect of stochastic resonance tended to decrease as the intensity of the random sub-threshold spike trains (signal) (more than 20 l/s) approached to that of the background noise (100 l/s). In conclusion, the computation results that the stochastic resonance can improve information processing in the hippocampal CA1 neuron model in which the intensity of the random sub-threshold spike trains was set at 5-20 l/s.

  16. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

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    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.

  17. Repeating firing fields of CA1 neurons shift forward in response to increasing angular velocity.

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    Cowen, Stephen L; Nitz, Douglas A

    2014-01-01

    Self-motion information influences spatially-specific firing patterns exhibited by hippocampal neurons. Moreover, these firing patterns can repeat across similar subsegments of an environment, provided that there is similarity of path shape and head orientations across subsegments. The influence of self-motion variables on repeating fields remains to be determined. To investigate the role of path shape and angular rotation on hippocampal activity, we recorded the activity of CA1 neurons from rats trained to run on spiral-shaped tracks. During inbound traversals of circular-spiral tracks, angular velocity increases continuously. Under this condition, most neurons (74%) exhibited repeating fields across at least three adjacent loops. Of these neurons, 86% exhibited forward shifts in the angles of field centers relative to centers on preceding loops. Shifts were absent on squared-spiral tracks, minimal and less reliable on concentric-circle tracks, and absent on outward-bound runs on circular-spiral tracks. However, outward-bound runs on the circular-spiral track in the dark were associated with backward shifts. Together, the most parsimonious interpretation of the results is that continuous increases or decreases in angular velocity are particularly effective at shifting the center of mass of repeating fields, although it is also possible that a nonlinear integration of step counts contributes to the shift. Furthermore, the unexpected absence of field shifts during outward journeys in light (but not darkness) suggests visual cues around the goal location anchored the map of space to an allocentric reference frame.

  18. 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

  19. The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease

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    Merino-Serrais, Paula; Benavides-Piccione, Ruth; Blazquez-Llorca, Lidia; Kastanauskaite, Asta; Rábano, Alberto; Avila, Jesús

    2013-01-01

    The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer’s disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer’s disease is likely to depend on the relative number of neurons that have well developed tangles. PMID:23715095

  20. Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons

    OpenAIRE

    Edelmann, Elke; Cepeda-Prado, Efrain; Leßmann, Volkmar

    2017-01-01

    Understanding learning and memory mechanisms is an important goal in neuroscience. To gain insights into the underlying cellular mechanisms for memory formation, synaptic plasticity processes are studied with various techniques in different brain regions. A valid model to scrutinize different ways to enhance or decrease synaptic transmission is recording of long-term potentiation (LTP) or long-term depression (LTD). At the single cell level, spike timing-dependent plasticity (STDP) protocols ...

  1. Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity.

    Science.gov (United States)

    Araujo, Daniel J; Toriumi, Kazuya; Escamilla, Christine O; Kulkarni, Ashwinikumar; Anderson, Ashley G; Harper, Matthew; Usui, Noriyoshi; Ellegood, Jacob; Lerch, Jason P; Birnbaum, Shari G; Tucker, Haley O; Powell, Craig M; Konopka, Genevieve

    2017-11-08

    Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 (FOXP1) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of

  2. Lercanidipine Rescues Hippocampus Pyramidal Neurons from Mild Ischemia-Induced Delayed Neuronal Death in SHRSP.

    OpenAIRE

    Sakurai-Yamashita, Yasuko; Harada, Noboru; Niwa, Masami

    2011-01-01

    Stroke-prone spontaneously hypertensive rats (SHRSPs) are vulnerable to ischemia and delayed neuronal death (DND) of hippocampus pyramidal cells when bilateral carotid arteries are occluded for only 10 min. Since this occlusion induces just mild ischemia, the resulting DND may be an appropriate animal model for dementia in patient with essential hypertension exposed to small ischemic insults. This study was designed to compare the effects of the antihypertensive drugs lercanidipine, nicardipi...

  3. Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

    Science.gov (United States)

    Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

    2017-12-19

    Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

  4. Influence of the on-line ELF-EMF stimulation on the electrophysiological properties of the rat hippocampal CA1 neurons in vitro

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    Zheng, Yu; Ma, Wei; Dong, Lei; Dou, Jun-rong; Gao, Yang; Xue, Jing

    2017-10-01

    The extremely low frequency electromagnetic fields (ELF-EMFs) have been shown to have an environmentally negative effect on humans' health; however, its treatment effect is beneficial for patients suffering from neurological disorders. Despite this success, the application of ELF-EMF has exceeded in the understanding of its internal mechanism. Recently, it was found that on-line magnetic stimulation may offer advantages over off-line magnetic exposure and has proven to be effective in activating the prefrontal cortex pyramidal neurons in vitro. Here, we perform computational simulations of the stimulation coils in COMSOL modeling to describe the uniformity of the distribution of the on-line magnetic field. Interestingly, the modeling data and actual measurements showed that the densities of the magnetic flux that was generated by the on-line stimulation coils were similar. The on-line magnetic stimulator induced sodium channel currents as well as field excitatory postsynaptic potentials of the rat hippocampal CA1 neurons and successfully demonstrated its extensive applications to activate neuronal tissue. These findings further raise the possibility that the instrument of on-line magnetic stimulation may be an effective alternative for studies in the field of bioelectromagnetics.

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

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    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.

  6. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

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    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

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

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    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

  8. Epileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats.

    Science.gov (United States)

    Qian, Binbin; Sun, Yajie; Wu, Zhen; Wan, Li; Chen, Lulan; Kong, Shuzhen; Zhang, Binhong; Zhang, Fayong; Wang, Zhen-Yu; Wang, Yun

    2011-05-01

    We have previously reported that cyclothiazide (CTZ) evokes epileptiform activities in hippocampal neurons and induces seizure behavior. Here we further studied in vivo the sensitivity of the hippocampal CA1 neurons in response to CTZ in epileptogenesis in comparison with two other classic convulsants of kainic acid (KA) and pentylenetetrazol (PTZ). CTZ administered intracerebral ventricle (i.c.v.) induced epileptiform activities from an initial of multiple evoked population spikes, progressed to spontaneous spikes and finally to highly synchronized burst activities in hippocampal CA1 neurons. PTZ, when given by subcutaneously, but not by intracerebral ventricle injection, evoked similar progressive epileptiform activities. In contrast, KA given by i.c.v. induced a quick development of epileptiform burst activities and then shortly switched to continuous high frequency firing as acute status epilepticus (ASE). Pharmacologically, alprazolam, a high-potency benzodiazepine ligand, inhibited CTZ and PTZ, but not KA, induced epileptiform burst activities while GYKI 53784, an AMPA receptor antagonist, suppressed CTZ and KA but not PTZ evoked epileptiform activities. In conclusion, CTZ and PTZ induced epileptiform activities are most likely to share a similar progressive pattern in hippocampus with GABAergic mechanism dominant in epileptogenesis, while CTZ model involves additional glutamate receptor activation. KA induced seizure in hippocampus is different to that of both CTA and PTZ. The results from this study indicate that hippocampal neurons respond to various convulsant stimulation differently which may reflect the complicated causes of the seizure in clinics. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. Pyramidal cells make specific connections onto smooth (GABAergic neurons in mouse visual cortex.

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    Rita Bopp

    2014-08-01

    Full Text Available One of the hallmarks of neocortical circuits is the predominance of recurrent excitation between pyramidal neurons, which is balanced by recurrent inhibition from smooth GABAergic neurons. It has been previously described that in layer 2/3 of primary visual cortex (V1 of cat and monkey, pyramidal cells filled with horseradish peroxidase connect approximately in proportion to the spiny (excitatory, 95% and 81%, respectively and smooth (GABAergic, 5% and 19%, respectively dendrites found in the neuropil. By contrast, a recent ultrastructural study of V1 in a single mouse found that smooth neurons formed 51% of the targets of the superficial layer pyramidal cells. This suggests that either the neuropil of this particular mouse V1 had a dramatically different composition to that of V1 in cat and monkey, or that smooth neurons were specifically targeted by the pyramidal cells in that mouse. We tested these hypotheses by examining similar cells filled with biocytin in a sample of five mice. We found that the average composition of the neuropil in V1 of these mice was similar to that described for cat and monkey V1, but that the superficial layer pyramidal cells do form proportionately more synapses with smooth dendrites than the equivalent neurons in cat or monkey. These distributions may underlie the distinct differences in functional architecture of V1 between rodent and higher mammals.

  10. Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

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    Shields, L Y; Kim, H; Zhu, L; Haddad, D; Berthet, A; Pathak, D; Lam, M; Ponnusamy, R; Diaz-Ramirez, L G; Gill, T M; Sesaki, H; Mucke, L; Nakamura, K

    2015-04-16

    Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons.

  11. Sensory deprivation differentially impacts the dendritic development of pyramidal versus non-pyramidal neurons in layer 6 of mouse barrel cortex.

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    Chen, Chia-Chien; Tam, Danny; Brumberg, Joshua C

    2012-04-01

    Early postnatal sensory experience can have profound impacts on the structure and function of cortical circuits affecting behavior. Using the mouse whisker-to-barrel system we chronically deprived animals of normal sensory experience by bilaterally trimming their whiskers every other day from birth for the first postnatal month. Brain tissue was then processed for Golgi staining and neurons in layer 6 of barrel cortex were reconstructed in three dimensions. Dendritic and somatic parameters were compared between sensory-deprived and normal sensory experience groups. Results demonstrated that layer 6 non-pyramidal neurons in the chronically deprived group showed an expansion of their dendritic arbors. The pyramidal cells responded to sensory deprivation with increased somatic size and basilar dendritic arborization but overall decreased apical dendritic parameters. In sum, sensory deprivation impacted on the neuronal architecture of pyramidal and non-pyramidal neurons in layer 6, which may provide a substrate for observed physiological and behavioral changes resulting from whisker trimming.

  12. Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons.

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    Lin, Yu-Ting; Chen, Chien-Chung; Huang, Chiung-Chun; Nishimori, Katsuhiko; Hsu, Kuei-Sen

    2017-09-14

    In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; however, the mechanisms underlying the action of oxytocin are still unclear. Taking advantage of the conditional knockout mouse model, we show here that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons. Through bidirectional chemogenetic manipulations, we also uncover a significant role for CA3 pyramidal neuron activity in regulating adult neurogenesis in the dentate gyrus. Retrograde neuronal tracing combined with immunocytochemistry revealed that the oxytocin neurons in the paraventricular nucleus project directly to the CA3 region of the hippocampus. Our findings reveal a critical role for oxytocin signaling in adult neurogenesis.Oxytocin (OXT) has been implicated in adult neurogenesis. Here the authors show that CA3 pyramidal cells in the adult mouse hippocampus express OXT receptors and receive inputs from hypothalamic OXT neurons; activation of OXT signaling in CA3 pyramidal cells promotes the survival and maturation of newborn neurons in the dentate gyrus in a non-cell autonomous manner.

  13. Topological organization of CA3-to-CA1 excitation.

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    Hongo, Yoshie; Ogawa, Koichi; Takahara, Yuji; Takasu, Keiko; Royer, Sebastien; Hasegawa, Minoru; Sakaguchi, Gaku; Ikegaya, Yuji

    2015-09-01

    The CA1-projecting axons of CA3 pyramidal cells, called Schaffer collaterals, constitute one of the major information flow routes in the hippocampal formation. Recent anatomical studies have revealed the non-random structural connectivity between CA3 and CA1, but little is known regarding the functional connectivity (i.e. how CA3 network activity is functionally transmitted downstream to the CA1 network). Using functional multi-neuron calcium imaging of rat hippocampal slices, we monitored the spatiotemporal patterns of spontaneous CA3 and CA1 burst activity under pharmacological GABAergic blockade. We found that spatially clustered CA3 activity patterns were transformed into layered CA1 activity sequences. Specifically, synchronized bursts initiated from multiple hot spots in CA3 ensembles, and CA1 neurons located deeper in the pyramidal cell layer were recruited during earlier phases of the burst events. The order of these sequential activations was maintained across the bursts, but the sequence velocity varied depending on the inter-burst intervals. Thus, CA3 axons innervate CA1 neurons in a highly topographical fashion. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. TRH modulates glutamatergic synaptic inputs on CA1 neurons of the mouse hippocampus in a biphasic manner.

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    Zarif, Hadi; Petit-Paitel, Agnès; Heurteaux, Catherine; Chabry, Joëlle; Guyon, Alice

    2016-11-01

    Thyrotropin Releasing Hormone (TRH) is a tripeptide that induces the release of Thyroid Stimulating Hormone (TSH) in the blood. Besides its role in the thyroid system, TRH has been shown to regulate several neuronal systems in the brain however its role in hippocampus remains controversial. Using electrophysiological recordings in acute mouse brain slices, we show that TRH depresses glutamate responses at the CA3-CA1 synapse through an action on NMDA receptors, which, as a consequence, decreases the ability of the synapse to establish a long term potentiation (LTP). TRH also induces a late increase in AMPA/kainate responses. Together, these results suggest that TRH plays an important role in the modulation of hippocampal neuronal activities, and they contribute to a better understanding of the mechanisms by which TRH impacts synaptic function underlying emotional states, learning and memory processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition.

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    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.

  16. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

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    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density. DOI: http://dx.doi.org/10.7554/eLife.13424.001 PMID:27549340

  17. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-08-23

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density.

  18. Anatomy and physiology of the thick-tufted layer 5 pyramidal neuron.

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    Ramaswamy, Srikanth; Markram, Henry

    2015-01-01

    The thick-tufted layer 5 (TTL5) pyramidal neuron is one of the most extensively studied neuron types in the mammalian neocortex and has become a benchmark for understanding information processing in excitatory neurons. By virtue of having the widest local axonal and dendritic arborization, the TTL5 neuron encompasses various local neocortical neurons and thereby defines the dimensions of neocortical microcircuitry. The TTL5 neuron integrates input across all neocortical layers and is the principal output pathway funneling information flow to subcortical structures. Several studies over the past decades have investigated the anatomy, physiology, synaptology, and pathophysiology of the TTL5 neuron. This review summarizes key discoveries and identifies potential avenues of research to facilitate an integrated and unifying understanding on the role of a central neuron in the neocortex.

  19. Anatomy and Physiology of the Thick-tufted Layer 5 Pyramidal Neuron

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    Srikanth eRamaswamy

    2015-06-01

    Full Text Available The thick-tufted layer 5 (TTL5 pyramidal neuron is one of the most extensively studied neuron types in the mammalian neocortex and has become a benchmark for understanding information processing in excitatory neurons. By virtue of having the widest local axonal and dendritic arborization, the TTL5 neuron encompasses various local neocortical neurons and thereby defines the dimensions of neocortical microcircuitry. The TTL5 neuron integrates input across all neocortical layers and is the principal output pathway funneling information flow to subcortical structures. Several studies over the past decades have investigated the anatomy, physiology, synaptology, and pathophysiology of the TTL5 neuron. This review summarizes key discoveries and identifies potential avenues of research to facilitate an integrated and unifying understanding on the role of a central neuron in the neocortex.

  20. The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

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    Rossner Moritz

    2007-10-01

    Full Text Available Abstract Background The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD, RNA amplification, and array hybridization. Results Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel

  1. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, Stefan; de Kock, Christiaan P. J.; Stuart, Greg J.; Kole, Maarten H. P.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action

  2. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, S.; de Kock, C.P.J.; Stuart, G.J.; Kole, M.H.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na + and K + ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na +K + charge overlap as a measure of action

  3. Photolysis of Postsynaptic Caged Ca2+ Can Potentiate and Depress Mossy Fiber Synaptic Responses in Rat Hippocampal CA3 Pyramidal Neurons

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    Wang, Jun; Yeckel, Mark F.; Johnston, Daniel; Zucker, Robert S.

    2010-01-01

    The induction of mossy fiber-CA3 long-term potentiation (LTP) and depression (LTD) has been variously described as being dependent on either pre- or postsynaptic factors. Some of the postsynaptic factors for LTP induction include ephrin-B receptor tyrosine kinases and a rise in postsynaptic Ca2+ ([Ca2+]i). Ca2+ is also believed to be involved in the induction of the various forms of LTD at this synapse. We used photolysis of caged Ca2+ compounds to test whether a postsynaptic rise in [Ca2+]i is sufficient to induce changes in synaptic transmission at mossy fiber synapses onto rat hippocampal CA3 pyramidal neurons. We were able to elevate postsynaptic [Ca2+]i to approximately 1 μm for a few seconds in pyramidal cell somata and dendrites. We estimate that CA3 pyramidal neurons have approximately fivefold greater endogenous Ca2+ buffer capacity than CA1 neurons, limiting the rise in [Ca2+]i achievable by photolysis. This [Ca2+]i rise induced either a potentiation or a depression at mossy fiber synapses in different preparations. Neither the potentiation nor the depression was accompanied by consistent changes in paired-pulse facilitation, suggesting that these forms of plasticity may be distinct from synaptically induced LTP and LTD at this synapse. Our results are consistent with a postsynaptic locus for the induction of at least some forms of synaptic plasticity at mossy fiber synapses. PMID:14645386

  4. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.

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    Arion, D; Corradi, J P; Tang, S; Datta, D; Boothe, F; He, A; Cacace, A M; Zaczek, R; Albright, C F; Tseng, G; Lewis, D A

    2015-11-01

    Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a lesser extent, in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell-type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or 5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at the time of death, on the patterns of gene expression in pyramidal neurons. Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by quantitative PCR validation. Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly downregulated in the patient group (P-values for MT-related and UPS-related pathways were schizoaffective disorder subjects (diagnosis of schizoaffective disorder was the most significant covariate, Pschizoaffective disorder, providing a potential molecular-cellular basis of differences in clinical phenotypes.

  5. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

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    Kerkhofs, Amber; Xavier, Ana C.; da Silva, Beatriz S.; Canas, Paula M.; Idema, Sander; Baayen, Johannes C.; Ferreira, Samira G.; Cunha, Rodrigo A.; Mansvelder, Huibert D.

    2018-01-01

    Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans. PMID:29354052

  6. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

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    Amber Kerkhofs

    2018-01-01

    Full Text Available Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R, neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans.

  7. Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia/Reperfusion-Induced Damage to CA1 Hippocampal Neurons

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    Lingyun Hao

    2016-07-01

    Full Text Available Nitric oxide (NO can regulate signaling pathways via S-nitrosylation. Fyn can be post-translationally modified in many biological processes. In the present study, using a rat four-vessel-occlusion ischemic model, we aimed to assess whether Fyn could be S-nitrosylated and to evaluate the effects of Fyn S-nitrosylation on brain damage. In vitro, Fyn could be S-nitrosylated by S-nitrosoglutathione (GSNO, an exogenous NO donor, and in vivo, endogenous NO synthesized by NO synthases (NOS could enhance Fyn S-nitrosylation. Application of GSNO, 7-nitroindazole (7-NI, an inhibitor of neuronal NOS and hydrogen maleate (MK-801, the N-methyl-d-aspartate receptor (NMDAR antagonist could decrease the S-nitrosylation and phosphorylation of Fyn induced by cerebral ischemia/reperfusion (I/R. Cresyl violet staining validated that these compounds exerted neuroprotective effects against the cerebral I/R-induced damage to hippocampal CA1 neurons. Taken together, in this study, we demonstrated that Fyn can be S-nitrosylated both in vitro and in vivo and that inhibiting S-nitrosylation can exert neuroprotective effects against cerebral I/R injury, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stroke and the development of novel treatment strategies.

  8. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    Science.gov (United States)

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  9. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  10. Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans.

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    Bianchi, Serena; Stimpson, Cheryl D; Duka, Tetyana; Larsen, Michael D; Janssen, William G M; Collins, Zachary; Bauernfeind, Amy L; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Hopkins, William D; Wildman, Derek E; Lipovich, Leonard; Kuzawa, Christopher W; Jacobs, Bob; Hof, Patrick R; Sherwood, Chet C

    2013-06-18

    Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans ≈ 25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3-5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages.

  11. Transient receptor potential vanilloid 4 inhibits γ-aminobutyric acid-activated current in hippocampal pyramidal neurons

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    Zhiwen Hong

    2016-08-01

    Full Text Available The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system. The activation of transient receptor potential vanilloid 4 (TRPV4 is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA is the major inhibitory neurotransmitter in the central nervous system. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4 synthetic (GSK1016790A or 4-PDD or endogenous agonist (5,6-EET inhibited GABA-activated current (IGABA in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK and decreased the phosphorylated protein kinase B (p-Akt protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited IGABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K agonist. GSK1016790A-induced inhibition of IGABA was also significantly attenuated by a protein kinase C (PKC antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation.

  12. 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.

  13. Permanent reduction of seizure threshold in post-ischemic CA3 pyramidal neurons.

    Science.gov (United States)

    Congar, P; Gaïarsa, J L; Popovici, T; Ben-Ari, Y; Crépel, V

    2000-04-01

    The effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2-4 mo after a global forebrain insult. With intracellular recordings, CA3 post-ischemic neurons had a more depolarized resting membrane potential but no change of the input resistance, spike threshold and amplitude, fast and slow afterhyperpolarization (AHP) or ADP, and firing properties in response to depolarizing pulses. With both field and whole-cell recordings, synaptic responses were similar in control and post-ischemic neurons. Although there were no spontaneous network-driven discharges, the post-ischemic synaptic network had a smaller threshold to generate evoked and spontaneous synchronized burst discharges. Thus lower concentrations of convulsive agents (kainate, high K(+)) triggered all-or-none network-driven synaptic events in post-ischemic neurons more readily than in control ones. Also, paired-pulse protocol generates, in post-ischemics but not controls, synchronized field burst discharges when interpulse intervals ranged from 60 to 100 ms. In conclusion, 2-4 mo after the insult, the post-ischemic CA3 pyramidal cells are permanently depolarized and have a reduced threshold to generate synchronized bursts. This may explain some neuropathological and behavioral consequences of ischemia as epileptic syndromes observed several months to several years after the ischemic insult.

  14. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

    Science.gov (United States)

    den Boon, Femke S; Chameau, Pascal; Schaafsma-Zhao, Qiluan; van Aken, Willem; Bari, Monica; Oddi, Sergio; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2012-02-28

    The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

  15. Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

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    Takahashi Susumu

    2009-09-01

    Full Text Available Abstract Background The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder. Results The activity of small neuronal ensembles (6-18 cells over brief time intervals (2-50 ms contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison. The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals. Conclusion The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.

  16. Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in Hippocampal Pyramidal Neurons

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    Soledad Ferreras

    2017-11-01

    Full Text Available Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant’s effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus. Primary cultures and organotypic slice cultures were used for cellular, molecular, pharmacological and biochemical analyses of the role of Cdk5/p25 in amphetamine-induced dendritic spine formation. Amphetamine (two-injection protocol increased dendritic spine density in hippocampal neurons of thy1-green fluorescent protein (GFP mice, as well as in hippocampal cultured neurons and organotypic slice cultures. Either genetic or pharmacological inhibition of Cdk5 activity prevented the amphetamine–induced increase in dendritic spine density. Amphetamine also increased spine density in neurons overexpressing the strong Cdk5 activator p25. Finally, inhibition of calpain, the protease necessary for the conversion of p35 to p25, prevented amphetamine’s effect on dendritic spine density. We demonstrate, for the first time, that amphetamine increases the density of dendritic spine in hippocampal pyramidal neurons in vivo and in vitro. Moreover, we show that the Cdk5/p25 signaling and calpain activity are both necessary for the effect of amphetamine on dendritic spine density. The identification of molecular mechanisms underlying psychostimulant effects provides novel and promising therapeutic approaches for the treatment of drug addiction.

  17. Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

    KAUST Repository

    Virtanen, Mari A.

    2018-01-10

    Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

  18. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Age-dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats.

    Science.gov (United States)

    Gawlak, Maciej; Szulczyk, Bartłomiej; Berłowski, Adam; Grzelka, Katarzyna; Stachurska, Anna; Pełka, Justyna; Czarzasta, Katarzyna; Małecki, Maciej; Kurowski, Przemysław; Nurowska, Ewa; Szulczyk, Paweł

    2017-12-01

    Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na + current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX-resistant, low-threshold, noninactivating, and voltage-dependent Na + current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017. © 2017 Wiley Periodicals, Inc.

  20. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond

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    Branka Hrvoj-Mihic

    2017-08-01

    Full Text Available Williams syndrome (WS is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC—the frontal pole (Brodmann area 10 and the orbitofrontal cortex (Brodmann area 11—and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18. The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10 and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other

  1. Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: a model study.

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    Jun Xu

    2008-04-01

    Full Text Available A critical property of some neurons is burst firing, which in the hippocampus plays a primary role in reliable transmission of electrical signals. However, bursting may also contribute to synchronization of electrical activity in networks of neurons, a hallmark of epilepsy. Understanding the ionic mechanisms of bursting in a single neuron, and how mutations associated with epilepsy modify these mechanisms, is an important building block for understanding the emergent network behaviors. We present a single-compartment model of a CA3 hippocampal pyramidal neuron based on recent experimental data. We then use the model to determine the roles of primary depolarizing currents in burst generation. The single compartment model incorporates accurate representations of sodium (Na(+ channels (Na(V1.1 and T-type calcium (Ca(2+ channel subtypes (Ca(V3.1, Ca(V3.2, and Ca(V3.3. Our simulations predict the importance of Na(+ and T-type Ca(2+ channels in hippocampal pyramidal cell bursting and reveal the distinct contribution of each subtype to burst morphology. We also performed fast-slow analysis in a reduced comparable model, which shows that our model burst is generated as a result of the interaction of two slow variables, the T-type Ca(2+ channel activation gate and the Ca(2+-dependent potassium (K(+ channel activation gate. The model reproduces a range of experimentally observed phenomena including afterdepolarizing potentials, spike widening at the end of the burst, and rebound. Finally, we use the model to simulate the effects of two epilepsy-linked mutations: R1648H in Na(V1.1 and C456S in Ca(V3.2, both of which result in increased cellular excitability.

  2. NK-3 receptor activation depolarizes and induces an after-depolarization in pyramidal neurons in gerbil cingulate cortex

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2004-01-01

    M), a selective NK3 receptor agonist, induced a transient increase in spontaneous EPSPs in layer V pyramidal neurons, accompanied by a small depolarization ( approximately 4 mV). EPSPs during senktide had a larger amplitude and faster 10-90% rise time than during control. Senktide induced a transient...... depolarization in layer II/III pyramidal neurons, which often reached threshold for spikes. The depolarization ( approximately 6 mV) persisted in TTX, and was accompanied by an increase in input resistance. Senktide also transiently induced a slow after-depolarization, which appeared following a depolarizing...... pulse. The slow after-depolarization persisted in TTX. These data suggest that activation of NK3 receptors on layer II/III pyramidal neurons induce post-synaptic depolarization and an after-depolarization, which could be mediated by blockade of a leak potassium conductance and a non-selective cation...

  3. Inhibitory Gating of Input Comparison in the CA1 Microcircuit.

    Science.gov (United States)

    Milstein, Aaron D; Bloss, Erik B; Apostolides, Pierre F; Vaidya, Sachin P; Dilly, Geoffrey A; Zemelman, Boris V; Magee, Jeffrey C

    2015-09-23

    Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter. However, during ECIII and CA3 input comparison, supralinear dendritic integration is dynamically balanced by feedforward and feedback inhibition, resulting in suppression of dendritic complex spiking. We find that a particular subpopulation of CA1 interneurons expressing neuropeptide Y (NPY) contributes prominently to this dynamic filter by integrating both ECIII and CA3 input pathways and potently inhibiting CA1 pyramidal neuron dendrites. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Dendritic morphology of pyramidal neurones of the visual cortex of the rat. IV: Electrical geometry.

    Science.gov (United States)

    Larkman, A U; Major, G; Stratford, K J; Jack, J J

    1992-09-08

    Features of the dendritic morphology of pyramidal neurones of the visual cortex of the rat that are relevant to the development of models of their passive electrical geometry were investigated. The sample of 39 neurones that was used came from layers 2/3 and 5. They had been recorded from and injected intracellularly with horseradish peroxidase (HRP) in vitro as part of a previous study (Larkman and Mason, J. Neurosci 10:1407, 1990). These cells had been reconstructed and measured previously by light microscopy. The relationship between the diameters of parent and daughter dendrites during branching was examined. It was found that most dendrites did not closely obey the "3/2 branch power relationship" required for representation of the dendrites as single equivalent cylinders. Estimates of total neuronal membrane area ranged from 27,100 +/- 7,900 microns2 for layer 2/3 cells to 52,200 +/- 11,800 microns2 for thick layer 5 cells. Dendritic spines contributed approximately half the total membrane area. Both neuronal input resistance and the ratio of membrane time constant to input resistance were correlated with neuronal membrane area as measured anatomically. The relative electrical lengths of the different dendrites of individual neurones were investigated, by using simple transformations to take account of the differences in diameter and spine density between dendritic segments. A novel "morphotonic" transformation is described that represents the purely morphological component of electrotonic length. Morphotonic lengths can be converted into electrotonic lengths by division by a "morphoelectric factor" ([Rm/Ri]1/2). This procedure has the advantage of separating the steps involving anatomical and electrical parameters. These transformations indicated that the dendrites of the apical terminal arbor were much longer electrically than the basal or apical oblique dendrites. In relative electrical terms, most apical oblique trees arose extremely close to the soma, and

  5. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex.

    Science.gov (United States)

    de Vivo, Luisa; Nelson, Aaron B; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-04-01

    The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

  6. Enhancement of information transmission of sub-threshold signals applied to distal positions of dendritic trees in hippocampal CA1 neuron models with stochastic resonance.

    Science.gov (United States)

    Mino, Hiroyuki; Durand, Dominique M

    2010-09-01

    Stochastic resonance (SR) has been shown to enhance the signal-to-noise ratio and detection of low level signals in neurons. It is not yet clear how this effect of SR plays an important role in the information processing of neural networks. The objective of this article is to test the hypothesis that information transmission can be enhanced with SR when sub-threshold signals are applied to distal positions of the dendrites of hippocampal CA1 neuron models. In the computer simulation, random sub-threshold signals were presented repeatedly to a distal position of the main apical branch, while the homogeneous Poisson shot noise was applied as a background noise to the mid-point of a basal dendrite in the CA1 neuron model consisting of the soma with one sodium, one calcium, and five potassium channels. From spike firing times recorded at the soma, the mutual information and information rate of the spike trains were estimated. The simulation results obtained showed a typical resonance curve of SR, and that as the activity (intensity) of sub-threshold signals increased, the maximum value of the information rate tended to increased and eventually SR disappeared. It is concluded that SR can play a key role in enhancing the information transmission of sub-threshold stimuli applied to distal positions on the dendritic trees.

  7. Comparison of the Upper Marginal Neurons of Cortical Layer 2 with Layer 2/3 Pyramidal Neurons in Mouse Temporal Cortex

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    Huan Luo

    2017-12-01

    Full Text Available Layer 2/3 (L2/3 excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs, have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS activity (neurons, L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively, evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications

  8. Comparison of the Upper Marginal Neurons of Cortical Layer 2 with Layer 2/3 Pyramidal Neurons in Mouse Temporal Cortex.

    Science.gov (United States)

    Luo, Huan; Hasegawa, Kayoko; Liu, Mingsheng; Song, Wen-Jie

    2017-01-01

    Layer 2/3 (L2/3) excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs), have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS) activity (neurons), L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively), evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD) examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications, and the

  9. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

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    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

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

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    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.

  11. The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons.

    Science.gov (United States)

    Chameau, Pascal; Inta, Dragos; Vitalis, Tania; Monyer, Hannah; Wadman, Wytse J; van Hooft, Johannes A

    2009-04-28

    Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells receive a major excitatory synaptic input via serotonin 5-HT(3) receptors. Blocking this input using pharmacological tools or neutralization of reelin signaling results in hypercomplexity of apical, but not basal, dendrites of cortical layer II/III pyramidal neurons. A similar hypercomplexity is observed in the cortex of the 5-HT(3A) receptor knockout mouse. The increased dendritic complexity can be rescued by application of recombinant full-length reelin or its N-terminal fragment, but not by the central fragment of reelin, and involves a signal transduction pathway independent of the activation of the canonical reelin receptors. Taken together, our results reveal a novel role of serotonin, Cajal-Retzius cells, and reelin in the postnatal maturation of the cortex.

  12. 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.

  13. Mechanism-Based and Input-Output Modeling of the Key Neuronal Connections and Signal Transformations in the CA3-CA1 Regions of the Hippocampus.

    Science.gov (United States)

    Geng, Kunling; Shin, Dae C; Song, Dong; Hampson, Robert E; Deadwyler, Samuel A; Berger, Theodore W; Marmarelis, Vasilis Z

    2018-01-01

    This letter examines the results of input-output (nonparametric) modeling based on the analysis of data generated by a mechanism-based (parametric) model of CA3-CA1 neuronal connections in the hippocampus. The motivation is to obtain biological insight into the interpretation of such input-output (Volterra-equivalent) models estimated from synthetic data. The insights obtained may be subsequently used to interpretat input-output models extracted from actual experimental data. Specifically, we found that a simplified parametric model may serve as a useful tool to study the signal transformations in the hippocampal CA3-CA1 regions. Input-output modeling of model-based synthetic data show that GABAergic interneurons are responsible for regulating neuronal excitation, controlling the precision of spike timing, and maintaining network oscillations, in a manner consistent with previous studies. The input-output model obtained from real data exhibits intriguing similarities with its synthetic-data counterpart, demonstrating the importance of a dynamic resonance in the system/model response around 2 Hz to 3 Hz. Using the input-output model from real data as a guide, we may be able to amend the parametric model by incorporating more mechanisms in order to yield better-matching input-output model. The approach we present can also be applied to the study of other neural systems and pathways.

  14. Neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress in rats with streptozotocin-induced type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Sang Gun Lee

    2015-01-01

    Full Text Available In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxidant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin (75 mg/kg was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental parameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels significantly increased by 20.7-21.9 mM after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons significantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modified by oxidative stress, significantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment.

  15. Action potential changes associated with the inhibitory effects on voltage-gated sodium current of hippocampal CA1 neurons by silver nanoparticles.

    Science.gov (United States)

    Liu, Zhaowei; Ren, Guogang; Zhang, Tao; Yang, Zhuo

    2009-10-29

    Nano-sized materials are now being used in medicine, biotechnology, energy, and environmental technology. Although a wide and growing number of applications for nanomaterials exist, there are limited studies available on toxicity of nanoparticles for their human risk and environmental assessment. The aim of this study was to investigate the effects of silver nanoparticles (nano-Ag) on voltage-activated sodium currents in hippocampal CA1 neurons. Nano-Ag was tested at increasing concentrations (10(-6), 5 x 10(-6), 10(-5) g/ml). The research results showed that only nano-Ag (10(-5) g/ml) reduced the amplitude of voltage-gated sodium current (I(Na)). The nano-Ag particles produced a hyperpolarizing shift in the activation-voltage curve of I(Na) and also delayed the recovery of I(Na) from inactivation. Action potential properties and the pattern of repetitive firing were examined using whole cell current-clamp recordings. Peak amplitude and overshoot of the evoked single action potential were decreased and half-width was increased in the present of the 10(-5) g/ml nano-Ag solution, and the firing rate of repetitive firing had no change. The results suggest that nano-Ag may alter the action potential of hippocampal CA1 neurons by depressing voltage-gated sodium current.

  16. Conditional bursting enhances resonant firing in neocortical layer 2-3 pyramidal neurons.

    Science.gov (United States)

    Higgs, Matthew H; Spain, William J

    2009-02-04

    The frequency response properties of neurons are critical for signal transmission and control of network oscillations. At subthreshold membrane potential, some neurons show resonance caused by voltage-gated channels. During action potential firing, resonance of the spike output may arise from subthreshold mechanisms and/or spike-dependent currents that cause afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs). Layer 2-3 pyramidal neurons (L2-3 PNs) have a fast ADP that can trigger bursts. The present study investigated what stimuli elicit bursting in these cells and whether bursts transmit specific frequency components of the synaptic input, leading to resonance at particular frequencies. We found that two-spike bursts are triggered by step onsets, sine waves in two frequency bands, and noise. Using noise adjusted to elicit firing at approximately 10 Hz, we measured the gain for modulation of the time-varying firing rate as a function of stimulus frequency, finding a primary peak (7-16 Hz) and a high-frequency resonance (250-450 Hz). Gain was also measured separately for single and burst spikes. For a given spike rate, bursts provided higher gain at the primary peak and lower gain at intermediate frequencies, sharpening the high-frequency resonance. Suppression of bursting using automated current feedback weakened the primary and high-frequency resonances. The primary resonance was also influenced by the SK channel-mediated medium AHP (mAHP), because the SK blocker apamin reduced the sharpness of the primary peak. Our results suggest that resonance in L2-3 PNs depends on burst firing and the mAHP. Bursting enhances resonance in two distinct frequency bands.

  17. Pyramidal Neurons in Different Cortical Layers Exhibit Distinct Dynamics and Plasticity of Apical Dendritic Spines

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    Michelle Tjia

    2017-06-01

    Full Text Available The mammalian cerebral cortex is typically organized in six layers containing multiple types of neurons, with pyramidal neurons (PNs being the most abundant. PNs in different cortical layers have distinct morphology, physiology and functional roles in neural circuits. Therefore, their development and synaptic plasticity may also differ. Using in vivo transcranial two-photon microscopy, we followed the structural dynamics of dendritic spines on apical dendrites of layer (L 2/3 and L5 PNs at different developmental stages. We show that the density and dynamics of spines are significantly higher in L2/3 PNs than L5 PNs in both adolescent (1 month old and adult (4 months old mice. While spine density of L5 PNs decreases during adolescent development due to a higher rate of spine elimination than formation, there is no net change in the spine density along apical dendrites of L2/3 PNs over this period. In addition, experiences exert differential impact on the dynamics of apical dendritic spines of PNs resided in different cortical layers. While motor skill learning promotes spine turnover on L5 PNs in the motor cortex, it does not change the spine dynamics on L2/3 PNs. In addition, neonatal sensory deprivation decreases the spine density of both L2/3 and L5 PNs, but leads to opposite changes in spine dynamics among these two populations of neurons in adolescence. In summary, our data reveal distinct dynamics and plasticity of apical dendritic spines on PNs in different layers in the living mouse cortex, which may arise from their distinct functional roles in cortical circuits.

  18. Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex

    DEFF Research Database (Denmark)

    Nielsen, Jakob V; Thomassen, Mads; Møllgård, Kjeld

    2014-01-01

    Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate...... that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data...... reveal a novel regulatory mechanism by which Zbtb20 suppresses the acquisition of an isocortical fate during archicortical neurogenesis to ensure commitment to a CA1 pyramidal neuron fate. We further show that the expression pattern of Zbtb20 is evolutionary conserved in the fetal human hippocampus...

  19. Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

    Science.gov (United States)

    Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-02-01

    Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. RNA interference of Marlin-1/Jakmip1 results in abnormal morphogenesis and migration of cortical pyramidal neurons.

