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Sample records for striate cortex neurons

  1. Prenatal Co 60-irradiation effects on visual acuity, maturation of the fovea in the retina, and the striate cortex of squirrel monkey offspring

    International Nuclear Information System (INIS)

    Ordy, J.M.; Brizzee, K.R.; Young, R.

    1982-01-01

    In the present study, foveal striate cortex depth increased significantly from 1400 μm to 1650 μm by 90 days, whereas prenatal 100 rad exposure resulted in a significant reduction of foveal striate cortex thickness at 90 days of age. From birth to 90 days, cell packing density decreased, whereas overall neuropil density increased in both control and 100 rad exposed offspring. Regarding the effects of prenatal radiation on Meynert cells, there was a significant difference in the time course of early postnatal spine frequency reduction on apical dendrites of Meynert cells, particularly in laminae V and IV. It seems possible that the significant differences in the time course of perinatal increases and subsequent decreases of spines and synapses on such pyramidal neurons as Meynert cells in the deep layers of the striate cortex may play an important role in the development of binocular acuity. Future follow-up studies will be essential from 90 days to 1 and 2 years to determine the extent of recovery from, and persistence of visual acuity impairments in relation to structural alterations in the foveal projection of the retino-geniculo-striate system of diurnal primates. (orig./MG)

  2. Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions.

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    Barleben, Maria; Stoppel, Christian M; Kaufmann, Jörn; Merkel, Christian; Wecke, Thoralf; Goertler, Michael; Heinze, Hans-Jochen; Hopf, Jens-Max; Schoenfeld, Mircea A

    2015-04-01

    Patients with striate cortex lesions experience visual perception loss in the contralateral visual field. In few patients, however, stimuli within the blind field can lead to unconscious (blindsight) or even conscious perception when the stimuli are moving (Riddoch syndrome). Using functional magnetic resonance imaging (fMRI), we investigated the neural responses elicited by motion stimulation in the sighted and blind visual fields of eight patients with lesions of the striate cortex. Importantly, repeated testing ensured that none of the patients exhibited blindsight or a Riddoch syndrome. Three patients had additional lesions in the ipsilesional pulvinar. For blind visual field stimulation, great care was given that the moving stimulus was precisely presented within the borders of the scotoma. In six of eight patients, the stimulation within the scotoma elicited hemodynamic activity in area human middle temporal (hMT) while no activity was observed within the ipsilateral lesioned area of the striate cortex. One of the two patients in whom no ipsilesional activity was observed had an extensive lesion including massive subcortical damage. The other patient had an additional focal lesion within the lateral inferior pulvinar. Fiber-tracking based on anatomical and functional markers (hMT and Pulvinar) on individual diffusion tensor imaging (DTI) data from each patient revealed the structural integrity of subcortical pathways in all but the patient with the extensive subcortical lesion. These results provide clear evidence for the robustness of direct subcortical pathways from the pulvinar to area hMT in patients with striate cortex lesions and demonstrate that ipsilesional activity in area hMT is completely independent of conscious perception. © 2014 Wiley Periodicals, Inc.

  3. Methylmercury intoxication and histochemical demonstration of NADPH-diaphorase activity in the striate cortex of adult cats

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    R.B. Oliveira

    1998-09-01

    Full Text Available The effects of methylmercury (MeHg on histochemical demonstration of the NADPH-diaphorase (NADPH-d activity in the striate cortex were studied in 4 adult cats. Two animals were used as control. The contaminated animals received 50 ml milk containing 0.42 µg MeHg and 100 g fish containing 0.03 µg MeHg daily for 2 months. The level of MeHg in area 17 of intoxicated animals was 3.2 µg/g wet weight brain tissue. Two cats were perfused 24 h after the last dose (group 1 and the other animals were perfused 6 months later (group 2. After microtomy, sections were processed for NADPHd histochemistry procedures using the malic enzyme method. Dendritic branch counts were performed from camera lucida drawings for control and intoxicated animals (N = 80. Average, standard deviation and Student t-test were calculated for each data group. The concentrations of mercury (Hg in milk, fish and brain tissue were measured by acid digestion of samples, followed by reduction of total Hg in the digested sample to metallic Hg using stannous chloride followed by atomic fluorescence analysis. Only group 2 revealed a reduction of the neuropil enzyme activity and morphometric analysis showed a reduction in dendritic field area and in the number of distal dendrite branches of the NADPHd neurons in the white matter (P<0.05. These results suggest that NADPHd neurons in the white matter are more vulnerable to the long-term effects of MeHg than NADPHd neurons in the gray matter.

  4. A functional magnetic resonance imaging investigation of visual hallucinations in the human striate cortex.

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    Abid, Hina; Ahmad, Fayyaz; Lee, Soo Y; Park, Hyun W; Im, Dongmi; Ahmad, Iftikhar; Chaudhary, Safee U

    2016-11-29

    Human beings frequently experience fear, phobia, migraine and hallucinations, however, the cerebral mechanisms underpinning these conditions remain poorly understood. Towards this goal, in this work, we aim to correlate the human ocular perceptions with visual hallucinations, and map them to their cerebral origins. An fMRI study was performed to examine the visual cortical areas including the striate, parastriate and peristriate cortex in the occipital lobe of the human brain. 24 healthy subjects were enrolled and four visual patterns including hallucination circle (HCC), hallucination fan (HCF), retinotopy circle (RTC) and retinotopy cross (RTX) were used towards registering their impact in the aforementioned visual related areas. One-way analysis of variance was used to evaluate the significance of difference between induced activations. Multinomial regression and and K-means were used to cluster activation patterns in visual areas of the brain. Significant activations were observed in the visual cortex as a result of stimulus presentation. The responses induced by visual stimuli were resolved to Brodmann areas 17, 18 and 19. Activation data clustered into independent and mutually exclusive clusters with HCC registering higher activations as compared to HCF, RTC and RTX. We conclude that small circular objects, in rotation, tend to leave greater hallucinating impressions in the visual region. The similarity between observed activation patterns and those reported in conditions such as epilepsy and visual hallucinations can help elucidate the cortical mechanisms underlying these conditions. Trial Registration 1121_GWJUNG.

  5. Colour-related oscillations in the striate cortex of awake monkeys: "reverse" observations

    NARCIS (Netherlands)

    Lamme, V.A.F.; Bondar, I.; Kruger, J.

    2001-01-01

    Gamma oscillations of 30-70 Hz in local electroencephalograms (EEGs) were observed in primary visual cortex (V1) of monkeys when they viewed coloured stimuli under conditions which were not part of a training paradigm. No oscillatory modulations were detected in simultaneously recorded spike trains,

  6. Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1984-01-01

    The purpose of this investigation was to determine the relationship between the repetition rate of a simple sensory stimulus and regional cerebral blood flow (rCBF) in the human brain. Positron emission tomography (PET), using intravenously administered H 2 ( 15 )O as the diffusible blood-flow tracer, was employed for all CBF measurements. The use of H 2 ( 15 )O with PET allowed eight CBF measurements to be made in rapid sequence under multiple stimulation conditions without removing the subject from the tomograph. Nine normal volunteers each underwent a series of eight H2( 15 )O PET measurements of CBF. Initial and final scans were made during visual deprivation. The six intervening scans were made during visual activation with patterned-flash stimuli given in random order at 1.0-, 3.9-, 7.8-, 15.5-, 33.1-, and 61-Hz repetition rates. The region of greatest rCBF increase was determined. Within this region the rCBF was determined for every test condition and then expressed as the percentage change from the value of the initial unstimulated scan (rCBF% delta). In every subject, striate cortex rCBF% delta varied systematically with stimulus rate. Between 0 and 7.8 Hz, rCBF% delta was a linear function of stimulus repetition rate. The rCBF response peaked at 7.8 Hz and then declined. The rCBF% delta during visual stimulation was significantly greater than that during visual deprivation for every stimulus rate except 1.0 Hz. The anatomical localization of the region of peak rCBF response was determined for every subject to be the mesial occipital lobes along the calcarine fissure, primary visual cortex. Stimulus rate is a significant determinant of rCBF response in the visual cortex. Investigators of brain responses to selective activation procedures should be aware of the potential effects of stimulus rate on rCBF and other measurements of cerebral metabolism

  7. Mnemonic neuronal activity in somatosensory cortex.

    Science.gov (United States)

    Zhou, Y D; Fuster, J M

    1996-09-17

    Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.

  8. Effects of acetylcholine on neuronal properties in entorhinal cortex

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    James G Heys

    2012-07-01

    Full Text Available The entorhinal cortex receives prominent cholinergic innervation from the medial septum and the vertical limb of the diagonal band of Broca (MSDB. To understand how cholinergic neurotransmission can modulate behavior, research has been directed towards identification of the specific cellular mechanisms in entorhinal cortex that can be modulated through cholinergic activity. This review focuses on intrinsic cellular properties of neurons in entorhinal cortex that may underlie functions such as working memory, spatial processing and episodic memory. In particular, the study of stellate cells in medial entorhinal has resulted in discovery of correlations between physiological properties of these neurons and properties of the unique spatial representation that is demonstrated through unit recordings of neurons in medial entorhinal cortex from awake-behaving animals. A separate line of investigation has demonstrated persistent firing behavior among neurons in entorhinal cortex that is enhanced by cholinergic activity and could underlie working memory. There is also evidence that acetylcholine plays a role in modulation of synaptic transmission that could also enhance mnemonic function in entorhinal cortex. Finally, the local circuits of entorhinal cortex demonstrate a variety of interneuron physiology, which is also subject to cholinergic modulation. Together these effects alter the dynamics of entorhinal cortex to underlie the functional role of acetylcholine in memory.

  9. Spindle neurons of the human anterior cingulate cortex

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    Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

  10. Responses of primate frontal cortex neurons during natural vocal communication

    OpenAIRE

    Miller, Cory T.; Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

    2015-01-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed ...

  11. Diverse coupling of neurons to populations in sensory cortex.

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    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  12. Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

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    Anderson, B; Harvey, T

    1996-06-07

    Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

  13. Mirror neurons: reflecting on the motor cortex and spinal cord.

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    Schieber, Marc H

    2013-02-18

    Neurons in the monkey motor cortex that project to the spinal cord to control particular muscle contractions and movements have been found to discharge again while the monkey simply watches another primate make similar movements: monkey see; monkey not do. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Sensory cortex lesion triggers compensatory neuronal plasticity.

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    Depner, Manfred; Tziridis, Konstantin; Hess, Andreas; Schulze, Holger

    2014-05-01

    Lesions to the human brain often cause dramatic impairments in the life of patients because of the very limited capacity of the mammalian nervous system to regenerate. On the other hand, neuronal tissue has a high capacity to reorganize itself so that loss of function due to brain damage may be compensated through neuroplastic reorganization of undamaged tissue in brain regions adjacent or contralateral to the lesion site. In this study we investigated the effect of serial lesions of the auditory cortices (AC) in both hemispheres of Mongolian gerbils on discrimination performance for fast amplitude modulated tones (AM). Healthy animals were trained to discriminate two fast AM, an ability that has previously been shown to critically depend on cortical processing. Their ability to maintain significant discrimination performance was retested after unilateral AC lesion, and again after lesion of the contralateral AC, with 15 days of continuing training in between the two lesions. After bilateral cortical ablation of both AC and 45 days of training the animals show no change in pure tone detection threshold as measured with modulation of the acoustic startle reflex which has been shown to rely on subcortical structures. In contrast to simultaneous bilateral ablation of AC that results in complete loss of AM discrimination ability in this paradigm we found compensatory plasticity that seems to be triggered by unilateral cortical ablation with subsequent training and that is able to almost fully compensate for the lost cortical functions. Our results demonstrate that AM discrimination ability that normally depends on AC may be transferred to other brain regions when the brain has time to activate compensatory plasticity between the lesions of the two AC hemispheres. For this process to take place obviously one intact AC hemisphere is needed. This finding may open perspectives for new therapeutic strategies that may alleviate the impairments after multiple ischemic strokes.

  15. How do auditory cortex neurons represent communication sounds?

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    Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris; Laudanski, Jonathan; Occelli, Florian; Edeline, Jean-Marc

    2013-11-01

    A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 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.

  17. Neuronal activity in somatosensory cortex related to tactile exploration

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    Fortier-Poisson, Pascal

    2015-01-01

    The very light contact forces (∼0.60 N) applied by the fingertips during tactile exploration reveal a clearly optimized sensorimotor strategy. To investigate the cortical mechanisms involved with this behavior, we recorded 230 neurons in the somatosensory cortex (S1), as two monkeys scanned different surfaces with the fingertips in search of a tactile target without visual feedback. During the exploration, the monkeys, like humans, carefully controlled the finger forces. High-friction surfaces offering greater tangential shear force resistance to the skin were associated with decreased normal contact forces. The activity of one group of neurons was modulated with either the normal or tangential force, with little or no influence from the orthogonal force component. A second group responded to kinetic friction or the ratio of tangential to normal forces rather than responding to a specific parameter, such as force magnitude or direction. A third group of S1 neurons appeared to respond to particular vectors of normal and tangential force on the skin. Although 45 neurons correlated with scanning speed, 32 were also modulated by finger forces, suggesting that forces on the finger should be considered as the primary parameter encoding the skin compliance and that finger speed is a secondary parameter that co-varies with finger forces. Neurons (102) were also tested with different textures, and the activity of 62 of these increased or decreased in relation to the surface friction. PMID:26467519

  18. Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

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    Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

    2016-01-01

    The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

  19. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

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    Sally A Marik

    2010-06-01

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  20. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

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    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

  1. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

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    Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

    2013-01-01

    How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later

  2. Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

    Directory of Open Access Journals (Sweden)

    Suzana eHerculano-Houzel

    2013-10-01

    Full Text Available How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005 to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes – with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (see companion paper and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity

  3. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

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    Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

    2014-01-01

    Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261

  4. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    Directory of Open Access Journals (Sweden)

    Rodrigo eSiqueira Kazu

    2014-11-01

    Full Text Available Quantitative analysis of the cellular composition of rodent, primate, insectivore and afrotherian brains has shown that nonneuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share nonneuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are however distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex.

  5. Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation

    International Nuclear Information System (INIS)

    Miller, M.W.

    1988-01-01

    Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation

  6. Number and laminar distribution of neurons in a thalamocortical projection column of rat vibrissal cortex

    NARCIS (Netherlands)

    Meyer, H.S.; Wimmer, V.C.; Oberlaender, M.; de Kock, C.P.J.; Sakmann, B.; Helmstaedter, M.

    2010-01-01

    This is the second article in a series of three studies that investigate the anatomical determinants of thalamocortical (TC) input to excitatory neurons in a cortical column of rat primary somatosensory cortex (S1). Here, we report the number and distribution of NeuN-positive neurons within the C2,

  7. Excitatory Neuronal Hubs Configure Multisensory Integration of Slow Waves in Association Cortex

    Directory of Open Access Journals (Sweden)

    Satoshi Kuroki

    2018-03-01

    Full Text Available Summary: Multisensory integration (MSI is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60 expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI. Video Abstract: : Kuroki et al. performed cell-type-specific, wide-field FRET-based calcium imaging to visualize cortical network activity induced by multisensory inputs. They observed phase-locking of cortical slow waves in excitatory neuronal hubs in association cortical areas that may underlie multisensory integration. Keywords: wide-field calcium imaging, multisensory integration, cortical slow waves, association cortex, phase locking, fluorescence resonance energy transfer, spontaneous activity, excitatory neuron, inhibitory neuron, mouse

  8. Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex.

    Science.gov (United States)

    Benedetti, B; Matyash, V; Kettenmann, H

    2011-03-01

    Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking' neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex.

  9. Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex

    Science.gov (United States)

    Benedetti, B; Matyash, V; Kettenmann, H

    2011-01-01

    Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking’ neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex. PMID:21224221

  10. Computational modeling of direct neuronal recruitment during intracortical microstimulation in somatosensory cortex

    Science.gov (United States)

    Overstreet, C. K.; Klein, J. D.; Helms Tillery, S. I.

    2013-12-01

    Objective. Electrical stimulation of cortical tissue could be used to deliver sensory information as part of a neuroprosthetic device, but current control of the location, resolution, quality, and intensity of sensations elicited by intracortical microstimulation (ICMS) remains inadequate for this purpose. One major obstacle to resolving this problem is the poor understanding of the neural activity induced by ICMS. Even with new imaging methods, quantifying the activity of many individual neurons within cortex is difficult. Approach. We used computational modeling to examine the response of somatosensory cortex to ICMS. We modeled the axonal arbors of eight distinct morphologies of interneurons and seven types of pyramidal neurons found in somatosensory cortex and identified their responses to extracellular stimulation. We then combined these axonal elements to form a multi-layered slab of simulated cortex and investigated the patterns of neural activity directly induced by ICMS. Specifically we estimated the number, location, and variety of neurons directly recruited by stimulation on a single penetrating microelectrode. Main results. The population of neurons activated by ICMS was dependent on both stimulation strength and the depth of the electrode within cortex. Strikingly, stimulation recruited interneurons and pyramidal neurons in very different patterns. Interneurons are primarily recruited within a dense, continuous region around the electrode, while pyramidal neurons were recruited in a sparse fashion both near the electrode and up to several millimeters away. Thus ICMS can lead to an unexpectedly complex spatial distribution of firing neurons. Significance. These results lend new insights to the complexity and range of neural activity that can be induced by ICMS. This work also suggests mechanisms potentially responsible for the inconsistency and unnatural quality of sensations initiated by ICMS. Understanding these mechanisms will aid in the design of

  11. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

    Science.gov (United States)

    Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

    2014-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

  12. Active Percolation Analysis of Pyramidal Neurons of Somatosensory Cortex:

    Science.gov (United States)

    Costa, Luciano Da Fontoura; Barbosa, Marconi Soares; Schierwagen, Andreas; Alpár, Alán; Gärtner, Ulrich; Arendt, Thomas

    This article describes the investigation of morphological variations among two sets of neuronal cells, namely a control group of wild type mouse cells and a group of cells of a transgenic line. Special attention is given to singular points in the neuronal structure, namely the branching points and extremities of the dendritic processes. The characterization of the spatial distribution of such points is obtained by using a recently reported morphological technique based on forced percolation and window-size compensation, which is particularly suited to the analysis of scattered points, presenting several coexisting densities. Different dispersions were identified in our statistical analysis, suggesting that the transgenic line of neurons is characterized by a more pronounced morphological variation. A classification scheme based on a canonical discriminant function was also considered in order to identify the morphological differences.

  13. Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

    Science.gov (United States)

    Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

  14. Morphometric characteristics of neuropeptide Y immunoreactive neurons in cortex of human inferior parietal lobule.

    Science.gov (United States)

    Krivokuća, Dragan; Puskas, Laslo; Puskas, Nela; Erić, Mirela

    2010-03-01

    The aim of this study was to demonstrate and precisely define the morphology of neurons immunoreactive to neuropeptide Y (NPY) in cortex of human inferior parietal lobule (IPL). Five human brains were used for immunohistochemical investigation of the shape and laminar distribution of NPY neurons in serial section in the supramarginal and angular gyrus. Immunoreactivity to NPY was detected in all six layers of the cortex of human IPL. However a great number of NPY immunoreactive neurons were found in the white matter under the IPL cortex. The following types of NPY immunoreactive neurons were found: Cajal-Retzius, pyramidal, inverted pyramidal, "double bouquet" (bitufted), rare type 6, multipolar nonspinous, bipolar, voluminous "basket", and chandelier cells. These informations about morphometric characteristics of NPY immunoreactive neurons in cortical layers, together with morphometric data taken from brains having schizophrenia or Alzheimer's-type dementia may contribute to better understanding patogenesis of these neurological diseases. The finding of Cajal-Retzius neurons immunoreactive to NPY points to the need for further investigations because of great importance of these cells in neurogenesis and involvement in mentioned diseases instead of their rarity.