    Science.gov (United States)

    Vidal, René L; Fuentes, Patricio; Valenzuela, José Ignacio; Alvarado-Diaz, Carlos P; Ramírez, Omar A; Kukuljan, Manuel; Couve, Andrés

    2012-08-01

    The formation of the nervous systems requires processes that coordinate proliferation, differentiation and migration of neuronal cells, which extend axons, generate dendritic branching and establish synaptic connections during development. The structural organization and dynamic remodeling of the cytoskeleton and its association to the secretory pathway are critical determinants of cell morphogenesis and migration. Marlin-1 (Jakmip1) is a microtubule-associated protein predominantly expressed in neurons and lymphoid cells. Marlin-1 participates in polarized secretion in lymphocytes, but its functional association with the neuronal cytoskeleton and its contribution to brain development have not been explored. Combining in vitro and in vivo approaches we show that Marlin-1 contributes to the establishment of neuronal morphology. Marlin-1 associates to the cytoskeleton in neurites, is required for the maintenance of an intact Golgi apparatus and its depletion produces the down-regulation of kinesin-1, a plus-end directed molecular motor with a central function in morphogenesis and migration. RNA interference of Marlin-1 in vivo results in abnormal migration of newborn pyramidal neurons during the formation of the cortex. Our results support the involvement of Marlin-1 in the acquisition of the complex architecture and migration of pyramidal neurons, two fundamental processes for the laminar layering of the cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Kv1 channels control spike threshold dynamics and spike timing in cortical pyramidal neurones.

    Science.gov (United States)

    Higgs, Matthew H; Spain, William J

    2011-11-01

    Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na(+) channel inactivation is the primary mechanism of threshold accommodation, the possible role of K(+) channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2-3 PNs, using α-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs.

  2. Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons.

    Science.gov (United States)

    Szulczyk, Bartlomiej; Nurowska, Ewa

    2017-09-16

    Valproic acid is frequently prescribed and used to treat epilepsy, bipolar disorder and other conditions. However, the mechanism of action of valproic acid has not been fully elucidated. The aim of this study was to assess the influence of valproic acid (200 μM) on TTX-resistant sodium currents in mPFC pyramidal neurons. Valproic acid inhibited the maximal amplitude and did not change the activation parameters of TTX-resistant sodium currents. Moreover, valproic acid (2 μM and 200 μM) shifted the TTX-resistant sodium channel inactivation curve towards hyperpolarisation. In the presence of valproic acid, TTX-resistant sodium currents recovered from inactivation more slowly. Valproic acid did not influence the use-dependent blockade of TTX-resistant sodium currents. This study suggests that a potential new mechanism of the antiepileptic action of valproic acid is, among others, inhibition of TTX-resistant sodium currents. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

    Science.gov (United States)

    Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

    2017-06-15

    TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α1, α2, β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β1 but not of α1- and α2-adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Science.gov (United States)

    Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

    2015-01-01

    This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

  5. Dendritic mRNAs encode diversified functionalities in hippocampal pyramidal neurons

    Directory of Open Access Journals (Sweden)

    Bloch Lisa M

    2006-02-01

    Full Text Available Abstract Background Targeted transport of messenger RNA and local protein synthesis near the synapse are important for synaptic plasticity. In order to gain an overview of the composition of the dendritic mRNA pool, we dissected out stratum radiatum (dendritic lamina from rat hippocampal CA1 region and compared its mRNA content with that of stratum pyramidale (cell body layer using a set of cDNA microarrays. RNAs that have over-representation in the dendritic fraction were annotated and sorted into function groups. Results We have identified 154 dendritic mRNA candidates, which can be arranged into the categories of receptors and channels, signaling molecules, cytoskeleton and adhesion molecules, and factors that are involved in membrane trafficking, in protein synthesis, in posttranslational protein modification, and in protein degradation. Previously known dendritic mRNAs such as MAP2, calmodulin, and G protein gamma subunit were identified from our screening, as were mRNAs that encode proteins known to be important for synaptic plasticity and memory, such as spinophilin, Pumilio, eEF1A, and MHC class I molecules. Furthermore, mRNAs coding for ribosomal proteins were also found in dendrites. Conclusion Our results suggest that neurons transport a variety of mRNAs to dendrites, not only those directly involved in modulating synaptic plasticity, but also others that play more common roles in cellular metabolism.

  6. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    Science.gov (United States)

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    the basal but not the apical dendrites of CA1 pyramidal neurons from rats chronically treated with caffeine, in comparison with their age- and littermate-matched controls. Altogether, the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging, and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Changes in neuronal excitability by activated microglia: Differential Na+ current up-regulation in pyramid-shaped and bipolar neurons by TNF-α and IL-18

    Directory of Open Access Journals (Sweden)

    Lars eKlapal

    2016-03-01

    Full Text Available Microglia are activated during pathological events in the brain and are capable of releasing various types of inflammatory cytokines. Here we demonstrate that the addition of 5% microglia activated by 1 µg/ml lipopolysaccharides (LPS to hippocampal cultures up-regulates Na+ current densities (INavD of bipolar as well as pyramid-shaped neurons, thereby increasing their excitability. Deactivation of microglia by the addition of 10 ng/ml transforming growth factor-β (TGF-β decreases INavD below control levels suggesting that the residual activated microglial cells influence neuronal excitability in control cultures. Preincubation of hippocampal cultures with 10 ng/ml tumor necrosis factor-α (TNF-α, a major cytokine released by activated microglia, up-regulated INavD significantly by ~30% in bipolar cells, whereas in pyramid-shaped cells the up-regulation only reached an increase of ~14%. Incubation of the cultures with antibodies against either TNF-receptor 1 or 2 blocked the up-regulation of INavD in bipolar cells, whereas in pyramid-shaped cells increases in INavD were exclusively blocked by antibodies against TNF-receptor 2, suggesting that both cell types respond differently to TNF-α exposure. Since additional cytokines, such as interleukin-18 (IL-18, are released from activated microglia we tested potential effects of IL-18 on INavD in both cell types. Exposure to 5-10 ng/ml IL-18 for 4 days increased INavD in both pyramid-shaped as well as bipolar neurons, albeit the dose-response curves were shifted to lower concentrations in bipolar cells. Our results suggest that by secretion of cytokines microglial cells up-regulate Na+ current densities in bipolar and pyramid-shaped neurons to some extent differentially. Depending on the exact cytokine composition and concentration released this could change the balance between the activity of inhibitory bipolar and excitatory pyramid-shaped cells. Since bipolar cells show a larger up-regulation of

  8. Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor.

    Science.gov (United States)

    van der Velden, Luuk; van Hooft, Johannes A; Chameau, Pascal

    2012-09-01

    We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT(3) receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT(3A) receptor showed exuberant apical dendrites of these cortical pyramidal neurons. Because model studies have shown the role of dendritic morphology on neuronal firing pattern, we used the 5-HT(3A) knockout mouse to explore the impact of dendritic hypercomplexity on the electrophysiological properties of this specific class of neurons. Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex.

  9. Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias.

    Science.gov (United States)

    Foster, Vincent; Oakley, Arthur E; Slade, Janet Y; Hall, Roslyn; Polvikoski, Tuomo M; Burke, Matthew; Thomas, Alan J; Khundakar, Ahmad; Allan, Louise M; Kalaria, Raj N

    2014-09-01

    Dementia associated with cerebrovascular disease is common. It has been reported that ∼30% of elderly patients who survive stroke develop delayed dementia (post-stroke dementia), with most cases being diagnosed as vascular dementia. The pathological substrates associated with post-stroke or vascular dementia are poorly understood, particularly those associated with executive dysfunction. Three separate yet interconnecting circuits control executive function within the frontal lobe involving the dorsolateral prefrontal cortex, anterior cingulate cortex and the orbitofrontal cortex. We used stereological methods, along with immunohistological and related cell morphometric analysis, to examine densities and volumes of pyramidal neurons of the dorsolateral prefrontal cortex, anterior cingulate cortex and orbitofrontal cortex in the frontal lobe from a total of 90 elderly subjects (age range 71-98 years). Post-mortem brain tissues from post-stroke dementia and post-stroke patients with no dementia were derived from our prospective Cognitive Function After Stroke study. We also examined, in parallel, samples from ageing controls and similar age subjects pathologically diagnosed with Alzheimer's disease, mixed Alzheimer's disease and vascular dementia, and vascular dementia. We found pyramidal cell volumes in layers III and V in the dorsolateral prefrontal cortex of post-stroke and vascular dementia and, of mixed and Alzheimer's disease subjects to be reduced by 30-40% compared to post-stroke patients with no dementia and controls. There were no significant changes in neuronal volumes in either the anterior cingulate or orbitofrontal cortices. Remarkably, pyramidal neurons within the orbitofrontal cortex were also found to be smaller in size when compared to those in the other two neocortical regions. To relate the cell changes to cognitive function, we noted significant correlations between neuronal volumes and total CAMCOG, orientation and memory scores and clinical

  10. Layer- and column-specific knockout of NMDA receptors in pyramidal neurons of the mouse barrel cortex.

    Directory of Open Access Journals (Sweden)

    Rachel Aronoff

    2007-11-01

    Full Text Available Viral vectors injected into the mouse brain offer the possibility for localized genetic modifications in a highly controlled manner. Lentivector injection into mouse neocortex transduces cells within a diameter of approximately 200µm, which closely matches the lateral scale of a column in barrel cortex. The depth and volume of the injection determines which cortical layer is transduced. Furthermore, transduced gene expression from the lentivector can be limited to predominantly pyramidal neurons by using a 1.3kb fragment of the αCaMKII promoter. This technique therefore allows genetic manipulation of a specific cell type in defined columns and layers of the neocortex. By expressing Cre recombinase from such a lentivector in gene-targeted mice carrying a floxed gene, highly specific genetic lesions can be induced. Here, we demonstrate the utility of this approach by specifically knocking out NMDA receptors (NMDARs in pyramidal neurons in the somatosensory barrel cortex of gene-targeted mice carrying floxed NMDAR 1 genes. Neurons transduced with lentivector encoding GFP and Cre recombinase exhibit not only reductions in NMDAR 1 mRNA levels, but reduced NMDAR-dependent currents and pairing-induced synaptic potentiation. This technique for knockout of NMDARs in a cell type, column- and layer-specific manner in the mouse somatosensory cortex may help further our understanding of the functional roles of NMDARs in vivo during sensory perception and learning.

  11. Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

    Science.gov (United States)

    Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T

    2017-06-21

    The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period.SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship

  12. Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity.

    Science.gov (United States)

    Courchesne, Eric; Pierce, Karen

    2005-01-01

    While abnormalities in head circumference in autism have been observed for decades, it is only recently that scientists have begun to focus in on the developmental origins of such a phenomenon. In this article we review past and present literature on abnormalities in head circumference, as well as recent developmental MRI studies of brain growth in this disorder. We hypothesize that brain growth abnormalities are greatest in frontal lobes, particularly affecting large neurons such as pyramidal cells, and speculate how this abnormality might affect neurofunctional circuitry in autism. The relationship to clinical characteristics and other disorders of macrencephaly are discussed.

  13. Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function.

    Science.gov (United States)

    Elston, Guy N

    2003-11-01

    Arguably the most complex cortical functions are seated in human cognition, the how and why of which have been debated for centuries by theologians, philosophers and scientists alike. In his best-selling book, An Astonishing Hypothesis: A Scientific Search for the Soul, Francis Crick refined the view that these qualities are determined solely by cortical cells and circuitry. Put simply, cognition is nothing more, or less, than a biological function. Accepting this to be the case, it should be possible to identify the mechanisms that subserve cognitive processing. Since the pioneering studies of Lorent de Nó and Hebb, and the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a few, much attention has been focused on the role of persistent neural activity in cognitive processes. Application of modern technologies and modelling techniques has led to new hypotheses about the mechanisms of persistent activity. Here I focus on how regional variations in the pyramidal cell phenotype may determine the complexity of cortical circuitry and, in turn, influence neural activity. Data obtained from thousands of individually injected pyramidal cells in sensory, motor, association and executive cortex reveal marked differences in the numbers of putative excitatory inputs received by these cells. Pyramidal cells in prefrontal cortex have, on average, up to 23 times more dendritic spines than those in the primary visual area. I propose that without these specializations in the structure of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. I also present data from both New World and Old World monkeys that show varying degrees of complexity in the pyramidal cell phenotype in their prefrontal cortices, suggesting that cortical circuitry and, thus, cognitive styles are evolving independently in different species.

  14. Muscarinic receptor control of pyramidal neuron membrane potential in the medial prefrontal cortex (mPFC) in rats.

    Science.gov (United States)

    Kurowski, P; Gawlak, M; Szulczyk, P

    2015-09-10

    Damage to the cholinergic input to the prefrontal cortex has been implicated in neuropsychiatric disorders. Cholinergic endings release acetylcholine, which activates nicotinic and/or G-protein-coupled muscarinic receptors. Muscarinic receptors activate transduction systems, which control cellular effectors that regulate the membrane potential in medial prefrontal cortex (mPFC) neurons. The mechanisms responsible for the cholinergic-dependent depolarization of mPFC layer V pyramidal neurons in slices obtained from young rats were elucidated in this study. Glutamatergic and GABAergic transmission as well as tetrodotoxin (TTX)-sensitive Na(+) and voltage-dependent Ca(++) currents were eliminated. Cholinergic receptor stimulation by carbamoylcholine chloride (CCh; 100 μM) evoked depolarization (10.0 ± 1.3 mV), which was blocked by M1/M4 (pirenzepine dihydrochloride, 2 μM) and M1 (VU 0255035, 5 μM) muscarinic receptor antagonists and was not affected by a nicotinic receptor antagonist (mecamylamine hydrochloride, 10 μM). CCh-dependent depolarization was attenuated by extra- (20 μM) or intracellular (50 μM) application of an inhibitor of the βγ-subunit-dependent transduction system (gallein). It was also inhibited by intracellular application of a βγ-subunit-binding peptide (GRK2i, 10μM). mPFC pyramidal neurons express Nav1.9 channels. CCh-dependent depolarization was abolished in the presence of antibodies against Nav1.9 channels in the intracellular solution and augmented by the presence of ProTx-I toxin (100 nM) in the extracellular solution. CCh-induced depolarization was not affected by the following reagents: intracellular transduction system blockers, including U-73122 (10 μM), chelerythrine chloride (5 μM), SQ 22536 (100 μM) and H-89 (2 μM); channel blockers, including Ba(++) ions (200 μM), apamin (100 nM), flufenamic acid (200 μM), 2-APB (200 μM), SKF 96365 (50 μM), and ZD 7288 (50 μM); and a Na(+)/Ca(++) exchanger blocker, benzamil (20

  15. Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through α4β2 nAChR subtype-mediated mechanisms.

    Science.gov (United States)

    Piao, M-H; Liu, Y; Wang, Y-S; Qiu, J-P; Feng, C-S

    2013-10-01

    Volatile anesthetic isoflurane contributes to postoperative cognitive dysfunction and inhibition of long-term potentiation (LTP), a synaptic model of learning and memory, but the mechanisms are uncertain. Central neuronal α4β2 subtype nicotinic acetylcholine receptors (nAChRs) are involved in the induction of LTP in the hippocampus. Isoflurane inhibits α4β2 nAChRs at concentrations lower than those used for anesthesia. Therefore, we hypothesized that isoflurane-inhibited LTP induction of hippocampal CA1 neurons via α4β2 nAChRs subtype inhibition. Transverse hippocampal slices (400μm thick) were obtained from male rats (6-8 weeks old). Population spikes were evoked using extracellular electrodes by electrical stimulation of the Schaffer collateral-commissural pathway of rat hippocampal slices. LTP was induced using high frequency stimulation (HFS; 100Hz, 1s). Clinically relevant concentrations (0.125-0.5mM) of isoflurane with or without nicotine (nAChRs agonist), mecamylamine (nAChRs antagonist), 3-[2(S)-2-azetidinylmethoxy] pyridine (A85380) and epibatidine (α4β2 nAChRs agonist), dihydro β erythroidine (DHβE) (α4β2 nAChRs antagonist) were added to the perfusion solution 20min before HFS to test their effects on LTP by HFS respectively. A brief HFS induced stable LTP in rat hippocampal slices, but LTP was significantly inhibited in the presence of isoflurane at concentrations of 0.125-0.5mM. The inhibitive effect of isoflurane on LTP was not only reversible and could be prevented by nAChRs agonist nicotine and α4β2 nAChRs agonist A85380 and epibatidine, but also mimicked and potentiated by nAChRs antagonist mecamylamine and α4β2 nAChRs antagonist DHβE. Inhibition of α4β2 nAChRs subtype of hippocampus participates in isoflurane-mediated LTP inhibition. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  16. Effects of 15 Hz square wave magnetic fields on the voltage-gated sodium and potassium channels in prefrontal cortex pyramidal neurons.

    Science.gov (United States)

    Zheng, Yu; Dou, Jun-Rong; Gao, Yang; Dong, Lei; Li, Gang

    2017-04-01

    Although magnetic fields have significant effects on neurons, little is known about the mechanisms behind their effects. The present study aimed to measure the effects of magnetic fields on ion channels in cortical pyramidal neurons. Cortical pyramidal neurons of Kunming mice were isolated and then subjected to 15 Hz, 1 mT square wave (duty ratio 50%) magnetic fields stimulation. Sodium currents (INa), transient potassium currents (IA) and delayed rectifier potassium currents (IK) were recorded by whole-cell patch clamp method. We found that magnetic field exposure depressed channel current densities, and altered the activation kinetics of sodium and potassium channels. The inactivation properties of INa and IA were also altered. Magnetic field exposure alters ion channel function in neurons. It is likely that the structures of sodium and potassium channels were influenced by the applied field. Sialic acid, which is an important component of the channels, could be the molecule responsible for the reported results.

  17. Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor.

    NARCIS (Netherlands)

    van der Velden, L.; van Hooft, J.A.; Chameau, P.

    2012-01-01

    We have previously shown that the serotonergic input on Cajal-Retzius cells, mediated by 5-HT3 receptors, plays an important role in the early postnatal maturation of the apical dendritic trees of layer 2/3 pyramidal neurons. We reported that knockout mice lacking the 5-HT(3A) receptor showed

  18. Sodium Dynamics in Pyramidal Neuron Dendritic Spines: Synaptically Evoked Entry Predominantly through AMPA Receptors and Removal by Diffusion.

    Science.gov (United States)

    Miyazaki, Kenichi; Ross, William N

    2017-10-11

    Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties using newly developed simultaneous sodium and calcium imaging with single-spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high-speed, low-noise CCD camera. Following subthreshold electrical stimulation, postsynaptic sodium entry is almost entirely through AMPA receptors with little contribution from entry through NMDA receptors or voltage-gated sodium channels. Sodium removal from the spine head is through rapid diffusion out to the dendrite through the spine neck with a half-removal time of ∼16 ms, which suggests the neck has low resistance. Peak [Na(+)]i changes during single EPSPs are ∼5 mm Stronger electrical stimulation evoked small plateau potentials that had significant longer-lasting localized [Na(+)]i increases mediated through NMDA receptors.SIGNIFICANCE STATEMENT Dendritic spines, small structures that are difficult to investigate, are important elements in the fundamental processes of synaptic integration and plasticity. The main tool for examining these structures has been calcium imaging. However, the kinds of information that calcium imaging reveals is limited. We used newly developed, high-speed, simultaneous sodium and calcium imaging to examine ion dynamics in spines in hippocampal pyramidal neurons. We found that following single subthreshold synaptic activation most sodium entry was through AMPA receptors and not through NMDA receptors or through voltage-gated sodium channels and that the spine neck is not a significant resistance barrier. Most spine mechanisms are linear. However, regenerative NMDA conductances can be activated with stronger stimulation

  19. Physiology and morphology of inverted pyramidal neurons in the rodent neocortex.

    Science.gov (United States)

    Steger, R M; Ramos, R L; Cao, R; Yang, Q; Chen, C-C; Dominici, J; Brumberg, J C

    2013-09-17

    An increasing number of studies indicate that there exists greater diversity of cortical neurons than previously appreciated. In the present report, we use a combination of physiological and morphological methods to characterize cortical neurons in infragranular layers with apical dendrites pointing toward the white-matter compared to those neurons with apical dendrites pointing toward the pia in both mouse and rat neocortex. Several features of the dendritic morphology and intrinsic and synaptic physiology of these "inverted" neurons revealed numerous differences among this cell type between species. We also found differences between the different cell types within the same species. These data reveal that similar cell types in the rat and mouse may not always share similar physiological and morphological properties. These data are relevant to models of information processing through micro- and larger neocortical circuits and indicate that different cell types found within similar lamina can have different functional properties. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Assessment of the effect of etomidate on voltage-gated sodium channels and action potentials in rat primary sensory cortex pyramidal neurons.

    Science.gov (United States)

    Zhang, Yu; He, Jiong-ce; Liu, Xing-kui; Zhang, Yi; Wang, Yuan; Yu, Tian

    2014-08-05

    Although it is known that general anesthetics can suppress cortical neurons׳ activity, the underlying mechanisms are still poorly understood, especially the kinetic changes of voltage-gated Na(+) channels, which are mostly related to neuronal excitability. Some general anesthetics have been reported to affect the voltage-gated Na(+) channels in cell culture derived from humans and animals. However no one has ever investigated the effects of etomidate on voltage-gated Na(+) channels in pyramidal neurons using a brain slice. The present study uses a whole cell patch-clamp technique to investigate the changes of voltage-gated Na(+) channels on primary somatosensory cortex pyramidal neurons under the influence of etomidate. We found that etomidate dose-dependently inhibited Na(+) currents of primary somatosensory cortex pyramidal neurons, while shifted the steady-state inactivation curve towards the left and prolonged the recovery time from inactivation. Conversely, etomidate has no effects on the steady-state activation curve. We demonstrated the detailed suppression process of neural voltage-gated Na(+) channels by etomidate on slice condition. This may offer new insights into the mechanical explanation for the etomidate anesthesia. Finding the effects of anesthetics on primary somatosensory cortex also provides evidence to help elucidate the potential mechanism by which tactile information integrates during general anesthesia. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Delayed neuronal migration of protein kinase C gamma immunoreactive cells in hippocampal CA1 area after 48 h of moderate hypoxemia in the near term ovine fetus

    NARCIS (Netherlands)

    Douma, BRK; Nyakas, C; Luiten, PGM; Aarnoudse, JG

    1999-01-01

    The brain is uniquely sensitive to disturbances in energy and oxygen supply, particularly during the early stage of life. Since hypoxemia can indirectly activate the intracellular messenger protein kinase C (PKC), we studied the PKC gamma-immunoreaction in the fetal hippocampal CA1 region of naive

  2. Delayed neuronal migration of protein kinase Cγ immunoreactive cells in hippocampal CA1 area after 48 h of moderate hypoxemia in the near term ovine fetus

    NARCIS (Netherlands)

    Braaksma, Margriethe A; Douma, Bas R K; Nyakas, Csaba; Luiten, Paul G.M.; Aarnoudse, Jan G

    1999-01-01

    The brain is uniquely sensitive to disturbances in energy and oxygen supply, particularly during the early stage of life. Since hypoxemia can indirectly activate the intracellular messenger protein kinase C (PKC), we studied the PKCγ-immunoreaction in the fetal hippocampal CA1 region of naive (n=4),

  3. Dopamine D2 Receptors Modulate Pyramidal Neurons in Mouse Medial Prefrontal Cortex through a Stimulatory G-Protein Pathway.

    Science.gov (United States)

    Robinson, Sarah E; Sohal, Vikaas S

    2017-10-18

    Dopaminergic modulation of prefrontal cortex (PFC) is thought to play key roles in many cognitive functions and to be disrupted in pathological conditions, such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically projecting (SC) pyramidal neurons within L5 of the PFC. These D2R-induced ADPs only occur following synaptic input, which activates NMDARs, even when the delay between the synaptic input and ADPs is relatively long (e.g., several hundred milliseconds). Here, we use a combination of electrophysiological, optogenetic, pharmacological, transgenic, and chemogenetic approaches to elucidate cellular mechanisms underlying this phenomenon in male and female mice. We find that knocking out D2Rs eliminates the ADP in a cell-autonomous fashion, confirming that this ADP depends on D2Rs. Hyperpolarizing current injection, but not AMPA receptor blockade, prevents synaptic stimulation from facilitating D2R-induced ADPs, suggesting that this phenomenon depends on the recruitment of voltage-dependent currents (e.g., NMDAR-mediated Ca 2+ influx) by synaptic input. Finally, the D2R-induced ADP is blocked by inhibitors of cAMP/PKA signaling, insensitive to pertussis toxin or β-arrestin knock-out, and mimicked by G s -DREADD stimulation, suggesting that D2R activation elicits the ADP by stimulating cAMP/PKA signaling. These results show that this unusual physiological phenomenon, in which D2Rs enhance cellular excitability in a manner that depends on synaptic input, is mediated at the cellular level through the recruitment of signaling pathways associated with G s , rather than the G i/o -associated mechanisms that have classically been ascribed to D2Rs. SIGNIFICANCE STATEMENT Dopamine D2 receptors (D2Rs) in the prefrontal cortex (PFC) are thought to play important roles in behaviors, including working memory and cognitive flexibility. Variation in D2Rs has also been

  4. Coincident Generation of Pyramidal Neurons and Protoplasmic Astrocytes in Neocortical Columns

    Science.gov (United States)

    Magavi, Sanjay; Friedmann, Drew; Banks, Garrett; Stolfi, Alberto

    2012-01-01

    Astrocytes, one of the most common cell types in the brain, are essential for processes ranging from neural development through potassium homeostasis to synaptic plasticity. Surprisingly, the developmental origins of astrocytes in the neocortex are still controversial. To investigate the patterns of astrocyte development in the neocortex we examined cortical development in a transgenic mouse in which a random, sparse subset of neural progenitors undergoes CRE/lox recombination, permanently labeling their progeny. We demonstrate that neural progenitors in neocortex generate discrete columnar structures that contain both projection neurons and protoplasmic astrocytes. Ninety-five percent of developmental cortical columns labeled in our system contained both astrocytes and neurons. The astrocyte to neuron ratio of labeled cells in a developmental column was 1:7.4, similar to the overall ratio of 1:8.4 across the entire gray matter of the neocortex, indicating that column-associated astrocytes account for the majority of protoplasmic astrocytes in neocortex. Most of the labeled columns contained multiple clusters of several astrocytes. Dividing cells were found at the base of neuronal columns at the beginning of gliogenesis, and later within the cortical layers, suggesting a mechanism by which astrocytes could be distributed within a column. These data indicate that radial glia are the source of both neurons and astrocytes in the neocortex, and that these two cell types are generated in a spatially restricted manner during cortical development. PMID:22492032

  5. Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via alpha4 beta2* nicotinic receptor activation

    Directory of Open Access Journals (Sweden)

    L. Andrew Bell

    2015-04-01

    Full Text Available Acetylcholine (ACh release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP-expressing interneurons that selectively innervate other interneurons (VIP/IS were excited by ACh through the activation of nicotinic receptors containing alpah4 and beta2 subunits (alpha4 beta2*. ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC barrages blocked by dihydro-beta-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by 42* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of 42* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.

  6. Disinhibition mediates a form of hippocampal long-term potentiation in area CA1.

    Directory of Open Access Journals (Sweden)

    Jake Ormond

    Full Text Available The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs followed rapidly by feedforward (disynaptic inhibitory postsynaptic potentials (IPSPs. Long-term potentiation (LTP of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs, required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

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

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Czéh, Boldizsár; Fuchs, Eberhard

    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

  8. The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

    NARCIS (Netherlands)

    Chameau, P.; Inta, D.; Vitalis, T.; Monyer, H.; Wadman, W.J.; van Hooft, J.A.

    2009-01-01

    Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells

  9. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

    NARCIS (Netherlands)

    den Boon, F.S.; Chameau, P.; Schaafsma-Zhao, Q.; van Aken, W.; Bari, M.; Oddi, S.; Kruse, C.G.; Maccarrone, M.; Wadman, W.J.; Werkman, T.R.

    2012-01-01

    The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that

  10. Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Hallermann, Stefan; Stuart, Greg J.

    2006-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of single Ih channels in the apical dendrites of

  11. Anemone toxin (ATX II)-induced increase in persistent sodium current: effects on the firing properties of rat neocortical pyramidal neurones

    Science.gov (United States)

    Mantegazza, Massimo; Franceschetti, Silvana; Avanzini, Giuliano

    1998-01-01

    The experiments were performed on sensorimotor cortex using current-clamp intracellular recordings in layer V pyramidal neurones and whole-cell voltage-clamp recordings in dissociated pyramidal neurones. The intracellularly recorded neurones were classified on the basis of their firing characteristics as intrinsically bursting (IB) and regular spiking (RS). The RS neurones were further subdivided into adapting (RSAD) or non-adapting (RSNA), depending on the presence or absence of spike frequency adaptation. Since burst firing in neocortical pyramidal neurones has previously been suggested to depend on the persistent fraction of Na+ current (INa,p), pharmacological manipulations with drugs affecting INa inactivation have been employed. ATX II, a toxin derived from Anemonia sulcata, selectively inhibited INa fast inactivation in dissociated neurones. In current-clamp experiments on neocortical slices, ATX II enhanced the naturally occurring burst firing in IB neurones and revealed the ability of RSNA neurones to discharge in bursts, whereas in RSAD neurones it increased firing frequency, without inducing burst discharges. During the ATX II effect, in all the three neuronal subclasses, episodes of a metastable condition occurred, characterized by long-lasting depolarizing shifts, triggered by action potentials, which were attributed to a peak in the toxin-induced inhibition of INa inactivation. The ATX II effect on IB and RSNA neurones was compared with that induced by veratridine and iodoacetamide. Veratridine induced a small increase in the INa and a large shift to the left in the voltage dependence of INa activation. Accordingly, its major effect on firing characteristics was the induction of prolonged tonic discharges, associated with burst facilitation less pronounced than that induced by ATX II. The alkylating agent iodoacetamide was able to induce a selective small increase in the INa,p, with a similar but less pronounced effect than ATX II on firing behaviour

  12. Steady-state dynamics and experience-dependent plasticity of dendritic spines of layer 4/5a pyramidal neurons in somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Amaya Miquelajauregui

    2014-04-01

    Full Text Available The steady state dynamics and experience-dependent plasticity of dendritic spines of layer (L 2/3 and L5B cortical pyramidal neurons have recently been assessed using in vivo two-photon microscopy (Trachtenberg et al., 2002; Zuo et al., 2005; Holtmaat et al., 2006. In contrast, not much is known about spine dynamics in L4/5a neurons, regarded as direct recipients of thalamocortical input (Constantinople and Bruno, 2013. In the adult mouse somatosensory cortex (SCx, the transcription factor Ebf2 is enriched in excitatory neurons of L4/5a, including pyramidal neurons. We assessed the molecular and electrophysiological properties of these neurons as well as the morphology of their apical tufts (Scholl analysis and cortical outputs (optogenetics within the SCx. To test the hypothesis that L4/5a pyramidal neurons play an important role in sensory processing (given their key laminar position; soma depth ~450-480 µm, we successfully labeled them in Ebf2-Cre mice with EGFP by expressing recombinant rAAV vectors in utero. Using longitudinal in vivo two-photon microscopy through a craniotomy (Mostany and Portera-Cailliau, 2008, we repeatedly imaged spines in apical dendritic tufts of L4/5a neurons under basal conditions and after sensory deprivation. Under steady-state conditions in adults, the morphology of the apical tufts and the mean spine density were stable at 0.39 ± 0.05 spines/μm (comparable to L5B, Mostany et al., 2011. Interestingly, spine elimination increases 4-8 days after sensory deprivation, probably due to input loss. This suggests that Ebf2+ L4/5a neurons could be involved in early steps of processing of thalamocortical information.

  13. Down-regulation of synaptic GluN2B subunit-containing N-methyl-D-aspartate receptors: a physiological brake on CA1 neuron α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hyperexcitability during benzodiazepine withdrawal.

    Science.gov (United States)

    Shen, Guofu; Tietz, Elizabeth I

    2011-01-01

    A significant link was previously established between benzodiazepine withdrawal anxiety and a progressive increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) potentiation in hippocampal CA1 neurons from rats withdrawn up to 2 days from 1-week oral administration of the benzodiazepine flurazepam (FZP). Despite AMPAR current potentiation, withdrawal anxiety was masked by a 2-fold reduction in CA1 neuron N-methyl-D-aspartate receptor (NMDAR) currents since preinjection of an NMDA antagonist restored NMDAR currents and unmasked anxiety in 2-day FZP-withdrawn rats. In the current study, GluN subunit levels in postsynaptic density (PSD)-enriched subfractions of CA1 minislices were compared with GluN2B-mediated whole-cell currents evoked in CA1 neurons in hippocampal slices from 1- and 2-day FZP-withdrawn rats. GluN1 and GluN2B, although not the phosphoSer1303-GluN2B ratio or GluN2A subunit levels, were decreased in PSD subfractions from 2-day, but not 1-day, FZP-withdrawn rats. Consistent with immunoblot analyses, GluN2B-mediated NMDAR currents evoked in slices from 2-day FZP-withdrawn rats were decreased in the absence, but not the presence, of the GluN2B subunit-selective antagonist ifenprodil. In contrast, ifenprodil-sensitive NMDAR currents were unchanged in slices from 1-day withdrawn rats. Because AMPA (1 μM) preincubation of slices from 1-day FZP-withdrawn rats induced depression of GluN2B subunit-mediated currents, depression of NMDAR currents was probably secondary to AMPAR potentiation. CA1 neuron NMDAR currents were depressed ∼50% after 2-day withdrawal and offset potentiation of AMPAR-mediated currents, leaving total charge transfer unchanged between groups. Collectively, these findings suggest that a reduction of GluN2B-containing NMDAR may serve as a homeostatic feedback mechanism to modulate glutamatergic synaptic strength during FZP withdrawal to alleviate benzodiazepine withdrawal symptoms.

  14. Ischemia leads to apoptosis--and necrosis-like neuron death in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Stadelmann, Christine; Bastholm, Lone

    2004-01-01

    pyramidal cells of the rat hippocampus. The earliest ischemic changes were found on day 2 and 3, reflected by an upregulation of phospho-c-Jun in a proportion of morphologically intact CA1 neurons, which matched the number of neurons that succumbed to ischemia at later time points. At day 3 and later 3...... and/or caspase-3 expression represented a minor fraction (neurons, while the vast majority followed a necrosis-like pathway. Our studies suggest that CA1 pyramidal cell death following transient forebrain ischemia may be initiated through c-Jun N-terminal kinase (JNK) pathway...

  15. Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons.

    Science.gov (United States)

    Woodward, Nicholas C; Pakbin, Payam; Saffari, Arian; Shirmohammadi, Farimah; Haghani, Amin; Sioutas, Constantinos; Cacciottolo, Mafalda; Morgan, Todd E; Finch, Caleb E

    2017-05-01

    Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, changes in the hippocampal CA1 region, with neurite atrophy (-25%), decreased MBP (-50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (-40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age-ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer's disease. We propose that TRAP-associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans

    OpenAIRE

    Bianchi, Serena; Stimpson, Cheryl D.; Duka, Tetyana; Larsen, Michael D.; Janssen, William G. M.; Collins, Zachary; Bauernfeind, Amy L.; Schapiro, Steven J.; Baze, Wallace B.; McArthur, Mark J; Hopkins, William D.; Wildman, Derek E.; Lipovich, Leonard; Kuzawa, Christopher W.; Jacobs, Bob

    2013-01-01

    Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relativ...

  17. Glutamatergic neurons of the mouse medial septum and diagonal band of Broca synaptically drive hippocampal pyramidal cells: relevance for hippocampal theta rhythm.

    Science.gov (United States)

    Huh, Carey Y L; Goutagny, Romain; Williams, Sylvain

    2010-11-24

    Neurons of the medial septum and diagonal band of Broca (MS-DBB) provide an important input to the hippocampus and are critically involved in learning and memory. Although cholinergic and GABAergic MS-DBB neurons are known to modulate hippocampal activity, the role of recently described glutamatergic MS-DBB neurons is unknown. Here, we examined the electrophysiological properties of glutamatergic MS-DBB neurons and tested whether they provide a functional synaptic input to the hippocampus. To visualize the glutamatergic neurons, we used MS-DBB slices from transgenic mice in which the green fluorescent protein is expressed specifically by vesicular glutamate transporter 2-positive neurons and characterized their properties using whole-cell patch-clamp technique. For assessing the function of the glutamatergic projection, we used an in vitro septohippocampal preparation, electrically stimulated the fornix or chemically activated the MS-DBB using NMDA microinfusions and recorded postsynaptic responses in CA3 pyramidal cells. We found that glutamatergic MS-DBB neurons as a population display a highly heterogeneous set of firing patterns including fast-, cluster-, burst-, and slow-firing. Remarkably, a significant proportion exhibited fast-firing properties, prominent I(h), and rhythmic spontaneous firing at theta frequencies similar to those found in GABAergic MS-DBB neurons. Activation of the MS-DBB led to fast, AMPA receptor-mediated glutamatergic responses in CA3 pyramidal cells. These results describe for the first time the electrophysiological signatures of glutamatergic MS-DBB neurons, their rhythmic firing properties, and their capacity to drive hippocampal principal neurons. Our findings suggest that the glutamatergic septohippocampal pathway may play an important role in hippocampal theta oscillations and relevant cognitive functions.

  18. 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

  19. Micro RNA detection in long-term fixed tissue of cortical glutamatergic pyramidal neurons after targeted laser-capture neuroanatomical microdissection.

    Science.gov (United States)

    Herai, Roberto R; Stefanacci, Lisa; Hrvoj-Mihic, Branka; Chailangkarn, Thanathom; Hanson, Kari; Semendeferi, Katerina; Muotri, Alysson R

    2014-09-30

    Formalin fixation (FF) is the standard and most common method for preserving postmortem brain tissue. FF stabilizes cellular morphology and tissue architecture, and can be used to study the distinct morphologic and genetic signatures of different cell types. Although the procedure involved in FF degrades messenger RNA over time, an alternative approach is to use small RNAs (sRNAs) for genetic analysis associated with cell morphology. Although genetic analysis is carried out on fresh or frozen tissue, there is limited availability or impossibility on targeting specific cell populations, respectively. The goal of this study is to detect miRNA and other classes of sRNA stored in formalin or in paraffin embedded for over decades. Two brain samples, one formed by a mixed population of cortical and subcortical cells, and one formed by pyramidal shaped cells collected by laser-capture microdissection, were subjected to sRNA sequencing. Performing bioinformatics analysis over the sequenced sRNA from brain tissue, we detected several classes of sRNA, such as miRNAs that play key roles in brain neurodevelopmental and maintenance pathways, and hsa-mir-155 expression in neurons. Comparison with existing method: Our method is the first to combine the approaches for: laser-capture of pyramidal neurons from long-term formalin-fixed brain; extract sRNA from laser-captured pyramidal neurons; apply a suite of bioinformatics tools to detect miRNA and other classes of sRNAs on sequenced samples having high levels of RNA degradation. This is the first study to show that sRNA can be rescued from laser-captured FF pyramidal neurons. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Deleterious impacts of a 900-MHz electromagnetic field on hippocampal pyramidal neurons of 8-week-old Sprague Dawley male rats.