  15. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  16. Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates.

    Science.gov (United States)

    Jacobs, Bob; Johnson, Nicholas L; Wahl, Devin; Schall, Matthew; Maseko, Busisiwe C; Lewandowski, Albert; Raghanti, Mary A; Wicinski, Bridget; Butti, Camilla; Hopkins, William D; Bertelsen, Mads F; Walsh, Timothy; Roberts, John R; Reep, Roger L; Hof, Patrick R; Sherwood, Chet C; Manger, Paul R

    2014-01-01

    Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee), carnivores (Siberian tiger, clouded leopard), cetartiodactyls (humpback whale, giraffe) and primates (human, common chimpanzee). Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317) of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant) and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967) and rodents (Palay and Chan-Palay, 1974), although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.

  17. Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates

    Directory of Open Access Journals (Sweden)

    Bob eJacobs

    2014-04-01

    Full Text Available Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee, carnivores (Siberian tiger, clouded leopard, cetartiodactyls (humpback whale, giraffe and primates (human, common chimpanzee. Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317 of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967 and rodents (Palay and Chan-Palay, 1974, although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.

  18. [Effect of nootropic agents on impulse activity of cerebral cortex neurons].

    Science.gov (United States)

    Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

    2001-01-01

    The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

  19. Morphometric Plasticity of Nitric Oxide Containing Neurons in the Barrel Cortex of De-whiskered Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Afarinesh

    2015-04-01

    Full Text Available Background: The rodent somatosensory barrel cortex is an ideal model to examine the effect of experience-dependent plasticity on developing brain circuitry. Sensory deprivation such as whisker deprivation may affect neuroanatomical aspects of the brain during developmental processes. The present study designed to investigate the possible effects of whisker deprivation on the morphometric characteristics of NADPH-d positive neurons in the barrel field cortex of adolescent rats.Materials and Methods: Pups were divided into the intact (n=4 and whisker-deprived groups (n=4. In whisker-deprived group, the total whiskers of subjects were trimmed every other day from postnatal day (PND 0 to PND 60. NADPH-d histochemistry reaction was processed to quantitatively analyze the feature of NADPH-d containing neurons of barrel cortex.Results: Our results showed that the number of NADPH-d positive neurons remained unchanged in whisker-deprived group compared to controls. The mean soma diameter, dendritic length and the number of 3rd order processes were significantly decreased in the whisker-deprived rats (p<0.05.Conclusion: Our results indicate that postnatal whisker deprivation possibly alter NADPH-d/NOS neuronal features in the barrel cortex. The functional implications of these data may relate the plasticity of synaptic receptive field and developmental brain circuits.

  20. [The Effect of Chronic Intermittent Hypoxia on Cognitive Function and Prefrontal Cortex Neurons in Rats].

    Science.gov (United States)

    Li, Li-qun; Cao, Jin-li; Li, Lin; Han, Xiao-qing; Wang, Hong-yang; Liang, Xiao-mei; Wang, Ling; Zhang, Min; Wang, Ya-nan; Duan, Li-jun

    2015-09-01

    To determine the effect of chronic intermittent hypoxia on cognitive function and prefrontal cortex neurons in rats. 48 adult male Wistar rats were randomly divided into two groups: control group and 50 mL/L intermittent hypoxia group (50 mL/L CIH). Rats in the CIH group were placed in the low oxygen tank, simulating intermittent hypoxia environment. At 7 d, 14 d, 21 d, and 28 d, the learning and memory ability of the rats was assessed with the Morris water maze (MWM) test; the expressions of cysteinyl aspartate specific protease (caspase)-8 protein in their prefrontal cortex were determined using Western blot method; the apoptosis of neurons was detected by the TdT mediated UTP nick end labeling (TUNEL) method. Compared with the controls, the CIH rats had significantly prolonged escape latency at 14 d, 21 d, and 28 d (Phypoxia (Phypoxia (Phypoxia can lead to pathological changes of frontal,cortex of rats, possibly

  1. Novel visual stimuli activate a population of neurons in the primate orbitofrontal cortex.

    Science.gov (United States)

    Rolls, Edmund T; Browning, Andrew S; Inoue, Kazuo; Hernadi, Istvan

    2005-09-01

    Neurons were found in the rhesus macaque anterior orbitofrontal cortex that respond to novel but not to familiar visual stimuli. Some of these neurons responded to all novel stimuli, and others to only a subset (e.g., to novel faces). The neurons have no responses to familiar reward- or punishment-associated visual stimuli, nor to taste, olfactory or somatosensory inputs. The responses of the neurons typically habituated with repeated presentations of a novel stimulus, and five presentations each 1s was the median number for the response to reach half-maximal. The neurons did not respond to stimuli which had been novel and shown a few times on the previous day, indicating that the neurons were involved in long-term memory. The median latency of the neuronal responses was 120 ms. The median spontaneous firing rate was 1.3 spikes/s, and the median response to novel visual stimuli was 6.0 spikes/s. These findings indicate that the long-term memory for visual stimuli is information that is represented in a region of the primate anterior orbitofrontal cortex.

  2. Functional diversity of supragranular GABAergic neurons in the barrel cortex

    Directory of Open Access Journals (Sweden)

    Luc J Gentet

    2012-08-01

    Full Text Available Although the neocortex forms a distributed system comprised of several functional areas, its vertical columnar organization is largely conserved across areas and species, suggesting the existence of a canonical neocortical microcircuit. In order to elucidate the principles governing the organization of such a cortical diagram, a detailed understanding of the dynamics binding different types of cortical neurons into a coherent algorithm is essential. Within this complex circuitry, GABAergic interneurons, while forming approximately only 15-20% of all cortical neurons, appear critical in maintaining a dynamic balance between excitation and inhibition. Despite their importance, cortical GABAergic neurons have not been extensively studied in vivo and their precise role in shaping the local microcircuit sensory response still remains to be determined. Their paucity, combined with their molecular, anatomical and physiological diversity, has made it difficult to even establish a consensual nomenclature.However, recent technological advances in microscopy and mouse genetics have fostered a renewed interest in neocortical interneurons by putting them within visible reach of experimenters. The anatomically well-defined whisker-to-barrel pathway of the rodent is particularly amenable to studies attempting to link cortical circuit dynamics to behavior. To each whisker corresponds a discrete cortical unit equivalent to a single column, specialized in the encoding and processing of the sensory information it receives. In this review, we will focus on the functional role that each subtype of supragranular GABAergic neuron embedded within such a single neocortical unit may play in shaping the dynamics of the local circuit during somatosensory integration.

  3. Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex.

    Science.gov (United States)

    Proulx, Eliane; Piva, Matthew; Tian, Michael K; Bailey, Craig D C; Lambe, Evelyn K

    2014-04-01

    Cholinergic modulation of prefrontal cortex is essential for attention. In essence, it focuses the mind on relevant, transient stimuli in support of goal-directed behavior. The excitation of prefrontal layer VI neurons through nicotinic acetylcholine receptors optimizes local and top-down control of attention. Layer VI of prefrontal cortex is the origin of a dense feedback projection to the thalamus and is one of only a handful of brain regions that express the α5 nicotinic receptor subunit, encoded by the gene chrna5. This accessory nicotinic receptor subunit alters the properties of high-affinity nicotinic receptors in layer VI pyramidal neurons in both development and adulthood. Studies investigating the consequences of genetic deletion of α5, as well as other disruptions to nicotinic receptors, find attention deficits together with altered cholinergic excitation of layer VI neurons and aberrant neuronal morphology. Nicotinic receptors in prefrontal layer VI neurons play an essential role in focusing attention under challenging circumstances. In this regard, they do not act in isolation, but rather in concert with cholinergic receptors in other parts of prefrontal circuitry. This review urges an intensification of focus on the cellular mechanisms and plasticity of prefrontal attention circuitry. Disruptions in attention are one of the greatest contributing factors to disease burden in psychiatric and neurological disorders, and enhancing attention may require different approaches in the normal and disordered prefrontal cortex.

  4. Local-circuit phenotypes of layer 5 neurons in motor-frontal cortex of YFP-H mice

    Directory of Open Access Journals (Sweden)

    Jianing Yu

    2008-12-01

    Full Text Available Layer 5 pyramidal neurons comprise an important but heterogeneous group of cortical projection neurons. In motor-frontal cortex, these neurons are centrally involved in the cortical control of movement. Recent studies indicate that local excitatory networks in mouse motor-frontal cortex are dominated by descending pathways from layer 2/3 to 5. However, those pathways were identified in experiments involving unlabeled neurons in wild type mice. Here, to explore the possibility of class-specific connectivity in this descending pathway, we mapped the local sources of excitatory synaptic input to a genetically labeled population of cortical neurons: YFP-positive layer 5 neurons of YFP-H mice. We found, first, that in motor cortex, YFP-positive neurons were distributed in a double blade, consistent with the idea of layer 5B having greater thickness in frontal neocortex. Second, whereas unlabeled neurons in upper layer 5 received their strongest inputs from layer 2, YFP-positive neurons in the upper blade received prominent layer 3 inputs. Third, YFP-positive neurons exhibited distinct electrophysiological properties, including low spike frequency adaptation, as reported previously. Our results with this genetically labeled neuronal population indicate the presence of distinct local-circuit phenotypes among layer 5 pyramidal neurons in mouse motor-frontal cortex, and present a paradigm for investigating local circuit organization in other genetically labeled populations of cortical neurons.

  5. Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Dahlke, Carolin; Saberi, Darius; Ott, Bastian

    2015-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of the upper and lower motor neurons, characterized by rapid progressive weakness, muscle atrophy, dysarthria, dysphagia, and dyspnea. Whereas the exact cause of ALS remains uncertain, the wobbler mouse (phenotype...... WR; genotype wr/wr) equally develops a progressive degeneration of motor neurons in the spinal cord and motor cortex with striking similarities to sporadic human ALS, suggesting the possibility of a common pathway to cell death. Methods With the aid of immunohistochemistry, confocal laser scanning...... microscopy, and transmission electron microscopy techniques, we analyze the proliferation behavior of microglial cells and astrocytes. We also investigate possible motor neuron death in the mouse motor cortex at different stages of the wobbler disease, which so far has not received much attention. Results...

  6. Influence of inter-field communication on neuronal response synchrony across auditory cortex.

    Science.gov (United States)

    Carrasco, Andres; Lomber, Stephen G

    2013-10-01

    Sensory information is encoded by cortical neurons in the form of synaptic discharge time and rate level. These neuronal codes generate response patterns across cell assemblies that are crucial to various cognitive functions. Despite pivotal information about structural and cognitive factors involved in the generation of synchronous neuronal responses such as stimulus context, attention, age, cortical depth, sensory experience, and receptive field properties, the influence of cortico-cortical connectivity on the emergence of neuronal response patterns is poorly understood. The present investigation assesses the role of cortico-cortical connectivity in the modulation of neuronal discharge synchrony across auditory cortex cell-assemblies. Acute single-unit recording techniques in combination with reversible cooling deactivation procedures were used in the domestic cat (Felis catus). Recording electrodes were positioned across primary and non-primary auditory fields and neuronal activity was measured before, during, and after synaptic deactivation of adjacent cortical regions in the presence of acoustic stimulation. Cross-correlation functions of simultaneously recorded units were generated and changes in response synchrony levels across cooling conditions were measured. Data analyses revealed significant decreases in response time coincidences between cortical neurons during periods of cortical deactivation. Collectively, the results of the present investigation demonstrate that cortical neurons participate in the modulation of response synchrony levels across neuronal assemblies of primary and non-primary auditory fields. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. The pyramidal neuron in cerebral cortex following prenatal X-irradiation

    International Nuclear Information System (INIS)

    Donoso, J.A.; Norton, S.

    1982-01-01

    Pregnant rats were subjected to whole body X-irradiation amounting to 125 R, on gestational day 15. Cortical pyramidal neurons were examined in irradiated and control offspring at 4 weeks and 4 to 6 months postnatally. All gestationally irradiated rats developed ectopic cortex located below the corpus callosum adjacent to the caudate nucleus in the forebrain. With the rapid Golgi stain, counts were made of dendritic spines on the apical dendrites of layer 5 pyramidal cells in the normally-located cortex and compared with similar neurons in the ectopias. Dendritic spines were present on all pyramidal cells but spines were more sparse on ectopic pyramidal cells. Electron microscopic examination of ectopic and layered cortex in irradiated rats showed axodendritic synapses on the spines and shafts of the dendrites and axosomatic synapses, all of which were indistinguishable morphologically from synapses in control cortex. As a result of the observations made with the light and electron microscopes, it is concluded that the ectopic cortex may contain functional cells in spite of the abnormal location of the tissue

  8. Neuronal correlate of pictorial short-term memory in the primate temporal cortexYasushi Miyashita

    Science.gov (United States)

    Miyashita, Yasushi; Chang, Han Soo

    1988-01-01

    It has been proposed that visual-memory traces are located in the temporal lobes of the cerebral cortex, as electric stimulation of this area in humans results in recall of imagery1. Lesions in this area also affect recognition of an object after a delay in both humans2,3 and monkeys4-7 indicating a role in short-term memory of images8. Single-unit recordings from the temporal cortex have shown that some neurons continue to fire when one of two or four colours are to be remembered temporarily9. But neuronal responses selective to specific complex objects10-18 , including hands10,13 and faces13,16,17, cease soon after the offset of stimulus presentation10-18. These results led to the question of whether any of these neurons could serve the memory of complex objects. We report here a group of shape-selective neurons in an anterior ventral part of the temporal cortex of monkeys that exhibited sustained activity during the delay period of a visual short-term memory task. The activity was highly selective for the pictorial information to be memorized and was independent of the physical attributes such as size, orientation, colour or position of the object. These observations show that the delay activity represents the short-term memory of the categorized percept of a picture.

  9. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

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    Yuri Gonchar

    2008-03-01

    Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

  10. Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals

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    Yohei Shinmyo

    2017-08-01

    Full Text Available Folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. However, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. By combining in utero electroporation and the CRISPR/Cas9 system, we succeeded in efficient gene knockout of Cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencephalic brains of ferrets. We show that Cdk5 knockout in the ferret cerebral cortex markedly impaired cortical folding. Furthermore, the results obtained from the introduction of dominant-negative Cdk5 into specific cortical layers suggest that Cdk5 function in upper-layer neurons is more important for cortical folding than that in lower-layer neurons. Cdk5 inhibition induced severe migration defects in cortical neurons. Taken together, our findings suggest that the appropriate positioning of upper-layer neurons is critical for cortical folding.

  11. Neuron Types in the Presumptive Primary Somatosensory Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Stimpson, Cheryl D; Gupta, Kanika; Raghanti, Mary Ann; Hof, Patrick R; Reep, Roger L; Sherwood, Chet C

    2015-01-01

    Within afrotherians, sirenians are unusual due to their aquatic lifestyle, large body size and relatively large lissencephalic brain. However, little is known about the neuron type distributions of the cerebral cortex in sirenians within the context of other afrotherians and aquatic mammals. The present study investigated two cortical regions, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2), in the presumptive primary somatosensory cortex (S1) in Florida manatees (Trichechus manatus latirostris) to characterize cyto- and chemoarchitecture. The mean neuron density for both cortical regions was 35,617 neurons/mm(3) and fell within the 95% prediction intervals relative to brain mass based on a reference group of afrotherians and xenarthrans. Densities of inhibitory interneuron subtypes labeled against calcium-binding proteins and neuropeptide Y were relatively low compared to afrotherians and xenarthrans and also formed a small percentage of the overall population of inhibitory interneurons as revealed by GAD67 immunoreactivity. Nonphosphorylated neurofilament protein-immunoreactive (NPNFP-ir) neurons comprised a mean of 60% of neurons in layer V across DL1 and CL2. DL1 contained a higher percentage of NPNFP-ir neurons than CL2, although CL2 had a higher variety of morphological types. The mean percentage of NPNFP-ir neurons in the two regions of the presumptive S1 were low compared to other afrotherians and xenarthrans but were within the 95% prediction intervals relative to brain mass, and their morphologies were comparable to those found in other afrotherians and xenarthrans. Although this specific pattern of neuron types and densities sets the manatee apart from other afrotherians and xenarthrans, the manatee isocortex does not appear to be explicitly adapted for an aquatic habitat. Many of the features that are shared between manatees and cetaceans are also shared with a diverse array of terrestrial mammals and likely represent highly conserved

  12. 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

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

    Science.gov (United States)

    Hrvoj-Mihic, Branka; Hanson, Kari L; Lew, Caroline H; Stefanacci, Lisa; Jacobs, Bob; Bellugi, Ursula; Semendeferi, Katerina

    2017-01-01

    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 neurodevelopmental disorders

  14. Primary visual cortex volume and total neuron number are reduced in schizophrenia

    DEFF Research Database (Denmark)

    Dorph-Petersen, Karl-Anton; Pierri, Joseph H.; Wu, Qiang

    2007-01-01

    with schizophrenia reported an increased density of neurons in the primary visual cortex (Brodmann's area 17, BA17). The observed changes in visual processing may thus be reflected in structural changes in the circuitry of BA17. To characterize the structural changes further we used stereological methods based...... area allocated to primary visual perception. This finding suggests the existence of a schizophrenia-related change in cortical parcellation...

  15. Excitatory Neuronal Hubs Configure Multisensory Integration of Slow Waves in Association Cortex.

    Science.gov (United States)

    Kuroki, Satoshi; Yoshida, Takamasa; Tsutsui, Hidekazu; Iwama, Mizuho; Ando, Reiko; Michikawa, Takayuki; Miyawaki, Atsushi; Ohshima, Toshio; Itohara, Shigeyoshi

    2018-03-13

    Multisensory integration (MSI) is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60) expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI. VIDEO ABSTRACT. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Adaptation in the visual cortex: influence of membrane trajectory and neuronal firing pattern on slow afterpotentials.

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    Vanessa F Descalzo

    Full Text Available The input/output relationship in primary visual cortex neurons is influenced by the history of the preceding activity. To understand the impact that membrane potential trajectory and firing pattern has on the activation of slow conductances in cortical neurons we compared the afterpotentials that followed responses to different stimuli evoking similar numbers of action potentials. In particular, we compared afterpotentials following the intracellular injection of either square or sinusoidal currents lasting 20 seconds. Both stimuli were intracellular surrogates of different neuronal responses to prolonged visual stimulation. Recordings from 99 neurons in slices of visual cortex revealed that for stimuli evoking an equivalent number of spikes, sinusoidal current injection activated a slow afterhyperpolarization of significantly larger amplitude (8.5 ± 3.3 mV and duration (33 ± 17 s than that evoked by a square pulse (6.4 ± 3.7 mV, 28 ± 17 s; p<0.05. Spike frequency adaptation had a faster time course and was larger during plateau (square pulse than during intermittent (sinusoidal depolarizations. Similar results were obtained in 17 neurons intracellularly recorded from the visual cortex in vivo. The differences in the afterpotentials evoked with both protocols were abolished by removing calcium from the extracellular medium or by application of the L-type calcium channel blocker nifedipine, suggesting that the activation of a calcium-dependent current is at the base of this afterpotential difference. These findings suggest that not only the spikes, but the membrane potential values and firing patterns evoked by a particular stimulation protocol determine the responses to any subsequent incoming input in a time window that spans for tens of seconds to even minutes.

  17. DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.

    Science.gov (United States)

    GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreact...

  18. How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

    LENUS (Irish Health Repository)

    Setty, Yaki

    2011-09-30

    Abstract Background Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise

  19. Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons.

    Science.gov (United States)

    Prsa, Mario; Galiñanes, Gregorio L; Huber, Daniel

    2017-02-22

    Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex. This artificial signal was necessary to rapidly learn to increase the conditioned activity, detect correct performance, and maintain the learned behavior. Population imaging in M1 revealed that learning-related activity changes are observed in the conditioned cell only, which highlights the functional potential of individual neurons in the neocortex. Our findings demonstrate the capacity of animals to use an artificially induced cortical channel in a behaviorally relevant way and reveal the remarkable speed and specificity at which this can occur. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Duration sensitivity of neurons in the primary auditory cortex of albino mouse.

    Science.gov (United States)

    Wang, Xin; Qi, Qiaozhen; Huang, Caifei; Chomiak, Taylor; Luo, Feng

    2016-02-01

    Many neurons in the central auditory system of a number of species have been found to be sensitive to the duration of sound stimuli. While previous studies have shown that γ-aminobutyric acid (GABA)-ergic inhibitory input is important for duration sensitivity in the inferior colliculus (IC), it is still unknown whether (GABA)-ergic inhibitory input plays an important role in generating duration sensitivity in the cortex. Using free-field sound stimulation and in vivo extracellular recording, we investigated duration sensitivity in primary auditory cortical (AI) neurons of the Nembutal anesthetized albino mouse (Mus musculus, Km) and examined the effect of the GABAA receptor antagonist bicuculline on AI neuron duration sensitivity. A total of 63 duration tuning curves were measured in AI neurons. Of these, 44% (28/63) exhibited duration sensitive responses, while 43% (27/63) lacked duration sensitivity. The remaining 13% (8/63) exhibited long-pass properties likely reflecting both duration sensitive and insensitive features. We found that duration sensitive neurons had shorter first spike latency (FSL) and longer firing duration (FD) when stimulated with best duration (p 0.05). Furthermore, 60% (6/10) of duration sensitive neurons and 75% (3/4) long-pass neurons lost duration sensitivity following bicuculline application. Taken together, our results show that cortical neurons in the albino mouse are sensitive to sound duration, and that GABAergic inhibition may play an important role in the formation of de novo duration sensitivity in AI. The possible mechanism and behavioral significance of duration sensitivity in AI neurons is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex

    Science.gov (United States)

    McCreery, Douglas; Cogan, Stuart; Kane, Sheryl; Pikov, Victor

    2016-06-01

    Objective. To quantify relations between the neuronal activity recorded with chronically-implanted intracortical microelectrodes and the histology of the surrounding tissue, using radial distance from the tip sites and time after array implantation as parameters. Approach. ‘Utah’-type intracortical microelectrode arrays were implanted into cats’ sensorimotor cortex for 275-364 days. The brain tissue around the implants was immuno-stained for the neuronal marker NeuN and for the astrocyte marker GFAP. Pearson’s product-moment correlations were used to quantify the relations between these markers and the amplitudes of the recorded neuronal action potentials (APs) and their signal-to-noise ratios (S/N). Main results. S/N was more stable over post-implant time than was AP amplitude, but its increased correlation with neuronal density after many months indicates ongoing loss of neurons around the microelectrodes. S/N was correlated with neuron density out to at least 140 μm from the microelectrodes, while AP amplitude was correlated with neuron density and GFAP density within ˜80 μm. Correlations between AP amplitude and histology markers (GFAP and NeuN density) were strongest immediately after implantation, while correlation between the neuron density and S/N was strongest near the time the animals were sacrificed. Unlike AP amplitude, there was no significant correlation between S/N and density of GFAP around the tip sites. Significance. Our findings indicate an evolving interaction between changes in the tissue surrounding the microelectrodes and the microelectrode’s electrical properties. Ongoing loss of neurons around recording microelectrodes, and the interactions between their delayed electrical deterioration and early tissue scarring around the tips appear to pose the greatest threats to the microelectrodes’ long-term functionality.

  2. Isolation of functionally active and highly purified neuronal mitochondria from human cortex.

    Science.gov (United States)

    Khattar, Nicolas K; Yablonska, Svitlana; Baranov, Sergei V; Baranova, Oxana V; Kretz, Eric S; Larkin, Timothy M; Carlisle, Diane L; Richardson, R Mark; Friedlander, Robert M

    2016-04-01

    Functional and structural properties of mitochondria are highly tissue and cell dependent, but isolation of highly purified human neuronal mitochondria is not currently available. We developed and validated a procedure to isolate purified neuronal mitochondria from brain tissue. The method combines Percoll gradient centrifugation to obtain synaptosomal fraction with nitrogen cavitation mediated synaptosome disruption and extraction of mitochondria using anti mitochondrial outer membrane protein antibodies conjugated to magnetic beads. The final products of isolation are non-synaptosomal mitochondria, which are a mixture of mitochondria isolated from different brain cells (i.e. neurons, astrocytes, oligodendrocytes, microglia) and synaptic mitochondria, which are of neuronal origin. This method is well suited for preparing functional mitochondria from human cortex tissue that is surgically extracted. The procedure produces mitochondria with minimal cytoplasmic contaminations that are functionally active based on measurements of mitochondrial respiration as well as mitochondrial protein import. The procedure requires approximately four hours for the isolation of human neuronal mitochondria and can also be used to isolate mitochondria from mouse/rat/monkey brains. This method will allow researchers to study highly enriched neuronal mitochondria without the confounding effect of cellular and organelle contaminants. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Refinement of neuronal synchronization with gamma oscillations in the medial prefrontal cortex after adolescence.

    Directory of Open Access Journals (Sweden)

    Julián de Almeida

    Full Text Available The marked anatomical and functional changes taking place in the medial prefrontal cortex (PFC during adolescence set grounds for the high incidence of neuropsychiatric disorders with adolescent onset. Although circuit refinement through synapse pruning may constitute the anatomical basis for the cognitive differences reported between adolescents and adults, a physiological correlate of circuit refinement at the level of neuronal ensembles has not been demonstrated. We have recorded neuronal activity together with local field potentials in the medial PFC of juvenile and adult mice under anesthesia, which allowed studying local functional connectivity without behavioral or sensorial interference. Entrainment of pyramidal neurons and interneurons to gamma oscillations, but not to theta or beta oscillations, was reduced after adolescence. Interneurons were synchronized to gamma oscillations across a wider area of the PFC than pyramidal neurons, and the span of interneuron synchronization was shorter in adults than juvenile mice. Thus, transition from childhood to adulthood is characterized by reduction of the strength and span of neuronal synchronization specific to gamma oscillations in the mPFC. The more restricted and weak ongoing synchronization in adults may allow a more dynamic rearrangement of neuronal ensembles during behavior and promote parallel processing of information.

  4. Target range-sensitive neurons in the auditory cortex of the mustache bat.

    Science.gov (United States)

    O'Neill, W E; Suga, N

    1979-01-05

    Echolocating bats determine distance to targets by the time delay between their emitted biosonar pulses and the returning echoes. By varying the delay between synthetic pulses and echoes in stimulus pairs at various repetition rates and durations, neurons have been found in the auditory cortex of the mustache bat (Pteronotus parnellii rubiginosus) which are sensitive to target range during the search, approach, and terminal phases of prey capture or landing. Two classes of range-sensitive neurons were found: (i) tracking neurons, whose best delay for response to an echo following the emitted pulse becomes shorter and narrower as the bat closes in on the target, and (ii) range-tuned neurons, whose best delay is constant, and which respond to the target only when it is within a certain narrow fixed range. Range-tuned neurons are specialized for processing echoes only during a particular period of the search, approach, or terminal phases of echolocation, and they provide support for a theory of ranging in bats that incorporates groups of neurons with a spectrum of preferred echo delays to detect target distance.

  5. 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

    The involvement of tachykinins in cortical function is poorly understood. To study the actions of neurokinin-3 (NK3) receptor activation in frontal cortex, whole cell patch clamp recordings were performed from pyramidal neurons in slices of cingulate cortex from juvenile gerbils. Senktide (500n...

  6. Muscarinic receptor activation enables persistent firing in pyramidal neurons from superficial layers of dorsal perirhinal cortex.

    Science.gov (United States)

    Navaroli, Vicky L; Zhao, Yanjun; Boguszewski, Pawel; Brown, Thomas H

    2012-06-01

    Persistent-firing neurons in the entorhinal cortex (EC) and the lateral nucleus of the amygdala (LA) continue to discharge long after the termination of the original, spike-initiating current. An emerging theory proposes that endogenous persistent firing helps support a transient memory system. This study demonstrated that persistent-firing neurons are also prevalent in rat perirhinal cortex (PR), which lies immediately adjacent to and is reciprocally connected with EC and LA. Several characteristics of persistent-firing neurons in PR were similar to those previously reported in LA and EC. Persistent firing in PR was enabled by the application of carbachol, a nonselective cholinergic agonist, and it was induced by injecting a suprathreshold current or by stimulating suprathreshold excitatory synaptic inputs to the neuron. Once induced, persistent firing lasted for seconds to minutes. Persistent firing could always be terminated by a sufficiently large and prolonged hyperpolarizing current; it was prevented by antagonists of muscarinic cholinergic receptors (mAChRs); and it was blocked by flufenamic acid. The latter has been suggested to inhibit a Ca(2+) -activated nonspecific cation conductance (G(CAN) ) that normally furnishes the sustained depolarization during persistent firing. In many PR neurons, the discharge rate during persistent firing was a graded function of depolarizing and/or hyperpolarizing inputs. Persistent firing was not prevented by blocking fast excitatory and inhibitory synaptic transmission, demonstrating that it can be generated endogenously. We suggest that persistent-firing neurons in PR, EC, LA, and certain other brain regions may cooperate in support of a transient-memory system. Copyright © 2011 Wiley Periodicals, Inc.

  7. Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

    Science.gov (United States)

    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

    The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

    International Nuclear Information System (INIS)

    Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

    2013-01-01

    Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

  9. Effects of continuous low-dose prenatal irradiation on neuronal migration in mouse cerebral cortex

    International Nuclear Information System (INIS)

    Hyodo-Taguchi, Yasuko; Ishikawa, Yuji; Hirobe, Tomohisa; Fushiki, Shinji; Kinoshita, Chikako.

    1997-01-01

    We investigated the effects of continuous exposure to γ-rays during corticogenesis on the migration of neuronal cells in developing cerebral cortex. Pregnant mice were injected with 0.5 mg of bromodeoxyuridine (BrdU) on day 14 of gestation to label cells in the S phase. The mice were then exposed to 137 Cs γ-rays (dose rates of 0.1, 0.3, and 0.94 Gy/day) continuously for 3 days. Brains from 17-day-old embryos and from offspring at 3 and 8 weeks after birth were processed immunohistochemically to track the movements of BrdU-labeled cells. Comparative analyses of the distribution pattern of BrdU-labeled cells in the cerebral cortex revealed that the migration of neurons was delayed during the embryonic period in mice irradiated at 0.94 Gy/day, in 3-week-old mice, there was a significant difference in the distribution pattern of BrdU-labeled cells in the cerebral cortex between the mice irradiated prenatally and control, and in 8-week-old mice, there were no differences in the distribution pattern of BrdU-labeled cells between control and animals irradiated with 0.1 and 0.3 Gy/day. In contrast, in the animals irradiated with 0.94 Gy/day, the significant difference in the distribution pattern of the labeled cells relative to control was maintained. These results suggest that the migration of neuronal cells in mouse cerebral cortex is disturbed by continuous prenatal irradiation at low-dose and some modificational process occurred during the postnatal period. (author)

  10. Auditory and audio-vocal responses of single neurons in the monkey ventral premotor cortex.

    Science.gov (United States)

    Hage, Steffen R

    2018-03-20

    Monkey vocalization is a complex behavioral pattern, which is flexibly used in audio-vocal communication. A recently proposed dual neural network model suggests that cognitive control might be involved in this behavior, originating from a frontal cortical network in the prefrontal cortex and mediated via projections from the rostral portion of the ventral premotor cortex (PMvr) and motor cortex to the primary vocal motor network in the brainstem. For the rapid adjustment of vocal output to external acoustic events, strong interconnections between vocal motor and auditory sites are needed, which are present at cortical and subcortical levels. However, the role of the PMvr in audio-vocal integration processes remains unclear. In the present study, single neurons in the PMvr were recorded in rhesus monkeys (Macaca mulatta) while volitionally producing vocalizations in a visual detection task or passively listening to monkey vocalizations. Ten percent of randomly selected neurons in the PMvr modulated their discharge rate in response to acoustic stimulation with species-specific calls. More than four-fifths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of the vocalization. Based on these audio-vocal interactions, the PMvr might be well positioned to mediate higher order auditory processing with cognitive control of the vocal motor output to the primary vocal motor network. Such audio-vocal integration processes in the premotor cortex might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

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    Samantha J Fung

    Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

  12. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

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    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  13. Distinct Physiological Maturation of Parvalbumin-Positive Neuron Subtypes in Mouse Prefrontal Cortex.

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    Miyamae, Takeaki; Chen, Kehui; Lewis, David A; Gonzalez-Burgos, Guillermo

    2017-05-10

    Parvalbumin-positive (PV + ) neurons control the timing of pyramidal cell output in cortical neuron networks. In the prefrontal cortex (PFC), PV + neuron activity is involved in cognitive function, suggesting that PV + neuron maturation is critical for cognitive development. The two major PV + neuron subtypes found in the PFC, chandelier cells (ChCs) and basket cells (BCs), are thought to play different roles in cortical circuits, but the trajectories of their physiological maturation have not been compared. Using two separate mouse lines, we found that in the mature PFC, both ChCs and BCs are abundant in superficial layer 2, but only BCs are present in deeper laminar locations. This distinctive laminar distribution was observed by postnatal day 12 (P12), when we first identified ChCs by the presence of axon cartridges. Electrophysiology analysis of excitatory synapse development, starting at P12, showed that excitatory drive remains low throughout development in ChCs, but increases rapidly before puberty in BCs, with an earlier time course in deeper-layer BCs. Consistent with a role of excitatory synaptic drive in the maturation of PV + neuron firing properties, the fast-spiking phenotype showed different maturation trajectories between ChCs and BCs, and between superficial versus deep-layer BCs. ChC and BC maturation was nearly completed, via different trajectories, before the onset of puberty. These findings suggest that ChC and BC maturation may contribute differentially to the emergence of cognitive function, primarily during prepubertal development. SIGNIFICANCE STATEMENT Parvalbumin-positive (PV + ) neurons tightly control pyramidal cell output. Thus PV + neuron maturation in the prefrontal cortex (PFC) is crucial for cognitive development. However, the relative physiological maturation of the two major subtypes of PV + neurons, chandelier cells (ChCs) and basket cells (BCs), has not been determined. We assessed the maturation of ChCs and BCs in different

  14. Representation of visual scenes by local neuronal populations in layer 2/3 of mouse visual cortex

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    Bjorn M Kampa

    2011-12-01

    Full Text Available How are visual scenes encoded in local neural networks of visual cortex? In rodents, visual cortex lacks a columnar organization so that processing of diverse features from a spot in visual space could be performed locally by populations of neighboring neurons. To examine how complex visual scenes are represented by local microcircuits in mouse visual cortex we measured visually-evoked responses of layer 2/3 neuronal populations using 3D two-photon calcium imaging. Both natural and artificial movie scenes (10-s duration evoked distributed and sparsely organized responses in local populations of 70 to 150 neurons within the sampled volumes. About 50% of neurons showed calcium transients during visual scene presentation, of which about half displayed reliable temporal activation patterns. The majority of the reliably responding neurons were activated primarily by one of the four visual scenes applied. Consequently, single neurons performed poorly in decoding, which visual scene had been presented. In contrast, high levels of decoding performance (>80% were reached when considering population responses, requiring about 80 randomly picked cells or 20 reliable responders. Furthermore, reliable responding neurons tended to have neighbors sharing the same stimulus preference. Because of this local redundancy, it was beneficial for efficient scene decoding to read out activity from spatially distributed rather than locally clustered neurons. Our results suggest a population code in layer 2/3 of visual cortex, where the visual environment is dynamically represented in the activation of distinct functional sub-networks.

  15. Three counting methods agree on cell and neuron number in chimpanzee primary visual cortex

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    Daniel James Miller

    2014-05-01

    Full Text Available Determining the cellular composition of specific brain regions is crucial to our understanding of the function of neurobiological systems. It is therefore useful to identify the extent to which different methods agree when estimating the same properties of brain circuitry. In this study, we estimated the number of neuronal and non-neuronal cells in the primary visual cortex (area 17 or V1 of both hemispheres from a single chimpanzee. Specifically, we processed samples distributed across V1 of the right hemisphere after cortex was flattened into a sheet using two variations of the isotropic fractionator cell and neuron counting method. We processed the left hemisphere as serial brain slices for stereological investigation. The goal of this study was to evaluate the agreement between these methods in the most direct manner possible by comparing estimates of cell density across one brain region of interest in a single individual. In our hands, these methods produced similar estimates of the total cellular population (approximately 1 billion as well as the number of neurons (approximately 675 million in chimpanzee V1, providing evidence that both techniques estimate the same parameters of interest. In addition, our results indicate the strengths of each distinct tissue preparation procedure, highlighting the importance of attention to anatomical detail. In summary, we found that the isotropic fractionator and the stereological optical fractionator produced concordant estimates of the cellular composition of V1, and that this result supports the conclusion that chimpanzees conform to the primate pattern of exceptionally high packing density in V1. Ultimately, our data suggest that investigators can optimize their experimental approach by using any of these counting methods to obtain reliable cell and neuron counts.

  16. Human Cerebral Cortex Cajal-Retzius Neuron: Development, Structure and Function. A Golgi Study

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    Miguel eMarín-Padilla

    2015-02-01

    Full Text Available The development, morphology and possible functional activity of the Cajal-Retzius cell of the developing human cerebral cortex have been explored herein. The C-RC, of extracortical origin, is the essential neuron of the neocortex first lamina. It receives inputs from subcortical afferent fibers that reach the first lamina early in development. Although the origin and function of these original afferent fibers remain unknown, they target the first lamina sole neuron: the C-RC. The neuron’ orchestrates the arrival, size and stratification of all pyramidal neurons (from ependymal origin of the neocortex gray matter. Its axonic terminals spread radially and horizontally throughout the entire first lamina establishing contacts with the dendritic terminals of all gray matter pyramidal cells regardless of size, location and/or eventual functional roles. While the neuron axonic terminals spread radially and horizontally throughout the first lamina, the neuron’ bodies undergoes progressive developmental dilution and locating any of them in the adult brain become quite difficult. The neuron bodies are probably retained in the older regions of the developing neocortex while their axonic collaterals will spread throughout its more recent ones that, eventually, will represent the great majority of the brain surface. This will explain their bodies progressive dilution in the developing neocortex and, later, in the adult brain. Although quite difficult to locate the body of any of them, they have been described in the adult brain.

  17. Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences.

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    Knyazeva, Stanislava; Selezneva, Elena; Gorkin, Alexander; Aggelopoulos, Nikolaos C; Brosch, Michael

    2018-01-01

    This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman's population separation model of auditory streaming.

  18. Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences

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    Stanislava Knyazeva

    2018-01-01

    Full Text Available This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman’s population separation model of auditory streaming.