    Science.gov (United States)

    Şahin, Arzu; Aslan, Ali; Baş, Orhan; İkinci, Ayşe; Özyılmaz, Cansu; Sönmez, Osman Fikret; Çolakoğlu, Serdar; Odacı, Ersan

    2015-10-22

    Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (pEMF exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

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    Amit Agarwal

    2014-08-01

    Full Text Available Neuregulin-1 (NRG1 gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an “optimal” level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.

  2. 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.

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

    Science.gov (United States)

    Korol, Sergiy V.; Jin, Zhe; Birnir, Bryndis

    2015-01-01

    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. PMID:25927918

  4. Injury and recovery of pyramidal neurons in the rat hippocampus after a single episode of oxidative stress induced by intracerebroventricular injection of ferrous ammonium citrate

    OpenAIRE

    Ong, Wei-Yi; Ling, Su-Fung; Yeo, Jin-Fei; Chiueh, Chuang-Chin; Farooqui, Akhlaq

    2005-01-01

    International audience; The present study was carried out to elucidate the effect of a single episode of oxidative stress on pyramidal neurons of the rat hippocampus. A significant increase in the number of neurons that were immunolabeled for the toxic lipid peroxidation product, 4-hydroxynonenal (HNE) was observed in field CA3 of the hippocampus, at 1 day, 7 days and 14 days after intracerebroventricular injection of 1 $\\mu$L of 5mM ferrous ammonium citrate, compared to ammonium citrate inje...

  5. Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of layer V pyramidal neurons in vivo and in vitro.

    Science.gov (United States)

    Voelker, Courtney C J; Garin, Nathalie; Taylor, Jeremy S H; Gähwiler, Beat H; Hornung, Jean-Pierre; Molnár, Zoltán

    2004-11-01

    There are two main types of layer V pyramidal neurons in rat cortex. Type I neurons have tufted apical dendrites extending into layer I, produce bursts of action potentials and project to subcortical targets (spinal cord, superior colliculus and pontine nuclei). Type II neurons have apical dendrites, which arborize in layers II-IV, do not produce bursts of action potentials and project to ipsilateral and contralateral cortex. The specific expression of different genes and proteins in these two distinct layer V neurons is unknown. To distinguish between distinct subpopulations, fluorescent microspheres were injected into subcortical targets (labeling type I neurons) or primary somatosensory cortex (labeling type II neurons) of adult rats. After transport, cortical sections were processed for immunohistochemistry using various antibodies. This study demonstrated that antigens recognized by SMI-32, N200 and FNP-7 antibodies were only expressed in subcortical (type I)--but not in contralateral (type II)--projecting neurons. NR1, NR2a/b, PLCbeta1, BDNF, NGF and TrkB antigens were highly expressed in all neuronal subpopulations examined. Organotypic culture experiments demonstrated that the development of neurofilament expression and laminar specificity does not depend on the presence of the subcortical targets. This study suggests specific markers for the subcortical projecting layer V neuron subpopulations.

  6. Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results Lovastatina reduz a lesão celular na região CA1 do hipocampo após o status epilepticus induzido pela pilocarpina: resultados preliminares

    Directory of Open Access Journals (Sweden)

    Pauline Rangel

    2005-12-01

    Full Text Available OBJECTIVE: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE METHOD: Adult male Wistar rats were divided into four groups: (A control rats, received neither pilocarpine nor lovastatin (n=5; (B control rats, received just lovastatin (n=5; (C rats that received just pilocarpine (n=5; (D rats that received pilocarpine and lovastatin (n=5. After pilocarpine injection (350mg/kg, i.p., only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p. after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1= 26.8 ± 13.67; CA3= 38.1 ± 7.2; hilus= 43.8 ± 3.95 when compared with control group animals (Group A: CA1= 53.2 ± 9.63; CA3= 63.5 ± 13.35; hilus= 59.08 ± 10.24; Group B: CA1= 74.3 ± 8.16; CA3= 70.1 ± 3.83; hilus= 70.6 ± 5.10. The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 ± 17.88 was statically significant increased when compared with animals that just presented SE. CONCLUSION: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.OBJETIVO: Capacidade da lovastatina em prevenir a perda de neurônios hipocampais após o status epilepticus (SE induzido pela pilocarpina. MÉTODO: Ratos adultos Wistar foram divididos em 4 grupos: (A ratos controles que não receberam pilocarpina nem lovastatina (n=5; (B ratos

  7. Effects of increasing CREB-dependent transcription on the storage and recall processes in a hippocampal CA1 microcircuit.

    Science.gov (United States)

    Bianchi, Daniela; De Michele, Pasquale; Marchetti, Cristina; Tirozzi, Brunello; Cuomo, Salvatore; Marie, Hélène; Migliore, Michele

    2014-02-01

    The involvement of the hippocampus in learning processes and major brain diseases makes it an ideal candidate to investigate possible ways to devise effective therapies for memory-related pathologies like Alzheimer's Disease (AD). It has been previously reported that augmenting CREB activity increases the synaptic Long-Term Potentiation (LTP) magnitude in CA1 pyramidal neurons and their intrinsic excitability in healthy rodents. It has also been suggested that hippocampal CREB signaling is likely to be down-regulated during AD, possibly degrading memory functions. Therefore, the concept of CREB-based memory enhancers, i.e. drugs that would boost memory by activation of CREB, has emerged. Here, using a model of a CA1 microcircuit, we investigate whether hippocampal CA1 pyramidal neuron properties altered by increasing CREB activity may contribute to improve memory storage and recall. With a set of patterns presented to a network, we find that the pattern recall quality under AD-like conditions is significantly better when boosting CREB function with respect to control. The results are robust and consistent upon increasing the synaptic damage expected by AD progression, supporting the idea that the use of CREB-based therapies could provide a new approach to treat AD. © 2013 Wiley Periodicals, Inc.

  8. A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons

    Science.gov (United States)

    Carrasquillo, Yarimar; Burkhalter, Andreas; Nerbonne, Jeanne M

    2012-01-01

    Rapidly activating and rapidly inactivating voltage-gated A-type K+ currents, IA, are key determinants of neuronal excitability and several studies suggest a critical role for the Kv4.2 pore-forming α subunit in the generation of IA channels in hippocampal and cortical pyramidal neurons. The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of IA channels in mature cortical pyramidal (CP) neurons and that Kv4.2-, Kv4.3- and Kv1.4-encoded IA channels play distinct roles in regulating the intrinsic excitability and the firing properties of mature CP neurons. In vivo loss of Kv4.2, for example, alters the input resistances, current thresholds for action potential generation and action potential repolarization of mature CP neurons. Elimination of Kv4.3 also prolongs action potential duration, whereas the input resistances and the current thresholds for action potential generation in Kv4.3−/− and WT CP neurons are indistinguishable. In addition, although increased repetitive firing was observed in both Kv4.2−/− and Kv4.3−/− CP neurons, the increases in Kv4.2−/− CP neurons were observed in response to small, but not large, amplitude depolarizing current injections, whereas firing rates were higher in Kv4.3−/− CP neurons only with large amplitude current injections. In vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic excitability and the firing properties of mature CP neurons. Comparison of the effects of pharmacological blockade of Kv4-encoded currents in Kv1.4−/− and WT CP neurons, however, revealed that Kv1.4-encoded IA channels do contribute to controlling resting membrane potentials, the regulation of current thresholds for action potential generation and repetitive firing rates in mature CP neurons. PMID:22615428

  9. Noradrenergic lesion of the locus coeruleus increases the firing activity of the medial prefrontal cortex pyramidal neurons and the role of alpha2-adrenoceptors in normal and medial forebrain bundle lesioned rats.

    Science.gov (United States)

    Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen Hua; Hui, Yan Ping; Wang, Tao; Chen, Li; Li, Qiang

    2010-04-09

    Degeneration of noradrenergic neurons in the locus coeruleus (LC) and dysfunction of the prefrontal cortex were regarded as playing a specific role in the occurrence of non-motor symptoms in Parkinson's disease. The present study examined the spontaneous firing rate and firing pattern of medial prefrontal cortex (mPFC) pyramidal neurons, and effects of alpha(2)-adrenoceptor agonist UK-14,304 and antagonist yohimbine on the neuronal activity in rats with 6-hydroxydopamine lesions of the LC, medial forebrain bundle (MFB) and with combined MFB and LC lesions. The firing rate of mPFC pyramidal neurons in rats with lesions of the LC and with combine LC and MFB lesions is significantly higher than that of normal and MFB-lesioned rats and the firing pattern of these neurons in rats with lesions of the LC and with combine LC and MFB lesions also changed significantly towards more regular compared with normal and MFB-lesioned rats. The local administration of UK-14,304 in the mPFC inhibited the firing activity of the pyramidal neurons in normal rats and rats with lesions of the LC, MFB and with combined LC and MFB lesions, while yohimbine increased the firing activity of the pyramidal neurons. These results indicate that the lesions of the LC lead to hyperactivity of mPFC pyramidal neurons in normal and MFB-lesioned rats, and the postsynaptic alpha(2)-adrenoceptors may partially mediate the inhibitory effects of LC-noradrenergic system on the firing activity of pyramidal neurons in the mPFC, suggesting that LC-noradrenergic system plays an important role in the functional disorders of mPFC in Parkinson's disease. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  10. AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.

    Science.gov (United States)

    Guggenhuber, Stephan; Monory, Krisztina; Lutz, Beat; Klugmann, Matthias

    2010-12-21

    The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant adeno-associated virus (AAV) genome with a short stop element flanked by loxP sites, for highly efficient attenuation of transgene expression on the transcriptional level. The presence of Cre-recombinase is strictly necessary for expression of reporter proteins or CB1 receptor in vitro and in vivo. Transgenic CB1 receptor immunoreactivity is targeted to glutamatergic neurons after stereotaxic delivery of AAV to the dorsal hippocampus of the driver mice NEX-cre. Increased CB1 receptor protein levels in hippocampal lysates of AAV-treated Cre-mice is paralleled by enhanced cannabinoid-induced G-protein activation. KA-induced seizure severity and mortality is reduced in CB1 receptor overexpressors compared with AAV-treated control animals. Neuronal damage in the hippocampal CA3 field is specifically absent from AAV-treated Cre-transgenics, but evident throughout cortical areas of both treatment groups. Our data provide further evidence for a role of increased CB1 signaling in pyramidal hippocampal neurons as a safeguard against the adverse effects of excessive excitatory network activity.

  11. AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.

    Directory of Open Access Journals (Sweden)

    Stephan Guggenhuber

    Full Text Available The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant adeno-associated virus (AAV genome with a short stop element flanked by loxP sites, for highly efficient attenuation of transgene expression on the transcriptional level. The presence of Cre-recombinase is strictly necessary for expression of reporter proteins or CB1 receptor in vitro and in vivo. Transgenic CB1 receptor immunoreactivity is targeted to glutamatergic neurons after stereotaxic delivery of AAV to the dorsal hippocampus of the driver mice NEX-cre. Increased CB1 receptor protein levels in hippocampal lysates of AAV-treated Cre-mice is paralleled by enhanced cannabinoid-induced G-protein activation. KA-induced seizure severity and mortality is reduced in CB1 receptor overexpressors compared with AAV-treated control animals. Neuronal damage in the hippocampal CA3 field is specifically absent from AAV-treated Cre-transgenics, but evident throughout cortical areas of both treatment groups. Our data provide further evidence for a role of increased CB1 signaling in pyramidal hippocampal neurons as a safeguard against the adverse effects of excessive excitatory network activity.

  12. A comparison of 15 Hz sine on-line and off-line magnetic stimulation affecting the voltage-gated sodium channel currents of prefrontal cortex pyramidal neurons

    Science.gov (United States)

    Zheng, Yu; Dong, Lei; Gao, Yang; Dou, Jun-Rong; Li, Ze-yan

    2016-10-01

    Combined with the use of patch-clamp techniques, repetitive transcranial magnetic stimulation (rTMS) has proven to be a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons after extensive research. The studies generally focused on the method: the neurons are first stimulated in an external standard magnetic exposure device, and then moved to the patch-clamp to record electrophysiological characteristics (off-line magnetic exposure). Despite its universality, real-time observation of the effects of magnetic stimulation on the neurons is more effective (on-line magnetic stimulation). In this study, we selected a standard exposure device for magnetic fields acting on mouse prefrontal cortex pyramidal neurons, and described a new method that a patch-clamp setup was modified to allow on-line magnetic stimulation. By comparing the off-line exposure and on-line stimulation of the same magnetic field intensity and frequency affecting the voltage-gated sodium channel currents, we succeeded in proving the feasibility of the new on-line stimulation device. We also demonstrated that the sodium channel currents of prefrontal cortex pyramidal neurons increased significantly under the 15 Hz sine 1 mT, and 2 mT off-line magnetic field exposure and under the 1 mT and 2 mT on-line magnetic stimulation, and the rate of acceleration was most significant on 2 mT on-line magnetic stimulation. This study described the development of a new on-line magnetic stimulator and successfully demonstrated its practicability for scientific stimulation of neurons.

  13. Disinhibition of the mediodorsal thalamus induces Fos-like immunoreactivity in both pyramidal and GABA-containing neurons in the medial prefrontal cortex of rats, but does not affect prefrontal extracellular GABA levels

    NARCIS (Netherlands)

    Bubser, M; Brabander, J.M; Timmerman, W; Feenstra, M.G P; Erdtsieck-Ernste, E.B H W; Rinkens, A; van Uum, J.F M; Westerink, B.H.C.

    1998-01-01

    Stimulation of the mediodorsal and midline thalamic nuclei excites cortical neurons and induces c-fos expression in the prefrontal cortex. Data in the literature data suggest that pyramidal neurons are the most likely cellular targets. In order to determine whether cortical interneurons are also

  14. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  15. Ischemic preconditioning inhibits expression of Na(+)/H(+) exchanger 1 (NHE1) in the gerbil hippocampal CA1 region after transient forebrain ischemia.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Cho, Geum-Sil; Chen, Bai Hui; Shin, Bich Na; Tae, Hyun-Jin; Park, Seung Min; Ahn, Ji Yun; Kim, Dong Won; Cho, Jun Hwi; Bae, Eun Joo; Yong, Jun-Hwan; Kim, Young-Myeong; Won, Moo-Ho; Lee, Yun Lyul

    2015-04-15

    The participation of Na(+)/H(+) exchanger (NHE) in neuronal damage/death in the hippocampal CA1 region (CA1) induced by transient forebrain ischemia has not been well established, although acidosis may be involved in neuronal damage/death. In the present study, we examined the effect of ischemic preconditioning (IPC) on NHE1 immunoreactivity following a 5min of transient forebrain ischemia in gerbils. The animals used in the study were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group and IPC+ischemia-operated-group). IPC was induced by subjecting animals to 2min of ischemia followed by 1day of recovery. A significant neuronal loss was found in the stratum pyramidale (SP) of the CA1, not the CA2/3, of the ischemia-operated-group at 5days post-ischemia. However, in the IPC+ischemia-operated-group, neurons in the SP of the CA1 were well protected. NHE1 immunoreactivity was not detected in any regions of the CA1-3 of the sham- and IPC+sham-operated-groups. However, the immunoreactivity was apparently expressed in the SP of the CA1-3 after ischemia, and the NHE1immunoreactivity was very weak 5days after ischemia; however, at this point in time, strong NHE1immunoreactivity was found in astrocytes in the CA1. In the CA2/3, NHE1immunoreactivity was slightly changed, although NHE1immunoreactivity was expressed in the SP. In the IPC+ischemia-operated-groups, NHE1 immunoreactivity was also expressed in the SP of the CA1-3; however, the immunoreactivity was more slightly changed than that in the ischemia-operated-groups. In brief, our findings show that IPC dramatically protected CA1 pyramidal neurons and strongly inhibited NHE1 expression in the SP of the CA1 after ischemia-reperfusion. These findings suggest that the inhibition of NHE1 expression may be necessary for neuronal survival from transient ischemic damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Augmented inhibition from cannabinoid sensitive interneurons diminishes CA1 output after traumatic brain injury

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    Brian Neal Johnson

    2014-12-01

    Full Text Available The neurological impairments associated with traumatic brain injury include learning and memory deficits and increased risk of seizures. The hippocampus is critically involved in both of these phenomena and highly susceptible to damage by traumatic brain injury. To examine network activity in the hippocampal CA1 region after lateral fluid percussion injury, we used a combination of voltage sensitive dye, field potential and patch clamp recording in mouse hippocampal brain slices. When the stratum radiatum was stimulated in slices from injured mice we found decreased depolarization in stratum radiatum and increased hyperpolarization in stratum oriens, together with a decrease in the percentage of pyramidal neurons firing stimulus-evoked action potentials. Increased hyperpolarization in stratum oriens persisted when glutamatergic transmission was blocked. However, we found no changes in stratum oriens responses when the alveus was stimulated to directly activate stratum oriens. These results suggest that the increased stratum oriens hyperpolarization evoked by stratum radiatum stimulation was mediated by interneurons that have cell bodies and/or axons in stratum radiatum, and form synapses in stratum pyramidale and stratum oriens. A low concentration (100 nM of the synthetic cannabinoid WIN55,212-2,restored CA1 output in slices from injured animals. These findings support the hypothesis that increased GABAergic signaling by cannabinoid sensitive interneurons contributes to the reduced CA1 output following traumatic brain injury.

  17. Ischemic damage in hippocampal CA1 is dependent on glutamate release and intact innervation from CA3

    DEFF Research Database (Denmark)

    Benveniste, H; Jørgensen, M B; Sandberg, M

    1989-01-01

    The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA1...... hippocampal tissue. In intact CA1 hippocampal tissue, glutamate increased sixfold during ischemia; in the CA3-lesioned CA1 region, however, glutamate only increased 1.4-fold during ischemia. To assess the neurotoxic potential of the ischemia-induced release of glutamate, we injected the same concentration...... of glutamate into the CA1 region as is released during ischemia in normal, CA3-lesioned, and ischemic CA1 tissue. We found that this particular concentration of glutamate was sufficient to destroy CA1 pyramids in the vicinity of the injection site in intact and CA3-lesioned CA1 tissue when administered during...

  18. In Rasmussen Encephalitis, Hemichannels Associated with Microglial Activation are linked to Cortical Pyramidal Neuron Coupling: A Possible Mechanism for Cellular Hyperexcitability

    Science.gov (United States)

    Cepeda, Carlos; Chang, Julia W.; Owens, Geoffrey C.; Huynh, My N.; Chen, Jane Y.; Tran, Conny; Vinters, Harry V.; Levine, Michael S.; Mathern, Gary W.

    2014-01-01

    Aims Rasmussen encephalitis (RE) is a rare but devastating condition, mainly in children, characterized by sustained brain inflammation, atrophy of one cerebral hemisphere, epilepsy and progressive cognitive deterioration. The etiology of RE-induced seizures associated with the inflammatory process remains unknown. Methods Cortical tissue samples from children undergoing surgical resections for the treatment of RE (n=16) and non-RE (n=12) were compared using electrophysiological, morphological, and immunohistochemical techniques to examine neuronal properties and the relationship with microglial activation using the specific microglia/macrophage calcium-binding protein, IBA1 in conjunction with connexins and pannexin expression. Results Compared with non-RE cases, pyramidal neurons from RE cases displayed increased cell capacitance and reduced input resistance. However, neuronal somatic areas were not increased in size. Instead, intracellular injection of biocytin led to increased dye-coupling between neurons from RE cases. By Western blot, expression of IBA1 and pannexin was increased while connexin 32 was decreased in RE cases compared with non-RE cases. IBA1 immunostaining overlapped with pannexin and connexin 36 in RE cases. Conclusions In RE, these results support the notion that a possible mechanism for cellular hyperexcitability may be related to increased intercellular coupling from pannexin linked to increased microglial activation. Such findings suggest that a possible anti-seizure treatment for RE may involve the use of gap junction blockers. PMID:25438677

  19. Activation of type-1 cannabinoid receptor shifts the balance between excitation and inhibition towards excitation in layer II/III pyramidal neurons of the rat prelimbic cortex.

    Science.gov (United States)

    den Boon, Femke S; Werkman, Taco R; Schaafsma-Zhao, Qiluan; Houthuijs, Kas; Vitalis, Tania; Kruse, Chris G; Wadman, Wytse J; Chameau, Pascal

    2015-07-01

    Activation of the endocannabinoid (eCB) system by exogenous cannabinoids (drug abuse) can alter the physiology of the brain circuits involved in higher-order cognitive functions such as the medial prefrontal cortex (mPFC). A proper balance between excitation and inhibition (E/I balance) is critical for neuronal network oscillations underlying cognitive functions. Since type-1 cannabinoid receptors (CB1Rs), expressed in many brain areas including the mPFC, can modulate excitatory and inhibitory neurotransmission, we aimed to determine whether CB1R activation results in modifications of the E/I balance. We first confirm the presence of functional presynaptic CB1Rs that can modulate both excitatory and inhibitory inputs to layer II/III pyramidal neurons of the prelimbic (PL) area of the mPFC. By decomposing the synaptic response evoked by layer I stimulation into its excitatory and inhibitory components, we show that in vitro CB1R activation with the cannabinoid receptor agonists WIN55,212-2 (WIN) and CP-55940 (CP) modulates the balance between excitation and inhibition (E/I balance) of layer II/III pyramidal neurons. This treatment caused a significant shift of the E/I balance towards excitation, from 18/82 % to 25/75 % (WIN) and from 17/83 to 30/70 % (CP). Finally, when animals were injected with a cannabinoid receptor agonist, we observed a shift of the E/I balance (measured in vitro) towards excitation 1 h after WIN (24/76 %) or after CP injection (30/70 %) when compared to vehicle-injected animals (18/82 %). This modulation of the E/I balance by CB1Rs may thus be fundamental in the regulation of local PL cortical network excitability and could be the mechanism through which excessive CB1R activation (cannabis abuse) affects cognitive functions.

  20. Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

    Science.gov (United States)

    Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

  1. Effect of Exercise Preconditioning on Memory Deficits and Neuronal Cell Death in the CA3 Pyramidal Cells of the Rat Hippocampus Following Transient Global Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    N Shamsaei

    2015-09-01

    Full Text Available Background & objectives: Brain ischemia leads to irreversible functional and structural damage in various regions of the brain, especially in the hippocampus. There is an evidence indicating the physical exercise has neuroprotective effects and may decrease the cerebral ischemia/ reperfusion injury in rats. The purpose of this study was the study of the effect of exercise preconditioning on memory deficits and neuronal cell death in CA3 pyramidal cells of the rat hippocampus following transient global ischemia.   Methods: 21 male rats weighing 260-300g were randomly selected and allocated into three groups (sham, ischemia and exercise+ischemia. The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia induced by occlusion both common carotid arteries (CCA for 20 minutes. The passive avoidance memory test using a Shuttle box used to assess the impairment of memory. The amount of cell death was measured using cresyl violet staining method.   Results: The results showed that cerebral ischemia is associated with memory impairment, and physical activity before ischemia improves ischemia-induced memory impairments significantly (p<0.05. In addition, ischemia leads to cell death in hippocampal CA3 area neurons and exercise also reduces ischemia-induced cell death significantly (p<0.05.   Conclusion: This study showed that exercise, when is used as a preconditioning stimulant , has a neuroprotective effects against brain ischemia.

  2. Regulation of neuronal input transformations by tunable dendritic inhibition.

    Science.gov (United States)

    Lovett-Barron, Matthew; Turi, Gergely F; Kaifosh, Patrick; Lee, Peter H; Bolze, Frédéric; Sun, Xiao-Hua; Nicoud, Jean-François; Zemelman, Boris V; Sternson, Scott M; Losonczy, Attila

    2012-01-15

    Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type-specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons.

  3. CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

    Science.gov (United States)

    Yu, Xiao-Wen; Curlik, Daniel M; Oh, M Matthew; Yin, Jerry CP; Disterhoft, John F

    2017-01-01

    The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline. DOI: http://dx.doi.org/10.7554/eLife.19358.001 PMID:28051768

  4. Modulation of local field potentials by high-frequency stimulation of afferent axons in the hippocampal CA1 region.

    Science.gov (United States)

    Yu, Ying; Feng, Zhouyan; Cao, Jiayue; Guo, Zheshan; Wang, Zhaoxiang; Hu, Na; Wei, Xuefeng

    2016-03-01

    Modulation of the rhythmic activity of local field potentials (LFP) in neuronal networks could be a mechanism of deep brain stimulation (DBS). However, exact changes of LFP during the periods of high-frequency stimulation (HFS) of DBS are unclear because of the interference of dense stimulation artifacts with high amplitudes. In the present study, we investigated LFP changes induced by HFS of afferent axons in the hippocampal CA1 region of urethane-anesthetized rats by using a proper algorithm of artifact removal. Afterward, the LFP changes in the frequency bands of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] rhythms were studied by power spectrum analysis and coherence analysis for the recorded signals collected in the pyramidal layer and in the stratum radiatum of CA1 region before, during and after 1-min long 100 and 200[Formula: see text]Hz HFS. Results showed that the power of LFP rhythms in higher-frequency band ([Formula: see text] rhythm) increased in the pyramidal layer and the power of LFP rhythms in lower-frequency bands ([Formula: see text], [Formula: see text] and [Formula: see text] rhythms) decreased in the stratum radiatum during HFS. The synchronization of [Formula: see text] rhythm decreased and the synchronization of [Formula: see text] rhythm increased during HFS in the stratum radiatum. These results suggest that axonal HFS could modulate LFP rhythms in the downstream brain areas with a plausible underlying mechanism of partial axonal blockage induced by HFS. The study provides new evidence to support the mechanism of DBS modulating rhythmic activity of neuronal populations.

  5. Hippocampal CA1 Ripples as Inhibitory Transients.

    Directory of Open Access Journals (Sweden)

    Paola Malerba

    2016-04-01

    Full Text Available Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

  6. Extended studies on the effect of glutamate antagonists on ischemic CA-1 damage

    DEFF Research Database (Denmark)

    Diemer, Nils Henrik; Balchen, T; Bruhn, T

    1996-01-01

    Glutamate receptors are numerous on the ischemia vulnerable CA-1 pyramidal cells. Postischemic use of the AMPA antagonist NBQX has shown up to 80% protection against cell death. Three aspects of this were studied: In the first study, male Wistar rats were given NBQX (30 mg/kg x 3) either 20 hours...

  7. Insulin reduces neuronal excitability by turning on GABA(A channels that generate tonic current.

    Directory of Open Access Journals (Sweden)

    Zhe Jin

    Full Text Available Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid decreases neuronal excitability by activating GABA(A channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM "turns on" new extrasynaptic GABA(A channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50 in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

  8. Morphometric characteristics of the neurons of the human subiculum proper

    Directory of Open Access Journals (Sweden)

    Živanović-Mačužić Ivana

    2012-01-01

    Full Text Available The human subiculum is a significant part of the hippocampal formation positioned between the hippocampus proper and the entorhinal and other cortices. It plays an important role in spatial navigation, memory processing and control of the response to stress. The aim of our study was identification of the morphometric characteristics of the neurons of the human subiculum proper: the maximum length and width of cell body and total dendritic length and volume of cell body. Comparing the measured parameters of different types of subicular neurons (bipolar, multipolar, pyramidal neurons with triangular-shaped soma and neurons with oval-shaped soma, we can conclude that bipolar neurons have the lowest values of the measured parameters: the maximum length of their cell body is 14.1 ± 0.2 µm, the maximum width is 13.9 ± 0.5 µm, and total dendritic length is 14597 ± 3.1 µm. The lowest volume value was observed in bipolar neurons; the polymorphic layer is 1152.99 ± 662.69 µm3. The pyramidal neurons of the pyramidal layer have the highest value for the maximal length of the cell body (44.43 ± 7.94 µm, maximum width (23.64 ± 1.89 µm, total dendritic length (1830 ± 466.3 µm and volume (11768.65±4004.9 µm3 These characteristics of the pyramidal neurons indicate their importance, because the axons of these neurons make up the greatest part of the fornix, along with the axons of neurons of the CA1 hippocampal field.

  9. Use of Colchicine in Cortical Area 1 of the Hippocampus Impairs Transmission of Non-Motivational Information by the Pyramidal Cells

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    Nosaibeh Riahi Zaniani

    2013-11-01

    Full Text Available Colchicine, a potent neurotoxin derived from plants, has been recently introduced as a degenerative toxin of small pyramidal cells in the cortical area 1 of the hippocampus (CA1. In this study, the effect of the alkaloid in CA1 on the behaviors in the conditioning task was measured. Injections of colchicine (1,5 μg/rat, intra-CA1 was performed in the male Wistar rats, while the animals were settled and cannulated in a stereotaxic apparatus. In the control group solely injection of saline (1 μl/rat, intra-CA1 was used. One week later, all the animals passed the saline conditioning task using a three-day schedule of an unbiased paradigm. They were administered saline (1 ml/kg, s.c. twice a day throughout the conditioning phase. To evaluate the possible effects of cell injury by the toxin on the pyramidal cells, both the motivational signals while in the conditioning box and the non-motivational locomotive signs of the treated and control rats were measured. Based on the present study the alkaloid caused no change in the score of place conditioning, but affected both the sniffing and grooming behaviors in the group that received colchicine. However, the alkaloid did not show the significant effect on the rearing or compartment entering in the rats. According to the findings, the intra-CA1 injection of colchicine may impair the neuronal transmission of non-motivational information by the pyramidal cells in the dorsal hippocampus.

  10. Pyramid Comet Sampler Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Based on the sampling requirements, we propose an Inverted Pyramid sampling system. Each face of the pyramid includes a cutting blade which is independently actuated...

  11. Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus

    DEFF Research Database (Denmark)

    Hosseini-Sharifabad, Mohammad; Nyengaard, Jens Randel

    2007-01-01

    Tools recently developed in stereology were employed for unbiased estimation of the neuronal number and volume in three major subdivisions of rat hippocampus (dentate granular, CA1 and CA3 pyramidal layers). The optical fractionator is used extensively in quantitative studies of the hippocampus......; however, the classical optical fractionator design may be affected by tissue deformation in the z-axis of the section. In this study, we applied an improved optical fractionator design to estimate total number of neurons on 100 microm thick vibratome sections that had been deformed, in the z...... vertical sections from the hippocampus. The volume of hippocampal neurons was estimated using the rotator principle on 40 microm thick plastic vertical uniform random sections and corrected for tissue shrinkage. Application of the proposed new design should result in more accurate estimates of neuron...

  12. Changes in rat hippocampal CA1 synapses following imipramine treatment

    DEFF Research Database (Denmark)

    Chen, Fenghua; Madsen, Torsten M; Wegener, Gregers

    2008-01-01

    of synapses) in subregions of the hippocampus by quantifying number of neurons and synapses. Adult male Sprague-Dawley rats were injected with imipramine or saline (i.p.) daily for 14 days. Unbiased stereological methods were used to quantify the number of neurons and synapses. No differences in the volume...... and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our...... results indicate that administration of imipramine for 14 days in normal rats could significantly increase the excitatory spine synapses, and change the relative distribution of spine and shaft synapses. We speculate that the present findings may be explained by the establishment of new synaptic...

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

    Directory of Open Access Journals (Sweden)

    Huaqiu Zhang

    2011-02-01

    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.

  14. 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 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.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.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 prolonged periods of hormone withdrawal.

  15. CA1 hippocampal network activity changes during sleep-dependent memory consolidation

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    Nicolette N Ognjanovski

    2014-04-01

    Full Text Available A period of sleep over the first few hours following single-trial contextual fear conditioning (CFC is essential for hippocampally-mediated memory consolidation. Recent studies have uncovered intracellular mechanisms required for memory formation that are affected by post-conditioning sleep and sleep deprivation. However, almost nothing is known about the circuit-level activity changes during sleep that underlie activation of these intracellular pathways. Here we continuously record neuronal activity from the CA1 region of freely-behaving mice to characterize neuronal and network activity changes occurring during active memory consolidation. C57BL/6J mice were implanted with custom stereotrode recording arrays to monitor activity of individual CA1 neurons, local field potentials (LFPs, and electromyographic activity. Sleep architecture and state-specific CA1 activity patterns were assessed during a 24 h baseline recording period, and for 24 h following either single-trial CFC or Sham conditioning. We find that consolidation of CFC is not associated with significant sleep architecture changes, but is accompanied by long-lasting increases in CA1 neuronal firing, as well as increases in delta, theta, and gamma-frequency CA1 LFP activity. These changes occurred in both sleep and wakefulness, and may drive synaptic plasticity within the hippocampus during memory formation. We also find that functional connectivity within the CA1 network, assessed through functional clustering analysis (FCA of spike timing relationships among recorded neurons, becomes more stable during consolidation of CFC. This increase in network stability was not present following Sham conditioning, was most evident during post-CFC slow wave sleep, and was negligible during post-CFC wakefulness. Thus in the interval between encoding and recall, slow wave sleep may stabilize the hippocampal contextual fear memory trace by promoting CA1 network stability.

  16. Rebuilding the Food Pyramid.

    Science.gov (United States)

    Willet, Walter C.; Stampfer, Meir J.

    2003-01-01

    Discusses the old food guide pyramid released in 1992 by the U.S. Department of Agriculture. Contradicts the message that fat is bad, which was presented to the public by nutritionists, and the effects of plant oils on cholesterol. Introduces a new food pyramid. (YDS)

  17. Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide a Target for the Treatment of Febrile Seizures

    Science.gov (United States)

    Radzicki, Daniel; Yau, Hau-Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong

    2013-01-01

    Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at ≥37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firing may play a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition. PMID:23761887

  18. Comparison of different neuron models to conductance-based post-stimulus time histograms obtained in cortical pyramidal cells using dynamic-clamp in vitro.

    Science.gov (United States)

    Pospischil, Martin; Piwkowska, Zuzanna; Bal, Thierry; Destexhe, Alain

    2011-08-01

    A wide diversity of models have been proposed to account for the spiking response of central neurons, from the integrate-and-fire (IF) model and its quadratic and exponential variants, to multiple-variable models such as the Izhikevich (IZ) model and the well-known Hodgkin-Huxley (HH) type models. Such models can capture different aspects of the spiking response of neurons, but there is few objective comparison of their performance. In this article, we provide such a comparison in the context of well-defined stimulation protocols, including, for each cell, DC stimulation, and a series of excitatory conductance injections, arising in the presence of synaptic background activity. We use the dynamic-clamp technique to characterize the response of regular-spiking neurons from guinea-pig visual cortex by computing families of post-stimulus time histograms (PSTH), for different stimulus intensities, and for two different background activities (low- and high-conductance states). The data obtained are then used to fit different classes of models such as the IF, IZ, or HH types, which are constrained by the whole data set. This analysis shows that HH models are generally more accurate to fit the series of experimental PSTH, but their performance is almost equaled by much simpler models, such as the exponential or pulse-based IF models. Similar conclusions were also reached by performing partial fitting of the data, and examining the ability of different models to predict responses that were not used for the fitting. Although such results must be qualified by using more sophisticated stimulation protocols, they suggest that nonlinear IF models can capture surprisingly well the response of cortical regular-spiking neurons and appear as useful candidates for network simulations with conductance-based synaptic interactions.

  19. Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine.

    Directory of Open Access Journals (Sweden)

    Hui Kuang

    2010-12-01

    Full Text Available Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.

  20. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  1. Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex

    OpenAIRE

    Anton-Sanchez, Laura; Bielza, Concha; Larra?aga, Pedro; Defelipe, Javier

    2016-01-01

    Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer...

  2. Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing

    Directory of Open Access Journals (Sweden)

    Yanjun Sun

    2014-04-01

    Full Text Available We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC, the medial septum (MS, and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  3. Difference in transient ischemia-induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils

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    Seung Min Park

    2016-05-01

    Full Text Available Objective(s: The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1-immunoreactive microvessels in their ischemic hippocampal CA1 region. Materials and Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. Results: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. Conclusion: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults.

  4. Turmeric extract inhibits apoptosis of hippocampal neurons of trimethyltin-exposed rats.

    Science.gov (United States)

    Yuliani, S; Widyarini, S; Mustofa; Partadiredja, G

    2017-01-01

    The aim of the present study was to reveal the possible antiapoptotic effect of turmeric (Curcuma longa Linn.) on the hippocampal neurons of rats exposed to trimethyltin (TMT). Oxidative damage in the hippocampus can induce the apoptosis of neurons associated with the pathogenesis of dementiaMETHODS. The ethanolic turmeric extract and a citicoline (as positive control) solution were administered to the TMT-exposed rats for 28 days. The body weights of rats were recorded once a week. The hippocampal weights and imumunohistochemical expression of caspase 3 proteins in the CA1 and CA2-CA3 regions of the hippocampi were examined at the end of the experiment. Immunohistochemical analysis showed that the injection of TMT increased the expression of caspase 3 in the CA1 and CA2-CA3 regions of hippocampus. TMT also decreased the body and hippocampal weights. Furthermore, the administration of 200 mg/kg bw dose of turmeric extract decreased the caspase 3 expression in the CA2-CA3 pyramidal neurons but not in the CA1 neurons. It also prevented the decrease of the body and hippocampal weights. We suggest that the 200 mg/kg bw dose of turmeric extract may exert antiapoptotic effect on the hippocampal neurons of the TMT-exposed rats (Tab. 1, Fig. 3, Ref. 49).

  5. Sturge-Weber Syndrome Is Associated with Cortical Dysplasia ILAE Type IIIc and Excessive Hypertrophic Pyramidal Neurons in Brain Resections for Intractable Epilepsy.

    Science.gov (United States)

    Wang, Dan-Dan; Blümcke, Ingmar; Coras, Roland; Zhou, Wen-Jing; Lu, De-Hong; Gui, Qiu-Ping; Hu, Jing-Xia; Zuo, Huan-Cong; Chen, Shi-Yun; Piao, Yue-Shan

    2015-05-01

    Sturge-Weber syndrome (SWS) is a rare syndrome characterized by capillary-venous malformations involving skin and brain. Many patients with SWS also suffer from drug-resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients' age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well preserved, which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for focal cortical dysplasia (FCD). Neuropathology revealed dysmorphic-like neurons with hypertrophic cell bodies reminiscent to those described for FCD type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD type IIa were missing, and we propose to classify this pattern as FCD ILAE type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n = 4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow-up period of 1.7 years. We concluded from our study that FCD type IIIc and PMG are frequently associated findings in SWS. FCD type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control. © 2014 International Society of Neuropathology.

  6. Klotho regulates CA1 hippocampal synaptic plasticity.

    Science.gov (United States)

    Li, Qin; Vo, Hai T; Wang, Jing; Fox-Quick, Stephanie; Dobrunz, Lynn E; King, Gwendalyn D

    2017-04-07

    Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function. To affect cognitive function, klotho could act in or on the synapse to modulate synaptic transmission or plasticity. However, it is not yet known if klotho is located at synapses, and little is known about its effects on synaptic function. To test this, we fractionated hippocampi and detected klotho expression in both pre and post-synaptic compartments. We find that loss of klotho enhances both pre and post-synaptic measures of CA1 hippocampal synaptic plasticity at 5weeks of age. However, a rapid loss of synaptic enhancement occurs such that by 7weeks, when mice are cognitively impaired, there is no difference from wild-type controls. Klotho overexpressing mice show no early life effects on synaptic plasticity, but decreased CA1 hippocampal long-term potentiation was measured at 6months of age. Together these data suggest that klotho affects cognition, at least in part, by regulating hippocampal synaptic plasticity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Pyramid image codes

    Science.gov (United States)

    Watson, Andrew B.