  19. Learning alters theta amplitude, theta-gamma coupling and neuronal synchronization in inferotemporal cortex

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    Nicol Alister U

    2011-06-01

    Full Text Available Abstract Background How oscillatory brain rhythms alone, or in combination, influence cortical information processing to support learning has yet to be fully established. Local field potential and multi-unit neuronal activity recordings were made from 64-electrode arrays in the inferotemporal cortex of conscious sheep during and after visual discrimination learning of face or object pairs. A neural network model has been developed to simulate and aid functional interpretation of learning-evoked changes. Results Following learning the amplitude of theta (4-8 Hz, but not gamma (30-70 Hz oscillations was increased, as was the ratio of theta to gamma. Over 75% of electrodes showed significant coupling between theta phase and gamma amplitude (theta-nested gamma. The strength of this coupling was also increased following learning and this was not simply a consequence of increased theta amplitude. Actual discrimination performance was significantly correlated with theta and theta-gamma coupling changes. Neuronal activity was phase-locked with theta but learning had no effect on firing rates or the magnitude or latencies of visual evoked potentials during stimuli. The neural network model developed showed that a combination of fast and slow inhibitory interneurons could generate theta-nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity in the model similar changes were produced as in inferotemporal cortex after learning. The model showed that these changes could potentiate the firing of downstream neurons by a temporal desynchronization of excitatory neuron output without increasing the firing frequencies of the latter. This desynchronization effect was confirmed in IT neuronal activity following learning and its magnitude was correlated with discrimination performance. Conclusions Face discrimination learning produces significant increases in both theta amplitude and the strength of theta-gamma coupling in the inferotemporal cortex

  20. Neuronal activity of somatosensory cortex in a cross-modal (visuo-haptic) memory task.

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    Zhou, Y D; Fuster, J M

    1997-10-01

    Studies have shown that in the monkey's associative cerebral cortex, cells undergo sustained activation of discharge while the animal retains information for a subsequent action. Recent work has revealed the presence of such "memory cells" in the anterior parietal cortex (Brodmann's areas 3a, 3b, 1, and 2)--the early stage of the cortical somatosensory system. Here we inferred that, in a cross-modal visuo-haptic short-term memory task, somatosensory cells would react to visual stimuli associated with tactile features. Single-unit discharge was recorded from the anterior parietal cortex--including areas of hand representation--of monkeys performing a visuo-haptic delayed matching-to-sample task. Units changed firing frequency during the presentation of a visual cue that the animal had to remember for making a correct tactile choice between two objects at the end of a delay (retention period). Some units showed sustained activation during the delay. In some of them that activation differed depending on the cue. These findings suggest that units in somatosensory cortex react to visual stimuli behaviorally associated with tactile information. Further, the results suggest that some of these neurons are involved in short-term active memory and may, therefore, be part of cross-modal memory networks.

  1. Dopamine control of pyramidal neuron activity in the primary motor cortex via D2 receptors

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    Clément eVitrac

    2014-02-01

    Full Text Available The primary motor cortex (M1 is involved in fine voluntary movements control. Previous studies have shown the existence of a dopamine (DA innervation in M1 of rats and monkeys that could directly modulate M1 neuronal activity. However, none of these studies have described the precise distribution of DA terminals within M1 functional region nor have quantified the density of this innervation. Moreover, the precise role of DA on pyramidal neuron activity still remains unclear due to conflicting results from previous studies regarding D2 effects on M1 pyramidal neurons.In this study we assessed in mice the neuroanatomical characteristics of DA innervation in M1 using unbiased stereological quantification of dopamine transporter-immunostained fibers. We demonstrated for the first time in mice that DA innervates the deep layers of M1 targeting preferentially the forelimb representation area of M1. To address the functional role of the DA innervation on M1 neuronal activity, we performed electrophysiological recordings of single neurons activity in vivo and pharmacologically modulated D2 receptors activity. Local D2 receptors activation by quinpirole enhanced pyramidal neurons spike firing rate without changes in spike firing pattern. Altogether, these results indicate that DA innervation in M1 can increase neuronal activity through D2 receptors activation and suggest a potential contribution to the modulation of fine forelimb movement. Given the demonstrated role for DA in fine motor skill learning in M1, our results suggest that altered D2 modulation of M1 activity may be involved in the pathophysiology of movement disorders associated with disturbed DA homeostasis.

  2. Latency modulation of collicular neurons induced by electric stimulation of the auditory cortex in Hipposideros pratti: In vivo intracellular recording.

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    Kang Peng

    Full Text Available In the auditory pathway, the inferior colliculus (IC receives and integrates excitatory and inhibitory inputs from the lower auditory nuclei, contralateral IC, and auditory cortex (AC, and then uploads these inputs to the thalamus and cortex. Meanwhile, the AC modulates the sound signal processing of IC neurons, including their latency (i.e., first-spike latency. Excitatory and inhibitory corticofugal projections to the IC may shorten and prolong the latency of IC neurons, respectively. However, the synaptic mechanisms underlying the corticofugal latency modulation of IC neurons remain unclear. Thus, this study probed these mechanisms via in vivo intracellular recording and acoustic and focal electric stimulation. The AC latency modulation of IC neurons is possibly mediated by pre-spike depolarization duration, pre-spike hyperpolarization duration, and spike onset time. This study suggests an effective strategy for the timing sequence determination of auditory information uploaded to the thalamus and cortex.

  3. Neuronal activity (c-Fos delineating interactions of the cerebral cortex and basal ganglia

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    Mei-Hong eQiu

    2014-03-01

    Full Text Available The cerebral cortex and basal ganglia (BG form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave EEG but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine (NMDA receptor antagonist and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist. Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN input to internal globus pallidus (GPi and substantia nigra pars reticulata (SNr, while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe, and STN but increased activity of the GPi, SNr and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders.

  4. Mirror Neurons of Ventral Premotor Cortex Are Modulated by Social Cues Provided by Others' Gaze.

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    Coudé, Gino; Festante, Fabrizia; Cilia, Adriana; Loiacono, Veronica; Bimbi, Marco; Fogassi, Leonardo; Ferrari, Pier Francesco

    2016-03-16

    Mirror neurons (MNs) in the inferior parietal lobule and ventral premotor cortex (PMv) can code the intentions of other individuals using contextual cues. Gaze direction is an important social cue that can be used for understanding the meaning of actions made by other individuals. Here we addressed the issue of whether PMv MNs are influenced by the gaze direction of another individual. We recorded single-unit activity in macaque PMv while the monkey was observing an experimenter performing a grasping action and orienting his gaze either toward (congruent gaze condition) or away (incongruent gaze condition) from a target object. The results showed that one-half of the recorded MNs were modulated by the gaze direction of the human agent. These gaze-modulated neurons were evenly distributed between those preferring a gaze direction congruent with the direction where the grasping action was performed and the others that preferred an incongruent gaze. Whereas the presence of congruent responses is in line with the usual coupling of hand and gaze in both executed and observed actions, the incongruent responses can be explained by the long exposure of the monkeys to this condition. Our results reveal that the representation of observed actions in PMv is influenced by contextual information not only extracted from physical cues, but also from cues endowed with biological or social value. In this study, we present the first evidence showing that social cues modulate MNs in the monkey ventral premotor cortex. These data suggest that there is an integrated representation of other's hand actions and gaze direction at the single neuron level in the ventral premotor cortex, and support the hypothesis of a functional role of MNs in decoding actions and understanding motor intentions. Copyright © 2016 the authors 0270-6474/16/363145-12$15.00/0.

  5. Von Economo neurons in autism: a stereologic study of the frontoinsular cortex in children.

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    Santos, Micaela; Uppal, Neha; Butti, Camilla; Wicinski, Bridget; Schmeidler, James; Giannakopoulos, Panteleimon; Heinsen, Helmut; Schmitz, Christoph; Hof, Patrick R

    2011-03-22

    The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a possible role in the integration of bodily feelings, emotional regulation, and goal-directed behaviors. They have also been implicated in fast intuitive evaluation of complex social situations. Several studies reported a decreased number of VENs in neuropsychiatric diseases in which the "embodied" dimension of social cognition is markedly affected. Neuropathological analyses of VENs in patients with autism are few and did not report alterations in VEN numbers. In this study we re-evaluated the possible presence of changes in VEN numbers and their relationship with the diagnosis of autism. Using a stereologic approach we quantified VENs and pyramidal neurons in layer V of FI in postmortem brains of four young patients with autism and three comparably aged controls. We also investigated possible autism-related differences in FI layer V volume. Patients with autism consistently had a significantly higher ratio of VENs to pyramidal neurons (p=0.020) than control subjects. This result may reflect the presence of neuronal overgrowth in young patients with autism and may also be related to alterations in migration, cortical lamination, and apoptosis. Higher numbers of VENs in the FI of patients with autism may also underlie a heightened interoception, described in some clinical observations. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Obesity-induced structural and neuronal plasticity in the lateral orbitofrontal cortex

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    Thompson, Jennifer L.; Drysdale, Michael; Baimel, Corey; Kaur, Manpreet; MacGowan, Taigan; Pitman, Kimberley A.; Borgland, Stephanie L.

    2016-01-01

    The orbitofrontal cortex (OFC) integrates sensory information with the current value of foods and updates actions based on this information. Obese humans and rats fed a cafeteria diet have impaired devaluation of food rewards, implicating a potential obesity-induced dysfunction of the OFC. We hypothesized that obesity alters OFC pyramidal neuronal structure and function and reduces conditioned suppression of feeding. Rats were given restricted (1 h/day), extended (23 h/day) or no (chow only) access to a cafeteria diet and tested for a conditioned suppression of feeding. Golgi-cox impregnation and whole-cell patch clamp experiments were performed in lateral OFC pyramidal neurons of rats from the 3 feeding groups. Rats with 40 days of extended, but not restricted, access to a cafeteria diet became obese and continued to feed during foot shock-predicting cues. Access to a cafeteria diet induced morphological changes in basilar dendrites of lateral OFC pyramidal neurons. While there were no alterations in excitatory synaptic transmission underlying altered spine density, we observed a more depolarized resting membrane potential. This was accompanied by decreased inhibitory synaptic transmission onto lateral OFC pyramidal neurons due to decreased release probability at GABAergic inputs. These changes could underlie the inability of the OFC to encode changes in the motivation value of food that is observed in obese rodents and humans. PMID:28042870

  7. Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving

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    Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

    2012-01-01

    In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104

  8. Alleviating Bone Cancer-induced Mechanical Hypersensitivity by Inhibiting Neuronal Activity in the Anterior Cingulate Cortex.

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    Chiou, Chiuan-Shiou; Chen, Chien-Chung; Tsai, Tsung-Chih; Huang, Chiung-Chun; Chou, Dylan; Hsu, Kuei-Sen

    2016-10-01

    The anterior cingulate cortex (ACC) is a brain region that has been critically implicated in the processing of pain perception and modulation. While much evidence has pointed to an increased activity of the ACC under chronic pain states, less is known about whether pain can be alleviated by inhibiting ACC neuronal activity. The authors used pharmacologic, chemogenetic, and optogenetic approaches in concert with viral tracing technique to address this issue in a mouse model of bone cancer-induced mechanical hypersensitivity by intratibia implantation of osteolytic fibrosarcoma cells. Bilateral intra-ACC microinjections of γ-aminobutyric acid receptor type A receptor agonist muscimol decreased mechanical hypersensitivity in tumor-bearing mice (n =10). Using adenoviral-mediated expression of engineered Gi/o-coupled human M4 (hM4Di) receptors, we observed that activation of Gi/o-coupled human M4 receptors with clozapine-N-oxide reduced ACC neuronal activity and mechanical hypersensitivity in tumor-bearing mice (n = 11). In addition, unilateral optogenetic silencing of ACC excitatory neurons with halorhodopsin significantly decreased mechanical hypersensitivity in tumor-bearing mice (n = 4 to 9), and conversely, optogenetic activation of these neurons with channelrhodopsin-2 was sufficient to provoke mechanical hypersensitivity in sham-operated mice (n = 5 to 9). Furthermore, we found that excitatory neurons in the ACC send direct descending projections to the contralateral dorsal horn of the lumbar spinal cord via the dorsal corticospinal tract. The findings of this study indicate that enhanced neuronal activity in the ACC contributes to maintain bone cancer-induced mechanical hypersensitivity and suggest that the ACC may serve as a potential therapeutic target for treating bone cancer pain.

  9. L-dopa methyl ester attenuates amblyopia-induced neuronal injury in visual cortex of amblyopic cat.

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    Li, Rong; Liang, Tao; Chen, Zhaoni; Zhang, Shijun; Lin, Xing; Huang, Renbin

    2013-09-15

    In the present study, we aimed to assess the potential anti-amblyopic effects of L-dopa methyl ester (LDME) on visual cortex area 17 in an amblyopic feline model induced by monocular vision deprivation. After LDME administration, pathophysiologic and ultrastructural observations were utilized to examine the morphological changes of nerve cells in visual cortex area 17. Dopamine (DA) and its metabolite contents in visual cortex area 17 were investigated through HPLC analysis. Apoptotic cells in visual cortex area 17 were evaluated by TUNEL assay. Additionally, the c-fos expression both at gene and protein levels was assessed using RT-PCR and immunohistochemistry analyses, respectively. The contents of DA and its metabolites were elevated in visual cortex area 17. Neuronal rejuvenation which occurred in visual cortex area 17 was observed through anatomical and physiological assessments. Similarly, TUNEL results showed that neuronal apoptosis was inhibited in the visual cortex of amblyopic cats by both L-dopa and LDME therapies. Meanwhile, the c-fos expression was notably up-regulated at both the mRNA and protein levels by the treatments. These findings suggested that LDME treatment could effectively increase DA and its metabolite contents, and restrain the apoptotic process, as well as elevate the c-fos expression in nerve cells of visual cortex area 17. Taken together, LDME might ameliorate the functional cytoarchitecture in visual cortex area 17 through mechanisms that elevate DA content and increase endogenous c-fos expression, as well as inhibit neuronal lesion in visual cortex tissue. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.

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    Qi, Hui-Xin; Reed, Jamie L; Franca, Joao G; Jain, Neeraj; Kajikawa, Yoshinao; Kaas, Jon H

    2016-04-01

    In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters. In 66% of our sample, neuron activity tended to display suppression of firing when regions of skin outside of the excitatory RF were stimulated. In a small proportion of neurons, single-site indentations suppressed firing without initial increases in response to any of the tested sites on the hand. Latencies of suppressive responses to skin indentation (usually 12-34 ms) were similar to excitatory response latencies. The duration of inhibition varied across neurons. Although most observations were from anesthetized animals, we also found similar neuron response properties in one awake galago. Notably, suppression of ongoing neuronal activity did not require conditioning stimuli or multi-site stimulation. The suppressive effects were generally seen following single-site skin indentations outside of the neuron's minimal RF and typically on different digits and palm pads, which have not often been studied in this context. Overall, the characteristics of widespread suppressive or inhibitory response properties with and without initial facilitative or excitatory responses add to the growing evidence that neurons in primary somatosensory cortex provide essential processing for integrating sensory stimulation from across the hand. Copyright © 2016 the American Physiological Society.

  11. Reduced synaptic facilitation between pyramidal neurons in the piriform cortex after odor learning.

    Science.gov (United States)

    Saar, D; Grossman, Y; Barkai, E

    1999-10-01

    Learning-related cellular modifications were studied in the rat piriform cortex after operand conditioning. Rats were trained to discriminate positive cues in pairs of odors. In one experimental paradigm, rats were trained to memorize 35-50 pairs of odors ("extensive training"). In another paradigm, training was continued only until rats acquired the rule of the task, usually after learning the first two pairs of odors ("short training"). "Pseudotrained" and "naive" rats served as controls. We have previously shown that "rule learning" of this task was accompanied by reduced spike afterhyperpolarization in pyramidal neurons in brain slices of the piriform cortex. In the present study, synaptic inputs to the same cells were examined. Pairs of electrical stimuli applied to the intrinsic fibers that interconnect layer II pyramidal neurons revealed significant reduction in paired-pulse facilitation (PPF) in this pathway even after short training. PPF in shortly trained rats was reduced to the same extent as in extensively trained rats. PPF reduction did not result from modification of membrane properties in the postsynaptic cells, change in postsynaptic inhibition, or impairment of the facilitation mechanism. Extracellular field potential recordings showed enhanced synaptic transmission in these synapses. The reduction in PPF became apparent only 3 d after task acquisition and returned to control value 5 d later. PPF evoked by stimulating the afferent fibers to the same neurons was increased 1 d after training for 2 d. We suggest that the transient enhancement in connectivity in the intrinsic pathway is related to the enhanced learning capability and not to memory for specific odors, which lasts for weeks.

  12. Noise-invariant Neurons in the Avian Auditory Cortex: Hearing the Song in Noise

    Science.gov (United States)

    Moore, R. Channing; Lee, Tyler; Theunissen, Frédéric E.

    2013-01-01

    Given the extraordinary ability of humans and animals to recognize communication signals over a background of noise, describing noise invariant neural responses is critical not only to pinpoint the brain regions that are mediating our robust perceptions but also to understand the neural computations that are performing these tasks and the underlying circuitry. Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant signal in a range of listening conditions have yet to be discovered. Here we found neurons in a secondary area of the avian auditory cortex that exhibit noise-invariant responses in the sense that they responded with similar spike patterns to song stimuli presented in silence and over a background of naturalistic noise. By characterizing the neurons' tuning in terms of their responses to modulations in the temporal and spectral envelope of the sound, we then show that noise invariance is partly achieved by selectively responding to long sounds with sharp spectral structure. Finally, to demonstrate that such computations could explain noise invariance, we designed a biologically inspired noise-filtering algorithm that can be used to separate song or speech from noise. This novel noise-filtering method performs as well as other state-of-the-art de-noising algorithms and could be used in clinical or consumer oriented applications. Our biologically inspired model also shows how high-level noise-invariant responses could be created from neural responses typically found in primary auditory cortex. PMID:23505354

  13. Characterization of neuronal intrinsic properties and synaptic transmission in layer I of anterior cingulate cortex from adult mice

    Directory of Open Access Journals (Sweden)

    Li Xiang-Yao

    2012-07-01

    Full Text Available Abstract The neurons in neocortex layer I (LI provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC, a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors, and inhibitory inputs (which were mediated by GABAA receptors. Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.

  14. The von Economo neurons in the frontoinsular and anterior cingulate cortex.

    Science.gov (United States)

    Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R

    2011-04-01

    The von Economo neurons (VENs) are large bipolar neurons located in the frontoinsular cortex (FI) and limbic anterior (LA) area in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week postconception, with numbers increasing during the first 8 months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. © 2011 New York Academy of Sciences.

  15. The von Economo neurons in fronto-insular and anterior cingulate cortex

    Science.gov (United States)

    Allman, John M.; Tetreault, Nicole A.; Hakeem, Atiya Y.; Manaye, Kebreten F.; Semendeferi, Katerina; Erwin, Joseph M.; Park, Soyoung; Goubert, Virginie; Hof, Patrick R.

    2011-01-01

    The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week post conception, with numbers increasing during the first eight months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of fronto-temporal dementia implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

  16. [Postsynaptic reactions of cerebral cortex neurons, activated by nociceptive afferents during stimulation of the Raphe nuclei].

    Science.gov (United States)

    Labakhua, T Sh; Dzhanashiia, T K; Gedevanishvili, G I; Dzhokhadze, L D; Tkemaladze, T T; Abzianidze, I V

    2012-01-01

    On cats, we studied the influence of stimulation of the Raphe nuclei (RN) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulation of the ventroposteromedial--VPN--nucleus of the thalamus) afferent inputs. 6 cells, selectively excited by stimulation of nocciceptors and 9 cells, activated by both the above nociceptive and non-nociceptive influences (nociceptive and convergent neurons, respectively) were recorded intracellular. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the letter of significant duration, up to 200-300 ms) compleх. Conditioning stimulation of the RN which preceded test stimulus applied to the tooth pulp or VPM nucleus by 100 to 800 ms, induced 40-60 % decrease of the IPSP amplitude only, while maхimal effect of influence, in both cases, was noted within intervals of 300-800 ms between conditioning and test stimulus. During stimulation of the RN, serotonin released via receptor and second messengers, provides postsynaptic modulation of GABAergic system, decreasing the IPSP amplitude which occurs after stimulation of both the tooth pulp and VPM thalamic nucleus. This process may be realized trough either pre- or postsynaptic mechanisms.

  17. Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

    Science.gov (United States)

    Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

  18. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    Science.gov (United States)

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

  19. Dynamic social adaptation of motion-related neurons in primate parietal cortex.

    Directory of Open Access Journals (Sweden)

    Naotaka Fujii

    Full Text Available Social brain function, which allows us to adapt our behavior to social context, is poorly understood at the single-cell level due largely to technical limitations. But the questions involved are vital: How do neurons recognize and modulate their activity in response to social context? To probe the mechanisms involved, we developed a novel recording technique, called multi-dimensional recording, and applied it simultaneously in the left parietal cortices of two monkeys while they shared a common social space. When the monkeys sat near each other but did not interact, each monkey's parietal activity showed robust response preference to action by his own right arm and almost no response to action by the other's arm. But the preference was broken if social conflict emerged between the monkeys-specifically, if both were able to reach for the same food item placed on the table between them. Under these circumstances, parietal neurons started to show complex combinatorial responses to motion of self and other. Parietal cortex adapted its response properties in the social context by discarding and recruiting different neural populations. Our results suggest that parietal neurons can recognize social events in the environment linked with current social context and form part of a larger social brain network.

  20. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Science.gov (United States)

    Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M.; de Castro Leal, Maria E.; Bertelsen, Mads F.; Alagaili, Abdulaziz N.; Mohammad, Osama B.; Manger, Paul R.; Herculano-Houzel, Suzana

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran

  1. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Directory of Open Access Journals (Sweden)

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  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. Differential activity patterns of putaminal neurons with inputs from the primary motor cortex and supplementary motor area in behaving monkeys.

    Science.gov (United States)

    Takara, Sayuki; Hatanaka, Nobuhiko; Takada, Masahiko; Nambu, Atsushi

    2011-09-01

    Activity patterns of projection neurons in the putamen were investigated in behaving monkeys. Stimulating electrodes were implanted chronically into the proximal (MI(proximal)) and distal (MI(distal)) forelimb regions of the primary motor cortex (MI) and the forelimb region of the supplementary motor area (SMA). Cortical inputs to putaminal neurons were identified by excitatory orthodromic responses to stimulation of these motor cortices. Then, neuronal activity was recorded during the performance of a goal-directed reaching task with delay. Putaminal neurons with inputs from the MI and SMA showed different activity patterns, i.e., movement- and delay-related activity, during task performance. MI-recipient neurons increased activity in response to arm-reach movements, whereas SMA-recipient neurons increased activity during delay periods, as well as during movements. The activity pattern of MI + SMA-recipient neurons was of an intermediate type between those of MI- and SMA-recipient neurons. Approximately one-half of MI(proximal)-, SMA-, and MI + SMA-recipient neurons changed activities before the onset of movements, whereas a smaller number of MI(distal)- and MI(proximal + distal)-recipient neurons did. Movement-related activity of MI-recipient neurons was modulated by target directions, whereas SMA- and MI + SMA-recipient neurons had a lower directional selectivity. MI-recipient neurons were located mainly in the ventrolateral part of the caudal aspect of the putamen, whereas SMA-recipient neurons were located in the dorsomedial part. MI + SMA-recipient neurons were found in between. The present results suggest that a subpopulation of putaminal neurons displays specific activity patterns depending on motor cortical inputs. Each subpopulation receives convergent or nonconvergent inputs from the MI and SMA, retains specific motor information, and sends it to the globus pallidus and the substantia nigra through the direct and indirect pathways of the basal ganglia.

  4. Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex

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    Emily K. Stephens

    2018-01-01

    Full Text Available Serotonin (5-HT selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current, or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs. However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation in commissural/callosal (COM projection neurons, a subpopulation of pyramidal neurons that exhibits 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%, rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances gated by 2A receptors. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50%, when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a non-specific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third

  5. 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.

  6. Evolutionary appearance of von Economo’s neurons in the mammalian cerebral cortex

    Science.gov (United States)

    Cauda, Franco; Geminiani, Giuliano Carlo; Vercelli, Alessandro

    2014-01-01

    von Economo’s neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the “social brain.” VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the “global Workspace” architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and

  7. Evolutionary appearance of von Economo's neurons in the mammalian cerebral cortex.

    Science.gov (United States)

    Cauda, Franco; Geminiani, Giuliano Carlo; Vercelli, Alessandro

    2014-01-01

    von Economo's neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the "social brain." VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the "global Workspace" architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental

  8. Evolutionary appearance of Von Economo’s Neurons in the mammalian cerebral cortex

    Directory of Open Access Journals (Sweden)

    Franco eCauda

    2014-03-01

    Full Text Available Von Economo’s neurons (VENs are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months.VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the social brain. VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain.However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the global Workspace architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication between salience-related insular and cingulate and other widely separated brain areas.Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the fMRI data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental investigatio

  9. [Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats].

    Science.gov (United States)

    Merzhanova, G Kh; Dolbakian, E E; Khokhlova, V N

    2003-01-01

    Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group.

  10. 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

  11. Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex.

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    Jara, J H; Stanford, M J; Zhu, Y; Tu, M; Hauswirth, W W; Bohn, M C; DeVries, S H; Özdinler, P H

    2016-03-01

    Direct gene delivery to the neurons of interest, without affecting other neuron populations in the cerebral cortex, represent a challenge owing to the heterogeneity and cellular complexity of the brain. Genetic modulation of corticospinal motor neurons (CSMN) is required for developing effective and long-term treatment strategies for motor neuron diseases, in which voluntary movement is impaired. Adeno-associated viruses (AAV) have been widely used for neuronal transduction studies owing to long-term and stable gene expression as well as low immunoreactivity in humans. Here we report that AAV2-2 transduces CSMN with high efficiency upon direct cortex injection and that transduction efficiencies are similar during presymptomatic and symptomatic stages in hSOD1(G93A) transgenic amyotrophic lateral sclerosis (ALS) mice. Our findings reveal that choice of promoter improves selectivity as AAV2-2 chicken β-actin promoter injection results in about 70% CSMN transduction, the highest percentage reported to date. CSMN transduction in both wild-type and transgenic ALS mice allows detailed analysis of single axon fibers within the corticospinal tract in both cervical and lumbar spinal cord and reveals circuitry defects, which mainly occur between CSMN and spinal motor neurons in hSOD1(G93A) transgenic ALS mice. Our findings set the stage for CSMN gene therapy in ALS and related motor neuron diseases.

  12. Neuron-oligodendrocyte myelination co-culture derived from embryonic rat spinal cord and cerebral cortex.

    Science.gov (United States)

    Pang, Yi; Zheng, Baoying; Kimberly, Simpson L; Cai, Zhengwei; Rhodes, Philip G; Lin, Rick C S

    2012-01-01

    An in vitro myelination model derived from rat central nervous system (CNS) remains to be established. Here, we describe a simple and reproducible myelination culture method using dissociated neuron-oligodendrocyte (OL) co-cultures from either the embryonic day 16 (E16) rat spinal cord or cerebral cortex. The dissociated cells are plated directly on poly-L-lysine-coated cover slips and maintained in a modified myelination medium that supports both OL and neuron differentiation. The spinal cord derived OL progenitor cells develop quickly into myelin basic protein (MBP)+ mature OLs and start to myelinate axons around 17 days in vitro (DIV17). Myelination reaches its peak around six weeks (DIV40) and the typical nodes of Ranvier are revealed by paranodal proteins Caspr and juxaparanodal protein Kv1.2 immunoreactivity. Electron microscopy (EM) shows typical myelination cytoarchitecture and synaptic organization. In contrast, the cortical-derived co-culture requires triiodothyronine (T3) in the culture medium for myelination. Finally, either hypomyelination and/or demyelination can be induced by exposing proinflammatory cytokines or demyelinating agents to the co-culture, suggesting the feasibility of this modified in vitro myelination model for myelin-deficit investigation.

  13. Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons.

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    Rueckemann, Jon W; DiMauro, Audrey J; Rangel, Lara M; Han, Xue; Boyden, Edward S; Eichenbaum, Howard

    2016-02-01

    The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information. © 2015 Wiley Periodicals, Inc.

  14. 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.

  15. Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep.

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    Wanger, Tim; Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

    2015-11-01

    It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats-rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale.

  16. Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

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    Christophe Heinrich

    2014-12-01

    Full Text Available The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

  17. Metabolic differences between primary cultures of astrocytes and neurons from cerebellum and cerebral cortex. Effects of fluorocitrate.

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    Hassel, B; Westergaard, N; Schousboe, A; Fonnum, F

    1995-04-01

    Astrocytes and neurons cultured from mouse cerebellum and cerebral cortex were analyzed with respect to content and synthesis of amino acids as well as export of metabolites to the culture medium and the response to fluorocitrate, an inhibitor of aconitase. The intracellular levels of amino acids were similar in the two astrocytic populations. The release of citrate, lactate and glutamine, however, was markedly higher from cerebellar than from cortical astrocytes. Neurons contained higher levels of glutamate, aspartate and GABA than astrocytic cultures. Cortical neurons were especially high in GABA and aspartate, and the level of aspartate increased specifically when the extracellular level of glutamine was elevated. Fluorocitrate inhibited the TCA cycle in the astrocytes, but was less effective in cerebellar neurons. Whereas neurons responded to fluorocitrate with an increase in the formation of lactate, reflecting glycolysis, astrocytes decreased the formation of lactate in the presence of fluorocitrate, indicating that astrocytes to a high degree synthesize pyruvate and hence lactate from TCA cycle intermediates.

  18. Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories.

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    Warren, Brandon L; Mendoza, Michael P; Cruz, Fabio C; Leao, Rodrigo M; Caprioli, Daniele; Rubio, F Javier; Whitaker, Leslie R; McPherson, Kylie B; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

    2016-06-22

    In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the

  19. Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

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    Roelf J. Cruz-Rizzolo

    2017-12-01

    Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

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

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    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

  1. 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

  2. Neuropeptide S facilitates mice olfactory function through activation of cognate receptor-expressing neurons in the olfactory cortex.

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    Yu-Feng Shao

    Full Text Available Neuropeptide S (NPS is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR. High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v. injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir neurons that also bear NPSR. NPS (0.1-1 nmol i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val(5]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON, piriform cortex (Pir, ventral tenia tecta (VTT, the anterior cortical amygdaloid nucleus (ACo and lateral entorhinal cortex (LEnt. The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice.

  3. Horizontal Synchronization of Neuronal Activity in the Barrel Cortex of the Neonatal Rat by Spindle-Burst Oscillations

    Science.gov (United States)

    Suchkov, Dmitrii; Sharipzyanova, Lyaila; Minlebaev, Marat

    2018-01-01

    During development, activity in the somatosensory cortex is characterized by intermittent oscillatory bursts at gamma (early gamma-oscillations, EGOs) and alpha–beta (spindle-bursts, SBs) frequencies. Here, we explored the topography of EGOs and SBs in the neighbor barrels of the whisker-related barrel cortex of neonatal rats (P4-7) during responses evoked by simultaneous activation of multiple whiskers as it occurs during natural conditions. We found that brief simultaneous deflection of all whiskers evoked complex neuronal responses comprised of EGOs and SBs. In contrast to EGOs, that specifically synchronized neuronal activity in each individual barrel, SBs efficiently synchronized activity between neighboring barrels. After plucking a single whisker, synchronous stimulation of spared whiskers evoked EGO-lacking responses in the whisker-deprived barrel, even though the remaining neuronal activity was synchronized by SBs in neighboring barrels. Thus, EGOs specifically support topographic synchronization of neuronal activity within barrels, whereas SBs support horizontal synchronization between neighboring barrels during stimulation of multiple whiskers. We suggest that these two co-existing activity patterns coordinate activity-dependent formation of topographic maps and support the emergence of integrative functions in the primary somatosensory cortex during the critical period of somatosensory maps development. PMID:29403359

  4. Horizontal Synchronization of Neuronal Activity in the Barrel Cortex of the Neonatal Rat by Spindle-Burst Oscillations

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    Dmitrii Suchkov

    2018-01-01

    Full Text Available During development, activity in the somatosensory cortex is characterized by intermittent oscillatory bursts at gamma (early gamma-oscillations, EGOs and alpha–beta (spindle-bursts, SBs frequencies. Here, we explored the topography of EGOs and SBs in the neighbor barrels of the whisker-related barrel cortex of neonatal rats (P4-7 during responses evoked by simultaneous activation of multiple whiskers as it occurs during natural conditions. We found that brief simultaneous deflection of all whiskers evoked complex neuronal responses comprised of EGOs and SBs. In contrast to EGOs, that specifically synchronized neuronal activity in each individual barrel, SBs efficiently synchronized activity between neighboring barrels. After plucking a single whisker, synchronous stimulation of spared whiskers evoked EGO-lacking responses in the whisker-deprived barrel, even though the remaining neuronal activity was synchronized by SBs in neighboring barrels. Thus, EGOs specifically support topographic synchronization of neuronal activity within barrels, whereas SBs support horizontal synchronization between neighboring barrels during stimulation of multiple whiskers. We suggest that these two co-existing activity patterns coordinate activity-dependent formation of topographic maps and support the emergence of integrative functions in the primary somatosensory cortex during the critical period of somatosensory maps development.

  5. Aging somatosensory cortex displays increased density of WFA-binding perineuronal nets associated with GAD-negative neurons.

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    Karetko-Sysa, M; Skangiel-Kramska, J; Nowicka, D

    2014-09-26

    The mechanisms of aging in the brain and the subsequent decrease in cognitive abilities remain elusive. While most studies refer to research conducted in old and senile animals, little is known about the early symptoms of normal, healthy aging. In this study, we examined whether perineuronal nets (PNNs), a special form of extracellular matrix (ECM) tightly associated with neurons that is thought to be involved in limiting neuronal plasticity, undergo changes in density during early aging. Using histochemistry and immunohistochemistry, we found that in middle-aged mice (1-year-old), the density of WFA-binding PNNs in the somatosensory cortex as well as in the visual cortex was increased in comparison to that in young adults (3-month-old). Moreover, in the somatosensory cortex, this increase was not associated with any of the GABAergic neuron types that were examined. We propose that early age-related changes in neuronal plasticity may be associated with this increase and can be conceptualized as the spreading of structural brakes for synaptic rearrangements. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Effects of epidural compression on stellate neurons and thalamocortical afferent fibers in the rat primary somatosensory cortex.

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    Yeh, Tzu-Yin; Tseng, Guo-Fang; Tseng, Chi-Yu; Huang, Yung-Hsin; Liu, Pei-Hsin

    2017-01-01

    A number of neurological disorders such as epidural hematoma can cause compression of cerebral cortex. We here tested the hypothesis that sustained compression of primary somatosensory cortex may affect stellate neurons and thalamocortical afferent (TCA) fibers. A rat model with barrel cortex subjected to bead epidural compression was used. Golgi-Cox staining analyses showed the shrinkage of dendritic arbors and the stripping of dendritic spines of stellate neurons for at least 3 months post-lesion. Anterograde tracing analyses exhibited a progressive decline of TCA fiber density in barrel field for 6 months post-lesion. Due to the abrupt decrease of TCA fiber density at 3 days after compression, we further used electron microscopy to investigate the ultrastructure of TCA fibers at this time. Some TCA fiber terminal profiles with dissolved or darkened mitochondria and fewer synaptic vesicles were distorted and broken. Furthermore, the disruption of mitochondria and myelin sheath was observed in some myelinated TCA fibers. In addition, expressions of oxidative markers 3-nitrotyrosine and 4-hydroxynonenal were elevated in barrel field post-lesion. Treatment of antioxidant ascorbic acid or apocynin was able to reverse the increase of oxidative stress and the decline of TCA fiber density, rather than the shrinkage of dendrites and the stripping of dendritic spines of stellate neurons post-lesion. Together, these results indicate that sustained epidural compression of primary somatosensory cortex affects the TCA fibers and the dendrites of stellate neurons for a prolonged period. In addition, oxidative stress is responsible for the reduction of TCA fiber density in barrels rather than the shrinkage of dendrites and the stripping of dendritic spines of stellate neurons.

  7. Reinforcement learning of targeted movement in a spiking neuronal model of motor cortex.

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    Chadderdon, George L; Neymotin, Samuel A; Kerr, Cliff C; Lytton, William W

    2012-01-01

    Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint "forearm" to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. The model consisted of 144 excitatory and 64 inhibitory event-based neurons, each with AMPA, NMDA, and GABA synapses. Proprioceptive cell input to this model encoded the 2 muscle lengths. Plasticity was only enabled in feedforward connections between input and output excitatory units, using spike-timing-dependent eligibility traces for synaptic credit or blame assignment. Learning resulted from a global 3-valued signal: reward (+1), no learning (0), or punishment (-1), corresponding to phasic increases, lack of change, or phasic decreases of dopaminergic cell firing, respectively. Successful learning only occurred when both reward and punishment were enabled. In this case, 5 target angles were learned successfully within 180 s of simulation time, with a median error of 8 degrees. Motor babbling allowed exploratory learning, but decreased the stability of the learned behavior, since the hand continued moving after reaching the target. Our model demonstrated that a global reinforcement signal, coupled with eligibility traces for synaptic plasticity, can train a spiking sensorimotor network to perform goal-directed motor behavior.

  8. Reinforcement learning of targeted movement in a spiking neuronal model of motor cortex.

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    George L Chadderdon

    Full Text Available Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint "forearm" to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. The model consisted of 144 excitatory and 64 inhibitory event-based neurons, each with AMPA, NMDA, and GABA synapses. Proprioceptive cell input to this model encoded the 2 muscle lengths. Plasticity was only enabled in feedforward connections between input and output excitatory units, using spike-timing-dependent eligibility traces for synaptic credit or blame assignment. Learning resulted from a global 3-valued signal: reward (+1, no learning (0, or punishment (-1, corresponding to phasic increases, lack of change, or phasic decreases of dopaminergic cell firing, respectively. Successful learning only occurred when both reward and punishment were enabled. In this case, 5 target angles were learned successfully within 180 s of simulation time, with a median error of 8 degrees. Motor babbling allowed exploratory learning, but decreased the stability of the learned behavior, since the hand continued moving after reaching the target. Our model demonstrated that a global reinforcement signal, coupled with eligibility traces for synaptic plasticity, can train a spiking sensorimotor network to perform goal-directed motor behavior.

  9. Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.

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    Soumier, Amelie; Sibille, Etienne

    2014-08-01

    Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons.

  10. [Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

    2017-05-01

    The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

  11. Deep layer neurons in the rat medial entorhinal cortex fire sparsely irrespective of spatial novelty

    Directory of Open Access Journals (Sweden)

    Andrea eBurgalossi

    2014-07-01

    Full Text Available Extracellular recordings in medial entorhinal cortex have revealed the existence of spatially-modulated firing patterns, which are thought to contribute to a cognitive map of external space. Previous work indicated that during exploration of novel environments, spiking activity in deep entorhinal layers is much sparser than in superficial layers. In the present report, we ask whether this laminar activity profile is a consequence of environmental novelty. We report on a large dataset of juxtacellularly-recorded neurons (n = 70 whose spiking activity was monitored while rats explored either a novel or a familiar environment, or both within the same session. Irrespective of previous knowledge of the environment, deep layer activity was very low during exploration (median firing rate 0.4 Hz for non-silent cells, with a large fraction of silent cells (n = 19 of a total 37, while superficial layer activity was several times higher (median firing rate 2.4 Hz; n = 33. The persistence of laminar differences in firing activity both under environmental novelty and familiarity, and even in head-restrained stationary animals, suggests that sparse coding might be a constitutive feature of deep entorhinal layers.