    1990-01-01

    All vision systems, both human and machine, transform the spatial image into a coded representation. Particular codes may be optimized for efficiency or to extract useful image features. Researchers explored image codes based on primary visual cortex in man and other primates. Understanding these codes will advance the art in image coding, autonomous vision, and computational human factors. In cortex, imagery is coded by features that vary in size, orientation, and position. Researchers have devised a mathematical model of this transformation, called the Hexagonal oriented Orthogonal quadrature Pyramid (HOP). In a pyramid code, features are segregated by size into layers, with fewer features in the layers devoted to large features. Pyramid schemes provide scale invariance, and are useful for coarse-to-fine searching and for progressive transmission of images. The HOP Pyramid is novel in three respects: (1) it uses a hexagonal pixel lattice, (2) it uses oriented features, and (3) it accurately models most of the prominent aspects of primary visual cortex. The transform uses seven basic features (kernels), which may be regarded as three oriented edges, three oriented bars, and one non-oriented blob. Application of these kernels to non-overlapping seven-pixel neighborhoods yields six oriented, high-pass pyramid layers, and one low-pass (blob) layer.

  8. Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation

    DEFF Research Database (Denmark)

    Petrone, Angiola; Battaglia, Fortunato; Wang, Cheng

    2003-01-01

    Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPa....... However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPalpha also underperform in the radial-arm water-maze test. These studies identify RPTPalpha as a key mediator of neuronal migration and synaptic plasticity....... neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice...

  9. Climbing the Needs Pyramids

    Directory of Open Access Journals (Sweden)

    J. C. Lomas

    2013-08-01

    Full Text Available Abraham Maslow’s theory of human adult motivation is often represented by a pyramid image showing two proposals: First, the five needs stages in emergent order of hierarchical ascension and second, a percentage of the adult population suggested to occupy each needs tier. Specifically, Maslow proposed that adults would be motivated to satisfy their unfilled needs until they reached the hierarchy’s apex and achieved self-transcendence. Yet how adults can purposefully ascend Maslow’s pyramid through satisfying unfilled needs remains elusive. This brief article challenges this on the theory’s 70th anniversary by presenting a new image of the needs hierarchy, based on ecological design principles to support adults’ purposeful endeavors to climb the needs pyramid.

  10. AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice.

    Directory of Open Access Journals (Sweden)

    Tomasz Jaworski

    Full Text Available In Alzheimer's disease tauopathy is considered secondary to amyloid, and the duality obscures their relation and the definition of their respective contributions.Transgenic mouse models do not resolve this problem conclusively, i.e. the relative hierarchy of amyloid and tau pathology depends on the actual model and the genes expressed or inactivated. Here, we approached the problem in non-transgenic models by intracerebral injection of adeno-associated viral vectors to express protein tau or amyloid precursor protein in the hippocampus in vivo. AAV-APP mutant caused neuronal accumulation of amyloid peptides, and eventually amyloid plaques at 6 months post-injection, but with only marginal hippocampal cell-death. In contrast, AAV-Tau, either wild-type or mutant P301L, provoked dramatic degeneration of pyramidal neurons in CA1/2 and cortex within weeks. Tau-mediated neurodegeneration proceeded without formation of large fibrillar tau-aggregates or tangles, but with increased expression of cell-cycle markers.We present novel AAV-based models, which demonstrate that protein tau mediates pyramidal neurodegeneration in vivo. The data firmly support the unifying hypothesis that post-mitotic neurons are forced to re-enter the cell-cycle in primary and secondary tauopathies, including Alzheimer's disease.

  11. PYRAMIDS AND POPPIES

    African Journals Online (AJOL)

    Flying. Cheetahs is recommended to those potential readers who do not have ready access to the original thesis. Major I.J. van der Waag, Documenta- tion Service, Private Bag X289, Pretoria. 0001. PYRAMIDS AND POPPIES. The 1st SA Infantry Brigade in Libya,. France and Flanders. 1915-1919. Peter K.A. Digby. 1993.

  12. Neuroprotection of ischemic preconditioning is mediated by thioredoxin 2 in the hippocampal CA1 region following a subsequent transient cerebral ischemia.

    Science.gov (United States)

    Lee, Jae-Chul; Park, Joon Ha; Kim, In Hye; Cho, Geum-Sil; Ahn, Ji Hyeon; Tae, Hyun-Jin; Choi, Soo Young; Cho, Jun Hwi; Kim, Dae Won; Kwon, Young-Guen; Kang, Il Jun; Won, Moo-Ho; Kim, Young-Myeong

    2017-05-01

    Preconditioning by brief ischemic episode induces tolerance to a subsequent lethal ischemic insult, and it has been suggested that reactive oxygen species are involved in this phenomenon. Thioredoxin 2 (Trx2), a small protein with redox-regulating function, shows cytoprotective roles against oxidative stress. Here, we had focused on the role of Trx2 in ischemic preconditioning (IPC)-mediated neuroprotection against oxidative stress followed by a subsequent lethal transient cerebral ischemia. Animals used in this study were randomly assigned to six groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group, IPC + ischemia-operated group, IPC + auranofin (a TrxR2 inhibitor) + sham-operated group and IPC + auranofin + ischemia-operated group. IPC was subjected to a 2 minutes of sublethal transient ischemia 1 day prior to a 5 minutes of lethal transient ischemia. A significant loss of neurons was found in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) in the ischemia-operated-group 5 days after ischemia-reperfusion; in the IPC + ischemia-operated-group, pyramidal neurons in the SP were well protected. In the IPC + ischemia-operated-group, Trx2 and TrxR2 immunoreactivities in the SP and its protein level in the CA1 were not significantly changed compared with those in the sham-operated-group after ischemia-reperfusion. In addition, superoxide dismutase 2 (SOD2) expression, superoxide anion radical ( O2-) production, denatured cytochrome c expression and TUNEL-positive cells in the IPC + ischemia-operated-group were similar to those in the sham-operated-group. Conversely, the treatment of auranofin to the IPC + ischemia-operated-group significantly increased cell damage/death and abolished the IPC-induced effect on Trx2 and TrxR2 expressions. Furthermore, the inhibition of Trx2R nearly cancelled the beneficial effects of IPC on SOD2 expression, O2- production, denatured cytochrome c

  13. Climbing the Needs Pyramids

    OpenAIRE

    J. C. Lomas

    2013-01-01

    Abraham Maslow’s theory of human adult motivation is often represented by a pyramid image showing two proposals: First, the five needs stages in emergent order of hierarchical ascension and second, a percentage of the adult population suggested to occupy each needs tier. Specifically, Maslow proposed that adults would be motivated to satisfy their unfilled needs until they reached the hierarchy’s apex and achieved self...

  14. Imaging the Cheops Pyramid

    CERN Document Server

    Bui, H D

    2012-01-01

    In this book Egyptian Archeology  and Mathematics meet. The author is an expert in theories and applications in Solid Mechanics and Inverse Problems, a former professor at Ecole Polytechnique and now works with Electricité de France on maintenance operations on nuclear power plants. In the Autumn of 1986, after the end of the operation on the King’s chamber conducted under the Technological and Scientific Sponsorship of EDF, to locate a cavity, he was called to solve a mathematical inverse problem, to find the unknown tomb of the King and the density structure of the whole pyramid based on measurements of microgravity made inside and outside of the pyramid. This book recounts the various search operations on the pyramid of Cheops made at the request of the Egyptian and French authorities in 1986-1987. After the premature end of the Cheops operation in the Autumn of 1986, following the fiasco of unsuccessful drillings in the area suspected by both architects G. Dormion and J.P. Goidin and microgravity aus...

  15. The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

    Science.gov (United States)

    Hermawati, Ery; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2015-09-01

    Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

  16. Is the Langevin phase equation an efficient model for oscillating neurons?

    Science.gov (United States)

    Ota, Keisuke; Tsunoda, Takamasa; Omori, Toshiaki; Watanabe, Shigeo; Miyakawa, Hiroyoshi; Okada, Masato; Aonishi, Toru

    2009-12-01

    The Langevin phase model is an important canonical model for capturing coherent oscillations of neural populations. However, little attention has been given to verifying its applicability. In this paper, we demonstrate that the Langevin phase equation is an efficient model for neural oscillators by using the machine learning method in two steps: (a) Learning of the Langevin phase model. We estimated the parameters of the Langevin phase equation, i.e., a phase response curve and the intensity of white noise from physiological data measured in the hippocampal CA1 pyramidal neurons. (b) Test of the estimated model. We verified whether a Fokker-Planck equation derived from the Langevin phase equation with the estimated parameters could capture the stochastic oscillatory behavior of the same neurons disturbed by periodic perturbations. The estimated model could predict the neural behavior, so we can say that the Langevin phase equation is an efficient model for oscillating neurons.

  17. Apamin induces plastic changes in hippocampal neurons in senile Sprague-Dawley rats.

    Science.gov (United States)

    Romero-Curiel, Alejandra; López-Carpinteyro, Diana; Gamboa, Citlalli; De la Cruz, Fidel; Zamudio, Sergio; Flores, Gonzalo

    2011-10-01

    Apamin is a neurotoxin extracted from honey bee venom and is a selective blocker of small-conductance Ca²⁺-activated K⁺ channels (SK). Several behavioral and electrophysiological studies indicate that SK-blockade by apamin may enhance neuron excitability, synaptic plasticity, and long-term potentiation in the CA1 hippocampal region, and, for that reason, apamin has been proposed as a therapeutic agent in Alzheimer's disease treatment. However, the dendritic morphological mechanisms implied in such enhancement are unknown. In the present work, Golgi-Cox stain protocol and Sholl analysis were used to study the effect of apamin on the dendritic morphology of pyramidal neurons from hippocampus and the prefrontal cortex as well as on the medium spiny neurons from the nucleus accumbens and granule cells from the dentate gyrus (DG) of the hippocampus. We found that only granule cells from the DG and pyramidal neurons from dorsal and ventral hippocampus were altered in senile rats injected with apamin. Our research suggests that apamin may increase the dendritic morphology in the hippocampus, which could be related to the neuronal excitability and synaptic plasticity enhancement induced by apamin. Copyright © 2011 Wiley-Liss, Inc.

  18. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Directory of Open Access Journals (Sweden)

    Tamara Berdyyeva

    Full Text Available Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65% significantly decreasing the rate of calcium transients, and a small subset (3% showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  19. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Science.gov (United States)

    Berdyyeva, Tamara; Otte, Stephani; Aluisio, Leah; Ziv, Yaniv; Burns, Laurie D; Dugovic, Christine; Yun, Sujin; Ghosh, Kunal K; Schnitzer, Mark J; Lovenberg, Timothy; Bonaventure, Pascal

    2014-01-01

    Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  20. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    María eLlorens-Martín

    2014-05-01

    Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  1. High-frequency network activity, global increase in neuronal activity, and synchrony expansion precede epileptic seizures in vitro.

    Science.gov (United States)

    Jiruska, Premysl; Csicsvari, Jozsef; Powell, Andrew D; Fox, John E; Chang, Wei-Chih; Vreugdenhil, Martin; Li, Xiaoli; Palus, Milan; Bujan, Alejandro F; Dearden, Richard W; Jefferys, John G R

    2010-04-21

    How seizures start is a major question in epilepsy research. Preictal EEG changes occur in both human patients and animal models, but their underlying mechanisms and relationship with seizure initiation remain unknown. Here we demonstrate the existence, in the hippocampal CA1 region, of a preictal state characterized by the progressive and global increase in neuronal activity associated with a widespread buildup of low-amplitude high-frequency activity (HFA) (>100 Hz) and reduction in system complexity. HFA is generated by the firing of neurons, mainly pyramidal cells, at much lower frequencies. Individual cycles of HFA are generated by the near-synchronous (within approximately 5 ms) firing of small numbers of pyramidal cells. The presence of HFA in the low-calcium model implicates nonsynaptic synchronization; the presence of very similar HFA in the high-potassium model shows that it does not depend on an absence of synaptic transmission. Immediately before seizure onset, CA1 is in a state of high sensitivity in which weak depolarizing or synchronizing perturbations can trigger seizures. Transition to seizure is characterized by a rapid expansion and fusion of the neuronal populations responsible for HFA, associated with a progressive slowing of HFA, leading to a single, massive, hypersynchronous cluster generating the high-amplitude low-frequency activity of the seizure.

  2. ESTIMATION OF THE NUMBER OF NEURONS IN THE HIPPOCAMPUS OF RATS WITH PENICILLIN INDUCED EPILEPSY

    Directory of Open Access Journals (Sweden)

    Ilgaz Akdogan

    2011-05-01

    Full Text Available Epilepsy is a neurological disease arising from strong and uncontrollable electrical firings of a group of neurons in the central nervous system. Experimental epileptic models have been developed to assess the physiopathology of epileptic seizures. This study was undertaken to estimate the number of neurons in the rat hippocampus with penicillin induced epilepsy, using a stereological method, "the optical fractionator". In the experimental group, 500 IU penicillin-G was injected intra-cortically, and in the control group, the same volume of saline was administered. A week later, the animals were decapitated and their brains were removed by craniatomy. Frozen brains were cut with a thickness of 150 ěm in a cryostat. Sections were collected by systematic random sampling and stained with hematoxylen-eosin. Microscopic images of pyramidal cell layers from hippocampus CA1, CA2 and CA3 subfields were then transferred to a monitor, using a 100x objective (N.A. = 1.25. Using the optical disector method, the neurons were counted in the frames and determined with a fractionator sampling scheme. The total pyramidal neuron number was then estimated using the optical fractionator method. The total pyramidal neuron number was found to be statistically lower in the experimental group (mean = 142,888 ± 11,745 than in the control group (mean = 177,953 ± 10,907 (p < 0.05. The results suggest that a decrease in the hippocampal neuronal number in a penicillin model of epilepsy can be determined objectively and efficiently using the optical fractionator method.

  3. Transient changes in excitability of rabbit CA3 neurons with a time course appropriate to support memory consolidation.

    Science.gov (United States)

    Thompson, L T; Moyer, J R; Disterhoft, J F

    1996-09-01

    1. The excitability of CA3 pyramidal neurons was assessed with intracellular recordings in hippocampal slices from behaviorally naive rabbits. CA3 pyramidal neurons had large (-13.1 +/- 0.3 mV; mean +/- SE) postburst afterhyperpolarization (AHPs) and exhibited robust spike-frequency adaptation (accommodation) to prolonged (800-ms) depolarizing current injection at resting potentials of -68 mV. AHP and accommodation measures differed in scale but not in kind from those obtained in stable recordings from CA1 pyramidal neurons in the same slices or from the same rabbits, with CA3 neurons having larger longer AHPs but fewer spikes during accommodation. 2. Groups of rabbits were trained in a simple, associative-learning task, trace eye-blink conditioning, which required an intact hippocampus for successful acquisition. Memory consolidation in this task also involves the hippocampus, whereas long-term retention of the learned response does not. The time course and magnitude of learning-specific changes in excitability were assessed in 201 CA3 pyramidal neurons. 3. Learning increased the excitability of CA3 pyramidal neurons soon after acquisition (within 1-24 h). The mean postburst AHP was reduced to approximately half (-6.4 +/- 0.3 mV) the basal amplitude of the AHP observed in naive controls. The area and duration of the postburst AHP similarly were reduced. Approximately half of all pyramidal neurons tested soon after learning exhibited significantly reduced AHPs, whereas none exhibited enhanced AHPs. 4. Trace conditioning also reduced accommodation of CA3 pyramidal neurons 1-24 h after learning. Neurons from successfully trained rabbits fired significantly more action potentials (5.6 +/- 1.5) in response to prolonged depolarization than did neurons from naive controls (4.1 +/- 0.2). The magnitude of the learning-specific change in accommodation was less than that for the AHP. Approximately 45% of neurons tested exhibited significantly reduced accommodation soon after

  4. CA1 contributes to microcalcification and tumourigenesis in breast cancer.

    Science.gov (United States)

    Zheng, Yabing; Xu, Bing; Zhao, Yan; Gu, He; Li, Chang; Wang, Yao; Chang, Xiaotian

    2015-10-12

    Although mammary microcalcification is frequently observed and has been associated with poor survival in patients with breast cancer, the genesis of calcification remains unclear. Carbonic anhydrase I (CA1) has been shown to promote calcification by catalysing the hydration of CO2. This study aimed to determine whether CA1 was correlated with microcalcification and with other processes that are involved in breast cancer tumourigenesis. CA1 expression in breast cancer tissues and blood samples was detected using western blotting, real-time PCR, immunohistochemistry and ELISA. Calcification was induced in the cultured 4T1 cell line originating from mouse breast tumours, using ascorbic acid and β-glycerophosphate. Acetazolamide, a chemical inhibitor of CA1, was also added to the culture to determine the role of CA1 in calcification. The MCF-7 human breast cancer cell line was treated with anti-CA1 siRNA and was assessed using a CCK-8 cell proliferation assay, an annexin V cell apoptosis assay, transwell migration assay and a human breast cancer PCR array. The tag SNP rs725605, which is located in the CA1 locus, was genotyped using TaqMan® genotyping. Increased CA1 expression was detected in samples of breast carcinoma tissues and blood obtained from patients with breast cancer. A total of 15.3 % of these blood samples exhibited a 2.1-fold or higher level of CA1 expression, compared to the average level of CA1 expression in samples from healthy controls. Following the induction of calcification of 4T1 cells, both the number of calcium-rich deposits and the expression of CA1 increased, whereas the calcification and CA1 expression were significantly supressed in the presence of acetazolamide. Increased migration and apoptosis were observed in MCF-7 cells that were treated with anti-CA1 siRNA. The PCR array detected up-regulation of the androgen receptor (AR) and down-regulation of X-box binding protein 1 (XBP1) in the treated MCF-7 cells. Significant differences in

  5. PYRAMID LAKE RENEWEABLE ENERGY PLAN

    Energy Technology Data Exchange (ETDEWEB)

    HIGH DESERT GEOCULTURE, LLC

    2009-06-06

    The Pyramid Lake Renewable Energy Plan covers these areas: energy potential (primarily focusing on geothermal resource potential, but also more generally addressing wind energy potential); renewable energy market potential; transmission system development; geothermal direct use potential; and business structures to accomplish the development objectives of the Pyramid Lake Paiute Tribe.

  6. Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats.

    Science.gov (United States)

    Penagos-Corzo, Julio C; Bonilla, Andrea; Rodríguez-Moreno, Antonio; Flores, Gonzalo; Negrete-Díaz, José V

    2015-11-01

    We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self-discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self-discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self-discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes. © 2015 Wiley Periodicals, Inc.

  7. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABAA, glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABAB, as well as an adenosine A1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  8. Postsynaptic pyramidal target selection by descending layer III pyramidal axons: dual intracellular recordings and biocytin filling in slices of rat neocortex.

    Science.gov (United States)

    Thomson, A M; Bannister, A P

    1998-06-01

    Paired intracellular recordings in slices of adult rat neocortex with biocytin filling of synaptically connected neurons were used to investigate the pyramidal targets, in layer V, of layer III pyramidal axons. The time-course and sensitivity of excitatory postsynaptic potentials to current injected at the soma, and locations of close appositions between presynaptic axons and postsynaptic dendrites, indicated that the majority of contributory synapses were located in layer V. Within a "column" of tissue, radius < or = 250 microm, the probability that a randomly selected layer III pyramid innervated a layer V pyramid was 1 in 4 if the target cell was a burst firing pyramid with an apical dendritic tuft in layers II/I. If, however, the potential target was a regular spiking pyramid, the probability of connectivity was only 1 in 40, and none of the 13 anatomically identified postsynaptic layer V targets had a slender apical dendrite terminating in layers IV/III. Morphological reconstructions indicated that layer III pyramids select target layer V cells whose apical dendrites pass within 50-100 microm of the soma of the presynaptic pyramid in layer III and which have overlapping apical dendritic tufts in the superficial layers. The probability that a layer V cell would innervate a layer III pyramid lying within 250 microm of its apical dendrite was much lower (one in 58). Both presynaptic layer III pyramids and their large postsynaptic layer V targets could therefore access similar inputs in layers I/II, while small layer V pyramids could not. One prediction from the present data would be that neither descending layer V inputs to the striatum or thalamus, nor transcallosal connections would be readily activated by longer distance cortico-cortical "feedback" connections that terminated in layers I/II. These could, however, activate corticofugal pathways to the superior colliculus or pons, both directly and via layer III.

  9. Exogenous dehydroisoandrosterone sulfate reverses the dendritic changes of the central neurons in aging male rats.

    Science.gov (United States)

    Chen, Jeng-Rung; Tseng, Guo-Fang; Wang, Yueh-Jan; Wang, Tsyr-Jiuan

    2014-09-01

    Sex hormones are known to help maintaining the cognitive ability in male and female rats. Hypogonadism results in the reduction of the dendritic spines of central neurons which is believed to undermine memory and cognition and cause fatigue and poor concentration. In our previous studies, we have reported age-related regression in dendrite arbors along with loss of dendritic spines in the primary somatosensory cortical neurons in female rats. Furthermore, castration caused a reduction of dendritic spines in adult male rats. In light of this, it was surmised that dendritic structures might change in normal aging male rats with advancing age. Recently, dehydroepiandrosterone sulfate (DHEAS) has been reported to have memory-enhancing properties in aged rodents. In this study, normal aging male rats, with a reduced plasma testosterone level of 75-80%, were used to explore the changes in behavioral performance of neuronal dendritic arbor and spine density. Aging rats performed poorer in spatial learning memory (Morris water maze). Concomitantly, these rats showed regressed dendritic arbors and spine loss on the primary somatosensory cortical and hippocampal CA1 pyramidal neurons. Exogenous DHEAS and testosterone treatment reversed the behavioral deficits and partially restored the spine loss of cortical neurons in aging male rats but had no effects on the dendritic arbor shrinkage of the affected neurons. It is concluded therefore that DHEAS, has the efficacy as testosterone, and that it can exert its effects on the central neuron level to effectively ameliorate aging symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Carbon monoxide-induced delayed amnesia, delayed neuronal death and change in acetylcholine concentration in mice

    Energy Technology Data Exchange (ETDEWEB)

    Nabeshima, T.; Katoh, A.; Ishimaru, H.; Yoneda, Y.; Ogita, K.; Murase, K.; Ohtsuka, H.; Inari, K.; Fukuta, T.; Kameyama, T. (Meijo Univ., Nagoya (Japan))

    1991-01-01

    We investigated the interrelationship of delayed amnesia, delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide (CO)-exposure in mice. In the test for retention of the passive avoidance task, amnesia was observed 5 and 7 days after CO-exposure when the mice were exposed to CO 1 day after training; in the case when the mice were exposed to CO 5 and 7 days before training, amnesia was also observed in a retention test given 1 day after training. The number of pyramidal cells in the hippocampal CA1 subfield was lower than that of the control 3, 5 and 7 days after CO-exposure. But the neurodegeneration in the parietal cortex, area 1, was not observed until 7 days after CO-exposure. The findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to CO. In addition, the delayed amnesia was closely related to the delayed neuronal death in the hippocampal CA1 subfield. Moreover, (3H)glutamate and (3H)glycine binding sites did not change after CO-exposure but, 7 days after CO-exposure, the concentration of acetylcholine and the binding of (3H)quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed, but those in the hippocampus did not show significant change. Therefore, we suggest that delayed amnesia induced by CO-exposure may result from delayed neuronal death in the hippocampal CA1 subfield and dysfunction in the acetylcholinergic neurons, in the frontal cortex, the striatum and/or the hippocampus.

  11. Transient Receptor Potential Vanilloid 4-Induced Modulation of Voltage-Gated Sodium Channels in Hippocampal Neurons.

    Science.gov (United States)

    Hong, Zhiwen; Jie, Pinghui; Tian, Yujing; Chen, Tingting; Chen, Lei; Chen, Ling

    2016-01-01

    Transient receptor potential vanilloid 4 (TRPV4) is reported to control the resting membrane potential and increase excitability in many types of cells. Voltage-gated sodium channels (VGSCs) play an important role in initiating action potentials in neurons. However, whether VGSCs can be modulated by the activation of TRPV4 in hippocampal pyramidal neurons remains unknown. In this study, we tested the effect of TRPV4 agonists (GSK1016790A and 4α-PDD) on voltage-gated sodium current (I Na) in hippocampal CA1 pyramidal neurons and the protein levels of α/β-subunit of VGSCs in the hippocampus of mice subjected to intracerebroventricular (icv.) injection of GSK1016790A (GSK-injected mice). Herein, we report that I Na was inhibited by acute application of GSK1016790A or 4α-PDD. In the presence of TRPV4 agonists, the voltage-dependent inactivation curve shifted to the hyperpolarization, whereas the voltage-dependent activation curve remained unchanged. The TRPV4 agonist-induced inhibition of I Na was blocked by the TRPV4 antagonist or tetrodotoxin. Moreover, blocking protein kinase A (PKA) markedly attenuated the GSK1016790A-induced inhibition of I Na, whereas antagonism of protein kinase C or p38 mitogen-activated protein kinase did not change GSK1016790A action. Finally, the protein levels of Nav1.1, Nav1.2, and Nav1.6 in the hippocampus increased in GSK-injected mice, whereas those of Nav1.3 and Navβ1 remained nearly unchanged. We conclude that I Na is inhibited by the acute activation of TRPV4 through PKA signaling pathway in hippocampal pyramidal neurons, but protein expression of α-subunit of VGSCs is increased by sustained TRPV4 activation, which may compensate for the acute inhibition of I Na and provide a possibility for hyper-excitability upon sustained TRPV4 activation.

  12. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    Control il ti. Human brain. Control epileptic. Mutani et al., 1994 ... of Calcium Transients Evoked in. Response to Spontaneous Epileptic ... Proof : Feed forward inhibition in subiculum. CA1. Subiculum. Stimulation artifact. -60 mV. Excitatory neuron. Inhibitory neuron. Excitatory neuron. Excitatory. Synapse. Inhibitory. Synapse.

  13. Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus.

    Science.gov (United States)

    Gangarossa, Giuseppe; Longueville, Sophie; De Bundel, Dimitri; Perroy, Julie; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-12-01

    The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor-expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ-Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network. Copyright © 2012 Wiley Periodicals, Inc.

  14. Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

    Science.gov (United States)

    Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

    2015-08-20

    Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the

  15. Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital cataract (HCC, is a neuronal protein.

    Directory of Open Access Journals (Sweden)

    Elisabetta Gazzerro

    Full Text Available "Hypomyelination and Congenital Cataract", HCC (MIM #610532, is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS. Using heterozygous mice expressing the b-galactosidase (LacZ gene under control of the Hyccin gene regulatory elements, we show that the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical pyramidal neurons, while it did not colocalize with oligodendroglial or astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from newborn mice. In the brain, Hyccin transcript levels were higher in early postnatal development (postnatal days 2 and 10 and then declined in adult mice. In a model of active myelinogenesis, organotypic cultures of rat Schwann cells (SC/Dorsal Root Ganglion (DRG sensory neurons, Hyccin was detected along the neurites, while it was absent from SC. Intriguingly, the abundance of the molecule was upregulated at postnatal days 10 and 15, in the initial steps of myelinogenesis and then declined at 30 days when the process is complete. As Hyccin is primarily expressed in neurons and its mutation leads to hypomyelination in human patients, we suggest that the protein is involved in neuron-to-glia signalling to initiate or maintain myelination.

  16. SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients.

    Science.gov (United States)

    Facchinetti, Patricia; Dorard, Emilie; Contremoulins, Vincent; Gaillard, Marie-Claude; Déglon, Nicole; Sazdovitch, Véronique; Guihenneuc-Jouyaux, Chantal; Brouillet, Emmanuel; Duyckaerts, Charles; Allinquant, Bernadette

    2014-05-01

    Caspase cleaved amyloid precursor protein (APPcc) and SET are increased and mislocalized in the neuronal cytoplasm in Alzheimer Disease (AD) brains. Translocated SET to the cytoplasm can induce tau hyperphosphorylation. To elucidate the putative relationships between mislocalized APPcc and SET, we studied their level and distribution in the hippocampus of 5 controls, 3 Down syndrome and 10 Alzheimer patients. In Down syndrome and Alzheimer patients, APPcc and SET levels were increased in CA1 and the frequency of both localizations in the neuronal cytoplasm was high in CA1, and low in CA4. As the increase of APPcc is already present at early stages of AD, we overexpressed APPcc in CA1 and the dentate gyrus neurons of adult mice with a lentiviral construct. APPcc overexpression in CA1 and not in the dentate gyrus induced endogenous SET translocation and tau hyperphosphorylation. These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. CA1 subfield contributions to memory integration and inference

    Science.gov (United States)

    Schlichting, Margaret L.; Zeithamova, Dagmar; Preston, Alison R.

    2014-01-01

    The ability to combine information acquired at different times to make novel inferences is a powerful function of episodic memory. One perspective suggests that by retrieving related knowledge during new experiences, existing memories can be linked to the new, overlapping information as it is encoded. The resulting memory traces would thus incorporate content across event boundaries, representing important relationships among items encountered during separate experiences. While prior work suggests that the hippocampus is involved in linking memories experienced at different times, the involvement of specific subfields in this process remains unknown. Using both univariate and multivariate analyses of high-resolution functional magnetic resonance imaging (fMRI) data, we localized this specialized encoding mechanism to human CA1. Specifically, right CA1 responses during encoding of events that overlapped with prior experience predicted subsequent success on a test requiring inferences about the relationships among events. Furthermore, we employed neural pattern similarity analysis to show that patterns of activation evoked during overlapping event encoding were later reinstated in CA1 during successful inference. The reinstatement of CA1 patterns during inference was specific to those trials that were performed quickly and accurately, consistent with the notion that linking memories during learning facilitates novel judgments. These analyses provide converging evidence that CA1 plays a unique role in encoding overlapping events and highlight the dynamic interactions between hippocampal-mediated encoding and retrieval processes. More broadly, our data reflect the adaptive nature of episodic memories, in which representations are derived across events in anticipation of future judgments. PMID:24888442

  18. Turmeric (Curcuma longa L.) extract may prevent the deterioration of spatial memory and the deficit of estimated total number of hippocampal pyramidal cells of trimethyltin-exposed rats.

    Science.gov (United States)

    Yuliani, Sapto; Mustofa; Partadiredja, Ginus

    2018-01-01

    Protection of neurons from degeneration is an important preventive strategy for dementia. Much of the dementia pathology implicates oxidative stress pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti-oxidative and neuro-protective effects. These effects are considered to be similar to those of citicoline which has been regularly used as one of standard medications for dementia. This study aimed at investigating the effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)-treated Sprague-Dawley rats. The rats were divided randomly into six groups, i.e., a normal control group (N); Sn group, which was given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT chloride; and three Sn-TE groups, which were treated with three different dosages of turmeric rhizome extract and TMT chloride. Morris water maze test was carried out to examine the spatial memory. The estimated total number of CA1 and CA2-CA3 pyramidal cells was calculated using a stereological method. The administration of turmeric extract at a dose of 200 mg/kg bw has been shown to prevent the deficits in the spatial memory performance and partially inhibit the reduction of the number of CA2-CA3 regions pyramidal neurons. TMT-induced neurotoxic damage seemed to be mediated by the generation of reactive oxygen species and reactive nitrogen species. Turmeric extract might act as anti inflammatory as well as anti-oxidant agent. The effects of turmeric extract at a dose of 200 mg/kg bw seem to be comparable to those of citicoline.

  19. The multimodal antidepressant vortioxetine may facilitate pyramidal cell firing by inhibition of 5-HT3 receptor expressing interneurons: An in vitro study in rat hippocampus slices.

    Science.gov (United States)

    Dale, Elena; Grunnet, Morten; Pehrson, Alan L; Frederiksen, Kristen; Larsen, Peter H; Nielsen, Jacob; Stensbøl, Tine B; Ebert, Bjarke; Yin, Haolan; Lu, Dunguo; Liu, Huiquing; Jensen, Thomas N; Yang, Charles R; Sanchez, Connie

    2017-12-21

    The multimodal antidepressant vortioxetine is thought to mediate its pharmacological effects via 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, 5-HT1D, 5-HT3, 5-HT7 receptor antagonism and 5-HT transporter inhibition. Here we studied vortioxetine's functional effects across species (canine, mouse, rat, guinea pig and human) in cellular assays with heterologous expression of 5-HT3A receptors (in Xenopus oocytes and HEK-293 cells) and in mouse neuroblastoma N1E-115 cells with endogenous expression of 5-HT3A receptors. Furthermore, we studied the effects of vortioxetine on activity of CA1 Stratum Radiatum interneurons in rat hippocampus slices using current- and voltage-clamping methods. The patched neurons were subsequently filled with biocytin for confirmation of 5-HT3 receptor mRNA expression by in situ hybridization. Whereas, both vortioxetine and the 5-HT3 receptor antagonist ondansetron potently antagonized 5-HT-induced currents in the cellular assays, vortioxetine had a slower off-rate than ondansetron in oocytes expressing 5-HT3A receptors. Furthermore, vortioxetine's but not ondansetron's 5-HT3 receptor antagonistic potency varied considerably across species. Vortioxetine had the highest potency at rat and the lowest potency at guinea pig 5-HT3A receptors. Finally, in 5-HT3 receptor-expressing GABAergic interneurons from the CA1 stratum radiatum, vortioxetine and ondansetron blocked depolarizations induced by superfusion of either 5-HT or the 5-HT3 receptor agonist mCPBG. Taken together, these data add to a growing literature supporting the idea that vortioxetine may inhibit GABAergic neurotransmission in some brain regions via a 5-HT3 receptor antagonism-dependent mechanism and thereby disinhibit pyramidal neurons and enhance glutamatergic signaling. Copyright © 2017. Published by Elsevier B.V.

  20. Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO

    Directory of Open Access Journals (Sweden)

    Luisa Perasso

    2010-01-01

    Full Text Available Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

  1. Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

    Science.gov (United States)

    Döhring, Juliane; Stoldt, Anne; Witt, Karsten; Schönfeld, Robby; Deuschl, Günther; Born, Jan; Bartsch, Thorsten

    2017-04-01

    Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology. Copyright © 2016

  2. The Digital Von Fahrenheid Pyramid

    Science.gov (United States)

    Bura, M.; Janowski, J.; Wężyk, P.; Zięba, K.

    2017-08-01

    3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland). By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS), thermal imaging, georadar measurements (around and inside the tomb) and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS) and airborne laser scanning (ALS) authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees) on the condition and visibility of the Pyramids in the landscape.

  3. The mammalian neocortical pyramidal cell: a new theory on prenatal development

    Directory of Open Access Journals (Sweden)

    Miguel eMarín-Padilla

    2014-01-01

    Full Text Available Mammals’ new cerebral cortex (neocortex and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities using essentially analogous anatomical and neural makeups. The human neocortex starts to develop in the 6-week-old embryo with the establishment of a primordial cortical organization that resembles the primitive cortices of amphibian and reptiles that operated his early motor activities. From the 8th to the 15th week of age, the new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divide its components into those above it (neocortex first lamina and those below it (neocortex subplate elements. From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating the animal muscular activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface without losing its original attachment to first lamina or the location of its soma retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs 2 pyramidal cell functional strata to carry out all its motor activities, the mouse three, cat four, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing including thinking as a premotor activity.

  4. Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.

    Science.gov (United States)

    Fiorenza, Anna; Lopez-Atalaya, Jose P; Rovira, Victor; Scandaglia, Marilyn; Geijo-Barrientos, Emilio; Barco, Angel

    2016-04-01

    The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Rosmarinic acid protects rat hippocampal neurons from cerebral ischemia/reperfusion injury via the Akt/JNK3/caspase-3 signaling pathway.

    Science.gov (United States)

    Zhang, Min; Yan, Hui; Li, Sumei; Yang, Jun

    2017-02-15

    Cerebral ischemia/reperfusion injury can result in neuronal death, which further results in brain damage and can even lead to death. Although recent studies showed that rosmarinic acid (RA) exerts neuroprotective effects and attenuates ischemia-induced brain injury and neuronal cell death, little is known about the precise mechanisms that occur during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to examine the underlying mechanism of the neuroprotective effects of RA against ischemic brain injury induced by cerebral I/R. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. We randomly divided rats into five groups: sham, I/R, I/R+RA, I/R+Vehicle and I/R+RA+LY. Open-field, closed-field and Morris water maze tests were carried our separately to examine the anxiety and cognitive behavior of each group. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. The levels of p-Akt, p-JNK3 and cleaved caspase-3 in the hippocampus were also examined by Western blotting. Our results showed that administration of RA protected locomotive ability, relieved anxiety behavior and protected cognitive ability in cerebral I/R-injured rats. Additionally, RA significantly protected neurons in the hippocampal CA1 region against cerebral I/R-induced damage. Furthermore, RA increased the phosphorylation of Akt1, downregulated the phosphorylation of JNK3 and reduced the expression of cleaved caspase-3. Finally, the Akt inhibitor LY294002 reversed all the protective effects of RA, indicating that RA protects neurons in the hippocampal CA1 region from ischemic damage through the Akt/JNK3/caspase-3 signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. BASIC PRINCIPLES OF THE PYRAMIDS TEMPORAL BONE RADIOGRAPHY

    Directory of Open Access Journals (Sweden)

    Mirko Krstić

    2007-10-01

    Full Text Available This paper shows the possibilities and advantages of certain methods of temporal bone radiography in diagnosing pathological conditions and diseases of temporal bones, with description of basic techniques of radiological examinations: Mayer’s axial view of the pyramids, the Stenvers view of the pyramids, the Arcelini view of the pyramids, comparative pyramid radiography by Hass, comparative pyramid radiography by Gras-hey, comparative pyramid radiography in submentovertical projection and comparative pyramid radiography in verticosubmental projection.

  7. Morphological Characteristics of Electrophysiologically Characterized Layer Vb Pyramidal Cells in Rat Barrel Cortex

    NARCIS (Netherlands)

    Staiger, J.F.; Loucif, A.J.; Schubert, D.; Mock, M.

    2016-01-01

    Layer Vb pyramidal cells are the major output neurons of the neocortex and transmit the outcome of cortical columnar signal processing to distant target areas. At the same time they contribute to local tactile information processing by emitting recurrent axonal collaterals into the columnar

  8. The Pyramidal Capacitated Vehicle Routing Problem

    DEFF Research Database (Denmark)

    Lysgaard, Jens

    This paper introduces the Pyramidal Capacitated Vehicle Routing Problem (PCVRP) as a restricted version of the Capacitated Vehicle Routing Problem (CVRP). In the PCVRP each route is required to be pyramidal in a sense generalized from the Pyramidal Traveling Salesman Problem (PTSP). A pyramidal...... route is defined as a route on which the vehicle first visits customers in increasing order of customer index, and on the remaining part of the route visits customers in decreasing order of customer index. Provided that customers are indexed in nondecreasing order of distance from the depot, the shape...

  9. The pyramidal capacitated vehicle routing problem

    DEFF Research Database (Denmark)

    Lysgaard, Jens

    2010-01-01

    This paper introduces the pyramidal capacitated vehicle routing problem (PCVRP) as a restricted version of the capacitated vehicle routing problem (CVRP). In the PCVRP each route is required to be pyramidal in a sense generalized from the pyramidal traveling salesman problem (PTSP). A pyramidal...... route is defined as a route on which the vehicle first visits customers in increasing order of customer index, and on the remaining part of the route visits customers in decreasing order of customer index. Moreover, this paper develops an exact branch-and-cut-and-price (BCP) algorithm for the PCVRP...

  10. Urban Public Health: Is There a Pyramid?

    Directory of Open Access Journals (Sweden)

    Meirong Su

    2013-01-01

    Full Text Available Early ecologists identified a pyramidal trophic structure in terms of number, biomass and energy transfer. In 1943, the psychologist Maslow put forward a pyramid model to describe layers of human needs. It is indicated that the pyramid principle is universally applicable in natural, humanistic and social disciplines. Here, we report that a pyramid structure also exists in urban public health (UPH. Based on 18 indicators, the UPH states of four cities (Beijing, Tokyo, New York, and London are compared from the point of view of five aspects, namely physical health, living conditions, social security, environmental quality, and education and culture. A pyramid structure was found in each city when focusing on 2000–2009 data. The pyramid of Beijing is relatively similar to that of Tokyo, and the pyramids of New York and London are similar to each other. A general development trend in UPH is proposed and represented by different pyramid modes. As a basic conjecture, the UPH pyramid model can be verified and developed with data of more cities over a longer period, and be used to promote healthy urban development.

  11. The pyramids of Greece: Ancient meridian observatories?

    Science.gov (United States)

    Theodossiou, Efstratios; Manimanis, Vassilios N.; Dimitrijević, Milan S.; Katsiotis, Marco

    Pyramids, "Dragon Houses" ("Drakospita") and megalithic structures in general create always a special interest. We postulate that, as happens with the Drakospita of Euboea, the pyramid-like structures of Argolis (Eastern Peloponnese) were constructed by the Dryops. It is known that, in addition to Euboea and some Cyclades islands, this prehellenic people had also settled in Argolis, where they founded the city of Asine. We also propose that the pyramids of Argolis and in particular the pyramid of Hellinikon village were very likely, besides being a burial monument or guard house, might be served also for astronomical observations.

  12. Layer 5 Pyramidal Neurons’ Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Directory of Open Access Journals (Sweden)

    Diana Urrego

    2015-01-01

    Full Text Available This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans.

  13. Synaptically activated Ca2+ waves and NMDA spikes locally suppress voltage-dependent Ca2+ signalling in rat pyramidal cell dendrites.

    Science.gov (United States)

    Manita, Satoshi; Miyazaki, Kenichi; Ross, William N

    2011-10-15

    Postsynaptic [Ca(2+)](i) changes contribute to several kinds of plasticity in pyramidal neurons. We examined the effects of synaptically activated Ca(2+) waves and NMDA spikes on subsequent Ca(2+) signalling in CA1 pyramidal cell dendrites in hippocampal slices. Tetanic synaptic stimulation evoked a localized Ca(2+) wave in the primary apical dendrites. The [Ca(2+)](i) increase from a backpropagating action potential (bAP) or subthreshold depolarization was reduced if it was generated immediately after the wave. The suppression had a recovery time of 30-60 s. The suppression only occurred where the wave was generated and was not due to a change in bAP amplitude or shape. The suppression also could be generated by Ca(2+) waves evoked by uncaging IP(3), showing that other signalling pathways activated by the synaptic tetanus were not required. The suppression was proportional to the amplitude of the [Ca(2+)](i) change of the Ca(2+) wave and was not blocked by a spectrum of kinase or phosphatase inhibitors, consistent with suppression due to Ca(2+)-dependent inactivation of Ca(2+) channels. The waves also reduced the frequency and amplitude of spontaneous, localized Ca(2+) release events in the dendrites by a different mechanism, probably by depleting the stores at the site of wave generation. The same synaptic tetanus often evoked NMDA spike-mediated [Ca(2+)](i) increases in the oblique dendrites where Ca(2+) waves do not propagate. These NMDA spikes suppressed the [Ca(2+)](i) increase caused by bAPs in those regions. [Ca(2+)](i) increases by Ca(2+) entry through voltage-gated Ca(2+) channels also suppressed the [Ca(2+)](i) increases from subsequent bAPs in regions where the voltage-gated [Ca(2+)](i) increases were largest, showing that all ways of raising [Ca(2+)](i) could cause suppression.

  14. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats.

    Science.gov (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg -1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups.

  15. Changes in cerebral blood flow and blood brain barrier in the gerbil hippocampal CA1 region following repeated brief cerebral ischemia.

    Science.gov (United States)

    Jingtao, J.; Sato, S.; Yamanaka, N.

    1999-12-01

    Neuronal damage and changes in cerebral blood flow (CBF) and the permeability of the blood-brain barrier (BBB) following repeated brief periods of ischemia were studied in Mongolian gerbils. The cerebral ischemia was produced by three repeated occlusions of bilateral common carotid arteries for 3 min at 1-h intervals. CBF and permeability of the BBB were examined with tracers (China ink and silver nitrate) at 1, 3, and 7 days post ischemia using light and electron microscopy. Three days after the reperfusion, significant extravasation of tracers, consequential reduction of CBF, extensive neuronal destruction, and intravascular platelet aggregation were observed. Such vascular changes in the CA1 region were more severe than those in the frontal cortex. These findings strongly support the view that microcirculatory disturbance may be a mechanism responsible for delayed neuronal death in the CA1 region of the hippocampus.

  16. Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex.

    Science.gov (United States)

    Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

    2016-01-01

    Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles.

  17. Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex.

    Directory of Open Access Journals (Sweden)

    Laura Anton-Sanchez

    Full Text Available Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%. We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles.

  18. Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex

    Science.gov (United States)

    Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

    2016-01-01

    Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles. PMID:27832100

  19. Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Hui Young; Tae, Hyun-Jin; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Won, Moo-Ho; Park, Chan Woo; Cho, Jun Hwi; Seo, Jeong Yeol; Lee, Jae-Chul

    2016-06-01

    In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils. IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given recovery times of 1 day, 2 days and 5 days and we examined change in c-myb immunoreactivity as well as neuronal damage/death in the hippocampus induced by a lethal transient ischemia. A lethal transient ischemia induced a significant loss of cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia, and this insult showed that c-myb immunoreactivity in cells of the SP of the CA1 region was significantly decreased at 2 days post-ischemia and disappeared at 5 days post-ischemia. However, IPC effectively prevented the neuronal loss in the SP and showed that c-myb immunoreactivity was constitutively maintained in the SP after a lethal transient ischemia. Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult.

  20. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    National Research Council Canada - National Science Library

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    .... Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation...

  1. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    NARCIS (Netherlands)

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we

  2. PYRAMIDAL TOURS AND THE TRAVELING SALESMAN PROBLEM

    NARCIS (Netherlands)

    VANDERVEEN, JAA; SIERKSMA, G; VANDAL, R

    1991-01-01

    A traveling salesman problem is studied, containing a shortest Hamiltonian tour that is as long as a shortest pyramidal tour. A tour is pyramidal if it consists of a path from city 1 to n with cities in between visited in ascending order, and a path from n to 1 with cities in between visited in

  3. Personalizing the Food Pyramid. Teaching Techniques.

    Science.gov (United States)

    Allen, Donna

    1996-01-01

    Presents a strategy for health and home economics teachers to use in evaluating secondary students' eating and nutritional patterns. Students keep two-day food journals then complete a colorful personal food pyramid with the results. This creates a personal pyramid of food choices that lets students explore their eating habits. (SM)

  4. Challenges to rebuilding the US food pyramid.

    Science.gov (United States)

    Kinney, John M

    2005-01-01

    Twelve years have passed since the US Department of Agriculture introduced the Food Guide Pyramid as a single visual expression of the major food groups and their relative amounts in a healthy diet. Unfortunately, no regular review has been conducted to incorporate new knowledge. Some feel that the pyramid format is too limited for modern use, while others wish it to continue with new information. It seems timely to review what features of the pyramid design have been useful over past years and how it can be improved with new concepts while maintaining ease of understanding by the average consumer. Examples are presented of adapting the pyramid to diets promoted by a special group or to support particular dietary beliefs, in contrast to the goal of seeking a single standardized format. Inherent limitations of the pyramid format are discussed. One proposal is discussed which seeks to redesign the pyramid into a modern educational tool presenting current concepts supported by recent studies and outcomes data. Popular beliefs about what is a healthy diet have perhaps never been as varied as now. This is partly due to sharply differing opinions about which highly publicized weight-loss diet is most effective. The educational benefits of the pyramid format need objective study in view of the inherent limitations of that configuration. Only when the specific visual advantages for the consumer are shown can a decision be made as to the benefit of major new efforts to construct a single modern pyramid.

  5. Interlaminar differences in the pyramidal cell phenotype in parietal cortex of an Indian bat, cynopterus sphinx.

    Science.gov (United States)

    Srivastava, U C; Pathak, S V

    2010-10-30

    To study interlaminar phenotypic variations in the pyramidal neurons of parietal isocortex in bat (Cynopterus sphinx), Golgi and Nissl methods have been employed. The parietal isocortex is relatively thin in the bat as compared to prototheria with layer III, V and VI accounting for more than two—thirds of total cortical thickness. Thick cell free layer I and thinnest accentuated layer II are quite in connotation with other chiropterids. Poor demarcation of layer III/IV in the present study is also in connotation with primitive eutherian mammal (i.e. prototherian) and other chiropterids. Most of the pyramidal cells in the different layers of the parietal isocortex are of typical type as seen in other eutherians but differ significantly in terms of soma shape and size, extent of dendritic arbor, diameter of dendrites and spine density. Percentage of pyramidal neurons, diameter of apical dendrite and spine density on apical dendrite appear to follow an increasing trend from primitive to advanced mammals; but extent of dendrites are probably governed by the specific life patterns of these mammals. It is thus concluded that 'typical' pyramidal neurons in parietal isocortex are similar in therians but different from those in prototherians. It is possible that these cells might have arisen among early eutherians after divergence from prototherian stock.

  6. Brief bursts self-inhibit and correlate the pyramidal network.

    Directory of Open Access Journals (Sweden)

    Thomas K Berger

    2010-09-01

    Full Text Available Inhibitory pathways are an essential component in the function of the neocortical microcircuitry. Despite the relatively small fraction of inhibitory neurons in the neocortex, these neurons are strongly activated due to their high connectivity rate and the intricate manner in which they interconnect with pyramidal cells (PCs. One prominent pathway is the frequency-dependent disynaptic inhibition (FDDI formed between layer 5 PCs and mediated by Martinotti cells (MCs. Here, we show that simultaneous short bursts in four PCs are sufficient to exert FDDI in all neighboring PCs within the dimensions of a cortical column. This powerful inhibition is mediated by few interneurons, leading to strongly correlated membrane fluctuations and synchronous spiking between PCs simultaneously receiving FDDI. Somatic integration of such inhibition is independent and electrically isolated from monosynaptic excitation formed between the same PCs. FDDI is strongly shaped by I(h in PC dendrites, which determines the effective integration time window for inhibitory and excitatory inputs. We propose a key disynaptic mechanism by which brief bursts generated by a few PCs can synchronize the activity in the pyramidal network.

  7. Experimentally constrained CA1 fast-firing parvalbumin-positive interneuron network models exhibit sharp transitions into coherent high frequency rhythms.

    Science.gov (United States)

    Ferguson, Katie A; Huh, Carey Y L; Amilhon, Bénédicte; Williams, Sylvain; Skinner, Frances K

    2013-01-01

    The coupling of high frequency oscillations (HFOs; >100 Hz) and theta oscillations (3-12 Hz) in the CA1 region of rats increases during REM sleep, indicating that it may play a role in memory processing. However, it is unclear whether the CA1 region itself is capable of providing major contributions to the generation of HFOs, or if they are strictly driven through input projections. Parvalbumin-positive (PV+) interneurons may play an essential role in these oscillations due to their extensive connections with neighboring pyramidal cells, and their characteristic fast-spiking. Thus, we created mathematical network models to investigate the conditions under which networks of CA1 fast-spiking PV+ interneurons are capable of producing high frequency population rhythms. We used whole-cell patch clamp recordings of fast-spiking, PV+ cells in the CA1 region of an intact hippocampal preparation in vitro to derive cellular properties, from which we constrained an Izhikevich-type model. Novel, biologically constrained network models were constructed with these individual cell models, and we investigated networks across a range of experimentally determined excitatory inputs and inhibitory synaptic strengths. For each network, we determined network frequency and coherence. Network simulations produce coherent firing at high frequencies (>90 Hz) for parameter ranges in which PV-PV inhibitory synaptic conductances are necessarily small and external excitatory inputs are relatively large. Interestingly, our networks produce sharp transitions between random and coherent firing, and this sharpness is lost when connectivity is increased beyond biological estimates. Our work suggests that CA1 networks may be designed with mechanisms for quickly gating in and out of high frequency coherent population rhythms, which may be essential in the generation of nested theta/high frequency rhythms.

  8. Experimentally constrained CA1 fast-firing parvalbumin-positive interneuron network models exhibit sharp transitions into coherent high frequency rhythms

    Directory of Open Access Journals (Sweden)

    Katie A Ferguson

    2013-10-01

    Full Text Available The coupling of high frequency oscillations (HFOs; >100 Hz and theta oscillations (3-12 Hz in the CA1 region of rats increases during REM sleep, indicating that it may play a role in memory processing. However, it is unclear whether the CA1 region itself is capable of providing major contributions to the generation of HFOs, or if they are strictly driven through input projections. Parvalbumin-positive (PV+ interneurons may play an essential role in these oscillations due to their extensive connections with neighbouring pyramidal cells, and their characteristic fast-spiking. Thus, we created mathematical network models to investigate the conditions under which networks of CA1 fast-spiking PV+ interneurons are capable of producing high frequency population rhythms.We used whole-cell patch clamp recordings of fast-spiking, PV+ cells in the CA1 region of an intact hippocampal preparation in vitro to derive cellular properties, from which we constrained an Izhikevich-type model. Novel, biologically constrained network models were constructed with these individual cell models, and we investigated networks across a range of experimentally determined excitatory inputs and inhibitory synaptic strengths. For each network, we determined network frequency and coherence.Network simulations produce coherent firing at high frequencies (> 90 Hz for parameter ranges in which PV-PV inhibitory synaptic conductances are necessarily small and external excitatory inputs are relatively large. Interestingly, our networks produce sharp transitions between random and coherent firing, and this sharpness is lost when connectivity is increased beyond biological estimates. Our work suggests that CA1 networks may be designed with mechanisms for quickly gating in and out of high frequency coherent population rhythms, which may be essential in the generation of nested theta/high frequency rhythms.

  9. Experimentally Verified Parameter Sets for Modelling Heterogeneous Neocortical Pyramidal-Cell Populations.

    Directory of Open Access Journals (Sweden)

    Paul M Harrison

    2015-08-01

    Full Text Available Models of neocortical networks are increasingly including the diversity of excitatory and inhibitory neuronal classes. Significant variability in cellular properties are also seen within a nominal neuronal class and this heterogeneity can be expected to influence the population response and information processing in networks. Recent studies have examined the population and network effects of variability in a particular neuronal parameter with some plausibly chosen distribution. However, the empirical variability and covariance seen across multiple parameters are rarely included, partly due to the lack of data on parameter correlations in forms convenient for model construction. To addess this we quantify the heterogeneity within and between the neocortical pyramidal-cell classes in layers 2/3, 4, and the slender-tufted and thick-tufted pyramidal cells of layer 5 using a combination of intracellular recordings, single-neuron modelling and statistical analyses. From the response to both square-pulse and naturalistic fluctuating stimuli, we examined the class-dependent variance and covariance of electrophysiological parameters and identify the role of the h current in generating parameter correlations. A byproduct of the dynamic I-V method we employed is the straightforward extraction of reduced neuron models from experiment. Empirically these models took the refractory exponential integrate-and-fire form and provide an accurate fit to the perisomatic voltage responses of the diverse pyramidal-cell populations when the class-dependent statistics of the model parameters were respected. By quantifying the parameter statistics we obtained an algorithm which generates populations of model neurons, for each of the four pyramidal-cell classes, that adhere to experimentally observed marginal distributions and parameter correlations. As well as providing this tool, which we hope will be of use for exploring the effects of heterogeneity in neocortical

  10. Mannitol induces selective astroglial death in the CA1 region of the rat hippocampus following status epilepticus

    Science.gov (United States)

    Ko, Ah-Reum; Kang, Tae-Cheon

    2015-01-01

    In the present study, we addressed the question of whether treatment with mannitol, an osmotic diuretic, affects astrogliovascular responses to status epilepticus (SE). In saline-treated animals, astrocytes exhibited reactive astrogliosis in the CA1-3 regions 2-4 days after SE. In the mannitol-treated animals, a large astroglial empty zone was observed in the CA1 region 2 days after SE. This astroglial loss was unrelated to vasogenic edema formation. There was no difference in SE-induced neuronal loss between saline- and mannitol-treated animals. Furthermore, mannitol treatment did not affect astroglial loss and vasogenic edema formation in the dentate gyrus and the piriform cortex. These findings suggest that mannitol treatment induces selective astroglial loss in the CA1 region independent of vasogenic edema formation following SE. These findings support the hypothesis that the susceptibility of astrocytes to SE is most likely due to the distinctive heterogeneity of astrocytes independent of hemodynamics. [BMB Reports 2015; 48(9): 507-512] PMID:25703536

  11. Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices

    Directory of Open Access Journals (Sweden)

    MacIver M Bruce

    2004-12-01

    Full Text Available Abstract Background Anesthesia is produced by a depression of central nervous system function, however, the sites and mechanisms of action underlying this depression remain poorly defined. The present study compared and contrasted effects produced by five general anesthetics on synaptic circuitry in the CA1 region of hippocampal slices. Results At clinically relevant and equi-effective concentrations, presynaptic and postsynaptic anesthetic actions were evident at glutamate-mediated excitatory synapses and at GABA-mediated inhibitory synapses. In addition, depressant effects on membrane excitability were observed for CA1 neuron discharge in response to direct current depolarization. Combined actions at several of these sites contributed to CA1 circuit depression, but the relative degree of effect at each site was different for each anesthetic studied. For example, most of propofol's depressant effect (> 70 % was reversed with a GABA antagonist, but only a minor portion of isoflurane's depression was reversed ( 50 %, but thiopental by only Conclusions These results, in as much as they may be relevant to anesthesia, indicate that general anesthetics act at several discrete sites, supporting a multi-site, agent specific theory for anesthetic actions. No single effect site (e.g. GABA synapses or mechanism of action (e.g. depressed membrane excitability could account for all of the effects produced for any anesthetic studied.

  12. Selective serotonergic excitation of callosal projection neurons

    Directory of Open Access Journals (Sweden)

    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  13. Cell Type-Specific Effects of Adenosine on Cortical Neurons

    Science.gov (United States)

    van Aerde, Karlijn I.; Qi, Guanxiao; Feldmeyer, Dirk

    2015-01-01

    The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3–6 were hyperpolarized (range 1.2–10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening. PMID:24108800

  14. Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Xiaohua Jin

    2016-01-01

    Full Text Available Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5 is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2 in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2KI/KI mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

  15. Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity

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    Anne eSinning

    2015-06-01

    Full Text Available Slc4a10 is a Na+-coupled Cl--HCO3- exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input-output relations as well as short and long term changes of evoked field potentials in Slc4a10 knockout and wildtype mice. While responses of CA1 pyramidal neurons to stimulation of Schaffer collaterals were increased in Slc4a10 knockout mice, evoked field potentials did not differ between genotypes in the stratum radiatum or the neocortical areas analyzed. Paired pulse facilitation was diminished in the hippocampus upon disruption of Slc4a10 and paired pulse depression was increased in the neocortex. Though short term plasticity is modulated via Slc4a10, long term potentiation appears independent of Slc4a10. Our data support that Slc4a10 dampens neuronal excitability and thus sheds light on the pathophysiology of SLC4A10 associated pathologies.

  16. Reduced pyramidal cell somal volume in auditory association cortex of subjects with schizophrenia.

    Science.gov (United States)

    Sweet, Robert A; Pierri, Joseph N; Auh, Sungyoung; Sampson, Allan R; Lewis, David A

    2003-03-01

    Subjects with schizophrenia have decreased gray matter volume of auditory association cortex in structural imaging studies, and exhibit deficits in auditory sensory memory processes subserved by this region. In dorsal prefrontal cortex (dPFC), similar in vivo observations of reduced regional volume and working memory deficits in subjects with schizophrenia have been related to reduced somal volume of deep layer 3 pyramidal cells. We hypothesized that deep layer 3 pyramidal cell somal volume would also be reduced in auditory association cortex (BA42) in schizophrenia. We used the nucleator to estimate the somal volume of pyramidal neurons in deep layer 3 of BA42 in 18 subjects with schizophrenia, each of whom was matched to one normal comparison subject for gender, age, and post-mortem interval. For all subject pairs, somal volume of pyramidal neurons in deep layer 3 of dPFC (BA9) had previously been determined. In BA42, somal volume was reduced by 13.1% in schizophrenic subjects (p=0.03). Reductions in somal volume were not associated with the history of antipsychotic use, alcohol dependence, schizoaffective disorder, or death by suicide. The percent change in somal volume within-subject pairs was highly correlated between BA42 and BA9 (r=0.67, p=0.002). Deep layer 3 pyramidal cell somal volume is reduced in BA42 of subjects with schizophrenia. This reduction may contribute to impairment in auditory function. The correlated reductions of somal volume in BA42 and BA9 suggest that a common factor may affect deep layer 3 pyramidal cells in both regions.

  17. Dim light at night provokes depression-like behaviors and reduces CA1 dendritic spine density in female hamsters.

    Science.gov (United States)

    Bedrosian, Tracy A; Fonken, Laura K; Walton, James C; Haim, Abraham; Nelson, Randy J

    2011-08-01

    The prevalence of major depression has increased in recent decades; however, the underlying causes of this phenomenon remain unspecified. One environmental change that has coincided with elevated rates of depression is increased exposure to artificial light at night. Shift workers and others chronically exposed to light at night are at increased risk of mood disorders, suggesting that nighttime illumination may influence brain mechanisms mediating affect. We tested the hypothesis that exposure to dim light at night may impact affective responses and alter morphology of hippocampal neurons. Ovariectomized adult female Siberian hamsters (Phodopus sungorus) were housed for 8 weeks in either a light/dark cycle (LD) or a light/dim light cycle (DM), and then behavior was assayed. DM-hamsters displayed more depression-like responses in the forced swim and the sucrose anhedonia tests compared with LD-hamsters. Conversely, in the elevated plus maze DM-hamsters reduced anxiety-like behaviors. Brains from the same animals were processed using the Golgi-Cox method and hippocampal neurons within CA1, CA3, and the dentate gyrus were analyzed for morphological characteristics. In CA1, DM-hamsters significantly reduced dendritic spine density on both apical and basilar dendrites, an effect which was not mediated by baseline cortisol, as concentrations were equivalent between groups. These results demonstrate dim light at night is sufficient to reduce synaptic spine connections to CA1. Importantly, the present results suggest that night-time low level illumination, comparable to levels that are pervasive in North America and Europe, may contribute to the increasing prevalence of mood disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Pascal Pyramids: a mathematical exploration using spreadsheets

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    John E Baker

    2013-05-01

    Full Text Available The features of Pascal’s Triangle are generalised to 3-variable and 4-variable expressions resulting in the formation of pyramids of coefficients. The steps required to create the coefficients are also given.

  19. Evaluation of the Green Egyptian Pyramid

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    Mohamed Gamal Ammar

    2012-12-01

    The research concluded to the need of developing the Egyptian pyramid system through studying more global systems, in addition to the need to benefit from the Egyptian experience stock of solutions and environmental treatments in ancient architecture.

  20. Modelling the Somatic Electrical Response of Hippocampal Pyramidal Neurons

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    1989-09-01

    Computational Neuroscience Hippocampus Modelling 20. ABSTiRACT (Cetlin.a i oed* Ofe EU neeeeap ena IEWhEtDif by blook 0=maw) A modelling study of hippocampal...threshold. 3. A sleep activation) curve at the lower threshold taken with the non- zero inaclivation at depolarized membrane potentials would result in an...pmo ( (gap ot- hack tvtpane-eixin)) (defun startup () (tyake-window ’plot-frame 269 ,panes ’((*plot-pane-1 tv:plotter-pane :label *Voltages In Soma And

  1. Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats.

    Science.gov (United States)

    Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo

    2017-03-01

    Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory. © 2016 Wiley Periodicals, Inc.

  2. The New Modern Mediterranean Diet Italian Pyramid.

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    Vitiello, V; Germani, A; Capuzzo Dolcetta, E; Donini, L M; Del Balzo, V

    2016-01-01

    Epidemiological studies have established the health benefits associated with the adherence to the MD (Mediterranean Diet), mainly in relation to reducing the risk of developing the non communicable diseases. The MD is a sustainable diet model that respects the environment, promotes the bio-diversity, the local cultural heritages, the social interaction and economic aspects. The pyramid is a graphical representation designed to represent the frequencies of consumption and portion sizes of each food according to the Mediterranean model and tradition. The pyramid was developed taking into account the LARN (Reference Intake of nutrients and energy for Italian Population) and the Italian Guidelines for a healthy diet. The frequency of consumption and the portion size recommended are located at the different level of the pyramid. At the base of the pyramid there are the foods that should be consumed every meal and some concepts typical of the Mediterranean culture. In the middle there are foods that should be consumed daily and at the top of the pyramid the foods consumed on a weekly basis. The new modern MD Italian Pyramid is an important tool to promote the MD and improve the adherence to the MD dietary pattern.

  3. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

    Science.gov (United States)

    Dale, Elena; Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-10-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. © The Author(s) 2014.

  4. Reward Expectancy Strengthens CA1 Theta and Beta Band Synchronization and Hippocampal-Ventral Striatal Coupling.

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    Lansink, Carien S; Meijer, Guido T; Lankelma, Jan V; Vinck, Martin A; Jackson, Jadin C; Pennartz, Cyriel M A

    2016-10-12

    The use of information from the hippocampal memory system in motivated behavior depends on its communication with the ventral striatum. When an animal encounters cues that signal subsequent reward, its reward expectancy is raised. It is unknown, however, how this process affects hippocampal dynamics and their influence on target structures, such as ventral striatum. We show that, in rats, reward-predictive cues result in enhanced hippocampal theta and beta band rhythmic activity during subsequent action, compared with uncued goal-directed navigation. The beta band component, also labeled theta's harmonic, involves selective hippocampal CA1 cell groups showing frequency doubling of firing periodicity relative to theta rhythmicity and it partitions the theta cycle into segments showing clear versus poor spike timing organization. We found that theta phase precession occurred over a wider range than previously reported. This was apparent from spikes emitted near the peak of the theta cycle exhibiting large "phase precessing jumps" relative to spikes in foregoing cycles. Neither this phenomenon nor the regular manifestation of theta phase precession was affected by reward expectancy. Ventral striatal neuronal firing phase-locked not only to hippocampal theta, but also to beta band activity. Both hippocampus and ventral striatum showed increased synchronization between neuronal firing and local field potential activity during cued compared with uncued goal approaches. These results suggest that cue-triggered reward expectancy intensifies hippocampal output to target structures, such as the ventral striatum, by which the hippocampus may gain prioritized access to systems modulating motivated behaviors. Here we show that temporally discrete cues raising reward expectancy enhance both theta and beta band activity in the hippocampus once goal-directed navigation has been initiated. These rhythmic activities are associated with increased synchronization of neuronal firing

  5. Complementary contributions of prefrontal neuron classes in abstract numerical categorization.

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    Diester, Ilka; Nieder, Andreas

    2008-07-30

    The primate prefrontal cortex (PFC) plays a cardinal role in forming abstract categories and concepts. However, it remains elusive how this is accomplished and to what extent the interaction of functionally distinct neuron classes underlies this representation. Here, we inferred the major cortical cell types, putative pyramidal cells, and interneurons by characterizing the waveforms of action potentials recorded in monkeys performing a cognitively demanding numerosity categorization task. Putative interneurons responded much faster than cells classified as pyramidal neurons and exhibited a higher reliability of category discrimination, whereas putative pyramidal cells showed a higher degree of category selectivity. An analysis of the numerosity tuning profiles and the temporal interactions of adjacent neurons indicated that inhibitory input by putative interneurons shapes the tuning to numerical categories of putative PFC pyramidal cells. These findings favor feedforward mechanisms subserving cognitive categorization and help to clarify cellular interactions in PFC microcircuits.

  6. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

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    Francisco J Rubio

    2013-05-01

    Full Text Available Antidepressant drugs are usually administered for long time for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor fluoxetine to naϊve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of treatment with 0.7 mg/kg of fluoxetine on long-term potentiation (LTP and long-term depression (LTD in the Schaffer collateral-CA1 synapses and the perforant path-CA1 synapses. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum together with increased GluA2-containing, Ca2+-impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

  7. Local Pyramidal Descriptors for Image Recognition.

    Science.gov (United States)

    Seidenari, Lorenzo; Serra, Giuseppe; Bagdanov, Andrew D; Del Bimbo, Alberto

    2014-05-01

    In this paper, we present a novel method to improve the flexibility of descriptor matching for image recognition by using local multiresolution pyramids in feature space. We propose that image patches be represented at multiple levels of descriptor detail and that these levels be defined in terms of local spatial pooling resolution. Preserving multiple levels of detail in local descriptors is a way of hedging one's bets on which levels will most relevant for matching during learning and recognition. We introduce the Pyramid SIFT (P-SIFT) descriptor and show that its use in four state-of-the-art image recognition pipelines improves accuracy and yields state-of-the-art results. Our technique is applicable independently of spatial pyramid matching and we show that spatial pyramids can be combined with local pyramids to obtain further improvement. We achieve state-of-the-art results on Caltech-101 (80.1%) and Caltech-256 (52.6%) when compared to other approaches based on SIFT features over intensity images. Our technique is efficient and is extremely easy to integrate into image recognition pipelines.

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

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    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.

  9. Selectivity of pyramidal cells and interneurons in the human medial temporal lobe

    Science.gov (United States)

    Mormann, Florian; Cerf, Moran; Koch, Christof; Fried, Itzhak; Quiroga, Rodrigo Quian

    2011-01-01

    Neurons in the medial temporal lobe (MTL) respond selectively to pictures of specific individuals, objects, and places. However, the underlying mechanisms leading to such degree of stimulus selectivity are largely unknown. A necessary step to move forward in this direction involves the identification and characterization of the different neuron types present in MTL circuitry. We show that putative principal cells recorded in vivo from the human MTL are more selective than putative interneurons. Furthermore, we report that putative hippocampal pyramidal cells exhibit the highest degree of selectivity within the MTL, reflecting the hierarchical processing of visual information. We interpret these differences in selectivity as a plausible mechanism for generating sparse responses. PMID:21715671

  10. The Babinski sign and the pyramidal syndrome.

    Science.gov (United States)

    Van Gijn, J

    1978-01-01

    The presence or absence of a Babinski sign can be puzzling, but in the light of existing pathological studies it is more fruitful to consider which pyramidal tract fibres release it than whether they release it. This was investigated clinically, by looking for correlations with other reflex changes and with motor deficits in the leg. A survey of 50 patients with a unilateral Babinski sign and six patients who lacked it in spite of other pyramidal tract signs was supplemented with follow-up of the patients who had acute lesions. Appearance of the Bibinski sign proved to depend on the interaction of two factors: (1) activity (not necessarily hyperactivity) in the segmental pathways of the flexion synergy; (2) a motor deficit of the foot, in some cases consisting only in an impairment of rapid foot movements, and probably representing a disturbance of direct pyramidal tract projections to distal motoneurones. PMID:310447

  11. Chronic fluoxetine administration enhances synaptic plasticity and increases functional dynamics in hippocampal CA3-CA1 synapses.

    Science.gov (United States)

    Popova, Dina; Castrén, Eero; Taira, Tomi

    2017-11-01

    Recent studies demonstrate that chronic administration of the widely used antidepressant fluoxetine (FLX) promotes neurogenesis, synaptogenesis and synaptic plasticity in the adult hippocampus, cortex and amygdala. However, the mechanisms underlying these effects and how are they related to the clinical antidepressant efficacy are still poorly understood. We show here that chronic FLX administration decreases hippocampus-associated neophobia in naïve mice. In parallel, electrophysiological recordings in hippocampal CA3-CA1 circuitry revealed that the FLX treatment resulted in increased short- and long-term plasticity likely attributed to changes in presynaptic function. These changes were accompanied by enhancement in the expression of proteins related to vesicular trafficking and release, namely synaptophysin, synaptotagmin 1, MUNC 18 and syntaxin 1. Thus, chronic FLX administration is associated with enhanced synaptic dynamics atypical of mature CA1 synapses, elevated hippocampal plasticity, improved hippocampus-dependent behavior as well as altered expression of synaptic proteins regulating neurotransmitter trafficking and release. The results support the idea that antidepressants can promote neuronal plasticity and show that they can increase the functional dynamic range and information processing in synaptic circuitries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Regional specialization in pyramidal cell structure in the visual cortex of the galago: an intracellular injection study of striate and extrastriate areas with comparative notes on new world and old world monkeys.

    Science.gov (United States)

    Elston, Guy N; Elston, Alejandra; Kaas, Jon H; Casagrande, Vivien

    2005-01-01

    Recent studies have revealed marked differences in the basal dendritic structure of layer III pyramidal cells in the cerebral cortex of adult simian primates. In particular, there is a consistent trend for pyramidal cells of increasing complexity with anterior progression through occipitotemporal cortical visual areas. These differences in pyramidal cell structure, and their systematic nature, are believed to be important for specialized aspects of visual processing within, and between, cortical areas. However, it remains unknown whether this regional specialization in the pyramidal cell phenotype is unique to simians, is unique to primates in general or is widespread amongst mammalian species. In the present study we investigated pyramidal cell structure in the prosimian galago (Otolemur garnetti). We found, as in simians, that the basal dendritic arbors of pyramidal cells differed between cortical areas. More specifically, pyramidal cells became progressively more spinous through the primary (V1), second (V2), dorsolateral (DL) and inferotemporal (IT) visual areas. Moreover, pyramidal neurons in V1 of the galago are remarkably similar to those in other primate species, in spite of large differences in the sizes of this area. In contrast, pyramidal cells in inferotemporal cortex are quite variable among primate species. These data suggest that regional specialization in pyramidal cell phenotype was a likely feature of cortex in a common ancestor of simian and prosimian primates, but the degree of specialization varies between species. Copyright 2005 S. Karger AG, Basel

  13. Tiling a Pyramidal Polycube with Dominoes

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    Olivier Bodini

    2007-05-01

    Full Text Available The notion of pyramidal polycubes, namely the piling-up of bricks of a non-increasing size, generalizes in ℝ n the concept of trapezoidal polyominoes. In the present paper, we prove that n-dimensional dominoes can tile a pyramidal polycube if and only if the latter is balanced, that is, if the number of white cubes is equal to the number of black ones for a chessboard-like coloration, generalizing the result of [BC92] when n=2

  14. Pyramids and roundtables: a reflection on leadership.

    Science.gov (United States)

    Murayama, Kenric M

    2014-12-01

    By the nature of their career choice, surgeons are leaders at a variety of levels. The rise to leadership positions in surgery often requires scaling a steep pyramid. Many young surgeons are poorly prepared for what is frequently a competition with their peers. Some of the qualities young surgeons must possess to ascend the leadership pyramid are summarized by the "HOPES" of leadership: Honesty, recognition of Opportunity, having a Plan, knowing your Environment, and Self-assessment. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Extinction procedure induces pruning of dendritic spines in CA1 hippocampal field depending on strength of training in rats

    Science.gov (United States)

    Garín-Aguilar, María E.; Díaz-Cintra, Sofía; Quirarte, Gina L.; Aguilar-Vázquez, Azucena; Medina, Andrea C.; Prado-Alcalá, Roberto A.

    2012-01-01

    Numerous reports indicate that learning and memory of conditioned responses are accompanied by genesis of dendritic spines in the hippocampus, although there is a conspicuous lack of information regarding spine modifications after behavioral extinction. There is ample evidence that treatments that typically produce amnesia become innocuous when animals are submitted to a procedure of enhanced training. We now report that extinction of inhibitory avoidance (IA), trained with relatively low foot-shock intensities, induces pruning of dendritic spines along the length of the apical dendrites of hippocampal CA1 neurons. When animals are trained with a relatively high foot-shock there is a high resistance to extinction, and pruning in the proximal and medial segments of the apical dendrite are seen, while spine count in the distal dendrite remains normal. These results indicate that pruning is involved in behavioral extinction, while maintenance of spines is a probable mechanism that mediates the protecting effect against amnesic treatments produced by enhanced training. PMID:22438840

  16. Extinction procedure induces pruning of dendritic spines in CA1 hippocampal field depending on strength of training in rats

    Directory of Open Access Journals (Sweden)

    María Eugenia Garín-Aguilar

    2012-03-01

    Full Text Available Numerous reports indicate that learning and memory of conditioned responses are accompanied by genesis of dendritic spines in the hippocampus, although there is a conspicuous lack of information regarding spine modifications after behavioral extinction. There is ample evidence that treatments that typically produce amnesia become innocuous when animals are submitted to a procedure of enhanced training. We now report that extinction of inhibitory avoidance, trained with relatively low foot-shock intensities, induces pruning of dendritic spines along the length of the apical dendrites of hippocampal CA1 neurons. When animals are trained with a relatively high foot-shock there is a high resistance to extinction, and pruning in the proximal and medial segments of the apical dendrite are seen, while spine count in the distal dendrite remains normal. These results indicate that pruning is involved in behavioral extinction, while maintenance of spines is a probable mechanism that mediates the protecting effect against amnesic treatments produced by enhanced training.

  17. Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

    Science.gov (United States)

    Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

    2016-01-01

    ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

  18. Cell-Type and State-Dependent Synchronization among Rodent Somatosensory, Visual, Perirhinal Cortex, and Hippocampus CA1

    Science.gov (United States)

    Vinck, Martin; Bos, Jeroen J.; Van Mourik-Donga, Laura A.; Oplaat, Krista T.; Klein, Gerbrand A.; Jackson, Jadin C.; Gentet, Luc J.; Pennartz, Cyriel M. A.

    2016-01-01

    Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1). S1BF spiking activity was strongly entrained by both beta and gamma S1BF oscillations, which were associated with deactivations and activations, respectively. We identified multiple classes of fast spiking and excitatory cells in S1BF, which showed prominent differences in rhythmic entrainment and in the extent to which phase locking was modulated by behavioral state. Using an additional dataset acquired by whole-cell recordings in head-fixed mice, these cell classes could be compared with identified phenotypes showing gamma rhythmicity in their membrane potential. We next examined how S1BF cells were entrained by rhythmic fluctuations in connected brain areas. Gamma-synchronization was detected in all four areas, however we did not detect significant gamma coherence among these areas. Instead, we only found long-range coherence in the theta-beta range among these areas. In contrast to local S1BF synchronization, we found long-range S1BF-spike to CA1–LFP synchronization to be homogeneous across inhibitory and excitatory cell types. These findings suggest distinct, cell-type contributions of low and high-frequency synchronization to intra- and inter-areal neuronal interactions. PMID:26834582

  19. Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid.