  12. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Quantitative comparison of striated toolmarks.

    Science.gov (United States)

    Baiker, Martin; Keereweer, Isaac; Pieterman, René; Vermeij, Erwin; van der Weerd, Jaap; Zoon, Peter

    2014-09-01

    A comparison of striated toolmarks by human examiners is dependent on the experience of the expert and includes a subjective judgment within the process. In this article an automated method is presented for objective comparison of striated marks of screwdrivers. The combination of multi-scale registration (alignment) of toolmarks, that accounts for shift and scaling, with global cross correlation as objective toolmark similarity metric renders the approach robust with respect to large differences in angle of attack and moderate toolmark compression. In addition, a strategy to distinguish between relevant and non-relevant spatial frequency ranges (geometric details) is presented. The performance of the method is evaluated using 3D topography scans of experimental toolmarks of 50 unused screwdrivers. Known match and known non-match similarity distributions are estimated including a large range of angles of attack (15, 30, 45, 60 and 75°) for the known matches. It is demonstrated that the system has high discriminatory power, even if the toolmarks are made at a difference in angle of attack of larger than 15°. The probability distributions are subsequently employed to determine likelihood ratios. A comparison of the results of the automated method with the outcome of a toolmark comparison experiment involving three experienced toolmark examiners reveals, that the automated system is more powerful in correctly supporting the hypothesis of common origin for toolmarks with a large difference in angle of attack (30°). In return, the rate of toolmark comparisons that yield incorrect support for the hypothesis of common origin is higher for the automated system. In addition, a comparison between estimating known match and known non-match distributions using 2D and 3D data is presented and it is shown that for toolmarks of unused screwdrivers, relying on 3D is slightly better than relying on 2D data. Finally, a comparison between estimating known match and known non

  14. 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.

  15. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Science.gov (United States)

    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  16. Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

    Science.gov (United States)

    Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang

    2017-07-01

    Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.

  17. Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex.

    Science.gov (United States)

    Cirstea, Carmen M; Choi, In-Young; Lee, Phil; Peng, Huiling; Kaufman, Christina L; Frey, Scott H

    2017-04-01

    Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels of N -acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees ( n = 19) compared with the analogous hand territory of age- and sex-matched healthy controls ( n = 28). We also tested whether former amputees [i.e., recipients of replanted ( n = 3) or transplanted ( n = 2) hands] exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower levels of NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation. NEW & NOTEWORTHY This study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory

  18. Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

    Science.gov (United States)

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

    2016-11-01

    The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  20. The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons

    DEFF Research Database (Denmark)

    Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta

    2018-01-01

    A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically...

  1. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  2. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

    Science.gov (United States)

    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  3. Acquisition, extinction, and recall of opiate reward memory are signaled by dynamic neuronal activity patterns in the prefrontal cortex.

    Science.gov (United States)

    Sun, Ninglei; Chi, Ning; Lauzon, Nicole; Bishop, Stephanie; Tan, Huibing; Laviolette, Steven R

    2011-12-01

    The medial prefrontal cortex (mPFC) comprises an important component in the neural circuitry underlying drug-related associative learning and memory processing. Neuronal activation within mPFC circuits is correlated with the recall of opiate-related drug-taking experiences in both humans and other animals. Using an unbiased associative place conditioning procedure, we recorded mPFC neuronal populations during the acquisition, recall, and extinction phases of morphine-related associative learning and memory. Our analyses revealed that mPFC neurons show increased activity both in terms of tonic and phasic activity patterns during the acquisition phase of opiate reward-related memory and demonstrate stimulus-locked associative activity changes in real time, during the recall of opiate reward memories. Interestingly, mPFC neuronal populations demonstrated divergent patterns of bursting activity during the acquisition versus recall phases of newly acquired opiate reward memory, versus the extinction of these memories, with strongly increased bursting during the recall of an extinction memory and no associative bursting during the recall of a newly acquired opiate reward memory. Our results demonstrate that neurons within the mPFC are involved in both the acquisition, recall, and extinction of opiate-related reward memories, showing unique patterns of tonic and phasic activity patterns during these separate components of the opiate-related reward learning and memory recall.

  4. 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.

  5. Top-down inputs enhance orientation selectivity in neurons of the primary visual cortex during perceptual learning.

    Directory of Open Access Journals (Sweden)

    Samat Moldakarimov

    2014-08-01

    Full Text Available Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently inconsistent experiments and providing a new hypothesis for a functional role of the feedback connections.

  6. High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

    Science.gov (United States)

    Lobier, Muriel; Palva, J Matias; Palva, Satu

    2018-01-15

    Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons

    Directory of Open Access Journals (Sweden)

    Ya-Ting eLei

    2014-09-01

    Full Text Available In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca2+-activated non-selective cation (CAN current (ICAN that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca2+-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN, remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential melastatin 5 channel (TRPM5, which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

  8. Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons.

    Science.gov (United States)

    Lei, Ya-Ting; Thuault, Sebastien J; Launay, Pierre; Margolskee, Robert F; Kandel, Eric R; Siegelbaum, Steven A

    2014-01-01

    In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP) in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca(2+)-activated non-selective cation (CAN) current (ICAN ) that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca(2+)-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN , remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential (TRP) melastatin 5 channel (TRPM5), which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

  9. Functional Near-Infrared Spectroscopy Signals Measure Neuronal Activity in the Cortex

    Science.gov (United States)

    Harrivel, Angela; Hearn, Tristan

    2013-01-01

    Functional near infrared spectroscopy (fNIRS) is an emerging optical neuroimaging technology that indirectly measures neuronal activity in the cortex via neurovascular coupling. It quantifies hemoglobin concentration ([Hb]) and thus measures the same hemodynamic response as functional magnetic resonance imaging (fMRI), but is portable, non-confining, relatively inexpensive, and is appropriate for long-duration monitoring and use at the bedside. Like fMRI, it is noninvasive and safe for repeated measurements. Patterns of [Hb] changes are used to classify cognitive state. Thus, fNIRS technology offers much potential for application in operational contexts. For instance, the use of fNIRS to detect the mental state of commercial aircraft operators in near real time could allow intelligent flight decks of the future to optimally support human performance in the interest of safety by responding to hazardous mental states of the operator. However, many opportunities remain for improving robustness and reliability. It is desirable to reduce the impact of motion and poor optical coupling of probes to the skin. Such artifacts degrade signal quality and thus cognitive state classification accuracy. Field application calls for further development of algorithms and filters for the automation of bad channel detection and dynamic artifact removal. This work introduces a novel adaptive filter method for automated real-time fNIRS signal quality detection and improvement. The output signal (after filtering) will have had contributions from motion and poor coupling reduced or removed, thus leaving a signal more indicative of changes due to hemodynamic brain activations of interest. Cognitive state classifications based on these signals reflect brain activity more reliably. The filter has been tested successfully with both synthetic and real human subject data, and requires no auxiliary measurement. This method could be implemented as a real-time filtering option or bad channel

  10. Distinction of neurons, glia and endothelial cells in the cerebral cortex: an algorithm based on cytological features

    Directory of Open Access Journals (Sweden)

    Miguel Ángel García-Cabezas

    2016-11-01

    Full Text Available The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic, and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease.

  11. Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.

    Science.gov (United States)

    Knaack, Gretchen L; Charkhkar, Hamid; Hamilton, Franz W; Peixoto, Nathalia; O'Shaughnessy, Thomas J; Pancrazio, Joseph J

    2013-07-01

    ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Striated Muscle Function, Regeneration, and Repair

    Science.gov (United States)

    Shadrin, I.Y.; Khodabukus, A.; Bursac, N.

    2016-01-01

    As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID:27271751

  13. Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency

    DEFF Research Database (Denmark)

    Castrop, H; Kammerl, M; Mann, Birgitte

    2000-01-01

    Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of n...... excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other....

  14. Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

    Directory of Open Access Journals (Sweden)

    Leon French

    2017-05-01

    Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

  15. Imaging Neuronal Populations in Behaving Rodents: Paradigms for Studying Neural Circuits Underlying Behavior in the Mammalian Cortex

    Science.gov (United States)

    Andermann, Mark L.; Keck, Tara; Xu, Ning-Long; Ziv, Yaniv

    2013-01-01

    Understanding the neural correlates of behavior in the mammalian cortex requires measurements of activity in awake, behaving animals. Rodents have emerged as a powerful model for dissecting the cortical circuits underlying behavior attributable to the convergence of several methods. Genetically encoded calcium indicators combined with viral-mediated or transgenic tools enable chronic monitoring of calcium signals in neuronal populations and subcellular structures of identified cell types. Stable one- and two-photon imaging of neuronal activity in awake, behaving animals is now possible using new behavioral paradigms in head-fixed animals, or using novel miniature head-mounted microscopes in freely moving animals. This mini-symposium will highlight recent applications of these methods for studying sensorimotor integration, decision making, learning, and memory in cortical and subcortical brain areas. We will outline future prospects and challenges for identifying the neural underpinnings of task-dependent behavior using cellular imaging in rodents. PMID:24198355

  16. Binocular neurons in parastriate cortex: interocular 'matching' of receptive field properties, eye dominance and strength of silent suppression.

    Directory of Open Access Journals (Sweden)

    Phillip A Romo

    Full Text Available Spike-responses of single binocular neurons were recorded from a distinct part of primary visual cortex, the parastriate cortex (cytoarchitectonic area 18 of anaesthetized and immobilized domestic cats. Functional identification of neurons was based on the ratios of phase-variant (F1 component to the mean firing rate (F0 of their spike-responses to optimized (orientation, direction, spatial and temporal frequencies and size sine-wave-luminance-modulated drifting grating patches presented separately via each eye. In over 95% of neurons, the interocular differences in the phase-sensitivities (differences in F1/F0 spike-response ratios were small (≤ 0.3 and in over 80% of neurons, the interocular differences in preferred orientations were ≤ 10°. The interocular correlations of the direction selectivity indices and optimal spatial frequencies, like those of the phase sensitivies and optimal orientations, were also strong (coefficients of correlation r ≥ 0.7005. By contrast, the interocular correlations of the optimal temporal frequencies, the diameters of summation areas of the excitatory responses and suppression indices were weak (coefficients of correlation r ≤ 0.4585. In cells with high eye dominance indices (HEDI cells, the mean magnitudes of suppressions evoked by stimulation of silent, extra-classical receptive fields via the non-dominant eyes, were significantly greater than those when the stimuli were presented via the dominant eyes. We argue that the well documented 'eye-origin specific' segregation of the lateral geniculate inputs underpinning distinct eye dominance columns in primary visual cortices of mammals with frontally positioned eyes (distinct eye dominance columns, combined with significant interocular differences in the strength of silent suppressive fields, putatively contribute to binocular stereoscopic vision.

  17. Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats

    Directory of Open Access Journals (Sweden)

    Chengdong Yuan

    2016-07-01

    Full Text Available Background: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine-induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. Methods: Sprague-Dawley rats (11–19 postnatal days, n=36 were used to obtain brain slices (300 μM. Spontaneous excitatory postsynaptic currents (data from 40 neurons were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 μM and strychnine (glycine receptor antagonist, 30 μM. Miniature excitatory postsynaptic currents (data from 40 neurons were also recorded when 1 μM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. Results: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration-dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. Conclusion: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors.

  18. Binocular Neurons in Parastriate Cortex: Interocular ‘Matching’ of Receptive Field Properties, Eye Dominance and Strength of Silent Suppression

    Science.gov (United States)

    Wang, Chun; Dreher, Bogdan

    2014-01-01

    Spike-responses of single binocular neurons were recorded from a distinct part of primary visual cortex, the parastriate cortex (cytoarchitectonic area 18) of anaesthetized and immobilized domestic cats. Functional identification of neurons was based on the ratios of phase-variant (F1) component to the mean firing rate (F0) of their spike-responses to optimized (orientation, direction, spatial and temporal frequencies and size) sine-wave-luminance-modulated drifting grating patches presented separately via each eye. In over 95% of neurons, the interocular differences in the phase-sensitivities (differences in F1/F0 spike-response ratios) were small (≤0.3) and in over 80% of neurons, the interocular differences in preferred orientations were ≤10°. The interocular correlations of the direction selectivity indices and optimal spatial frequencies, like those of the phase sensitivies and optimal orientations, were also strong (coefficients of correlation r ≥0.7005). By contrast, the interocular correlations of the optimal temporal frequencies, the diameters of summation areas of the excitatory responses and suppression indices were weak (coefficients of correlation r ≤0.4585). In cells with high eye dominance indices (HEDI cells), the mean magnitudes of suppressions evoked by stimulation of silent, extra-classical receptive fields via the non-dominant eyes, were significantly greater than those when the stimuli were presented via the dominant eyes. We argue that the well documented ‘eye-origin specific’ segregation of the lateral geniculate inputs underpinning distinct eye dominance columns in primary visual cortices of mammals with frontally positioned eyes (distinct eye dominance columns), combined with significant interocular differences in the strength of silent suppressive fields, putatively contribute to binocular stereoscopic vision. PMID:24927276

  19. Spatiotemporal Changes of Neuronal Responses in the Primary Somatosensory Cortex to Noxious Tail Stimulation in Awake and Pentobarbital-Anesthetized Rats.

    Science.gov (United States)

    Kuo, Chung-Chih; Lee, Jye-Chang; Chiou, Ruei-Jen; Tsai, Meng-Li; Yen, Chen-Tung

    2015-10-31

    Primary somatosensory cortex (SI) is a key area in the processing of nociceptor inputs to our consciousness. To clarify the columnar and laminar organization of SI for pain processing, we compared spatiotemporal changes in neuronal activities of the primary sensorimotor cortex (SmI) of the rat in response to noxious laser heat stimulation applied to the mid-tail. Longitudinal and vertical array microelectrodes were chronically implanted in the cerebral cortex. Evoked neuronal activities, including intracortical local field potentials (LFP) and ensemble single-unit activity (SU) around SmI were simultaneously recorded. The effect of pentobarbital on the neuronal responses was evaluated in comparison with the neuronal responses in conscious animals to explore the potential substrate of nociceptive processing in the conscious state. The results from the experiment with longitudinal microelectrode arrays indicated that noxious stimulation induced a neuronal response which was spread widely around the SmI of the conscious rat, and the range of neuronal responses was limited to the tail region of the SmI under anesthesia. The results from the experiment with vertical microelectrode arrays showed the universal neuronal responses through all cortical layers of the SmI in conscious rats, and sodium pentobarbital suppressed these neuronal responses in the supragranular layers significantly relative to the deeper layers and basal activity. These results imply that a wider range of cortical activation, both in the horizontal or vertical dimension, might be important for nociceptive processing in the conscious state.

  20. Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress

    Directory of Open Access Journals (Sweden)

    Kelly M. Moench

    2016-06-01

    Full Text Available Dysfunction in corticolimbic circuits that mediate the extinction of learned fear responses is thought to underlie the perseveration of fear in stress-related psychopathologies, including post-traumatic stress disorder. Chronic stress produces dendritic hypertrophy in basolateral amygdala (BLA and dendritic hypotrophy in medial prefrontal cortex, whereas acute stress leads to hypotrophy in both BLA and prelimbic cortex. Additionally, both chronic and acute stress impair extinction retrieval. Here, we examined the effects of a single elevated platform stress on extinction learning and dendritic morphology in infralimbic cortex, a region considered to be critical for extinction. Acute stress produced resistance to extinction, as well as dendritic retraction in infralimbic cortex. Spine density on apical and basilar terminal branches was unaffected by stress. However, animals that underwent conditioning and extinction had decreased spine density on apical terminal branches. Thus, whereas dendritic morphology in infralimbic cortex appears to be particularly sensitive to stress, changes in spines may more sensitively reflect learning. Further, in stressed rats that underwent conditioning and extinction, the level of extinction learning was correlated with spine densities, in that rats with poorer extinction retrieval had more immature spines and fewer thin spines than rats with better extinction retrieval, suggesting that stress may have impaired learning-related spine plasticity. These results may have implications for understanding the role of medial prefrontal cortex in learning deficits associated with stress-related pathologies.

  1. Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates

    Science.gov (United States)

    Ribeiro, Pedro F. M.; Manger, Paul R.; Catania, Kenneth C.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2014-01-01

    The olfactory bulb is an evolutionarily old structure that antedates the appearance of a six-layered mammalian cerebral cortex. As such, the neuronal scaling rules that apply to scaling the mass of the olfactory bulb as a function of its number of neurons might be shared across mammalian groups, as we have found to be the case for the ensemble of non-cortical, non-cerebellar brain structures. Alternatively, the neuronal scaling rules that apply to the olfactory bulb might be distinct in those mammals that rely heavily on olfaction. The group previously referred to as Insectivora includes small mammals, some of which are now placed in Afrotheria, a base group in mammalian radiation, and others in Eulipotyphla, a group derived later, at the base of Laurasiatheria. Here we show that the neuronal scaling rules that apply to building the olfactory bulb differ across eulipotyphlans and other mammals such that eulipotyphlans have more neurons concentrated in an olfactory bulb of similar size than afrotherians, glires and primates. Most strikingly, while the cerebral cortex gains neurons at a faster pace than the olfactory bulb in glires, and afrotherians follow this trend, it is the olfactory bulb that gains neurons at a faster pace than the cerebral cortex in eulipotyphlans, which contradicts the common view that the cerebral cortex is the fastest expanding structure in brain evolution. Our findings emphasize the importance of not using brain structure size as a proxy for numbers of neurons across mammalian orders, and are consistent with the notion that different selective pressures have acted upon the olfactory system of eulipotyphlans, glires and primates, with eulipotyphlans relying more on olfaction for their behavior than glires and primates. Surprisingly, however, the neuronal scaling rules for primates predict that the human olfactory bulb has as many neurons as the larger eulipotyphlan olfactory bulbs, which questions the classification of humans as microsmatic

  2. 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.

  3. Single Neurons in the Avian Auditory Cortex Encode Individual Identity and Propagation Distance in Naturally Degraded Communication Calls.

    Science.gov (United States)

    Mouterde, Solveig C; Elie, Julie E; Mathevon, Nicolas; Theunissen, Frédéric E

    2017-03-29

    One of the most complex tasks performed by sensory systems is "scene analysis": the interpretation of complex signals as behaviorally relevant objects. The study of this problem, universal to species and sensory modalities, is particularly challenging in audition, where sounds from various sources and localizations, degraded by propagation through the environment, sum to form a single acoustical signal. Here we investigated in a songbird model, the zebra finch, the neural substrate for ranging and identifying a single source. We relied on ecologically and behaviorally relevant stimuli, contact calls, to investigate the neural discrimination of individual vocal signature as well as sound source distance when calls have been degraded through propagation in a natural environment. Performing electrophysiological recordings in anesthetized birds, we found neurons in the auditory forebrain that discriminate individual vocal signatures despite long-range degradation, as well as neurons discriminating propagation distance, with varying degrees of multiplexing between both information types. Moreover, the neural discrimination performance of individual identity was not affected by propagation-induced degradation beyond what was induced by the decreased intensity. For the first time, neurons with distance-invariant identity discrimination properties as well as distance-discriminant neurons are revealed in the avian auditory cortex. Because these neurons were recorded in animals that had prior experience neither with the vocalizers of the stimuli nor with long-range propagation of calls, we suggest that this neural population is part of a general-purpose system for vocalizer discrimination and ranging. SIGNIFICANCE STATEMENT Understanding how the brain makes sense of the multitude of stimuli that it continually receives in natural conditions is a challenge for scientists. Here we provide a new understanding of how the auditory system extracts behaviorally relevant information

  4. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

    Science.gov (United States)

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2016-02-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

  5. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time...... spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin...

  6. Maximization of learning speed in the motor cortex due to neuronal redundancy.

    Directory of Open Access Journals (Sweden)

    Ken Takiyama

    2012-01-01

    Full Text Available Many redundancies play functional roles in motor control and motor learning. For example, kinematic and muscle redundancies contribute to stabilizing posture and impedance control, respectively. Another redundancy is the number of neurons themselves; there are overwhelmingly more neurons than muscles, and many combinations of neural activation can generate identical muscle activity. The functional roles of this neuronal redundancy remains unknown. Analysis of a redundant neural network model makes it possible to investigate these functional roles while varying the number of model neurons and holding constant the number of output units. Our analysis reveals that learning speed reaches its maximum value if and only if the model includes sufficient neuronal redundancy. This analytical result does not depend on whether the distribution of the preferred direction is uniform or a skewed bimodal, both of which have been reported in neurophysiological studies. Neuronal redundancy maximizes learning speed, even if the neural network model includes recurrent connections, a nonlinear activation function, or nonlinear muscle units. Furthermore, our results do not rely on the shape of the generalization function. The results of this study suggest that one of the functional roles of neuronal redundancy is to maximize learning speed.

  7. Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy.

    Science.gov (United States)

    Ottolini, Matteo; Barker, Bryan S; Gaykema, Ronald P; Meisler, Miriam H; Patel, Manoj K

    2017-08-09

    SCN8A encephalopathy, or early infantile epileptic encephalopathy 13 (EIEE13), is caused predominantly by de novo gain-of-function mutations in the voltage-gated Na channel Na v 1.6. Affected individuals suffer from refractory seizures, developmental delay, cognitive disability, and elevated risk of sudden unexpected death in epilepsy (SUDEP). A knock-in mouse model carrying the patient mutation p.Asn1768Asp (N1768D) reproduces many features of the disorder, including spontaneous seizures and SUDEP. We used the mouse model to examine the effects of the mutation on layer II stellate neurons of the medial entorhinal cortex (mEC), which transmit excitatory input to the hippocampus. Heterozygous ( Scn8a D/+ ), homozygous ( Scn8a D/D) ), and WT ( Scn8a +/+ ) littermates were compared at 3 weeks of age, the time of seizure onset for homozygous mice. Heterozygotes remain seizure free for another month. mEC layer II neurons of heterozygous and homozygous mice were hyperexcitable and generated long-lasting depolarizing potentials with bursts of action potentials after synaptic stimulation. Recording of Na currents revealed proexcitatory increases in persistent and resurgent currents and rightward shifts in inactivation parameters, leading to significant increases in the magnitude of window currents. The proexcitatory changes were more pronounced in homozygous mice than in heterozygotes, consistent with the earlier age of seizure onset in homozygotes. These studies demonstrate that the N1768D mutation increases the excitability of mEC layer II neurons by increasing persistent and resurgent Na currents and disrupting channel inactivation. The aberrant activities of mEC layer II neurons would provide excessive excitatory input to the hippocampus and contribute to hyperexcitability of hippocampal neurons in this model of SCN8A encephalopathy. SIGNIFICANCE STATEMENT SCN8A encephalopathy is a devastating neurological disorder that results from de novo mutations in the Na channel

  8. The response properties of neurons in different fields of the auditory cortex in the rat

    Czech Academy of Sciences Publication Activity Database

    Profant, Oliver; Burianová, Jana; Syka, Josef

    2013-01-01

    Roč. 296, February (2013), s. 51-59 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GAP303/12/1347; GA ČR(CZ) GBP304/12/G069 Institutional support : RVO:68378041 Keywords : auditory cortex * fequency representation * axon terminals Subject RIV: FH - Neurology Impact factor: 2.848, year: 2013

  9. Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats

    Czech Academy of Sciences Publication Activity Database

    Popelář, Jiří; Šuta, Daniel; Lindovský, Jiří; Bureš, Zbyněk; Pysaněnko, Kateryna; Chumak, Tetyana; Syka, Josef

    2016-01-01

    Roč. 332, feb (2016), s. 7-16 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP303/12/1347 Institutional support: RVO:68378041 Keywords : auditory cortex * cooling * cortical inactivation * efferent system Subject RIV: ED - Physiology Impact factor: 2.906, year: 2016

  10. Theory for the Development of Neuron Selectivity: Orientation Specificity and Binocular Interaction in Visual Cortex.

    Science.gov (United States)

    1981-06-05

    approximately the same half-width at half-height. ( Think *for instance of triangularly shaped tuning curves.) Typical values for orientation...Innate and enviromental factors in the development of the kitten’s visual cortex. J. Physiol. 248: 663-716. Brindley. G. S. (1969) Nerve net models of

  11. Length summation in simple cells of cat striate cortex.

    Science.gov (United States)

    Schumer, R A; Movshon, J A

    1984-01-01

    We have examined two models for the preference displayed by cortical simple cells for elongated stimuli having a particular orientation. Both assume that geniculate afferents with aligned receptive fields pool to form the receptive field of the cortical unit. The first model [Marr and Hildreth, Proc. R. Soc. Lond. Ser. B 200, 269-294 (1980)], includes AND gating along the length axis so that a simple cell does not fire unless a critical number of its afferents with adjacent receptive fields are firing. The second model assumes that geniculate input is simply summed over subunits and then passed through a firing threshold. Both models account for the unresponsiveness of simple cells to spots of light, but the AND model predicts a discontinuous length threshold, while the summation model predicts that length and contrast should be interchangeable in the determination of the response threshold. Experiments in which length and contrast were systematically varied support the summation model, and extend the notion of linear spatial summation to the length axis in simple cells.

  12. Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

    Science.gov (United States)

    Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

  13. 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

  14. [Comparative experimental study of the influence of drugs that improve brain metabolism (angiogen, cytoflavin) on neuronal apoptosis and function of cerebral cortex during aging].

    Science.gov (United States)

    Bazhanova, E D; Anisimov, V N; Sukhanov, D S; Teplyĭ, D L

    2015-01-01

    The safety of cortical neurons and their functional activity is essential for organism at all stages of ontogenesis. However, aging changes leading to an increase in apoptosis level may cause considerable damage to cerebral cortex function, including sensorimotor. We have studied the role of exogenous neurometabolites (angiogen, cytoflavin) in apoptosis regulation and correction of age-related motor and behavioral disturbances. To study the regulation of neuronal morphofunctional activity, we used accelerate-senescent transgenic HER2 mice in comparison to wild type FBV mice. Functional changes in cerebral cortex were studied by the Suok test and open field test, the level of neuronal apoptosis was assessed by TUNEL method, the expression of apoptosis-modulating proteins was detected by immunohistochemistry and Western blotting. We have revealed differences in psycho-emotional and locomotor activity of these strains of mice. In addition, results of our study showed morphological differences: increase in the apoptosis level of cortical neurons in aged FBV type mice, but no changes in aged HER2 mice. The investigated drugs induce cell death of cortical neurons in transgenic mice of both ages and in young wild-type mice by p53-dependent pathway. Increased apoptosis in the cortex of old transgenic mice has important clinical implications, because reduced apoptosis during aging is one of the causes of cancer. The treatment of old wild-type animals reduces elevated neuronal apoptosis, which decreases risk of age neurodegeneration. Thus, revealed morphological changes in the cerebral cortex are the basis for involutional disabilities (including reduced locomotor activity and increased anxiety level). The use of angiogen and cytoflavin treatment improves functional activity of the cortex and protects normal structure of nervous tissue.

  15. Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep

    OpenAIRE

    Wanger, Tim; Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W.; Goldschmidt, Jürgen

    2014-01-01

    It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethy...

  16. The role of α-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration

    Directory of Open Access Journals (Sweden)

    Marie-Theres eSchmid

    2014-08-01

    Full Text Available During brain development, radial glial cells possess an apico-basal polarity and are coupled by adherens junctions to an F-actin belt. To elucidate the role of the actin, we conditionally deleted the key component α-E-catenin in the developing cerebral cortex. Deletion at early stages resulted in severe disruption of tissue polarity due to uncoupling of adherens junctions with the intracellular actin fibers leading to the formation of subcortical band heterotopia. Interestingly, this phenotype closely resembled the phenotype obtained by conditional RhoA deletion, both in regard to the macroscopic subcortical band heterotopia and the subcellular increase in G-actin/F-actin ratio. These data therefore together corroborate the role of the actin cytoskeleton and its anchoring to the adherens junctions for neuronal migration disorders.

  17. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  18. A neuronal activation correlate in striatum and prefrontal cortex of prolonged cocaine intake

    NARCIS (Netherlands)

    Gao, Ping; de Munck, Jan C; Limpens, Jules H W; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-01-01

    Maladaptive changes in the involvement of striatal and frontal cortical regions in drug use are thought to underlie the progression to habitual drug use and loss of cognitive control over drug intake that occur with accumulating drug experience. The present experiments focus on changes in neuronal

  19. Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

    DEFF Research Database (Denmark)

    Golonzhka, Olga; Nord, Alex; Tang, Paul L F

    2015-01-01

    We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient...

  20. Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem

    Czech Academy of Sciences Publication Activity Database

    Lu, H. P.; Syka, Josef; Chiu, T. W.; Poon, P. W. F.

    2014-01-01

    Roč. 314, AUG 2014 (2014), s. 42-50 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GCP303/11/J005; GA ČR(CZ) GAP304/12/1342 Institutional support: RVO:68378041 Keywords : inferior colliculus * cochlear nucleus * neocortical neurons Subject RIV: FH - Neurology Impact factor: 2.968, year: 2014

  1. Orexin-A expression in dissociated neuronal cultures of the newborn rat cortex

    NARCIS (Netherlands)

    Stoyanova, Irina; le Feber, Jakob; Wiertz, Remy; Rutten, Wim

    2009-01-01

    Orexin A is a neuropeptide isolated from a small group of neurons in the hypothalamus, which orchestrates many different brain functions. Despite the extensive information about orexin A expression and function in the nervous system of adults, data about the formation and maturation of the orexin

  2. Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain.

    Science.gov (United States)

    Prakash, Dharmalingam; Sudhandiran, Ganapasam

    2015-12-01

    Dietary flavonoids have been suggested to promote brain health by protecting brain parenchymal cells. Recently, understanding the possible mechanism underlying neuroprotective efficacy of flavonoids is of great interest. Given that fisetin exerts neuroprotection, we have examined the mechanisms underlying fisetin in regulating Aβ aggregation and neuronal apoptosis induced by aluminium chloride (AlCl3) administration in vivo. Male Swiss albino mice were induced orally with AlCl3 (200 mg/kg. b.wt./day/8 weeks). Fisetin (15 mg/Kg. b.wt. orally) was administered for 4 weeks before AlCl3-induction and administered simultaneously for 8 weeks during AlCl3-induction. We found aggregation of Amyloid beta (Aβ 40-42), elevated expressions of Apoptosis stimulating kinase (ASK-1), p-JNK (c-Jun N-terminal Kinase), p53, cytochrome c, caspases-9 and 3, with altered Bax/Bcl-2 ratio in favour of apoptosis in cortex and hippocampus of AlCl3-administered mice. Furthermore, TUNEL and fluoro-jade C staining demonstrate neurodegeneration in cortex and hippocampus. Notably, treatment with fisetin significantly (P<0.05) reduced Aβ aggregation, ASK-1, p-JNK, p53, cytochrome c, caspase-9 and 3 protein expressions and modulated Bax/Bcl-2 ratio. TUNEL-positive and fluoro-jade C stained cells were also significantly reduced upon fisetin treatment. We have identified the involvement of fisetin in regulating ASK-1 and p-JNK as possible mediator of Aβ aggregation and subsequent neuronal apoptosis during AlCl3-induced neurodegeneration. These findings define the possibility that fisetin may slow or prevent neurodegneration and can be utilised as neuroprotective agent against Alzheimer's and Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Decision-related activity in sensory neurons may depend on the columnar architecture of cerebral cortex.

    Science.gov (United States)

    Nienborg, Hendrikje; Cumming, Bruce G

    2014-03-05

    Many studies have reported correlations between the activity of sensory neurons and animals' judgments in discrimination tasks. Here, we suggest that such neuron-behavior correlations may require a cortical map for the task relevant features. This would explain why studies using discrimination tasks based on disparity in area V1 have not found these correlations: V1 contains no map for disparity. This scheme predicts that activity of V1 neurons correlates with decisions in an orientation-discrimination task. To test this prediction, we trained two macaque monkeys in a coarse orientation discrimination task using band-pass-filtered dynamic noise. The two orientations were always 90° apart and task difficulty was controlled by varying the orientation bandwidth of the filter. While the trained animals performed this task, we recorded from orientation-selective V1 neurons (n = 82, n = 31 for Monkey 1, n = 51 for Monkey 2). For both monkeys, we observed significant correlation (quantified as "choice probabilities") of the V1 activity with the monkeys' perceptual judgments (mean choice probability 0.54, p = 10(-5)). In one of these animals, we had previously measured choice probabilities in a disparity discrimination task in V1, which had been at chance (0.49, not significantly different from 0.5). The choice probabilities in this monkey for the orientation discrimination task were significantly larger than those for the disparity discrimination task (p = 0.032). These results are predicted by our suggestion that choice probabilities are only observed for cortical sensory neurons that are organized in maps for the task-relevant feature.

  4. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    Science.gov (United States)

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  5. Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimens.

    Science.gov (United States)

    Cerqueira, João J; Taipa, Ricardo; Uylings, Harry B M; Almeida, Osborne F X; Sousa, Nuno

    2007-09-01

    We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi-Cox-stained material, we now demonstrate that corticosteroids can exert differential effects on dendritic arborizations of pyramidal neurons in lamina II/III of the mPFC. Treatment with the glucocorticoid receptor-selective agonist dexamethasone and with the natural adrenosteroid, corticosterone (CORT), results in significant reductions in the total length of apical dendrites in the pyramidal neurons in lamina II/III of the anterior cingulate/prelimbic and infralimbic cortices. Interestingly, although these treatments do not affect the number of dendritic branches, they are associated with impoverished arborizations in their distal portions and, in CORT-treated animals, with increased branching in the middle portions of the apical dendritic tree. Deprivation of corticosteroids by adrenalectomy leads to decreases in total apical dendritic length and spine number, but in this case, dendritic impoverishment was restricted to the middle/proximal segments of the dendritic trees. None of the treatments influenced the architecture of the basal dendrites. These results add to our knowledge of the morphological substrates through which corticosteroids may disrupt mPFC-dependent behaviors.

  6. Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex.

    Science.gov (United States)

    Fame, Ryann M; Dehay, Colette; Kennedy, Henry; Macklis, Jeffrey D

    2017-03-01

    Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Relationship between activity in human primary motor cortex during action observation and the mirror neuron system.

    Directory of Open Access Journals (Sweden)

    James M Kilner

    Full Text Available The attenuation of the beta cortical oscillations during action observation has been interpreted as evidence of a mirror neuron system (MNS in humans. Here we investigated the modulation of beta cortical oscillations with the viewpoint of an observed action. We asked subjects to observe videos of an actor making a variety of arm movements. We show that when subjects were observing arm movements there was a significant modulation of beta oscillations overlying left and right sensorimotor cortices. This pattern of attenuation was driven by the side of the screen on which the observed movement occurred and not by the hand that was observed moving. These results are discussed in terms of the firing patterns of mirror neurons in F5 which have been reported to have similar properties.

  8. Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in modulation of nociception: a virally mediated transsynaptic tracing study in spinally transected transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Da-Wei Ye

    Full Text Available Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex-periaqueductal gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP transgenic mice (n = 15. After a survival time of 4-6 days, the mice (n = 5 were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.

  9. Dynamic Regulation of Sarcomeric Actin Filaments in Striated Muscle

    OpenAIRE

    Ono, Shoichiro

    2010-01-01

    In striated muscle, the actin cytoskeleton is differentiated into myofibrils. Actin and myosin filaments are organized in sarcomeres and specialized for producing contractile forces. Regular arrangement of actin filaments with uniform length and polarity is critical for the contractile function. However, the mechanisms of assembly and maintenance of sarcomeric actin filaments in striated muscle are not completely understood. Live imaging of actin in striated muscle has revealed that actin sub...

  10. mGluR5 Exerts Cell-Autonomous Influences on the Functional and Anatomical Development of Layer IV Cortical Neurons in the Mouse Primary Somatosensory Cortex.

    Science.gov (United States)

    Ballester-Rosado, Carlos J; Sun, Hao; Huang, Jui-Yen; Lu, Hui-Chen

    2016-08-24

    Glutamate neurotransmission refines synaptic connections to establish the precise neural circuits underlying sensory processing. Deleting metabotropic glutamate receptor 5 (mGluR5) in mice perturbs cortical somatosensory map formation in the primary somatosensory (S1) cortex at both functional and anatomical levels. To examine the cell-autonomous influences of mGluR5 signaling in the morphological and functional development of layer IV spiny stellate glutamatergic neurons receiving sensory input, mGluR5 genetic mosaic mice were generated through in utero electroporation. In the S1 cortex of these mosaic brains, we found that most wild-type neurons were located in barrel rings encircling thalamocortical axon (TCA) clusters while mGluR5 knock-out (KO) neurons were placed in the septal area, the cell-sparse region separating barrels. These KO neurons often displayed a symmetrical dendritic morphology with increased dendritic complexity, in contrast to the polarized pattern of wild-type neurons. The dendritic spine density of mGluR5 KO spiny stellate neurons was significantly higher than in wild-type neurons. Whole-cell electrophysiological recordings detected a significant increase in the frequencies of spontaneous and miniature excitatory postsynaptic events in mGluR5 KO neurons compared with neighboring wild-type neurons. Our mosaic analysis provides strong evidence supporting the cell-autonomous influence of mGluR5 signaling on the functional and anatomical development of cortical glutamatergic neurons. Specifically, mGluR5 is required in cortical glutamatergic neurons for the following processes: (1) the placement of cortical glutamatergic neurons close to TCA clusters; (2) the regulation of dendritic complexity and outgrowth toward TCA clusters; (3) spinogenesis; and (4) tuning of excitatory inputs. Glutamatergic transmission plays a critical role in cortical circuit formation. Its dysfunction has been proposed as a core factor in the etiology of many

  11. Neuronal integration in visual cortex elevates face category tuning to conscious face perception.

    Science.gov (United States)

    Fahrenfort, Johannes J; Snijders, Tineke M; Heinen, Klaartje; van Gaal, Simon; Scholte, H Steven; Lamme, Victor A F

    2012-12-26

    The human brain has the extraordinary capability to transform cluttered sensory input into distinct object representations. For example, it is able to rapidly and seemingly without effort detect object categories in complex natural scenes. Surprisingly, category tuning is not sufficient to achieve conscious recognition of objects. What neural process beyond category extraction might elevate neural representations to the level where objects are consciously perceived? Here we show that visible and invisible faces produce similar category-selective responses in the ventral visual cortex. The pattern of neural activity evoked by visible faces could be used to decode the presence of invisible faces and vice versa. However, only visible faces caused extensive response enhancements and changes in neural oscillatory synchronization, as well as increased functional connectivity between higher and lower visual areas. We conclude that conscious face perception is more tightly linked to neural processes of sustained information integration and binding than to processes accommodating face category tuning.

  12. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  13. Altered neuronal activity patterns in the visual cortex of the adult rat after partial optic nerve crush--a single-cell resolution metabolic mapping study.