    Science.gov (United States)

    Nadler, J V; Perry, B W; Cotman, C W

    1980-01-20

    Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum and stratum oriens of area CA1. The responses of intact afferents to such lesions were then examined histologically. The hippocampal mossy fibers densely reinnervated the inner portion of the dentate molecular layer after bilateral destruction of CA4 neurons and to a lesser extent after unilateral destruction. Septohippocampal fibers replaced CA4-derived fibers in the dentate molecular layer only after particularly extensive bilateral CA4 lesions. Medial perforant path fibers showed no anatomical response to any of these lesions. Neither septohippocampal, temporoammonic nor mossy fibers proliferated in or grew into the denervated laminae of area CA1. These results show a preferential ordering in the reinnervation of dentate granule cells which is not readily explained by proximity to the degenerating fibers and also that removal of CA3-CA4-derived innervation more readily elicits translaminar growth in the fascia dentata than in area CA1. These results may be relevant to clinical situations in which neurons of the hippocampal end-blade are lost.

  20. Parkinsonian-Pyramidal syndromes: A systematic review.

    Science.gov (United States)

    Tranchant, Christine; Koob, Meriam; Anheim, Mathieu

    2017-06-01

    Parkinsonian-Pyramidal syndrome (PPS), defined as the combination of both pyramidal and parkinsonian signs is a concept that recently emerged. PPS may manifest itself in numerous neurodegenerative diseases, many of these being inherited. Their diagnosis is a major challenge for the clinical management, for the prognosis, for genetic counselling and, in a few cases, which should not be neglected, for specific treatment. Our objective is to provide a review of PPS and an algorithm in order to guide their diagnosis in clinical practice. We performed an exhaustive PubMed and OMIM research matching the following key words: "Parkinsonism and pyramidal signs" or "Parkinsonism and spasticity" or "pallido-pyramidal syndrome" or "Parkinsonism and spastic paraplegia". English publications from the last ten years were included. We propose a pragmatic presentation based on several established classifications and we will distinguish inherited PPS found in complex hereditary spastic paraplegia, young onset parkinsonism, neurodegeneration with brain iron accumulation, primary familial brain calcifications, inborn errors of metabolism, and few rare others inherited neurodegenerative diseases, then non-inherited neurodegenerative PPS. We therefore suggest guidelines (based on age at onset, family history, associated clinical signs, brain MRI findings as well as certain laboratory investigations), for the diagnosis and the management of PPS. Many pathophysiological pathways may underlie PPS but the most frequent are those usually involved in both inherited Parkinson's disease and spastic paraplegia, i.e. mitochondrial pathway, vesicular trafficking including endosomal and lysosomal pathways as well as autophagy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Traveling Salesman Problem: A Foveating Pyramid Model

    Science.gov (United States)

    Pizlo, Zygmunt; Stefanov, Emil; Saalweachter, John; Li, Zheng; Haxhimusa, Yll; Kropatsch, Walter G.

    2006-01-01

    We tested human performance on the Euclidean Traveling Salesman Problem using problems with 6-50 cities. Results confirmed our earlier findings that: (a) the time of solving a problem is proportional to the number of cities, and (b) the solution error grows very slowly with the number of cities. We formulated a new version of a pyramid model. The…

  2. The Fruit Group. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and eating plenty of servings of fruit. Colorful photographs support early readers in understanding the text. The repetition of words and…

  3. Food Pyramids and Bio-Accumulation.

    Science.gov (United States)

    Baker, Valerie

    1998-01-01

    Students learn about marine food chains, bioaccumulation, the energy pyramid, and potential ocean pollutants and their effects on ocean ecosystems in this activity which involves having students pull drawings of marine organisms which include diatoms, copepods, anchovies, bonito, and killer whale out of a bag, then demonstrating the food chain by…

  4. Vegetarian food guide pyramid: a conceptual framework.

    Science.gov (United States)

    Haddad, E H; Sabaté, J; Whitten, C G

    1999-09-01

    The purpose of this article and the accompanying vegetarian food guide pyramid graphic is to provide the conceptual framework for the development of a new and unique food guide. Food guides for vegetarians have tended to be adaptations of guides developed for the general nonvegetarian population instead of being designed to emphasize the healthy components of vegetarian dietary patterns. A subcommittee of the organizers of the Third International Congress on Vegetarian Nutrition began a process that led to the development of a pyramid-shaped graphic illustration and a supporting document, both of which were introduced at the congress. The 5 major plant-based food groups (whole grains, legumes, vegetables, fruit, nuts, and seeds) form the trapezoid-shaped lower portion of the pyramid. Optional food groups, which may be avoided by some vegetarians (vegetable oils, dairy, eggs, and sweets), form the smaller, separate, triangle-shaped top portion of the pyramid. The supporting document discusses the concepts that affect vegetarian food guidance and the rationale for selecting the food groups. It is hoped that this framework will provide the impetus for further research and discussion and will lead to the development of a guide that is nutritionally adequate, is conducive to good health, and can be adopted by vegetarians of diverse eating practices.

  5. The Grain Group. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and eating sufficient servings of grains. Colorful photographs support early readers in understanding the text. The repetition of words and…

  6. The Vegetable Group. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and eating plenty of vegetables. Colorful photographs support early readers in understanding the text. The repetition of words and phrases…

  7. Pyramid Servings Database (PSDB) for NHANES III

    Science.gov (United States)

    The National Cancer Institute developed a database to examine dietary data from the National Center for Health Statistics' Third National Health and Nutrition Examination Survey in terms of servings from each of United States Department of Agriculture's The Food Guide Pyramid's major and minor food groups.

  8. Eating Right. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the food groups of the food guide pyramid. Colorful photographs support early readers in understanding the text. The repetition of words and phrases helps early readers learn new words.…

  9. The Dairy Group. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and eating from the dairy group. Colorful photographs support early readers in understanding the text. The repetition of words and phrases…

  10. Jonestown in the Shadow of Maslow's Pyramid.

    Science.gov (United States)

    Easley, Edgar M.; Wigglesworth, David C.

    1979-01-01

    Reviews Maslow's hierarchy of needs in the light of the Jonestown tragedy. Maintains that members of the People's Temple felt frustrated in attaining the lower levels in the world of reality, and so moved outside the pyramid in search of the top, self-actualization. In the process, their primary needs were met. Journal availability: see SO 507…

  11. eIF2α phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation

    OpenAIRE

    Jiang, Zhihong; Belforte, Juan E; Lu, Yuan; Yabe, Yoko; Pickel, James; Smith, Carolyn Beebe; Je, Hyun-Soo; Lu, Bai; Nakazawa, Kazu

    2010-01-01

    Protein synthesis inhibitor antibiotics are widely used to produce amnesia, and have been recognized to inhibit general or global mRNA translation in the basic translational machinery. For instance, anisomycin interferes with protein synthesis by inhibiting peptidyl transferase or the 80S ribosomal function. Therefore, de novo general or global protein synthesis has been thought to be necessary for long-term memory formation. However, it is unclear which mode of translation — gene-specific tr...

  12. agronomic qualities of genetic pyramids of common bean developed ...

    African Journals Online (AJOL)

    ACSS

    2017-11-07

    Nov 7, 2017 ... (BCMNV); and Pythium ultimum (P.ult) root rots were combined into the same genotype at CIAT, a process referred to as pyramiding. Common bean genetic pyramids could, therefore, offer long-term strategies for managing major common bean diseases. However, in the process of developing pyramids ...

  13. Teacher Acquisition of Functional Analysis Methods Using Pyramidal Training

    Science.gov (United States)

    Pence, Sacha T.; St. Peter, Claire C.; Giles, Aimee F.

    2014-01-01

    Pyramidal training involves an experienced professional training a subset of individuals who, in turn, train additional individuals. Pyramidal training is effective for training a variety of behavior-analytic skills with direct-care staff, parents, and teachers. As teachers' roles in behavioral assessment increase, pyramidal training may be…

  14. Idea Bank: Assessing Your Curriculum with the Creative Rights Pyramid

    Science.gov (United States)

    Thibeault, Matthew D.

    2011-01-01

    This article presents a creative rights pyramid that was developed as part of the author's efforts to: (1) teach about copyright and intellectual property; and (2) increase students' awareness of their own intellectual property in and outside the music classroom. The pyramid is based on the U.S. Department of Agriculture's food pyramid to suggest…

  15. Using the Food Guide Pyramid: A Resource for Nutrition Educators.

    Science.gov (United States)

    Shaw, Anne; Fulton, Lois; Davis, Carole; Hogbin, Myrtle

    This booklet provides information to assist nutrition educators in helping their audiences use the Food Guide Pyramid to plan and prepare foods for a healthy diet. It reviews the objectives set in developing the Food Guide Pyramid and illustrates their impact on the application of the Food Guide Pyramid to planning menus. In particular, the…

  16. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats.

    Science.gov (United States)

    Oomura, Y; Hori, N; Shiraishi, T; Fukunaga, K; Takeda, H; Tsuji, M; Matsumiya, T; Ishibashi, M; Aou, S; Li, X L; Kohno, D; Uramura, K; Sougawa, H; Yada, T; Wayner, M J; Sasaki, K

    2006-11-01

    Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.

  17. Neonatal food restriction and binaural ear occlusion interfere with the maturation of cortical motor pyramids in the rat.

    Science.gov (United States)

    Torrero, Carmen; Regalado, Mirelta; Perez, Esther; Rubio, Lorena; Salas, Manuel

    2005-02-01

    Golgi-Cox-impregnated pyramidal neurons of layer five motor cortical area were investigated in control, binaural ear-occluded control, undernourished and binaural ear-occluded undernourished Wistar rats of 12, 20 and 30 days of age. In neonatally undernourished, binaural ear-occluded-undernourished and partly in ear-occluded-control subjects, there were significant reductions in both the number and extent of the distal part of the dendritic branches of motor pyramids compared to their controls. Moreover, minimal effects on perikarya measurements were observed. These findings suggest that neonatal undernutrition and the concurrent reduction of auditory cues affect dendritic arbor development and possibly the convergence of the auditory experience upon motor pyramids and may interfere with the neocortical modulation of postural and movements activities.

  18. Neocortical neuronal morphology in the Siberian Tiger (Panthera tigris altaica) and the clouded leopard (Neofelis nebulosa).

    Science.gov (United States)

    Johnson, Cameron B; Schall, Matthew; Tennison, Mackenzie E; Garcia, Madeleine E; Shea-Shumsky, Noah B; Raghanti, Mary Ann; Lewandowski, Albert H; Bertelsen, Mads F; Waller, Leona C; Walsh, Timothy; Roberts, John F; Hof, Patrick R; Sherwood, Chet C; Manger, Paul R; Jacobs, Bob

    2016-12-01

    Despite extensive investigations of the neocortex in the domestic cat, little is known about neuronal morphology in larger felids. To this end, the present study characterized and quantified the somatodendritic morphology of neocortical neurons in prefrontal, motor, and visual cortices of the Siberian tiger (Panthera tigris altaica) and clouded leopard (Neofelis nebulosa). After neurons were stained with a modified Golgi technique (N = 194), dendritic branching and spine distributions were analyzed using computer-assisted morphometry. Qualitatively, aspiny and spiny neurons in both species appeared morphologically similar to those observed in the domestic cat. Although the morphology of spiny neurons was diverse, with the presence of extraverted, inverted, horizontal, and multiapical pyramidal neurons, the most common variant was the typical pyramidal neuron. Gigantopyramidal neurons in the motor cortex were extremely large, confirming the observation of Brodmann ([1909] Vergleichende Lokalisationlehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Leipzig, Germany: J.A. Barth), who found large somata for these neurons in carnivores in general, and felids in particular. Quantitatively, a MARSplines analysis of dendritic measures differentiated typical pyramidal neurons between the Siberian tiger and the clouded leopard with 93% accuracy. In general, the dendrites of typical pyramidal neurons were more complex in the tiger than in the leopards. Moreover, dendritic measures in tiger pyramidal neurons were disproportionally large relative to body/brain size insofar as they were nearly as extensive as those observed in much larger mammals (e.g., African elephant). Comparison of neuronal morphology in a more diverse collection of larger felids may elucidate the comparative context for the relatively large size of the pyramidal neurons observed in the present study. J. Comp. Neurol. 524:3641-3665, 2016. © 2016 Wiley Periodicals, Inc.

  19. [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].

    Science.gov (United States)

    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

  20. Local-moment formation and metal–nonmetal transition in Ca1 ...

    Indian Academy of Sciences (India)

    temperature dependence of resistivity shows no resistance-minimum in these systems. 3. Discussion. 3.1 Phase diagrams of Ca1−x Yx VO3 and Ca1−x Yx TiO3. In these systems, it is well-known that the electron correlation increases with increasing d electron number and the systems change from a metal to a magnetic ...

  1. Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Hasseldam, Henrik; Rasmussen, Rune Skovgaard

    2014-01-01

    Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and ...

  2. Graph pyramids for protein function prediction.

    Science.gov (United States)

    Sandhan, Tushar; Yoo, Youngjun; Choi, Jin; Kim, Sun

    2015-01-01

    Uncovering the hidden organizational characteristics and regularities among biological sequences is the key issue for detailed understanding of an underlying biological phenomenon. Thus pattern recognition from nucleic acid sequences is an important affair for protein function prediction. As proteins from the same family exhibit similar characteristics, homology based approaches predict protein functions via protein classification. But conventional classification approaches mostly rely on the global features by considering only strong protein similarity matches. This leads to significant loss of prediction accuracy. Here we construct the Protein-Protein Similarity (PPS) network, which captures the subtle properties of protein families. The proposed method considers the local as well as the global features, by examining the interactions among 'weakly interacting proteins' in the PPS network and by using hierarchical graph analysis via the graph pyramid. Different underlying properties of the protein families are uncovered by operating the proposed graph based features at various pyramid levels. Experimental results on benchmark data sets show that the proposed hierarchical voting algorithm using graph pyramid helps to improve computational efficiency as well the protein classification accuracy. Quantitatively, among 14,086 test sequences, on an average the proposed method misclassified only 21.1 sequences whereas baseline BLAST score based global feature matching method misclassified 362.9 sequences. With each correctly classified test sequence, the fast incremental learning ability of the proposed method further enhances the training model. Thus it has achieved more than 96% protein classification accuracy using only 20% per class training data.

  3. Preserving the Pyramid of STI Using Buckets

    Science.gov (United States)

    Nelson, Michael L.; Maly, Kurt

    2004-01-01

    The product of research projects is information. Through the life cycle of a project, information comes from many sources and takes many forms. Traditionally, this body of information is summarized in a formal publication, typically a journal article. While formal publications enjoy the benefits of peer review and technical editing, they are also often compromises in media format and length. As such, we consider a formal publication to represent an abstract to a larger body of work: a pyramid of scientific and technical information (STI). While this abstract may be sufficient for some applications, an in-depth use or analysis is likely to require the supporting layers from the pyramid. We have developed buckets to preserve this pyramid of STI. Buckets provide an archive- and protocol-independent container construct in which all related information objects can be logically grouped together, archived, and manipulated as a single object. Furthermore, buckets are active archival objects and can communicate with each other, people, or arbitrary network services. Buckets are an implementation of the Smart Object, Dumb Archive (SODA) DL model. In SODA, data objects are more important than the archives that hold them. Much of the functionality traditionally associated with archives is pushed down into the objects, such as enforcing terms and conditions, negotiating display, and content maintenance. In this paper, we discuss the motivation, design, and implication of bucket use in DLs with respect to grey literature.

  4. Contribution of hippocampal area CA1 to acetone cyanohydrin-induced loss of motor coordination in rats.

    Science.gov (United States)

    Rivadeneyra-Domínguez, E; Vázquez-Luna, A; Díaz-Sobac, R; Briones-Céspedes, E E; Rodríguez-Landa, J F

    2017-05-01

    Some vegetable foodstuffs contain toxic compounds that, when consumed, favour the development of certain diseases. Cassava (Manihot esculenta Crantz) is an important food source, but it contains cyanogenic glucosides (linamarin and lotaustralin) that have been associated with the development of tropical ataxic neuropathy and konzo. In rats, intraperitoneal administration of acetone cyanohydrin (a metabolite of linamarin) produces neurological disorders and neuronal damage in the hippocampus. However, it is unknown whether hippocampal area CA1 plays a role in neurological disorders associated with acetone cyanohydrin. A total of 32 male Wistar rats 3 months old were assigned to 4 groups (n=8 per group) as follows: vehicle (1μl physiological saline), and 3 groups with acetone cyanohydrin (1μl of 10, 15, and 20mM solution, respectively). The substances were microinjected intrahippocampally every 24hours for 7 consecutive days, and their effects on locomotor activity, rota-rod and swim tests were assessed daily. On the fifth day post-treatment, rats underwent further assessment with behavioural tests to identify or rule out permanent damage induced by acetone cyanohydrin. Microinjection of acetone cyanohydrin 20mM resulted in hyperactivity, motor impairment, and reduced exploration from the third day of treatment. All concentrations of acetone cyanohydrin produced rotational behaviour in the swim test from the first day of microinjection. The hippocampal area CA1 is involved in motor alterations induced by microinjection of acetone cyanohydrin, as has been reported for other cassava compounds. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. 17 CFR 240.15Ca1-1 - Notice of government securities broker-dealer activities.

    Science.gov (United States)

    2010-04-01

    ... securities broker-dealer activities. 240.15Ca1-1 Section 240.15Ca1-1 Commodity and Securities Exchanges... Brokers and Government Securities Dealers § 240.15Ca1-1 Notice of government securities broker-dealer activities. (a) Every government securities broker or government securities dealer that is a broker or dealer...

  6. Expression of GABA(A) receptor subunit mRNAs by layer V pyramidal cells of the rat primary visual cortex.

    Science.gov (United States)

    Ruano, D; Perrais, D; Rossier, J; Ropert, N

    1997-04-01

    The expression of the GABA(A) receptor subunit mRNAs by layer V pyramidal neurons of the primary visual cortex and cerebellar Purkinje cells was analysed by single-cell reverse transcription of the mRNAs and amplification of the resulting cDNAs by the polymerase chain reaction. Neurons were identified by infrared videomicroscopy, and GABA(A)-mediated miniature inhibitory postsynaptic currents were recorded. In Purkinje cells, alpha1, beta2, beta3, gamma2S and gamma2L subunit mRNAs were detected within a single cell. In layer V pyramidal cells, a total of ten GABA(A) receptor subunit mRNAs could be detected, with a mean of seven subunit mRNAs per cell, suggesting GABA(A) receptor heterogeneity within a single pyramidal cell.

  7. Centre of pressure correlates with pyramid performance in acrobatic gymnastics.

    Science.gov (United States)

    Floría, Pablo; Gómez-Landero, Luis Arturo; Harrison, Andrew J

    2015-01-01

    Acrobatic gymnasts need excellent balance control to execute pyramids where one gymnast is supported by another. The objectives of this study were: (1) to describe balance performance by assessing the centre of pressure displacement in a group of acrobatic gymnasts executing pyramids; (2) to determine the relationship between the parameters describing the centre of pressure oscillations and pyramid score; and (3) to examine the role of each foot in providing a solid base of support to maintain the balance of the pyramid. Sixteen acrobatic gymnasts grouped in pairs performed a Half pyramid and a Straddle pyramid held for 7 s on two force platforms. Path length, variance, range trajectory, and surface area of the centre of pressure of each foot were examined to analyse the balance of the pyramid. The path length was correlated with the pyramid score (Straddle: p = 0.692 [large]; Half: p = 0.407 [moderate]). There were differences in the functions of each leg to maintain balance, with the non-preferred leg supporting a higher weight of the pyramid while the preferred leg performed control movements to maintain balance. The results suggested that quantitative analysis of balance can provide important information on pyramid performance.

  8. Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus.

    Science.gov (United States)

    Kovács, Krisztián A; O'Neill, Joseph; Schoenenberger, Philipp; Penttonen, Markku; Ranguel Guerrero, Damaris K; Csicsvari, Jozsef

    2016-01-01

    During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles.

  9. Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus.

    Directory of Open Access Journals (Sweden)

    Krisztián A Kovács

    Full Text Available During hippocampal sharp wave/ripple (SWR events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles.

  10. Sodium entry during action potentials of mammalian central neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons

    OpenAIRE

    Carter, Brett C.; Bean, Bruce P.

    2009-01-01

    We measured the time course of sodium entry during action potentials of mouse central neurons at 37 °C to examine how efficiently sodium entry is coupled to depolarization. In cortical pyramidal neurons, sodium entry was nearly completely confined to the rising phase of the spike: only ~25% more sodium enters than the theoretical minimum necessary for spike depolarization. However, in fast-spiking GABAergic neurons (cerebellar Purkinje cells and cortical interneurons), twice as much sodium en...

  11. Network models provide insights into how oriens–lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations

    Directory of Open Access Journals (Sweden)

    Katie A Ferguson

    2015-08-01

    Full Text Available Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens--lacunosum-moleculare (OLM interneurons and bistratified cells (BiCs, make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations. Our cellular models were constrained with properties from patch clamp recordings in the CA1 region of an intact hippocampus preparation in vitro. Our network models are composed of three different types of interneurons: parvalbumin-positive (PV+ basket and axo-axonic cells (BC/AACs, PV+ BiCs, and somatostatin-positive OLM cells. Also included is a spatially extended pyramidal cell model to allow for a simplified local field potential representation, as well as experimentally-constrained, theta frequency synaptic inputs to the interneurons. The network size, connectivity, and synaptic properties were constrained with experimental data. To determine how the interactions between OLM cells and BiCs could affect local theta power, we explored a number of OLM-BiC connections and connection strengths.We found that our models operate in regimes in which OLM cells minimally or strongly affected the power of network theta oscillations due to balances that, respectively, allow compensatory effects or not. Inactivation of OLM cells could result in no change or even an increase in theta power. We predict that the dis-inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a critical role in the power of network theta oscillations. Our network models reveal a dynamic interplay between different classes of interneurons in influencing local theta

  12. A Simulation Study on the Effects of Dendritic Morphology on Layer V Prefontal Pyramidal Cell Firing Behavior

    Directory of Open Access Journals (Sweden)

    Maria ePsarrou

    2014-09-01

    Full Text Available Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1 repetitive action potentials (Regular Spiking - RS, and (2 an initial cluster of 2-5 action potentials with short ISIs followed by single spikes (Intrinsic Bursting - IB. A correlation between firing behavior and dendritic morphology has recently been reported. In this work we use computational modeling to investigate quantitatively the effects of the basal dendritic tree morphology on the firing behavior of 112 three-dimensional reconstructions of layer V PFC rat pyramidal cells. Particularly, we focus on how different morphological (diameter, total length, volume and branch number and passive (Mean Electrotonic Path length features of basal dendritic trees shape somatic firing when the spatial distribution of ionic mechanisms in the basal dendritic trees is uniform or non-uniform. Our results suggest that total length, volume and branch number are the best morphological parameters to discriminate the cells as RS or IB, regardless of the distribution of ionic mechanisms in basal trees. The discriminatory power of total length, volume and branch number remains high in the presence of different apical dendrites. These results suggest that morphological variations in the basal dendritic trees of layer V pyramidal neurons in the PFC influence their firing patterns in a predictive manner and may in turn influence the information processing capabilities of these neurons.

  13. Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC.

    Science.gov (United States)

    Rao, S G; Williams, G V; Goldman-Rakic, P S

    1999-04-01

    Studies on the cellular mechanisms of working memory demonstrated that neurons in dorsolateral prefrontal cortex (dPFC) exhibit directionally tuned activity during an oculomotor delayed response. To determine the particular contributions of pyramidal cells and interneurons to spatial tuning in dPFC, we examined both individually and in pairs the tuning properties of regular-spiking (RS) and fast-spiking (FS) units that represent putative pyramidal cells and interneurons, respectively. Our main finding is that FS units possess spatially tuned sensory, motor, and delay activity (i. e., "memory fields") similar to those found in RS units. Furthermore, when recorded simultaneously at the same site, the majority of neighboring neurons, whether FS or RS, displayed isodirectional tuning, i.e., they shared very similar tuning angles for the sensory and delay phases of the task. As the trial entered the response phase of the task, many FS units shifted their direction of tuning and became cross-directional to adjacent RS units by the end of the trial. These results establish that a large part of inhibition in prefrontal cortex is spatially oriented rather than being untuned and simply regulating the threshold response of pyramidal cell output. Moreover, the isodirectional tuning between adjacent neurons supports a functional microcolumnar organization in dPFC for spatial memory fields similar to that found in other areas of cortex for sensory receptive fields.

  14. Protective effect of melatonin against transient global cerebral ischemia-induced neuronal cell damage via inhibition of matrix metalloproteinase-9.

    Science.gov (United States)

    Kim, Su-Jin; Lee, Seong-Ryong

    2014-01-14

    Melatonin possesses various pharmacological effects including neuroprotective effects against brain ischemia. Post-ischemic increases in matrix metalloproteinase-9 (MMP-9) expression and activity mainly contribute to neuronal damage by degradation of the extracellular matrix. This study was designed to examine whether melatonin has a neuroprotective effect and an influence on MMP-9 in transient global brain ischemia. Mice were subjected to 20 min of global brain ischemia and sacrificed 72h later. Melatonin (30 mg/kg) was administered 30 min before and 2h after ischemia as well as once daily until sacrifice. Hippocampal pyramidal cell damage after ischemia was significantly decreased by melatonin. As observed by zymography, melatonin inhibited the increase of MMP-9 activity after ischemia. In the brain sections, the increased gelatinase activity was mainly observed in the hippocampus after ischemia and melatonin also reduced gelatinase activity. The laminin and NeuN expression levels were reduced in the hippocampal CA1 and CA2 regions after ischemia, and melatonin reduced laminin degradation and neuronal loss. A TUNEL assay demonstrated that there were TUNEL-positive cells in the hippocampus and the number of TUNEL-positive cells was significantly decreased by melatonin. There was no difference in the ischemia-induced hippocampal neuronal damage between the vehicle- and melatonin-treated groups of MMP-9 knock-out mice. These data demonstrate that melatonin suppressed the occurrence of neuronal injury, which might be partly due to its inhibitory effects on MMP-9 in addition to its anti-oxidative effects. MMP-9 may be an important key target of melatonin in neuroprotection against global ischemia. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Astrocytic Ca(2+) waves mediate activation of extrasynaptic NMDA receptors in hippocampal neurons to aggravate brain damage during ischemia.

    Science.gov (United States)

    Dong, Qi-Ping; He, Jing-Quan; Chai, Zhen

    2013-10-01

    Excitotoxicity plays a central role in the neuronal damage during ischemic stroke. Although growing evidence suggests that activation of extrasynaptic NMDA receptors initiates neuronal death, no direct evidence demonstrated their activation during ischemia. Using rat hippocampal slices, we detected oxygen-glucose deprivation (OGD) induced slow inward currents (SICs) mediated by extrasynaptic NMDA receptors in CA1 pyramidal neurons. Moreover, Ca(2+) chelator BAPTA dialysis into astrocytic network decreased the frequency of OGD induced SICs, indicating that the activation of extrasynaptic NMDA receptors depended on astrocytic Ca(2+) activity. To further demonstrate the importance of astrocytic Ca(2+) activity, we tested hippocampal slices from inositol triphosphate receptor type 2 (IP3R2) knock-out mice which abolished the astrocytic Ca(2+) activity. As expected, the frequency of OGD induced SICs was reduced. Using two-photon Ca(2+) imaging, we characterized the astrocytic Ca(2+) dynamics. By controlling Ca(2+) level in the individual astrocytes using targeted photolysis, we found that OGD facilitated the propagation of intercellular Ca(2+) waves, which were inhibited by gap junction blocker carbenoxolone (CBX). CBX also inhibited the Ca(2+) activity of the astrocytic network and decreased the SIC frequency during OGD. Functionally, the infarct volumes from brain ischemia were reduced in IP3R2 knock-out mice and in rat intracerebrally delivered with CBX. Our results demonstrate that enhanced Ca(2+) activity of the astrocytic network plays a key role on the activation of extrasynaptic NMDA receptors in hippocampal neurons, which enhances brain damage during ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of hippocampus of rats after sleep deprivation

    Directory of Open Access Journals (Sweden)

    Jiang-hua SI

    2014-04-01

    Full Text Available Objective To investigate the effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of the hippocampus of Wistar rats in sleep deprivation (SD.  Methods SD was induced in Wistar rats by employing "flower pot" technique. Sixty-four rats were randomly divided into 2 groups: Lanzhou group (at an altitude of 1520 m and Kekexili group (at an altitude of 4767 m, and each group was further divided into 4 subgroups according to the time of SD (0, 1, 3 and 5 d. The behaviors of rats were studied by Morris water maze test at given time points. The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM.  Results 1 Compared with Lanzhou group, rat behavior of Kekexili group presented excitement-irritation-suppression changes with the extension of SD time, but the extent was weakened gradually, and time of sleepiness increased obviously. 2 Compared with Lanzhou group, neurons in CA1 region of hippocampus showed enlarged cell body, disappeared nuclear membrane, shrunken nuclei and decreased organelle. End-feet of glia cells sticking to capillaries swelled and ruptured, and the typical synaptic structure disappeared. 3 Morris water maze test: as compared with Lanzhou group, the escape latency of Kekexili group prolonged (P < 0.05, for all, the ability of distance exploration increased (P < 0.05, for all, and the times across plot decreased (P < 0.05, for all in 1, 3 and 5 d of SD.  Conclusions High-altitude environment may significantly influence the cognitive function of rats in SD, and there was close correlation between the cognitive disorders and the changes in the ultrastructure of hippocampal CA1 region. doi: 10.3969/j.issn.1672-6731.2014.04.012

  17. L-system modeling of neurons

    Science.gov (United States)

    McCormick, Bruce H.; Mulchandani, K.

    1994-09-01

    A formal representation of neuron morphology, adequate for the geometric modeling of manually-traced neurons, is presented. The concept of a stochastic L-system is then introduced and the critical distribution functions governing the stochastic generation of dendritic and axonal trees are defined. Experiments with various stochastic L-system models for pyramidal, motoneuron, and Purkinje cells are reported which generate synthetic neurons with promising proximity to neurons in the neurobiology literature. Work is in progress to improve this degree of proximity, but more importantly to validate the derived stochastic models against available databases of manually-traced neurons. To this end a neuron morphology modeler is described which provides a methodology for iterative refinement of the stochastic L-system model.

  18. Regional specialization in pyramidal cell structure in the limbic cortex of the vervet monkey (Cercopithecus pygerythrus): an intracellular injection study of the anterior and posterior cingulate gyrus.

    Science.gov (United States)

    Elston, Guy N; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul; Defelipe, Javier

    2005-12-01

    The pyramidal cell phenotype varies quite dramatically in structure among different cortical areas in the primate brain. Comparative studies in visual cortex, in particular, but also in sensorimotor and prefrontal cortex, reveal systematic trends for pyramidal cell specialization in functionally related cortical areas. Moreover, there are systematic differences in the extent of these trends between different primate species. Recently we demonstrated differences in pyramidal cell structure in the cingulate cortex of the macaque monkey; however, in the absence of other comparative data it remains unknown as to whether the neuronal phenotype differs in cingulate cortex between species. Here we extend the basis for comparison by studying the structure of the basal dendritic trees of layer III pyramidal cells in the posterior and anterior cingulate gyrus of the vervet monkey (Brodmann's areas 23 and 24, respectively). Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors were determined, and somal areas measured. As in the macaque monkey, we found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). In addition, the extent of the difference in pyramidal cell structure between these two cortical regions was less in the vervet monkey than in the macaque monkey.

  19. The effects of CA1 5HT4 receptors in MK801-induced amnesia and hyperlocomotion.

    Science.gov (United States)

    Nasehi, Mohammad; Tabatabaie, Maryam; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

    2015-02-05

    In this study, the effects of 5-HT4 receptors of the CA1 on MK801-induced amnesia and hyperlocomotion were examined. One-trial step-down method was used to assess memory retention and then, the hole-board method to assess exploratory behaviors. The results showed that post-training intra-CA1 administration of RS67333 (62.5 and 625 ng/mouse) and RS23597 (1 and 10 ng/mouse) decreased memory consolidation, but it did not alter head-dip counts, head-dip latency and locomotor activity. Similarly, MK801 (0.5 and 1 μg/mouse) decreased memory consolidation, but had no effect on head-dip counts and head-dip latency. Interestingly, it increased locomotor activity. The results also showed that post-training intra-CA1 injection of a sub-threshold dose of RS67333 (6.25 ng/mouse) or RS23597 (0.1 ng/mouse) could heighten MK801 induced amnesia and decrease locomotor activity, but it did not alter head-dip counts and head-dip latency. In conclusion, our findings suggest that the CA1 5-HT4 receptors are involved in MK801-induced amnesia and hyperlocomotion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Electrical conductivity of the hippocampal CA1 layers and application to current-source-density analysis

    NARCIS (Netherlands)

    Holsheimer, J.

    1987-01-01

    The microstructure of the layers in the hippocampal CA1 area suggests that differences may exist between the electrical conductivities of these layers. In order to quantify these differences a sinusoidal current was applied to hippocampal slices in a bathing medium and potential differences were

  1. Electrically evoked GABA release in rat hippocampus CA1 region and its changes during kindling epileptogenesis.

    NARCIS (Netherlands)

    Ghijsen, W.E.J.M.; Zuiderwijk, M.; Lopes da Silva, F.H.

    2007-01-01

    Previous findings on changes in K(+)-induced GABA release from hippocampal slices during kindling epileptogenesis were reinvestigated using physiological electrical stimulation. For that purpose, a procedure was developed enabling neurochemical monitoring of GABA release locally in the CA1 region of

  2. Altered synaptic plasticity in hippocampal CA1 area of apolipoprotein E deficient mice

    NARCIS (Netherlands)

    Krugers, HJ; Mulder, M; Korf, J; Havekes, L; deKloet, ER; Joëls, M

    1997-01-01

    IN mice with a homozygous or heterozygous deficiency for ApoE as well as in wild-type animals we established synaptic responsiveness in the hippocampal CA1 area following stimulation of the SchafFer/commissural fibers. The maximal population spike amplitude was significantly larger in wild-type

  3. 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.

  4. Mediterranean diet pyramids: towards the Italian model.

    Science.gov (United States)

    del Balzo, V; Diolordi, L; Pinto, A; Giusti, A M; Vitiello, V; Cannella, C; Dernini, S; Donini, L M; Berry, E M

    2012-01-01

    There is a long history to the representation of the Mediterranean Diet Pyramid which may be seen as a form of cultural--culinary evolution as each country applies the foods best suited to its national diet. Different Mediterranean Diet pyramids have been designed for the population of Greece, Spain and Italy, tailored for their different food habits. These refer variously to portion sizes and frequency of consumption--daily, weekly and monthly and are not standardized. The 3rd CIISCAM Conference held in Parma, Italy was devoted to highlight the overall biodiversity and nutritional well being values and the sustainable benefits of the Mediterranean diet, recognised as one of the healthiest dietary pattern, and to reduce the rapid erosion of "lifestyle and food habits. It is necessary, therefore, to refer more to a Mediterranean Lifestyle of which diet is only a part. It should include physical and social activity, recreation and rest. It may be possible to construct a Mediterranean food lifestyle index both to assess such a holistic aspect and to correlate with improved morbidity & mortality.

  5. Hippocampal epileptiform activity induced by magnesium-free medium: differences between areas CA1 and CA2-3.

    Science.gov (United States)

    Lewis, D V; Jones, L S; Mott, D D

    1990-07-01

    Hippocampal slices, from which the entorhinal cortex had been removed, were exposed to artificial cerebrospinal fluid containing no magnesium (0-Mg ACSF) to elicit interictal bursts (IIBs) and electrographic seizures (EGSs). In 0-Mg ACSF, IIBs and EGSs occurred in both area CA1 and area CA3. The IIBs in CA3 led the IIBs in CA1 by several milliseconds. The epileptiform bursts occurring during the EGSs seemed to have the opposite relationship, with bursts in CA1 leading those in CA3 by several milliseconds. When the connections between CA1 and CA2-3 were cut, the IIBs ceased in CA1 and continued in CA3. To further characterize the local differences in epileptiform activity, totally separate minislices of area CA1 and area CA2-3 were prepared. In the CA2-3 minislices, a few EGSs occurred and thereafter only persistent IIBs prevailed. Conversely, in the CA1 minislices, many spontaneous EGSs occurred for long periods of time and no IIBs were seen. Periodic stimulation of the CA1 minislices triggered IIBs that suppressed the recurrent EGSs. In the hippocampal slice exposed to low magnesium, IIBs originate in CA2-3 and are propagated to CA1, where they can have a suppressant effect on EGSs. Furthermore, unlike IIBs, the bursts making up the EGSs seem to start in CA1 and invade CA2-3.

  6. Virtual Reality Tumor Resection: The Force Pyramid Approach.

    Science.gov (United States)

    Sawaya, Robin; Bugdadi, Abdulgadir; Azarnoush, Hamed; Winkler-Schwartz, Alexander; Alotaibi, Fahad E; Bajunaid, Khalid; AlZhrani, Gmaan A; Alsideiri, Ghusn; Sabbagh, Abdulrahman J; Del Maestro, Rolando F

    2017-09-05

    The force pyramid is a novel visual representation allowing spatial delineation of instrument force application during surgical procedures. In this study, the force pyramid concept is employed to create and quantify dominant hand, nondominant hand, and bimanual force pyramids during resection of virtual reality brain tumors. To address 4 questions: Do ergonomics and handedness influence force pyramid structure? What are the differences between dominant and nondominant force pyramids? What is the spatial distribution of forces applied in specific tumor quadrants? What differentiates "expert" and "novice" groups regarding their force pyramids? Using a simulated aspirator in the dominant hand and a simulated sucker in the nondominant hand, 6 neurosurgeons and 14 residents resected 8 different tumors using the CAE NeuroVR virtual reality neurosurgical simulation platform (CAE Healthcare, Montréal, Québec and the National Research Council Canada, Boucherville, Québec). Position and force data were used to create force pyramids and quantify tumor quadrant force distribution. Force distribution quantification demonstrates the critical role that handedness and ergonomics play on psychomotor performance during simulated brain tumor resections. Neurosurgeons concentrate their dominant hand forces in a defined crescent in the lower right tumor quadrant. Nondominant force pyramids showed a central peak force application in all groups. Bimanual force pyramids outlined the combined impact of each hand. Distinct force pyramid patterns were seen when tumor stiffness, border complexity, and color were altered. Force pyramids allow delineation of specific tumor regions requiring greater psychomotor ability to resect. This information can focus and improve resident technical skills training.

  7. Improvement of Information Transmission of Suprathreshold Input Signal with Stochastic Resonance in Hippocampal CA1 Neuron Network

    Science.gov (United States)

    Kawaguchi, Minato; Mino, Hiroyuki; Momose, Keiko; Durand, Dominique M.

    We investigate if and how SR (stochastic resonance) can be shown in the presence of supra-threshold signals (SSR) in physiologically realistic neural networks. The mutual information was maximized at a specific amplitude of noise in larger neural networks, implying SSR.

  8. The neocortex of cetartiodactyls: I. A comparative Golgi analysis of neuronal morphology in the bottlenose dolphin (Tursiops truncatus), the minke whale (Balaenoptera acutorostrata), and the humpback whale (Megaptera novaeangliae).

    Science.gov (United States)

    Butti, Camilla; Janeway, Caroline M; Townshend, Courtney; Wicinski, Bridget A; Reidenberg, Joy S; Ridgway, Sam H; Sherwood, Chet C; Hof, Patrick R; Jacobs, Bob

    2015-11-01

    The present study documents the morphology of neurons in several regions of the neocortex from the bottlenose dolphin (Tursiops truncatus), the North Atlantic minke whale (Balaenoptera acutorostrata), and the humpback whale (Megaptera novaeangliae). Golgi-stained neurons (n = 210) were analyzed in the frontal and temporal neocortex as well as in the primary visual and primary motor areas. Qualitatively, all three species exhibited a diversity of neuronal morphologies, with spiny neurons including typical pyramidal types, similar to those observed in primates and rodents, as well as other spiny neuron types that had more variable morphology and/or orientation. Five neuron types, with a vertical apical dendrite, approximated the general pyramidal neuron morphology (i.e., typical pyramidal, extraverted, magnopyramidal, multiapical, and bitufted neurons), with a predominance of typical and extraverted pyramidal neurons. In what may represent a cetacean morphological apomorphy, both typical pyramidal and magnopyramidal neurons frequently exhibited a tri-tufted variant. In the humpback whale, there were also large, star-like neurons with no discernable apical dendrite. Aspiny bipolar and multipolar interneurons were morphologically consistent with those reported previously in other mammals. Quantitative analyses showed that neuronal size and dendritic extent increased in association with body size and brain mass (bottlenose dolphin whale humpback whale). The present data thus suggest that certain spiny neuron morphologies may be apomorphies in the neocortex of cetaceans as compared to other mammals and that neuronal dendritic extent covaries with brain and body size.

  9. Pyramidal nanowire tip for atomic force microscopy and thermal imaging

    NARCIS (Netherlands)

    Burouni, N.; Sarajlic, Edin; Siekman, Martin Herman; Abelmann, Leon; Tas, Niels Roelof

    2012-01-01

    We present a novel 3D nanowire pyramid as scanning microscopy probe for thermal imaging and atomic force microscopy. This probe is fabricated by standard micromachining and conventional optical contact lithography. The probe features an AFM-type cantilever with a sharp pyramidal tip composed of four

  10. Tribonacci-like sequences and generalized Pascal's pyramids

    Science.gov (United States)

    Anatriello, Giuseppina; Vincenzi, Giovanni

    2014-11-01

    A well-known result of Feinberg and Shannon states that the tribonacci sequence can be detected by the so-called Pascal's pyramid. Here we will show that any tribonacci-like sequence can be obtained by the diagonals of the Feinberg's triangle associated to a suitable generalized Pascal's pyramid. The results also extend similar properties of Fibonacci-like sequences.

  11. Content-adaptive pyramid representation for 3D object classification

    DEFF Research Database (Denmark)

    Kounalakis, Tsampikos; Boulgouris, Nikolaos; Triantafyllidis, Georgios

    2016-01-01

    In this paper we introduce a novel representation for the classification of 3D images. Unlike most current approaches, our representation is not based on a fixed pyramid but adapts to image content and uses image regions instead of rectangular pyramid scales. Image characteristics, such as depth...

  12. Estimation of Food Guide Pyramid Serving Sizes by College Students.

    Science.gov (United States)

    Knaust, Gretchen; Foster, Irene M.

    2000-01-01

    College students (n=158) used the Food Guide Pyramid to select serving sizes on a questionnaire (73% had been instructed in its use). Overall mean scores (31% correct) indicated they generally did not know recommended serving sizes. Those who had read about or received instruction in the pyramid had higher mean scores. (SK)

  13. A study of correlation technique on pyramid processed images

    Indian Academy of Sciences (India)

    The pyramid algorithm is potentially a powerful tool for advanced television image processing and for pattern recognition. An attempt is made to design and develop both hardware and software for a system which performs decomposition and reconstruction of digitized images by implementing the Burt pyramid algorithm.

  14. Marker-assisted pyramiding of Thinopyrumderived leaf rust ...

    Indian Academy of Sciences (India)

    2017-03-20

    Mar 20, 2017 ... Key words: Wheat, leaf rust, molecular marker, gene pyramiding,marker assisted selection. Abstract. The study was undertaken to pyramid two effective leaf rust resistance genes (Lr19 and Lr24) derived from Thinopyrum(syn.Agropyron), in the susceptible but agronomically superior wheat cultivar HD2733 ...

  15. Science and Technology Innovation for the Base of the Pyramid ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Science and Technology Innovation for the Base of the Pyramid (Southeast Asia). Approximately four billion of the world's people subsist at the base of the social and economic pyramid, while a mere 75-100 million make up the top. Despite the many challenges facing those at the base, it is the affluent minority at the top ...

  16. A multi octaves directive dielectric lens: The Pyramid Antenna

    NARCIS (Netherlands)

    Marliani, L.; Bruni, S.; Neto, A.

    2005-01-01

    Leaky wave antennas have been investigated for a long time and are typically an inexpensive solution for beam scanning antennas. We have designed a novel antenna topology, named the pyramid antenna, based on the broadband leaky concept. The pyramid antenna, currently covered by a patent application,

  17. Creating Gymnastic Pyramids and Balances. A Safe and Fun Approach!

    Science.gov (United States)

    Fodero, Joseph M.; Furblur, Ernest E.

    This guide to creating gymnastic pyramids and balances for physical educators, cheerleading coaches, and gymnastics instructors, has safety as its primary focus. It is pointed out that all pyramids and balances should meet the safety requirements of cheerleading and gymnastics organizations. The book provides thorough instructions and more than…

  18. The 2005 Food Guide Pyramid: an opportunity lost?

    Science.gov (United States)

    Chiuve, Stephanie E; Willett, Walter C

    2007-11-01

    Dietary quality has a vital role in the prevention of chronic disease. In 2005, the US Department of Agriculture released a new food guide, MyPyramid, because the previous pyramid was in substantial discordance with current scientific evidence. The US Department of Agriculture pyramids are the most visible source of US nutrition policy and dietary guidance and it is, therefore, imperative they provide scientifically derived recommendations for a healthy diet. Unfortunately, MyPyramid strays from much of the evidence generated through years of research and, in our opinion, fails to provide the public with clear information about healthy food choices. In this Review, we discuss the policy and process behind the development of MyPyramid, assess the current evidence linking diet to chronic diseases, including cardiovascular disease, cancer and diabetes, and suggest potential alternatives for dietary recommendations.

  19. The effect of CA1 dopaminergic system in harmaline-induced amnesia.

    Science.gov (United States)

    Nasehi, M; Ketabchi, M; Khakpai, F; Zarrindast, M-R

    2015-01-29

    In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmaline-induced amnesia were examined in male mice. A one-trial step-down passive avoidance task was used for the assessment of memory retention in adult male mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1 mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of dopamine D1 receptor antagonist, SCH23390 (0.02 μg/mouse), dopamine D1 receptor agonist, SKF38393 (0.5 μg/mouse), dopamine D2 receptor antagonist, sulpiride (1 μg/mouse) and dopamine D2 receptor agonist, quinpirole (0.25 and 0.5 μg/mouse) suppressed the learning of a single-trial passive avoidance task. Also, pre-training intra-CA1 injection of subthreshold doses of SCH23390 (0.001 μg/mouse) or sulpiride (0.25 μg/mouse) with the administration of harmaline (1 mg/kg, i.p.) reversed impairment of memory formation. However, pre-training intra-CA1 injection of SKF38393 (0.1 μg/mouse) or quinpirole (0.1 μg/mouse) increased pre-training harmaline (0.25 and 0.5 mg/kg, i.p.)-induced retrieval impairment. Moreover, SKF Ca blocker (SKF) (0.01 μg/mouse) decrease the amnesia induced by harmaline (1 mg/kg), while co-administration of SKF (0.01 μg/mouse)/sulpiride (0.25 μg/mouse) or SCH23390 (0.001 μg/mouse)/sulpiride (0.25 μg/mouse) potentiate amnesia caused by harmaline. These findings implicate the involvement of CA1 dopaminergic mechanism in harmaline-induced impairment of memory acquisition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Specialization in pyramidal cell structure in the sensory-motor cortex of the vervet monkey (Cercopethicus pygerythrus).

    Science.gov (United States)

    Elston, G N; Benavides-Piccione, R; Elston, A; Defelipe, J; Manger, P R

    2005-01-01

    Recent studies have revealed systematic differences in the pyramidal cell structure between functionally related cortical areas of primates. Trends for a parallel in pyramidal cell structure and functional complexity have been reported in visual, somatosensory, motor, cingulate and prefrontal cortex in the macaque monkey cortex. These specializations in structure have been interpreted as being fundamental in determining cellular and systems function, endowing circuits in these different cortical areas with different computational power. In the present study we extend our initial finding of systematic specialization of pyramidal cell structure in sensory-motor cortex in the macaque monkey [Cereb Cortex 12 (2002) 1071] to the vervet monkey. More specifically, we investigated pyramidal cell structure in somatosensory and motor areas 1/2, 5, 7, 4 and 6. Neurones in fixed, flat-mounted, cortical slices were injected intracellularly with Lucifer Yellow and processed for a light-stable 3,3'-diaminobenzidine reaction product. The size of, number of branches in, and spine density of the basal dendritic arbors varied systematically such that there was a trend for increasing complexity in arbor structure with progression through 1/2, 5 and 7. In addition, cells in area 6 were larger, more branched, and more spinous than those in area 4.

  1. Sodium fluoride does not affect the working memory and number of pyramidal cells in rat medial prefrontal cortex.

    Science.gov (United States)

    Pulungan, Zulhaini Sartika A; Sofro, Zaenal Muttaqien; Partadiredja, Ginus

    2018-01-01

    Fluoride is a chemical compound known to bring about fluorosis. It is thought to disrupt the central nervous system because of its ability to induce excitotoxicity and oxidative stress. Any damage of pyramidal cells in the prefrontal cortex would result in cognitive function and working memory regulation disorders. The present study aimed at investigating the effects of sodium fluoride (NaF) on the working memory and estimated total number of medial prefrontal cortex pyramidal cells of adult male rats. Thirty-two male Wistar rats were assigned into four groups, namely control and three treated groups receiving 5, 10 and 20 mg/kg BW, respectively, of oral NaF solution for 30 days. The working memory test was carried out using a Y-maze. The number of pyramidal cells in the medial prefrontal cortex was estimated using an unbiased stereological method. There was no significant difference among groups in the working memory and number of pyramidal neurons in the medial prefrontal cortex cells.

  2. Caffeine and REM sleep deprivation: Effect on basal levels of signaling molecules in area CA1.

    Science.gov (United States)

    Alkadhi, Karim A; Alhaider, Ibrahim A

    2016-03-01

    We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Diffusion-weighted imaging in transient global amnesia exposes the CA1 region of the hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ho Yun; Kim, Jae Hyoung; Weon, Young-Cheol; Youn, Sung Won; Kim, Sung Hyun [Seoul National University Bundang Hospital, Department of Radiology, Seoul National University College of Medicine, Seongnam-si (Korea); Lee, Jung Seok; Kim, Sang Yun [Seoul National University Bundang Hospital, Department of Neurology, Seoul National University College of Medicine, Seongnam-si (Korea)

    2007-06-15

    Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia without alteration of consciousness or personal identity. Interestingly, recent studies have reported a high frequency of small high-signal abnormalities in the hippocampus with diffusion-weighted (DW) imaging, and ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, known to be susceptible to ischemia. Over a 30-month period 34 patients with TGA underwent MRI including DW imaging within 4 days of symptom onset. Patients with high-signal abnormalities in the hippocampus on the initial DW images underwent subsequent DW and T2-weighted imaging in the coronal plane to identify the precise lesion locations. Fourteen patients had small (1-3 mm) high-signal abnormalities in the hippocampus unilaterally on DW images. One of these patients had two lesions in one hippocampus and therefore in total 15 lesions were identified: four in the hippocampal head, and 11 in the body. Eleven lesions in ten patients with available coronal images were clearly demonstrated on both coronal DW and T2-weighted images and were localized to the lateral portion of the hippocampus, corresponding to the CA1 region. Lesions associated with TGA were localized exclusively to the lateral portion of the hippocampus corresponding to the CA1 region. This finding supports the ischemic etiology of TGA; however, the pathophysiological mechanism involved requires further study. (orig.)

  4. Organizational connectivity among the CA1, subiculum, presubiculum, and entorhinal cortex in the rabbit.

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    Honda, Yoshiko; Shibata, Hideshi

    2017-12-01

    The laminar and topographical organization of connections between the hippocampal formation and parahippocampal regions was investigated in the rabbit following in vivo injection of cholera toxin B subunit as a retro- and antero-grade tracer and biotinylated dextran amine as an anterograde tracer. We confirmed several connectional features different from those of the rat, that is, the rabbit presubiculum received abundant afferents from CA1 and had many reciprocal connections with the entorhinal cortex. On the other hand, we identified many similarities with the rat: both the CA1 and subicular afferents that originated from the entorhinal cortex were abundant; moreover, the presubiculum received many inputs from the subiculum and sent massive projections to the entorhinal cortex. By plotting retrograde and anterograde labels in two-dimensional unfolded maps of the entire hippocampal and parahippocampal regions, we found that each group of entorhinal cells that project to CA1, subiculum, and presubiculum, and also the termination of the presubiculo-entorhinal projection, was distributed in band-like zones in layers II-III, extending across the medial and lateral entorhinal cortex. Our results suggest that the rabbit has a basic connectivity that is common with that of the rat, and also has additional hippocampal-presubicular and entorhino-presubicular connections that may reflect functional evolution in learning and memory. © 2017 Wiley Periodicals, Inc.

  5. Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

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    Roman A Sandler

    2017-07-01

    Full Text Available Much of the research on cannabinoids (CBs has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC, the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

  6. Imaging a Pyramid Interior by ERT-3D Methods, Preliminar Results at El Castillo Pyramid, Chichen Itza, Mexico

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    Chavez, R. E.; Tejero, A.; Cifuentes, G.; HernaNdez-Quintero, J. E.; Garcia-Serrano, A.

    2016-12-01

    The well known Pyramid El Castillo, located in the archaeological site of Chichen Itza, in the Yucatan Peninsula is the emblematic structure of this archaeological site and elected as one of the man-made world seven wonders. The archaeological team that restored this structure during the 1920's discovered a smaller pyramid inside this prehispanic body, which corresponded to an older Mayan period. The possibility of finding other constructive periods inside this edifice should be important to reconstruct the Mayan history. Previous geophysical studies carried out by us in 2014, employed novel Electrical Resistivity Tomography (ERT) arrays that surrounded the pyramids surface with flat electrodes to obtain a 3D image of the subsoil. At that time, a low resistivity body was found beneath the pyramid, which was associated to a sinkhole filled with sweet water. Employing the same technique, a series of flat electrodes were deployed on each body conforming the pyramid, a total of 10 bodies were covered, employing a different number of electrodes trying to keep the distance between each electrode constant ( 3 m). Each body was treated as a single observation cube, where the apparent resistivity data measured was later inverted. A precise topographic control for each electrode was realized and introduced in the inversion process. 45,000 observation points within the pyramid were obtained. Initially, each working cube corresponding to a given pyramid's body was inverted. A composition of each inversion was assembled to form the resistivity distribution within the pyramid using a smooth interpolation method. A high resistivity anomaly was found towards the northern portion of the model that could be associated to the main stairway of the inner pyramid. The cavity detected during the 2014 survey was observed as a low resistivity anomaly found at the pyramid's base. At the moment, we are assembling the full observed resistivity data as a single file to compute an integrated

  7. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

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    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  8. Astrocyte calcium signalling orchestrates neuronal synchronization in organotypic hippocampal slices

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    Sasaki, Takuya; Ishikawa, Tomoe; Abe, Reimi; Nakayama, Ryota; Asada, Akiko; Matsuki, Norio; Ikegaya, Yuji

    2014-01-01

    Astrocytes are thought to detect neuronal activity in the form of intracellular calcium elevations; thereby, astrocytes can regulate neuronal excitability and synaptic transmission. Little is known, however, about how the astrocyte calcium signal regulates the activity of neuronal populations. In this study, we addressed this issue using functional multineuron calcium imaging in hippocampal slice cultures. Under normal conditions, CA3 neuronal networks exhibited temporally correlated activity patterns, occasionally generating large synchronization among a subset of cells. The synchronized neuronal activity was correlated with astrocyte calcium events. Calcium buffering by an intracellular injection of a calcium chelator into multiple astrocytes reduced the synaptic strength of unitary transmission between pairs of surrounding pyramidal cells and caused desynchronization of the neuronal networks. Uncaging the calcium in the astrocytes increased the frequency of neuronal synchronization. These data suggest an essential role of the astrocyte calcium signal in the maintenance of basal neuronal function at the circuit level. PMID:24710057

  9. Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism.

    Science.gov (United States)

    Wu, Hongmei; Wang, Xuelai; Gao, Jingquan; Liang, Shuang; Hao, Yanqiu; Sun, Caihong; Xia, Wei; Cao, Yonggang; Wu, Lijie

    2017-03-15

    To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection. Copyright © 2017. Published by Elsevier Inc.

  10. Diversity of Reporter Expression Patterns in Transgenic Mouse Lines Targeting Corticotropin-Releasing Hormone-Expressing Neurons.

    Science.gov (United States)

    Chen, Yuncai; Molet, Jenny; Gunn, Benjamin G; Ressler, Kerry; Baram, Tallie Z

    2015-12-01

    Transgenic mice, including lines targeting corticotropin-releasing factor (CRF or CRH), have been extensively employed to study stress neurobiology. These powerful tools are poised to revolutionize our understanding of the localization and connectivity of CRH-expressing neurons, and the crucial roles of CRH in normal and pathological conditions. Accurate interpretation of studies using cell type-specific transgenic mice vitally depends on congruence between expression of the endogenous peptide and reporter. If reporter expression does not faithfully reproduce native gene expression, then effects of manipulating unintentionally targeted cells may be misattributed. Here, we studied CRH and reporter expression patterns in 3 adult transgenic mice: Crh-IRES-Cre;Ai14 (tdTomato mouse), Crfp3.0CreGFP, and Crh-GFP BAC. We employed the CRH antiserum generated by Vale after validating its specificity using CRH-null mice. We focused the analyses on stress-salient regions, including hypothalamus, amygdala, bed nucleus of the stria terminalis, and hippocampus. Expression patterns of endogenous CRH were consistent among wild-type and transgenic mice. In tdTomato mice, most CRH-expressing neurons coexpressed the reporter, yet the reporter identified a few non-CRH-expressing pyramidal-like cells in hippocampal CA1 and CA3. In Crfp3.0CreGFP mice, coexpression of CRH and the reporter was found in central amygdala and, less commonly, in other evaluated regions. In Crh-GFP BAC mice, the large majority of neurons expressed either CRH or reporter, with little overlap. These data highlight significant diversity in concordant expression of reporter and endogenous CRH among 3 available transgenic mice. These findings should be instrumental in interpreting important scientific findings emerging from the use of these potent neurobiological tools.

  11. Effects of fructose-1,6-bisphosphate on morphological and functional neuronal integrity in rat hippocampal slices during energy deprivation.

    Science.gov (United States)

    Izumi, Y; Benz, A M; Katsuki, H; Matsukawa, M; Clifford, D B; Zorumski, C F

    2003-01-01

    D-fructose-1,6-bisphosphate, a high energy glycolytic intermediate, attenuates ischemic damage in a variety of tissues, including brain. To determine whether D-fructose-1,6-bisphosphate serves as an alternate energy substrate in the CNS, rat hippocampal slices were treated with D-fructose-1,6-bisphosphate during glucose deprivation. Unlike pyruvate, an endproduct of glycolysis, 10 mM D-fructose-1,6-bisphosphate did not preserve synaptic transmission or morphological integrity of CA1 pyramidal neurons during glucose deprivation. Moreover, during glucose deprivation, 10-mM D-fructose-1,6-bisphosphate failed to maintain adenosine triphosphate levels in slices. D-fructose-1,6-bisphosphate, however, attenuated acute neuronal degeneration produced by 200 microM iodoacetate, an inhibitor of glycolysis downstream of D-fructose-1,6-bisphosphate. Because (5S, 10R)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine, an antagonist of N-methyl-D-aspartate receptors, exhibited similar protection against iodoacetate damage, we examined whether (5S, 10R)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine and D-fructose-1,6-bisphosphate share a common neuroprotective mechanism. Indeed, D-fructose-1,6-bisphosphate diminished N-methyl-D-aspartate receptor-mediated synaptic responses and partially attenuated neuronal degeneration induced by 100-microM N-methyl-D-aspartate. Taken together, these results indicate that D-fructose-1,6-bisphosphate is unlikely to serve as an energy substrate in the hippocampus, and that neuroprotective effects of D-fructose-1,6-bisphosphate are mediated by mechanisms other than anaerobic energy supply. Copyright 2003 IBRO

  12. Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

    Science.gov (United States)

    Child, Nicholas D; Benarroch, Eduardo E

    2014-03-18

    Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

  13. Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Álvarez, N; Díez, L; Avellaneda, C; Serra, M; Rubio, M Á

    Pyramidal signs (hyperreflexia, spasticity, Babinski sign) are essential for the diagnosis of amyotrophic lateral sclerosis (ALS). However, these signs are not always present at onset and may vary over time, besides which their role in disease evolution is controversial. Our goal was to describe which pyramidal signs were present and how they evolved in a cohort of patients with ALS, as well as their role in prognosis. Retrospective analysis of prospectively collected patients diagnosed with ALS in our centre from 1990 to 2015. Of a total of 130 patients with ALS, 34 (26.1%) patients showed no pyramidal signs at the first visit while 15 (11.5%) had a complete pyramidal syndrome. Of those patients without initial pyramidal signs, mean time of appearance of the first signs was 4.5 months. Babinski sign was positive in 64 (49.2%) patients, hyperreflexia in 90 (69.2%) and 22 (16.9%) patients had spasticity. Pyramidal signs tended to remain unchanged over time, although they seem to appear at later stages or even disappear with time in some patients. We found no association between survival and the presence of changes to pyramidal signs, although decreased spasticity was associated with greater clinical deterioration (ALSFR scale) (P<.001). A quarter of patients with ALS initially showed no pyramidal signs and in some cases they even disappear over time. These data support the need for tools that assess the pyramidal tract. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

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    Kelli Lauderdale

    2015-09-01

    Full Text Available Cellular edema (cell swelling is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs, which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8–20 weeks old compared with juvenile (P15–P21 mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space.

  15. Papillary Carcinoma Arising from the Pyramidal Lobe of the Thyroid

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    Kim, Hyun Gi; Lee, Sarah; Kim, Eun Kyung; Moon, Hee Jung; Kwak, Jin Young [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    The authors present a rare case of papillary carcinoma arising from the pyramidal lobe of the thyroid in a 54-year-old woman, who presented with a right submental palpable mass. An ultrasound evaluation depicted a 3 cm mixed echoic mass from the thyroid cartilage level without a focal lesion in the thyroid gland. Surgical specimens obtained during bilateral thyroidectomy confirmed papillary carcinoma of the pyramidal lobe. To the authors' knowledge, this is the first case report to describe papillary carcinoma arising from the pyramidal lobe of the thyroid gland

  16. Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

    Science.gov (United States)

    Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Hioki, Hiroyuki; Tsumoto, Tadaharu

    2017-10-06

    Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.

  17. Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys.

    Science.gov (United States)

    Elston, Guy N; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul R; Defelipe, Javier

    2005-09-01

    The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species. Copyright 2005

  18. Diversity of glutamate receptors in neocortical neurons: implications for synaptic plasticity.

    Science.gov (United States)

    Audinat, E; Lambolez, B; Cauli, B; Ropert, N; Perrais, D; Hestrin, S; Rossier, J

    1996-01-01

    The biochemical and functional characteristics of the AMPA subtype of the glutamate receptors expressed by pyramidal and non-pyramidal neurons of the neocortex have been studied in acute slices by means of single-cell RT-PCR and fast applications of glutamate on outside-out patches. Our results suggest that the predominant expression of the flop splice variants of the GluR1-4 AMPA subunits contributes to the faster desensitization of these receptors in non-pyramidal neurons compared to pyramidal cells where flip variants of GluR1-4 are dominant. Alternative splicing of AMPA receptors may therefore play an important role in regulating synaptic function in a cell-type specific manner.

  19. Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to benzodiazepine modulation in rat CA1 hippocampus.

    Science.gov (United States)

    Costa, A M; Spence, K T; Smith, S S; ffrench-Mullen, J M

    1995-07-01

    1. The withdrawal properties of the endogenous steroid progesterone (P) were tested in female rats as a function of benzodiazepine modulation of gamma-aminobutyric acid-A (GABAA)-gated current with the use of the whole cell patch-clamp technique on acutely dissociated CA1 hippocampal neurons. In a previous study, this steroid was shown to exhibit withdrawal properties, behaviorally. 2. One day withdrawal from in vivo administration of physiological doses of P (5 mg ip, 5 days/wk for 3 withdrawal cycles) or its metabolite, the GABAA modulator 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP or allopregnanolone, 20 mg/kg ip) prevented the normally potentiating effect of lorazepam (LZM; 10(-7)-10(-4) M) on GABAA-gated current. Withdrawal from 500 micrograms P administered concomitantly with 2 micrograms 17 beta-estradiol also markedly diminished LZM potentiation of GABAA current. This effect was seen only after three withdrawal cycles. 3. P withdrawal produced no inhibitory effect on either basal levels of GABAA-evoked current, the GABAA EC50, or barbiturate (+/-Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter. 4. The effect of steroid withdrawal on LZM modulation of GABAA-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABAA modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABAA receptor function produced by 3 alpha,5 alpha-THP.

  20. Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells.

    Science.gov (United States)

    Staiger, Jochen F; Flagmeyer, Iris; Schubert, Dirk; Zilles, Karl; Kötter, Rolf; Luhmann, Heiko J

    2004-06-01

    Previous analyses of the spiny layer IV neurons have almost exclusively focused on spiny stellate cells. Here we provide detailed morphological data characterizing three subpopulations of spiny neurons in slices of adolescent rats: (i) spiny stellate cells (58%), (ii) star pyramidal cells (25%) and (iii) pyramidal cells (17%), which can be distinguished objectively by the preferential orientation of their dendritic stems. Spiny stellate cells lacked an apical dendrite and frequently confined their dendritic and axonal arbors to the respective column. Star pyramidal and pyramidal cells possessed an apical dendrite, which reached the supragranular layers. Their axonal arbors were similar, showing both a columnar component and transcolumnar branches with direct transbarrel projections. However, a small fraction of star pyramidal cells possessed few or even no transcolumnar branches. Electrophysiologically, all three types of neurons were either regular-spiking or intrinsically burst-spiking without a significant relation to the morphological subtypes. The basic synaptic properties of thalamic inputs were also independent of the type of target layer IV spiny neuron. All remained subthreshold and showed paired-pulse depression. In conclusion, the columnar axonal arborization of spiny stellate cells is supplemented by a significant oblique to horizontal projection pattern in pyramidal-like neurons. This offers a structural basis for either segregation or early context-dependent integration of tactile information, in a cell-type specific manner.

  1. Specialization of pyramidal cell structure in the visual areas V1, V2 and V3 of the South American rodent, Dasyprocta primnolopha.

    Science.gov (United States)

    Elston, Guy N; Elston, Alejandra; Freire, Marco Aurelio M; Gomes Leal, Wallace; Dias, Ivanira Amaral; Pereira, Antonio; Silveira, Luiz Carlos L; Picanço Diniz, Cristovam W

    2006-08-23

    Marked phenotypic variation has been reported in pyramidal cells in the primate cerebral cortex. These extent and systematic nature of these specializations suggest that they are important for specialized aspects of cortical processing. However, it remains unknown as to whether regional variations in the pyramidal cell phenotype are unique to primates or if they are widespread amongst mammalian species. In the present study we determined the receptive fields of neurons in striate and extrastriate visual cortex, and quantified pyramidal cell structure in these cortical regions, in the diurnal, large-brained, South American rodent Dasyprocta primnolopha. We found evidence for a first, second and third visual area (V1, V2 and V3, respectively) forming a lateral progression from the occipital pole to the temporal pole. Pyramidal cell structure became increasingly more complex through these areas, suggesting that regional specialization in pyramidal cell phenotype is not restricted to primates. However, cells in V1, V2 and V3 of the agouti were considerably more spinous than their counterparts in primates, suggesting different evolutionary and developmental influences may act on cortical microcircuitry in rodents and primates.

  2. How They (Should Have) Built the Pyramids

    Science.gov (United States)

    Gallagher, Gregory; West, Joseph; Waters, Kevin

    2014-03-01

    A novel ``polygon method'' is proposed for moving large stone blocks. The method is implemented by the attachment of rods of analytically chosen radii to the block by means of rope. The chosen rods are placed on each side of the square-prism block in order to transform the square prism into a prism of higher order polygon, i.e. octagon, dodecagon etc. Experimental results are presented and compared to other methods proposed by the authors, including a dragging method and a rail method which includes the idea of dragging the block on rails made from arbitrarily chosen rod-shaped ``tracks,'' and to independent work by another group which utilized wooden attachments providing a cylindrical shape. It is found that the polygon method when used on small scale stone blocks across level open ground has an equivalent of a coefficient of friction order of 0.1. For full scale pyramid blocks, the wooden ``rods'' would need to be of order 30 cm in diameter, certainly within reason, given the diameter of wooden masts used on ships in that region during the relevant time period in Egypt. This project also inspired a ``spin-off'' project in which the behavior or rolling polygons is investigated and preliminary data is presented.

  3. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  4. Searching for Chambers and Caves in Teotihuacan's Sun Pyramid

    Science.gov (United States)

    Alfaro, R.; Arrieta, E.; Barba P., L.; Becerril, A. D.; Belmont, E.; Carrillo, I.; Cabrera M., J. I.; Esquivel, O.; Grabski, V.; López R., J. M.; Manzanilla N., L.; Martínez D., A.; Menchaca R., A.; Moreno, M.; Núñez C., R.; Plascencia, J. C.; Rangel, M.; Villoro, M.

    2003-06-01

    In this work a status report of a search for caves in the Sun pyramid in Teotihuacan, México is presented. From an archeological perspective the main goal is to gather evidence to determine whether the pyramid was a state or a funerary temple. The general layout of the detector that is being built is an updated version of the one originally proposed by Alvarez et al..

  5. The temporoammonic input to the hippocampal CA1 region displays distinctly different synaptic plasticity compared to the Schaffer collateral input in vivo: significance for synaptic information processing

    Directory of Open Access Journals (Sweden)

    Ayla eAksoy Aksel

    2013-08-01

    Full Text Available In terms of its sub-regional differentiation, the hippocampal CA1 region receives cortical information directly via the perforant (temporoammonic path (pp-CA1 synapse and indirectly via the tri-synaptic pathway where the last relay station is the Schaffer collateral-CA1 synapse (Sc-CA1 synapse. Research to date on pp-CA1 synapses has been conducted predominantly in vitro and never in awake animals, but these studies hint that information processing at this synapse might be distinct to processing at the Sc-CA1 synapse. Here, we characterized synaptic properties and synaptic plasticity at the pp-CA1 synapse of freely behaving adult rats. We established that field excitatory postsynaptic potentials at the pp-CA1 have longer onset latencies and a shorter time-to-peak compared to the Sc-CA1 synapse. LTP (> 24h was successfully evoked by tetanic afferent stimulation of pp-CA1 synapses. Low frequency stimulation evoked synaptic depression at Sc-CA1 synapses, but did not elicit LTD at pp-CA1 synapses unless the Schaffer collateral afferents to the CA1 region had been severed. Paired-pulse responses also showed significant differences. Our data suggest that synaptic plasticity at the pp-CA1 synapse is distinct from the Sc-CA1 synapse and that this may reflect its specific role in hippocampal information processing.

  6. Comparison of the Effects of Adenosine A1 Receptors Activity in CA1 Region of the Hippocampus on Entorhinal Cortex and Amygdala Kindled Seizures in Rats

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    A. Heidarianpour

    2008-10-01

    Full Text Available Introduction & Objective: In the CNS, adenosine is known to suppress repetitive neuronal Firing, suggesting a role as an endogenous modifier of seizures. Indeed, intracerebral adenosine concentrations rise acutely during seizure activity and are thought to be responsible for terminating seizures and establishing a period of post-ictal refractoriness. However, it is unclear whether this suppression results from a general depression of brain excitability or through action on particular sites critical for the control of after discharge generation and/or seizure development and propagation. In this regard, comparison of the effects of adenosine A1 receptors of CA1 (region of the ‎hippocampus on entorhinal cortex and amygdala kindled seizures was ‎investigated in this study. Materials & Methods: In this experimental study, Animals were kindled by daily electrical stimulation of amygdale (group A or entorhinal cortex (group B. In the fully kindled animals, N6-‎cyclohexyladenosine (CHA;1 and 10 M; a selective adenosine A1 receptor ‎agonist and 1,3-dimethyl-8-cyclohexylxanthine(CPT;1 ‎µ‎M; a selective ‎adenosine A1 receptors antagonist were microinfused bilaterally into the CA1 ‎region of hippocampus (1l/2min and animals were stimulated at 5 and 15 minutes after drug ‎injection. All animals were received artificial cerebrospinal fluid, 24 h before ‎each drug injection and this result were used as control. Results: The seizure parameters were measured at 5 and 15min post injection. Obtained data showed that CHA at concentrations of 10 ‎µ‎M reduced ‎entorhinal cortex and amygdala after discharge and stage5 seizure durations and ‎increased stage4 latency. CHA at concentration 1‎µ‎M significantly alters ‎seizure parameters of group A but not effect on group B. Intrahippocampal (CA1 region pretreatment of CPT (1 ‎µ‎M before CHA abolished the effects of CHA on seizure parameters.Conclusion: It ‎may be

  7. Structural reorganization of neurocytes of CA1 field of hippocampus in dynamic after experimental thermal trauma and application of lyophilized xenograft

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    S. O. Lytvynyuk

    2017-04-01

    Full Text Available reorganization of animals in dynamics after experimental thermal injury and use of lyophilized xenograft. Materials and Methods. In the experiment on 35 mature white male rats microscopic, electronmicroscopic and morphometric study of animals’ hippocampus were made after severe thermal injury in terms of early necrectomy of affected area and closure by lyophilized xenograft. Experimental animals of the third experimental group were decapitated on the 7th, 14th and 21st days of experiment. Sections of the brain tissue have been taken from the hippocampus area for histological studies, fixed in 96o alcohol and 10 % neutral formalin and embedded in the paraffin blocks. Obtained on microtome sections were stained with hematoxylin and eosin and toluidine blue with Nissl method. Ultrathin sections were contrasted by uranyl acetate and lead citrate according to Reynolds method and were studied in the electron microscope PEM-125K. Morphometric study was performed using system of visual analysis of histological specimens. Results. It has been established that on the 7th day of the experiment with the usage of corrective factor the number of destroyed neurons in CA1 field of hippocampus was less, but still not significant compared to burned untreated animals. Neurocytes were in state of peripheral or segmental tigrolysis, and there was an increase in the square of hypochromic cells nuclei, some of them contained large nucleoli. Microscopically and electronmicroscopically on the 14th and especially on the 21st days of the experiment, there was found a significant improvement of histological condition of neurocytes, numerical density of the nerve cells in the CA1 field of hippocampus was significantly 1.25 times higher, and the number of normochromic cells 5.52 times more than in the animals with burns. Conclusions. Thus, the application of lyophilized xenograft after early necrectomy of burned skin earlier (the 7th day of experiment after burn injury

  8. The "healthy lifestyle guide pyramid" for children and adolescents.

    Science.gov (United States)

    González-Gross, M; Gómez-Lorente, J J; Valtueña, J; Ortiz, J C; Meléndez, A

    2008-01-01

    Increasing evidence demonstrates that risk factors for chronic diseases are established during childhood and adolescence. Consensus about the need to increase prevention efforts makes the adoption of a healthy lifestyle seem desirable from early childhood onwards. After reviewing educational tools for children and adolescents aimed at promoting a healthy lifestyle, it was recognized that there was a need to develop a simple educational tool specifically designed for these age groups. Development of the healthy lifestyle pyramid for children and adolescents. We propose a three-dimensional, truncated and staggered pyramid with 4 faces and a base, which introduces a completely new concept that goes beyond other published pyramids. Each of the faces is oriented towards achieving a different goal. Two faces (faces 1 and 2) are formulated around achieving a goal on a daily basis (daily food intake, face 1, and daily activities, face 2). Face 3 is an adaptation of the traditional food guide pyramid, adapted to children's energy, nutritional and hydration needs. Face 4 deals with both daily and life-long habits. On the base of the pyramid, there is advice about adequate nutrition alternating with advice about physical activity and sports. The Healthy Lifestyle Pyramid is specifically developed for children and adolescents according to current scientific knowledge and evidence-based data and includes easy-to-follow advice and full colour pictures. Following these guidelines should improve health and reduce risk factors, promoting enjoyable and appropriate development towards adulthood.

  9. Choline acetyltransferase-containing neurons in the human parietal neocortex

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    V Benagiano

    2009-06-01

    Full Text Available A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT, the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

  10. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-01-13

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  11. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.

    Science.gov (United States)

    Norris, Christopher M; Sompol, Pradoldej; Roberts, Kelly N; Ansari, Mubeen; Scheff, Stephen W

    2016-02-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague-Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10 mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Appearance of amyloid beta-like substances and delayed-type apoptosis in rat hippocampus CA1 region through aging and oxidative stress.

    Science.gov (United States)

    Fukui, Koji; Takatsu, Hirokatsu; Shinkai, Tadashi; Suzuki, Shozo; Abe, Kouichi; Urano, Shiro

    2005-12-01

    To elucidate whether oxidative stress induces cognitive deficit, and whether nerve cells in the hippocampus, which modulates learning and memory functions in the brain, are damaged by oxidative stress and during aging, the influence of hyperoxia as oxidative stress on either the cognitive function of rats or the oxidative damage of nerve cells was investigated. Young rats showed better learning ability than both old rats and vitamin E-deficient young rats. Vitamin E- supplemented young rats showed similar ability to young control rats. After they learned the location of the platform in the Morris water maze test, the young rats and vitamin E-supplemented young rats were subjected to oxidative stress for 48 h, and the old rats and vitamin E-deficient young rats were kept in normal atmosphere. The memory function of the old rats and vitamin E-deficient young rats declined even when they were not subjected to oxidative stress for 48 h. In contrast, the young rats maintained their memory function for 4 days after the oxidative stress. However, their learning abilities suddenly declined toward that of the normal old rats after 5 days. At this point, nerve cell loss and apoptosis were observed in the hippocampal CA 1 region of young rats. Vitamin E-supplementation in the young rats prevented either memory deficit or the induction of delayed-type apoptosis. The old rats and vitamin E-deficient young rats kept in normal atmosphere for 48 h also showed apoptosis in the hippocampus. Also, 10 days after oxidative stress, amyloid beta-like substances appeared in the CA-1 region of control young rats; these substances were also observed in the CA-1 region of the old rats and vitamin E- deficient young rats. These results suggest that reactive oxygen species (ROS) generated by oxidative stress induced amyloid beta-like substances and delayed-type apoptosis in the rat hippocampus, resulting in cognitive deficit. Since amyloid beta in Alzheimer's disease characterized by cognitive

  13. Functional differences in the backward shifts of CA1 and CA3 place fields in novel and familiar environments.

    Directory of Open Access Journals (Sweden)

    Eric D Roth

    Full Text Available Insight into the processing dynamics and other neurophysiological properties of different hippocampal subfields is critically important for understanding hippocampal function. In this study, we compared shifts in the center of mass (COM of CA3 and CA1 place fields in a familiar and completely novel environment. Place fields in CA1 and CA3 were simultaneously recorded as rats ran along a closed loop track in a familiar room followed by a session in a completely novel room. This process was repeated each day over a 4-day period. CA3 place fields shifted backward (opposite to the direction of motion of the rat only in novel environments. This backward shift gradually diminished across days, as the novel environment became more familiar with repeated exposures. Conversely, CA1 place fields shifted backward across all days in both familiar and novel environments. Prior studies demonstrated that CA1 place fields on average do not exhibit a backward shift during the first exposure to an environment in which the familiar cues are rearranged into a novel configuration, although CA3 place fields showed a strong backward shift. Under the completely novel conditions of the present study, no dissociation was observed between CA3 and CA1 during the first novel session (although a strong dissociation was observed in the familiar sessions and the later novel sessions. In summary, this is the first study to use simultaneous recordings in CA1 and CA3 to compare place field COM shift and other associated properties in truly novel and familiar environments. This study further demonstrates functional differentiation between CA1 and CA3 as the plasticity of CA1 place fields is affected differently by exposure to a completely novel environment in comparison to an altered, familiar environment, whereas the plasticity of CA3 place fields is affected similarly during both types of environmental novelty.

  14. Functional Differences in the Backward Shifts of CA1 and CA3 Place Fields in Novel and Familiar Environments

    OpenAIRE

    Roth, Eric D.; Yu, Xintian; Rao, Geeta; Knierim, James J.

    2012-01-01

    Insight into the processing dynamics and other neurophysiological properties of different hippocampal subfields is critically important for understanding hippocampal function. In this study, we compared shifts in the center of mass (COM) of CA3 and CA1 place fields in a familiar and completely novel environment. Place fields in CA1 and CA3 were simultaneously recorded as rats ran along a closed loop track in a familiar room followed by a session in a completely novel room. This process was re...

  15. Pyramidal cells of rodent presubiculum express a tetrodotoxin-insensitive Na+ current.

    Science.gov (United States)

    Fricker, Desdemona; Dinocourt, Céline; Eugène, Emmanuel; Wood, John N; Wood, John; Miles, Richard

    2009-09-01

    Presubicular neurons are activated physiologically by a specific preferred head direction. Here we show that firing in these neurones is characterized by action potentials with a large overshoot and a reduced firing frequency adaptation during repetitive firing. We found that a component of the sodium current of presubicular cells was not abolished by tetrodotoxin (TTX, 10 mum) and was activated at more depolarized voltages than TTX-sensitive currents. This inward current was completely abolished by the removal of external sodium, suggesting that sodium is the charge carrier of this TTX-insensitive (TTX-I) current. The channels responsible for the TTX-I sodium current seemed to be expressed at sites distant from the soma, giving rise to a voltage-dependent delay in current activation. The voltage required for half-maximal activation was 21 mV, and 36 mV for inactivation, which is similar to that reported for Na(V)1.8 sodium channels. However, the kinetics were considerably slower, with a time constant of current decay of 1.4 s. The current was not abolished in pyramidal cells from animals lacking either the Na(V)1.8 or the Na(V)1.9 subunit. This, possibly novel, TTX-I sodium current could contribute to the coding functions of presubicular neurons, specifically the maintained firing associated with signalling of a stable head position.

  16. Superconductivity in Heavily Nd-doped La2Ca1Ba2Cu5Oz System

    Science.gov (United States)

    Mankadia, S. R.; Dalsaniya, S. M.; Okram, G. S.; Igalwar, Pallavi; Gonal, M. R.; Bhalodia, J. A.

    2011-07-01

    We have investigated the influence of Nd doping at La-site in La2-xNdxCa1Ba2Cu5Oz (La-2125) (x = 0.0, 0.5, 1.0, 1.5, 2.0) system using X-ray diffraction (XRD), d. c. resistivity and iodometric titration studies. Rietveld analysis of XRD confirms the single-phase tetragonal structure with the space group P4/mmm for all the samples. Samples with x = 0.0-1.5 are superconducting with superconducting transition temperature, Tc ranging from 60 K to 38 K. Sample with x = 2.0 shows semiconducting behavior up to 39 K. It is interesting to note that Tc exhibit a strong correlation with increasing dopant concentration. The possible reasons for Tc suppression are discussed in this communication.

  17. Investigations on bulk Eu_xCa_1-xMnO_3.

    Science.gov (United States)

    Kebede, A.; Oliver, F. W.; Seifu, D.; Hoffman, E.; Williams, C.; Kannan, E.; Tessema, G.

    1998-03-01

    We report on the preparation and experimental studies of the bulk manganite Eu_xCa_1-xMnO_3. It has been demonstrated by Fontcuberta et al(J. Fontcuberta et al., J. Appl. Phys. 79(8), 5182(1996).) that one can use Mössbauer spectroscopy as a local probe of the magnetic ordering by doping at the manganese site with ^57Fe in the colossal magnetoresistance material La-Ca-Mn-O. We have successfully synthesized a polycrystalline Eu substituted manganite to investigate the environment at the lanthanum site. Mössbauer measurements were performed between liquid nitrogen and room temperature using a ^151Eu source. The spectrum at room temperature is a single line which is indicative of paramagnetism. Isomer shift measurements show that the Eu is trivalent. A discussion will be reported on the preparation of the compound and the interpretation of the various Mössbauer parameters.

  18. Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.

    Directory of Open Access Journals (Sweden)

    Nada M Porter

    Full Text Available Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses.F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES, and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD-aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging.We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter

  19. Hippocampal CA1 local field potential oscillations induced by olfactory cue of liked food.

    Science.gov (United States)

    Samerphob, Nifareeda; Cheaha, Dania; Chatpun, Surapong; Kumarnsit, Ekkasit

    2017-07-01

    Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally...... late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume....

  1. Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1.

    Science.gov (United States)

    Kiritoshi, Takaki; Sun, Hao; Ren, Wenjie; Stauffer, Shaun R; Lindsley, Craig W; Conn, P Jeffrey; Neugebauer, Volker

    2013-03-01

    The medial prefrontal cortex (mPFC) serves executive cognitive functions such as decision-making that are impaired in neuropsychiatric disorders and pain. We showed previously that amygdala-driven abnormal inhibition and decreased output of mPFC pyramidal cells contribute to pain-related impaired decision-making (Ji et al., 2010). Therefore, modulating pyramidal output is desirable therapeutic goal. Targeting metabotropic glutamate receptor subtype mGluR5 has emerged as a cognitive-enhancing strategy in neuropsychiatric disorders, but synaptic and cellular actions of mGluR5 in the mPFC remain to be determined. The present study determined synaptic and cellular actions of mGluR5 to test the hypothesis that increasing mGluR5 function can enhance pyramidal cell output. Whole-cell voltage- and current-clamp recordings were made from visually identified pyramidal neurons in layer V of the mPFC in rat brain slices. Both the prototypical mGluR5 agonist CHPG and a positive allosteric modulator (PAM) for mGluR5 (VU0360172) increased synaptically evoked spiking (E-S coupling) in mPFC pyramidal cells. The facilitatory effects of CHPG and VU0360172 were inhibited by an mGluR5 antagonist (MTEP). CHPG, but not VU0360172, increased neuronal excitability (frequency-current [F-I] function). VU0360172, but not CHPG, increased evoked excitatory synaptic currents (EPSCs) and amplitude, but not frequency, of miniature EPSCs, indicating a postsynaptic action. VU0360172, but not CHPG, decreased evoked inhibitory synaptic currents (IPSCs) through an action that involved cannabinoid receptor CB1, because a CB1 receptor antagonist (AM281) blocked the inhibitory effect of VU0360172 on synaptic inhibition. VU0360172 also increased and prolonged CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI). Activation of CB1 with ACEA decreased inhibitory transmission through a presynaptic mechanism. The results show that increasing mGluR5 function enhances mPFC output. This

  2. Optical design of infrared pyramid wavefront sensor for the MMT

    Science.gov (United States)

    Chen, Shaojie; Sivanandam, Suresh; Liu, Siqi; Veran, Jean-Pierre; Hinz, Phil; Mieda, Etsuko; Hardy, Tim; Lardiere, Olivier

    2017-09-01

    We report the optical design of an infrared (0.85-1.8 μm) pyramid wavefront sensor (IRPWFS) that is designed for the 6.5m MMT on telescope adaptive optics system using the latest developments in low-noise infrared avalanche photodiode arrays. The comparison between the pyramid and the double-roof prism based wavefront sensors and the evaluation of their micro pupils' quality are presented. According to our analysis, the use of two double-roof prisms with achromatic materials produces the competitive performance when compared to the traditional pyramid prism, which is difficult to manufacture. The final micro pupils on the image plane have the residual errors of pupil position, chromatism, and distortion within 1/10 pixel over the 2×2 arcsecond field of view, which meet the original design goals.

  3. Pyramid Algorithm Framework for Real-Time Image Effects

    DEFF Research Database (Denmark)

    Sangüesa, Adriá Arbués; Ene, Andreea-Daniela; Jørgensen, Nicolai Krogh

    2017-01-01

    Pyramid methods are useful for certain image processing techniques due to their linear time complexity. Implementing them using compute shaders provides a basis for rendering image effects with reduced impact on performance compared to conventional methods. Although pyramid methods are used...... in the game industry, they are not easily accessible to all developers because many game engines do not include built-in support. We present a framework for a popular game engine that allows users to take advantage of pyramid methods for developing image effects. In order to evaluate the performance...... and to demonstrate the framework, a few image effects were implemented. These effects were compared to built-in effects of the same game engine. The results showed that the built-in image effects performed slightly better. The performance of our framework could potentially be improved through optimisation, mainly...

  4. Models of neocortical layer 5b pyramidal cells capturing a wide range of dendritic and perisomatic active properties.

    Directory of Open Access Journals (Sweden)

    Etay Hay

    2011-07-01

    Full Text Available The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na(+-spiking behavior as well as key dendritic active properties, including Ca(2+ spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca(2+ spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities.

  5. A gradual depth-dependent change in connectivity features of supragranular pyramidal cells in rat barrel cortex.

    Science.gov (United States)

    Staiger, Jochen F; Bojak, Ingo; Miceli, Stéphanie; Schubert, Dirk

    2015-01-01

    Recent experimental evidence suggests a finer genetic, structural and functional subdivision of the layers which form a cortical column. The classical layer II/III (LII/III) of rodent neocortex integrates ascending sensory information with contextual cortical information for behavioral read-out. We systematically investigated to which extent regular-spiking supragranular pyramidal neurons, located at different depths within the cortex, show different input-output connectivity patterns. Combining glutamate uncaging with whole-cell recordings and biocytin filling, we revealed a novel cellular organization of LII/III: (1) "Lower LII/III" pyramidal cells receive a very strong excitatory input from lemniscal LIV and much fewer inputs from paralemniscal LVa. They project to all layers of the home column, including a feedback projection to LIV, whereas transcolumnar projections are relatively sparse. (2) "Upper LII/III" pyramidal cells also receive their strongest input from LIV, but in addition, a very strong and dense excitatory input from LVa. They project extensively to LII/III as well as LVa and Vb of their home and neighboring columns. (3) "Middle LII/III" pyramidal cell shows an intermediate connectivity phenotype that stands in many ways in between the features described for lower versus upper LII/III. "Lower LII/III" intracolumnarly segregates and transcolumnarly integrates lemniscal information, whereas "upper LII/III" seems to integrate lemniscal with paralemniscal information. This suggests a fine-grained functional subdivision of the supragranular compartment containing multiple circuits without any obvious cytoarchitectonic, other structural or functional correlate of a laminar border in rodent barrel cortex.

  6. Expression of Bacillus thuringiensis cytolytic toxin (Cyt2Ca1) in citrus roots to control Diaprepes abbreviatus larvae.

    Science.gov (United States)

    Mahmoud, Sulley Ben; Ramos, John E; Shatters, Robert G; Hall, David G; Lapointe, Stephen L; Niedz, Randall P; Rougé, Pierre; Cave, Ronald D; Borovsky, Dov

    2017-03-01

    Diaprepes abbreviatus (L.) is an important pest of citrus in the USA. Currently, no effective management strategies of D. abbreviatus exist in citriculture, and new methods of control are desperately sought. To protect citrus against D. abbreviatus a transgenic citrus rootstock expressing Bacillus thuringiensis Cyt2Ca1, an insect toxin protein, was developed using Agrobacterium-mediated transformation of 'Carrizo' citrange [Citrus sinensis (L) Osbeck Poncirus trifoliate (L) Raf]. The transgenic citrus root stock expressed the cytolytic toxin Cyt2Ca1 constitutively under the control of a 35S promoter in the transgenic Carrizo citrange trifoliate hybrid including the roots that are the food source of larval D. abbreviatus. The engineered citrus was screened by Western blot and RT-qPCR analyses for cyt2Ca1 and positive citrus identified. Citrus trees expressing different levels of cyt2Ca1 transcripts were identified (Groups A-C). High expression of the toxin in the leaves (109 transcripts/ng RNA), however, retarded plant growth. The transgenic plants were grown in pots and the roots exposed to 3week old D. abbreviatus larvae using no-choice plant bioassays. Three cyt2Ca1 transgenic plants were identified that sustained less root damage belonging to Group B and C. One plant caused death to 43% of the larvae that fed on its roots expressed 8×106cyt2Ca1 transcripts/ng RNA. These results show, for the first time, that Cyt2Ca1 expressed in moderate amounts by the roots of citrus does not retard citrus growth and can protect it from larval D. abbreviatus. Published by Elsevier Inc.

  7. Navigated transcranial magnetic stimulation possibilities in difficult diagnostic cases upper motor neuron lesions – case report

    Directory of Open Access Journals (Sweden)

    I. S. Bakulin

    2015-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterized with lesions of both upper and lower motor neurons. In accordance with modern diagnostics criteria, only clinical symptoms are used for revealing lesions of the upper motor neuron with the ALS, which often causes serious difficulties. Absence of the pyramidal syndrome does not allow diagnosing ALS, and the diagnosis of progressive muscular atrophy should be set in these cases. We describe a case of an isolated generalized lesion of the lower motor neuron with the signs of cortical motor neurons lesion revealed in the course of navigational transcranial magnetic stimulation. Possible reasons for difficulties in detecting pyramidal syndrome are discussed together with the necessity of working out the criteria of instrumental diagnostics of lesions of the upper motor neuron in ALS.

  8. Computational Modeling of Neuronal Current MRI Signals with Rat Somatosensory Cortical Neurons.

    Science.gov (United States)

    BagheriMofidi, Seyed Mehdi; Pouladian, Majid; Jameie, Seyed Behnammodin; Abbaspour Tehrani-Fard, Ali

    2016-09-01

    Magnetic field generated by active neurons has recently been considered to determine location of neuronal activity directly with magnetic resonance imaging (MRI), but controversial results have been reported about detection of such small magnetic fields. In this study, multiple neuronal morphologies of rat tissue were modeled to investigate better estimation of MRI signal change produced by neuronal magnetic field (NMF). Ten pyramidal neurons from layer II to VI of rat somatosensory area with realistic morphology, biophysics, and neuronal density were modeled to simulate NMF of neuronal tissue, from which effects of NMF on MRI signals were obtained. Neuronal current MRI signals, which consist of relative magnitude signal change (RMSC) and phase signal change (PSC), were at least three and one orders of magnitude less than a tissue with single neuron type, respectively. Also, a reduction in voxel size could increase signal alterations. Furthermore, with selection of zenith angle of external main magnetic field related to tissue surface near to 90°, RMSC could be maximized. This value for PSC would be 90° for small voxel size and zero degree for large ones.

  9. [Arabian food pyramid: unified framework for nutritional health messages].

    Science.gov (United States)

    Shokr, Adel M

    2008-01-01

    There are several ways to present nutritional health messages, particularly pyramidic indices, but they have many deficiencies such as lack of agreement on a unified or clear methodology for food grouping and ignoring nutritional group inter-relation and integration. This causes confusion for health educators and target individuals. This paper presents an Arabian food pyramid that aims to unify the bases of nutritional health messages, bringing together the function, contents, source and nutritional group servings and indicating the inter-relation and integration of nutritional groups. This provides comprehensive, integrated, simple and flexible health messages.

  10. Transgenic rice plants expressing a modified cry1Ca1 gene are resistant to Spodoptera litura and Chilo suppressalis.

    Science.gov (United States)

    Zaidi, Mohsin Abbas; Ye, Gongyin; Yao, Hongwei; You, Taek H; Loit, Evelin; Dean, Donald H; Riazuddin, Sheikh; Altosaar, Illimar

    2009-11-01

    Nucleotide sequence encoding the truncated insecticidal Cry1Ca1 protein from Bacillus thuringiensis was extensively modified based on the codon usage of rice genes. The overall G + C contents of the synthetic cry1Ca1 coding sequence were raised to 65% with an additional bias of enriching for G and C ending codons as preferred by monocots. The synthetic gene was introduced into the Chinese japonica variety, Xiushui 11, by Agrobacterium-mediated transformation. Transgenic rice plants harboring this gene were highly resistant to Chilo suppressalis and Spodoptera litura larvae as revealed by insect bioassays. High levels of Cry1Ca1 protein were obtained in the leaves of transgenic rice, which were effective in achieving 100% mortality of S. litura and C. suppressalis larvae. The levels of Cry1Ca1 expression in the leaves of these transgenic plants were up to 0.34% of the total soluble proteins. The larvae of C. suppressalis and S. litura could consume a maximum of 1.89 and 4.89 mm2 of transgenic leaf area whereas the consumption of nontransgenic leaves by these larvae was significantly higher; 58.33 and 61.22 mm2, respectively. Analysis of R1 transgenic plants indicated that the cry1Ca1 was inherited by the progeny plants and provided complete protection against C. suppressalis and S. litura larvae.

  11. Sex Differences in Long-Term Potentiation at Temporoammonic-CA1 Synapses: Potential Implications for Memory Consolidation.

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Qi

    Full Text Available Sex differences in spatial memory have long been observed in humans, non-human primates and rodents, but the underlying cellular and molecular mechanisms responsible for these differences remain obscure. In the present study we found that adolescent male rats outperformed female rats in 7 d and 28 d retention probes, but not in learning trials and immediate probes, in the Morris water maze task. Male rats also had larger long-term potentiation (LTP at hippocampal temproammonic-CA1 (TA-CA1 synapses, which have been implicated to play a key role in place field and memory consolidation, when protocols designed to elicit late-stage LTP (LLTP were used. Interestingly, the ratio of evoked AMPA/NMDA currents was found to be smaller at TA-CA1 synapses in male rats compared to female rats. Protein biotinylation experiments showed that male rats expressed more surface GluN1 receptors in hippocampal CA1 stratum lacunosum-moleculare (SLM than female rats, although GluA1 expression was also slightly higher in male rats. Taken together, our results suggest that differences in the expression of AMPA and NMDA receptors may affect LTP expression at TA-CA1 synapses in adolescent male and female rats, and thus possibly contribute to the observed sex difference in spatial memory.

  12. Task-dependent and independent synchronous activity of monkey hippocampal neurons in real and virtual translocation.

    Science.gov (United States)

    Hori, Etsuro; Tabuchi, Eiichi; Matsumura, Nobuhisa; Ono, Taketoshi; Nishijo, Hisao

    2011-01-01

    Previous neurophysiological and behavioral studies relate hippocampal functions to place learning and memory, and encoding of task (or context)-specific information. Encoding of both task-specific information and own location is essential for episodic memory and for animals to navigate to reward-related places. It is suggested that different neural circuits with different assemblies of different hippocampal neurons are created in different environments or behavioral contexts for the hippocampal formation (HF) to encode and retrieve episodic memory. To investigate whether synchronous activity of hippocampal neurons, suggesting functional connectivity between those neurons, is task and position dependent, multiple single unit activities were recorded during performance of real and virtual translocation (VT) tasks. The monkey moved to one of four reward areas by driving a cab (real translocation) or by moving a pointer on a monitor. Of 163 neuron pairs, significant peaks in cross-correlograms (CCGs) were observed in 98 pairs. Most CCGs had positive peaks within 50 ms. Task-dependent cross-correlations (CCRs) were observed in 44% of the neuron pairs, and similarly observed in both the real and VT tasks. These CCRs were frequently observed in pyramidal vs. pyramidal neuron pairs with positive peak and peak shift. However, no consistent patterns of peak polarity, peak shift, and neuronal types were seen in task-independent CCRs. There was no significant difference in frequency of CCG peaks between real and VT tasks. These results suggest that the task-dependent information may be encoded by interaction among pyramidal neurons, and the common information across tasks may be encoded by interaction among pyramidal neurons and interneurons in the HF. These neuronal populations could provide a neural basis for episodic memory to disambiguously guide animals to places associated with reward in different situations.

  13. Task-Dependent and Independent Synchronous Activity of Monkey Hippocampal Neurons in Real and Virtual Translocation

    Science.gov (United States)

    Hori, Etsuro; Tabuchi, Eiichi; Matsumura, Nobuhisa; Ono, Taketoshi; Nishijo, Hisao

    2011-01-01

    Previous neurophysiological and behavioral studies relate hippocampal functions to place learning and memory, and encoding of task (or context)-specific information. Encoding of both task-specific information and own location is essential for episodic memory and for animals to navigate to reward-related places. It is suggested that different neural circuits with different assemblies of different hippocampal neurons are created in different environments or behavioral contexts for the hippocampal formation (HF) to encode and retrieve episodic memory. To investigate whether synchronous activity of hippocampal neurons, suggesting functional connectivity between those neurons, is task and position dependent, multiple single unit activities were recorded during performance of real and virtual translocation (VT) tasks. The monkey moved to one of four reward areas by driving a cab (real translocation) or by moving a pointer on a monitor. Of 163 neuron pairs, significant peaks in cross-correlograms (CCGs) were observed in 98 pairs. Most CCGs had positive peaks within 50 ms. Task-dependent cross-correlations (CCRs) were observed in 44% of the neuron pairs, and similarly observed in both the real and VT tasks. These CCRs were frequently observed in pyramidal vs. pyramidal neuron pairs with positive peak and peak shift. However, no consistent patterns of peak polarity, peak shift, and neuronal types were seen in task-independent CCRs. There was no significant difference in frequency of CCG peaks between real and VT tasks. These results suggest that the task-dependent information may be encoded by interaction among pyramidal neurons, and the common information across tasks may be encoded by interaction among pyramidal neurons and interneurons in the HF. These neuronal populations could provide a neural basis for episodic memory to disambiguously guide animals to places associated with reward in different situations. PMID:21808612

  14. Damage to the pyramidal tracts is necessary and sufficient for the production of the pyramidal syndrome in man.

    Science.gov (United States)

    de Oliveira-Souza, Ricardo

    2015-07-01

    The causal role played by damage to the pyramidal tracts in the production of spastic hemiplegia in man has been hotly debated over the past hundred years. Two broad streams of thought have emerged from this dispute. The first, which is grounded on the clinicopathological schools of Jean-Martin Charcot (1825-1893) and Paul Flechsig (1847-1929), claimed that the four cardinal signs of hemiplegia, namely (i) paralysis, (ii) spasticity, (iii) hyperactive phasic muscle reflexes ("tendon jerks") and (iv) the sign of Babinski, are caused by injury or dysfunction of the pyramidal tracts. The second school, championed by John Farquhar Fulton (1899-1960) and Derek Denny-Brown (1901-1981), reflects the increasing influence of experimental neurology on clinicopathological concepts after World War II. According to this school, most elements of the pyramidal syndrome are caused by the added release or injury of extrapyramidal structures at different levels of the forebrain and brainstem. Most symptoms of spastic hemiplegia were thus interpreted as signs of extrapyramidal (e.g., reticulospinal) release or damage. However, consensus on which symptoms of spastic hemiplegia were due to pyramidal or extrapyramidal changes was never reached. To add to this uncertainty, a number of clinicopathological cases that supported the old view were sporadically published over the same period. The purpose of the present essay is to provide clinicoanatomic perspective to the neurological literature in support of the hypothesis that damage to the pyramidal tracts is a necessary and sufficient condition for the production of the complete pyramidal syndrome in man. Copyright © 2015. Published by Elsevier Ltd.

  15. Morphological development of thick-tufted layer V pyramidal cells in the rat somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Sandrine eRomand

    2011-02-01

    Full Text Available The thick-tufted layer V pyramidal (TTL5 neuron is a key neuron providing output from the neocortex. Although it has been extensively studied, principles governing its dendritic and axonal arborization during development are still not fully quantified. Using 3D model neurons reconstructed from biocytin-labeled cells in the rat somatosensory cortex, this study provides a detailed morphological analysis of TTL5 cells at postnatal day (P 7, 14, 21, 36 and 60. Three developmental periods were revealed, which were characterized by distinct growing rates and properties of alterations in different compartments. From P7 to P14, almost all compartments grew fast, and filopodia-like segments along apical dendrite disappeared; From P14 to P21, the growth was localized on specified segments of each compartment, and the densities of spines and boutons were significantly increased; From P21 to P60, the number of basal dendritic segments was significantly increased at specified branch orders, and some basal and oblique dendritic segments were lengthened or thickened. Development changes were therefore seen in two modes: the fast overall growth during the first period and the slow localized growth (thickening mainly on intermediates or lengthening mainly on terminals at the subsequent stages. The lengthening may be accompanied by the retraction on different segments. These results reveal a differential regulation in the arborization of neuronal compartments during development, supporting the notion of functional compartmental development. This quantification provides new insight into the potential value of the TTL5 morphology for information processing, and for other purposes as well.

  16. Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics

    Directory of Open Access Journals (Sweden)

    Cary Soares

    2017-10-01

    Full Text Available Summary: Hebbian and homeostatic forms of plasticity operate on different timescales to regulate synaptic strength. The degree of mechanistic overlap between these processes and their mutual influence are still incompletely understood. Here, we report that homeostatic synaptic strengthening induced by prolonged network inactivity compromised the ability of CA1 synapses to exhibit LTP. This effect could not be accounted for by an obvious deficit in the postsynaptic capacity for LTP expression, since neither the fraction of silent synapses nor the ability to induce LTP by two-photon glutamate uncaging were reduced by the homeostatic process. Rather, optical quantal analysis reveals that homeostatically strengthened synapses display a reduced capacity to maintain glutamate release fidelity during repetitive stimulation, ultimately impeding the induction, and thus expression, of LTP. By regulating the short-term dynamics of glutamate release, the homeostatic process thus influences key aspects of dynamic network function and exhibits features of metaplasticity. : Several forms of synaptic plasticity operating over distinct spatiotemporal scales have been described at hippocampal synapses. Whether these distinct plasticity mechanisms interact and influence one another remains incompletely understood. Here, Soares et al. show that homeostatic plasticity induced by network silencing influences short-term release dynamics and Hebbian plasticity rules at hippocampal synapses. Keywords: synapse, LTP, homeostatic plasticity, metaplasticity, iGluSNFR

  17. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  18. Pyramidal anchor stone from Baga waters of Goa, west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.

    Underwater exploration in the coastal region off Baga (Goa, India) led to the recovery of an isolated stone artefact, which resembles a pyramidal type of anchor stone. This anchor stone is unlike to other pyramidal anchor stones found elsewhere...

  19. Correlation between kinetics and RNA splicing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in neocortical neurons.

    Science.gov (United States)

    Lambolez, B; Ropert, N; Perrais, D; Rossier, J; Hestrin, S

    1996-03-05

    In the cortex fast excitatory synaptic currents onto excitatory pyramidal neurons and inhibitory nonpyramidal neurons are mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors exhibiting cell-type-specific differences in their kinetic properties. AMPA receptors consist of four subunits (GluR1-4), each existing as two splice variants, flip and flop, which critically affect the desensitization properties of receptors expressed in heterologous systems. Using single cell reverse transcription PCR to analyze the mRNA of AMPA receptor subunits expressed in layers I-III neocortical neurons, we find that 90% of the GluR1-4 in nonpyramidal neurons are flop variants, whereas 92% of the GluR1-4 in pyramidal neurons are flip variants. We also find that nonpyramidal neurons predominantly express GluR1 mRNA (GluR1/GluR1-4 = 59%), whereas pyramidal neurons contain mainly GluR2 mRNA (GluR2/GluR1-4 = 59%). However, the neuron-type-specific splicing is exhibited by all four AMPA receptor subunits. We suggest that the predominance of the flop variants contributes to the faster and more extensive desensitization in nonpyramidal neurons, compared to pyramidal cells where flip variants are dominant. Alternative splicing of AMPA receptors may play an important role in regulating synaptic function in a cell-type-specific manner, without changing permeation properties.

  20. Setting aside transactions from pyramid schemes as impeachable ...

    African Journals Online (AJOL)

    The point of contention in this case was whether the illegality of the business of the scheme was a relevant consideration in determining whether the pay-outs were made in the ordinary course of business of the scheme. This paper discusses pyramid schemes in the context of impeachable dispositions in terms of the ...

  1. A pyramid algorithm for the Haar discrete wavelet packet transform ...

    African Journals Online (AJOL)

    WPT) in which Mallat's pyramid algorithm is applied to the multiresolution analysis (MRA) of both the approximation and detail subspaces of a signal. As a contribution to the computer-aided signal processing of non-stationary signals, this ...

  2. Marker-assisted pyramiding of Thinopyrum-derived leaf rust ...

    Indian Academy of Sciences (India)

    Mona Singh

    2017-12-08

    Dec 8, 2017 ... ilies carrying both Lr19 and Lr24 in homozygous state were developed. The details of gene pyramiding scheme are given in figure 1. Apart from the use of molecular markers, shuttle breed- ing was used to accelerate the development of NILs. Two generations in a year were raised; one at IARI, New Delhi,.

  3. Organizing innovation in base-of-the-pyramid projects

    NARCIS (Netherlands)

    Boer, J. de; Steen, M.G.D.; Posthumus, A.L.

    2013-01-01

    Base-of-the-Pyramid (BoP) inclusive innovation projects aim to design, produce and market products and services for large and relatively poor market segments in developing countries, for example for people who have less than several dollars to spend per day. BoP projects have ‘normal’ goals,

  4. Nano-pyramid arrays for nano-particle trapping

    NARCIS (Netherlands)

    Sun, Xingwu; Veltkamp, Henk-Willem; Berenschot, Johan W.; Gardeniers, Johannes G.E.; Tas, Niels Roelof

    2016-01-01

    Abstract In this paper we present the drastic miniaturization of nano-wire pyramids fabricated by corner lithography. A particle trapping device was fabricated in a well-defined and symmetrical array. The entrance and exit hole-size can be tuned by adjusting fabrication parameters. We describe here

  5. The pyramid model as a structured way of quality management

    Directory of Open Access Journals (Sweden)

    van der Tuuk Adriani Willem

    2008-01-01

    Full Text Available Three quality systems that can be used in blood establishments are briefly explained. The Pyramid model is described as a tool to manage the quality systems. Finally, some experiences in other countries are given to prove the validity of the system.

  6. Surgical anatomy of the pyramidal lobe and its significance in ...

    African Journals Online (AJOL)

    Aim. The purpose of this prospective study was to highlight some new findings about anatomical and morphological variations of the thyroid pyramidal lobe and to emphasise the necessity and importance of exploration of the visceral compartment of the neck and resection of this structure in primary thyroid operations.

  7. Budding Architects: Exploring the Designs of Pyramids and Prisms

    Science.gov (United States)

    Leavy, Aisling; Hourigan, Mairéad

    2015-01-01

    The context of students as architects is used to examine the similarities and differences between prisms and pyramids. Leavy and Hourigan use the Van Hiele Model as a tool to support teachers to develop expectations for differentiating geometry in the classroom using practical examples.

  8. Design data brochure for a pyramidal optics solar system

    Energy Technology Data Exchange (ETDEWEB)

    1980-09-01

    This Design Data Brochure provides information on a Pyramidal Optics Solar System for solar heating and domestic hot water. The system is made up of the collecting, storage, and distribution subsystems. Contained in the brochure are such items as system description, available accessories, installation arrangements, physical data, piping and wiring diagrams, and guide specifications.

  9. Catalyzing new product adoption at the base of the pyramid

    NARCIS (Netherlands)

    Marinakis, Yorgos; Walsh, Steven Thomas; Harms, Rainer

    2016-01-01

    One of the more perplexing of the entrepreneurial issues at the Base of the Pyramid (BoP) is how to catalyze new product adoption by BoP consumers. Because S-shaped adoption dynamics are the result of cultural transmission bias, the question can be rephrased as, how can an entrepreneur overcome

  10. Microfinance for the Urban Bottom of the Pyramid Segment in ...

    African Journals Online (AJOL)

    Although mainstream research on investing in the Bottom of the Pyramid (BOP) segment focus heavily on investors' expected returns, there is less focus on the fast increasing gaps on the role of financial training in academic literature. In addition, there is a lack of deliberate focus on the wellbeing and success of targeted ...

  11. The Sphinx and the Pyramids at Giza. Educational Packet.

    Science.gov (United States)

    Gagliano, Sara; Rapport, Wendy

    This packet of materials was created to accompany the exhibit "The Sphinx and the Pyramids: 100 Years of American Archaeology at Giza" at the Semitic Museum of Harvard University. The lessons and teacher's guide focus on the following: (1) "The Mystery of the Secret Tomb" where students take on the role of an archaeologist by…

  12. The Meat and Protein Group. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and eating from the meat and protein group. Colorful photographs support early readers in understanding the text. The repetition of words…

  13. The FINUT Healthy Lifestyles Guide: Beyond the Food Pyramid123

    Science.gov (United States)

    Gil, Angel; Ruiz-Lopez, Maria Dolores; Fernandez-Gonzalez, Miguel; Martinez de Victoria, Emilio

    2014-01-01

    The WHO has proposed that health be promoted and protected through the development of an environment that enables sustainable actions at individual, community, national, and global levels. Indeed, food-based dietary guidelines, i.e., food pyramids, have been developed in numerous countries to disseminate nutritional information to the general population. However, wider recommendations are needed, with information on an active healthy lifestyle, not just healthy eating. The objective of the present work is to propose a three-dimensional pyramid as a new strategy for promoting adequate nutrition and active healthy lifestyles in a sustainable way. Indeed, the Iberoamerican Nutrition Foundation (FINUT) pyramid of healthy lifestyles has been designed as a tetrahedron, with its 3 lateral faces corresponding to the facets of food and nutrition, physical activity and rest, and education and hygiene. Each lateral face is divided into 2 triangles. These faces show the following: 1) food-based guidelines and healthy eating habits as related to a sustainable environment; 2) recommendations for rest and physical activity and educational, social, and cultural issues; and 3) selected hygiene and educational guidelines that, in conjunction with the other 2 faces, would contribute to better health for people in a sustainable planet. The new FINUT pyramid is addressed to the general population of all ages and should serve as a guide for living a healthy lifestyle within a defined social and cultural context. It includes an environmental and sustainability dimension providing measures that should contribute to the prevention of noncommunicable chronic diseases. PMID:24829489

  14. Fats, Oils, and Sweets. The Food Guide Pyramid.

    Science.gov (United States)

    Frost, Helen

    This booklet for young children is part of a series that supports national science standards related to physical health and nutrition, describing and illustrating the importance of using the Food Guide Pyramid and avoiding excesses of fats, oils, and sweets. It presents appealing alternatives to these unhealthy foods. Colorful photographs support…

  15. Building trust at the Base of the Pyramid

    NARCIS (Netherlands)

    Grootveld, P.; Vermeulen, P.A.M.

    2014-01-01

    More and more companies are serving the poorest communities of our world, the so-called Base of the Pyramid (BoP). Wal-Mart, for example, moved into the Mexican retail-banking sector, claiming not only to “sell more stuff” but also to compete against the entrenched domestic businesses that are not

  16. Agronomic qualities of genetic pyramids of common bean ...

    African Journals Online (AJOL)

    Nine superior lines with desirable qualities, such as earliness (95 days), high seed rate (290 seeds per plant), and climbing ability, were obtained. Pyramiding R genes did not affect yield traits, except time to flowering and number of flower buds per plant due to transgressive segregation. Key Words: Backcrossing, marker ...

  17. Using the Pyramid Approach to Teaching Marketing Research.

    Science.gov (United States)

    Peltier, James W.; Westfall, John; Ainscough, Thomas L.

    2001-01-01

    Underscores the need for teaching marketing research skills at the secondary level and shows how marketing research fits into marketing education. Provides an example of how to use the pyramid approach to research, which involves review of secondary sources, key informant interviews, focus groups, and quantitative research. (Author/JOW)

  18. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

    Science.gov (United States)

    Baliasnyĭ, M M

    1991-01-01

    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

  19. Gene pyramiding as a Bt resistance management strategy: How ...

    African Journals Online (AJOL)

    Questions have been raised on the sustainability of gene pyramiding since the use of insecticide mixtures has shown that cross resistance and/or multiple resistance can render such strategies to be less effective in the long term. Current theoretical and practical evidence in insect population genetics suggest that gene ...

  20. Nanopore formation on Au coated pyramid under electron beam irradiations (plasmonic nanopore on pyramid

    Directory of Open Access Journals (Sweden)

    Seong Soo Choi

    2016-03-01

    Full Text Available There have been tremendous interests about the single molecule analysis using a sold-state nanopore. The solid-state nanopore can be fabricated either by drilling technique, or diffusion technique by using electron beam irradiations. The solid-state SiN nanopore device with electrical detection technique recently fabricated, however, the solid-state Au nanopore with optical detection technique can be better utilized as the next generation single molecule sensor. In this report, the nanometer size openings with its size less than 10 nm on the diffused membrane on the 200 nm Au pyramid were fabricated by using field emission scanning electron microscopy (FESEM electron beam irradiations, transmission electron microscopy (TEM, etc. After the sample was being kept under a room environment for several months, several Au (111 clusters with ~6 nm diameter formed via Ostwald ripening are observed using a high resolution TEM imaging. The nanopore with Au nanoclusters on the diffused membrane can be utilized as an optical nanopore device.

  1. Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via K(Ca) 1.1 upregulation.

    Science.gov (United States)

    Choi, Shinkyu; Kim, Ji Aee; Kim, Tae Hun; Li, Hai-Yan; Shin, Kyong-Oh; Lee, Yong-Moon; Oh, Seikwan; Pewzner-Jung, Yael; Futerman, Anthony H; Suh, Suk Hyo

    2015-12-01

    K(Ca) 1.1 regulates smooth muscle contractility by modulating membrane potential, and age-associated changes in K(Ca) 1.1 expression may contribute to the development of motility disorders of the gastrointestinal tract. Sphingolipids (SLs) are important structural components of cellu