    Science.gov (United States)

    Macharadze, Tamar; Pielot, Rainer; Wanger, Tim; Scheich, Henning; Gundelfinger, Eckart D; Budinger, Eike; Goldschmidt, Jürgen; Kreutz, Michael R

    2012-08-01

    Thallium autometallography (TIAMG) is a novel method for high-resolution mapping of neuronal activity. With this method, we found that a general depression of neuronal activity occurs in response to optic nerve crush (ONC) within the first 2 weeks postinjury in the contralateral dorsal lateral geniculate nucleus (dLGN) as well as in the contralateral primary visual cortex (V1). Interestingly, the neuronal activity recovered thereafter in both brain regions and reached a plateau in the tenth week postinjury in layers IV and V of V1, monocular area (V1m). Several clusters of highly active neurons in V1m were found 6 weeks after ONC in layers IV and V on the side contralateral to the lesion. We reasoned that these clusters appeared due to a reorganization of the corticocolliucular projections. Employing a combination of biotinylated dextran amine retrograde tract tracing from the superior colliculus (SC) with TIAMG in the same animal, we indeed found that the clusters of neurons with high Tl(+) uptake in V1m are spatially in register with those neuronal subpopulations that project to the SC. These data suggest that extensive reorganization plasticity exists in the adult rat visual cortex following ONC.

  14. Neural mechanisms of memory retrieval: role of the prefrontal cortex.

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

    In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

  15. Neural Plasticity: Single Neuron Models for Discrimination and Generalization and an Experimental Ensemble Approach.

    Science.gov (United States)

    1983-06-01

    in pamp/cm has been computed by Agin (1964) from the equations of Hodgkin and Huxley (1952) to give the response frequency (pulses/sec) of an axon...J.- Y . (1981) lumunocytochem- ical localization of glutamic acid decarboxylase in monkey striate cortex. Nature2i2.: 605-607. Hodgkin . A. L. and...used to express the output y of a neuron to its inputs zi (1). The coefficients ei i_____i___i __ i_______’____’_____,________’__’___"___i 10 are the

  16. Assessing neuronal density in peri-infarct cortex with PET: Effects of cortical topology and partial volume correction.

    Science.gov (United States)

    Funck, Thomas; Al-Kuwaiti, Mohammed; Lepage, Claude; Zepper, Peter; Minuk, Jeffrey; Schipper, Hyman M; Evans, Alan C; Thiel, Alexander

    2017-01-01

    The peri-infarct cortex (PIC) is the site of long-term physiologic changes after ischemic stroke. Traditional methods for delineating the peri-infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition. This was done in 11 patients with [F-18]-Flumazenil ([18-F]-FMZ) positron emission tomography (PET) scans at 2 weeks post-stroke and at 6 month follow-up. FMZ is a PET radiotracer with specific binding to the alpha subunits of the type A γ-aminobutyric acid (GABAA) receptor. Additionally, we used partial-volume correction (PVC) of the PET images to compensate for potential cortical thinning and long-term neuronal loss in follow-up images. The difference in non-displaceable binding potential (BP ND ) between the stroke unaffected and affected hemispheres was 35% larger in the geodesic versus the Euclidean peri-infarct models in initial PET images and 48% larger in follow-up PET images. The inter-hemispheric BP ND difference was approximately 17-20% larger after PVC when compared to uncorrected PET images. PET studies of peri-infarct GM in cortical strokes should use a geodesic model and include PVC as a preprocessing step. Hum Brain Mapp 38:326-338, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Cognitive phase transitions in the cerebral cortex enhancing the neuron doctrine by modeling neural fields

    CERN Document Server

    Kozma, Robert

    2016-01-01

    This intriguing book was born out of the many discussions the authors had in the past 10 years about the role of scale-free structure and dynamics in producing intelligent behavior in brains. The microscopic dynamics of neural networks is well described by the prevailing paradigm based in a narrow interpretation of the neuron doctrine. This book broadens the doctrine by incorporating the dynamics of neural fields, as first revealed by modeling with differential equations (K-sets).  The book broadens that approach by application of random graph theory (neuropercolation). The book concludes with diverse commentaries that exemplify the wide range of mathematical/conceptual approaches to neural fields. This book is intended for researchers, postdocs, and graduate students, who see the limitations of network theory and seek a beachhead from which to embark on mesoscopic and macroscopic neurodynamics.

  18. 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

  19. The causal role of category-specific neuronal representations in the left ventral premotor cortex (PMv) in semantic processing.

    Science.gov (United States)

    Cattaneo, Zaira; Devlin, Joseph T; Salvini, Francesca; Vecchi, Tomaso; Silvanto, Juha

    2010-02-01

    The left ventral premotor cortex (PMv) is preferentially activated by exemplars of tools, suggestive of category specificity in this region. Here we used state-dependent transcranial magnetic stimulation (TMS) to investigate the causal role of such category-specific neuronal representations in the encoding of tool words. Priming to a category name (either "Tool" or "Animal") was used with the objective of modulating the initial activation state of this region prior to application of TMS and the presentation of the target stimulus. When the target word was an exemplar of the "Tool" category, the effects of TMS applied over PMv (but not PMd) interacted with priming history by facilitating reaction times on incongruent trials while not affecting congruent trials. This congruency/TMS interaction implies that the "Tool" and "Animal" primes had a differential effect on the initial activation state of the left PMv and implies that this region is one neural locus of category-specific behavioral priming for the "Tool" category. TMS applied over PMv had no behavioral effect when the target stimulus was an exemplar of the "Animal" category, regardless of whether the target word was congruent or incongruent with the prime. That TMS applied over the left PMv interacted with a priming effect that extended from the category name ("Tool") to exemplars of that category suggests that this region contains neuronal representation associated with a specific semantic category. Our results also demonstrate that the state-dependent effects obtained in the combination of visual priming and TMS are useful in the study of higher-level cognitive functions. Copyright (c) 2009 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  1. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla.

    Science.gov (United States)

    Bednařík, Petr; Tkáč, Ivan; Giove, Federico; DiNuzzo, Mauro; Deelchand, Dinesh K; Emir, Uzay E; Eberly, Lynn E; Mangia, Silvia

    2015-03-31

    Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms.

  2. Wnt Signaling Regulates Multipolar-to-Bipolar Transition of Migrating Neurons in the Cerebral Cortex

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    Michael Boitard

    2015-03-01

    Full Text Available The precise timing of pyramidal cell migration from the ventricular germinal zone to the cortical plate is essential for establishing cortical layers, and migration errors can lead to neurodevelopmental disorders underlying psychiatric and neurological diseases. Here, we report that Wnt canonical as well as non-canonical signaling is active in pyramidal precursors during radial migration. We demonstrate using constitutive and conditional genetic strategies that transient downregulation of canonical Wnt/β-catenin signaling during the multipolar stage plays a critical role in polarizing and orienting cells for radial migration. In addition, we show that reduced canonical Wnt signaling is triggered cell autonomously by time-dependent expression of Wnt5A and activation of non-canonical signaling. We identify ephrin-B1 as a canonical Wnt-signaling-regulated target in control of the multipolar-to-bipolar switch. These findings highlight the critical role of Wnt signaling activity in neuronal positioning during cortical development.

  3. Neuronal connections of eye-dominance columns in the cat cerebral cortex after monocular deprivation.

    Science.gov (United States)

    Alekseenko, S V; Toporova, S N; Shkorbatova, P Yu

    2008-09-01

    Plastic changes in intrahemisphere neuronal connections of the eye-dominance columns of cortical fields 17 and 18 were studied in monocularly deprived cats. The methodology consisted of microintophoretic administration of horseradish peroxidase into cortical columns and three-dimensional reconstruction of the areas of retrograde labeled cells. The eye dominance of columns was established, as were their coordinates in the projection of the visual field. In field 17, the horizontal connections of columns receiving inputs from the non-deprived eye via the crossed-over visual tracts were longer than the connections of the "non-crossed" columns of this eye and were longer than in normal conditions; the connections of the columns of the deprived eye were significantly reduced. Changes in the spatial organization of horizontal connections in field 17 were seen for the columns of the non-deprived eye (areas of labeled cells were rounder and the density of labeled cells in these areas were non-uniform). The longest horizontal connections in deprived cats were no longer than the lengths of these connections in cats with strabismus. It is suggested that the axon length of cells giving rise to the horizontal connections of cortical columns has a limit which is independent of visual stimulation during the critical period of development of the visual system.

  4. Temporal structure in neuronal activity during working memory in Macaque parietal cortex

    CERN Document Server

    Pesaran, B; Sahami, M; Mitra, P; Andersen, R A

    2000-01-01

    A number of cortical structures are reported to have elevated single unit firing rates sustained throughout the memory period of a working memory task. How the nervous system forms and maintains these memories is unknown but reverberating neuronal network activity is thought to be important. We studied the temporal structure of single unit (SU) activity and simultaneously recorded local field potential (LFP) activity from area LIP in the inferior parietal lobe of two awake macaques during a memory-saccade task. Using multitaper techniques for spectral analysis, which play an important role in obtaining the present results, we find elevations in spectral power in a 50--90 Hz (gamma) frequency band during the memory period in both SU and LFP activity. The activity is tuned to the direction of the saccade providing evidence for temporal structure that codes for movement plans during working memory. We also find SU and LFP activity are coherent during the memory period in the 50--90 Hz gamma band and no consisten...

  5. 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

  6. Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

    DEFF Research Database (Denmark)

    Severino, Maurizio; Pedersen, Anja F; Trajkovska, Viktorija

    2007-01-01

    Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT(2A) receptors, are also associated with early AD. The aim of this study was to investigate whether...... elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT(2A) receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 microg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT(2A......) protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT(2A) receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 Ig...

  7. The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

    Science.gov (United States)

    Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

    2013-01-01

    The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID

  8. The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

    Directory of Open Access Journals (Sweden)

    Pedro F. M. Ribeiro

    2013-09-01

    Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

  9. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    Science.gov (United States)

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  10. Diffusion tensor imaging detects early cerebral cortex abnormalities in neuronal architecture induced by bilateral neonatal enucleation: An experimental model in the ferret

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    Andrew S Bock

    2010-10-01

    Full Text Available Diffusion tensor imaging (DTI is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA, that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7 in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally-adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally-enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy.

  11. Tyrosine hydroxylase-producing neurons in the human cerebral cortex do not colocalize with calcium-binding proteins or the serotonin 3A receptor.

    Science.gov (United States)

    Asmus, Stephen E; Raghanti, Mary Ann; Beyerle, Eric R; Fleming-Beattie, Julia C; Hawkins, Sarah M; McKernan, Courtney M; Rauh, Nicholas A

    2016-12-01

    Interneurons of the cerebral cortex play a significant role in cortical information processing and are of clinical interest due to their involvement in neurological disorders. In the human neocortex, three subsets of interneurons can be identified based on the production of the calcium-binding proteins parvalbumin, calretinin or calbindin. A subset of interneurons in the mouse cortex expresses the serotonin 3A receptor (5-HT 3A R). Previous work in humans has also demonstrated the presence of a subgroup of cortical neurons that produces the catecholaminergic enzyme tyrosine hydroxylase (TH). Many TH-producing cells in the rat cortex coexpress calretinin and are adjacent to blood vessels. However, little is known about the phenotype of these TH interneurons in humans. Here we immunohistochemically examined the coexpression of TH with parvalbumin, calretinin, calbindin or 5-HT 3A R in human Brodmann's areas 10 and 24, cortical regions with high densities of TH-containing neurons. Colocalization of TH with these calcium-binding proteins and with 5-HT 3A R was not detected in either area. Cortical TH cells were rarely apposed to blood vessels, denoted by immunolabeling for the gliovascular marker aquaporin-4. Our results suggest that the TH-immunoreactive cells in the human cortex do not overlap with any known neurochemically-defined subsets of interneurons and provide further evidence of differences in the phenotype of these cells across species. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  13. Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

    Science.gov (United States)

    Insel, Nathan; Barnes, Carol A.

    2015-01-01

    The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

  14. Developmental changes in electrophysiological properties and a transition from electrical to chemical coupling between excitatory layer 4 neurons in the rat barrel cortex

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    Fliza eValiullina

    2016-01-01

    Full Text Available During development, sensory systems switch from an immature to an adult mode of function along with the emergence of the active cortical states. Here, we used patch-clamp recordings from neocortical slices in vitro to characterize the developmental changes in the basic electrophysiological properties of excitatory L4 neurons and their connectivity before and after the developmental switch, which occurs in the rat barrel cortex in vivo at postnatal day P8. Prior to the switch, L4 neurons had lower resting membrane potentials, higher input resistance, lower membrane capacity, as well as action potentials (APs with smaller amplitudes, longer durations and higher AP thresholds compared to the neurons after the switch. A sustained firing pattern also emerged around the switch. Dual patch-clamp recordings from L4 neurons revealed that recurrent connections between L4 excitatory cells do not exist before and develop rapidly across the switch. In contrast, electrical coupling between these neurons waned around the switch. We suggest that maturation of electrophysiological features, particularly acquisition of a sustained firing pattern, and a transition from the immature electrical to mature chemical synaptic coupling between excitatory L4 neurons, contributes to the developmental switch in the cortical mode of function.

  15. A mouse model of visual perceptual learning reveals alterations in neuronal coding and dendritic spine density in the visual cortex

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    Yan eWang

    2016-03-01

    Full Text Available Visual perceptual learning (VPL can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS and a 55% gain in visual acuity (VA. Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1 than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

  16. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Altered neuronal spontaneous activity correlates with glutamate concentration in medial prefrontal cortex of major depressed females: An fMRI-MRS study.

    Science.gov (United States)

    Zhang, Xiaoliu; Tang, Yingying; Maletic-Savatic, Mirjana; Sheng, Jianhua; Zhang, Xuanhong; Zhu, Yajing; Zhang, Tianhong; Wang, Junjie; Tong, Shanbao; Wang, Jijun; Li, Yao

    2016-09-01

    Major depressive disorder (MDD) is twice more prevalent in females than in males. Yet, there have only been a few studies on the functional brain activity in female MDD patients and the detailed mechanisms underlying their neurobiology merit further investigations. In the present work, we used combined fMRI-MRS methods to investigate the altered intrinsic neuronal activity and its association with neurotransmitter concentration in female MDD patients. The whole brain amplitude of low frequency fluctuation (ALFF) analysis using resting state functional magnetic resonance imaging (fMRI) was performed to explore the alteration of intrinsic neuronal signals in MDD females (n=11) compared with female healthy controls (n=11). With a specific interest in the medial prefrontal cortex (mPFC) area, we quantified the concentration of amino acid neurotransmitters including GABA ((r-aminobutyric acid)), Glu (Glutamate), and Glx (Glutamate + Glutamine) using (1)H-MRS technology. Moreover, we conducted Pearson correlation analysis between the ALFF value and neurotransmitter concentration to find out the functional-biochemical relation in mPFC area. The relationship between the metabolites concentration and MDD symptomatology was also examined through Spearman correlation analysis. We found that the female MDD patients showed increased neuronal spontaneous activity in left medial prefrontal cortex (mPFC) and left middle frontal cortex, with decreased ALFF level in right putamen and right middle temporal cortex (pconcentration in female MDD patients (r=0.67, p=0.023). The Glu concentration in mPFC was positively correlated with patients HAMA scores (r=0.641, p=0.033). The relatively small sample size, metabolite information acquired only in mPFC and not all patients were unmedicated are the major limitations of our study. Using combined fMRI-MRS methods, we found increased spontaneous neuronal activity was correlated with Glu concentration in mPFC of female MDD patients. Other

  18. 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.

  19. Dendritic morphology changes in neurons from the ventral hippocampus, amygdala and nucleus accumbens in rats with neonatal lesions into the prefrontal cortex.

    Science.gov (United States)

    Lazcano, Zayda; Solis, Oscar; Díaz, Alfonso; Brambila, Eduardo; Aguilar-Alonso, Patricia; Guevara, Jorge; Flores, Gonzalo

    2015-06-01

    Neonatal prefrontal cortex (nPFC) lesions in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the ventral hippocampus (VH) have been observed in post-mortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nPFC-lesions on the dendritic morphology of neurons from the VH, basolateral-amygdala (BLA) and the nucleus accumbens (NAcc) in rats. nPFC lesions were made on postnatal day 7 (PD7), after dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of PFC-lesions on locomotor activity caused by a novel environment. Adult animals with nPFC lesions showed a decreased spine density in pyramidal neurons from the VH and in medium spiny cells from the NAcc. An increased locomotion was observed in a novel environment for adult animals with a PFC-lesion. Our results indicate that PFC-lesions alter the neuronal dendrite morphology of the NAcc and the VH, suggesting a disconnection between these limbic structures. The locomotion paradigms suggest that dopaminergic transmission is altered in the PFC lesion model. This could help to understand the consequences of an earlier PFC dysfunction in schizophrenia. To evaluate possible dendritic changes in neonatal prefrontal cortex lesions in schizophrenia-related regions including nucleus accumbens, ventral hippocampus and basolateral amygdala, we used the Golgi-Cox stain samples at PD35 and PD70. Our results suggest that neonatal prefrontal cortex damage alters dendritic parameters in limbic regions, and this has potential implications for schizophrenia. © 2015 Wiley Periodicals, Inc.

  20. 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.

  1. Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats.

    Science.gov (United States)

    Cifani, Carlo; Koya, Eisuke; Navarre, Brittany M; Calu, Donna J; Baumann, Michael H; Marchant, Nathan J; Liu, Qing-Rong; Khuc, Thi; Pickel, James; Lupica, Carl R; Shaham, Yavin; Hope, Bruce T

    2012-06-20

    Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.

  2. Neurons in red nucleus and primary motor cortex exhibit similar responses to mechanical perturbations applied to the upper-limb during posture

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    Troy Michael Herter

    2015-04-01

    Full Text Available Primary motor cortex (M1 and red nucleus (RN are brain regions involved in limb motor control. Both structures are highly interconnected with the cerebellum and project directly to the spinal cord, although the contribution of RN is smaller than M1. It remains uncertain whether RN and M1 serve similar or distinct roles during posture and movement. Many neurons in M1 respond rapidly to mechanical disturbances of the limb, but it remains unclear whether RN neurons also respond to such limb perturbations. We have compared discharges of single neurons in RN (n = 49 and M1 (n = 109 of one monkey during a postural perturbation task. Neural responses to whole-limb perturbations were examined by transiently applying (300 ms flexor or extensor torques to the shoulder and/or elbow while the monkeys attempted to maintain a static hand posture. Relative to baseline discharges before perturbation onset, perturbations evoked rapid (<100 ms changes of neural discharges in many RN (28 of 49, 57% and M1 (43 of 109, 39% neurons. In addition to exhibiting a greater proportion of perturbation-related neurons, RN neurons also tended to exhibit higher peak discharge frequencies in response to perturbations than M1 neurons. Importantly, neurons in both structures exhibited similar response latencies and tuning properties (preferred torque directions and tuning widths in joint-torque space. Proximal arm muscles also displayed similar tuning properties in joint-torque space. These results suggest that RN is more sensitive than M1 to mechanical perturbations applied during postural control but both structures may play a similar role in feedback control of posture.

  3. Strychnine-sensitive glycine receptors on pyramidal neurons in layers II/III of the mouse prefrontal cortex are tonically activated.

    Science.gov (United States)

    Salling, Michael C; Harrison, Neil L

    2014-09-01

    Processing of signals within the cerebral cortex requires integration of synaptic inputs and a coordination between excitatory and inhibitory neurotransmission. In addition to the classic form of synaptic inhibition, another important mechanism that can regulate neuronal excitability is tonic inhibition via sustained activation of receptors by ambient levels of inhibitory neurotransmitter, usually GABA. The purpose of this study was to determine whether this occurs in layer II/III pyramidal neurons (PNs) in the prelimbic region of the mouse medial prefrontal cortex (mPFC). We found that these neurons respond to exogenous GABA and to the α4δ-containing GABAA receptor (GABA(A)R)-selective agonist gaboxadol, consistent with the presence of extrasynaptic GABA(A)R populations. Spontaneous and miniature synaptic currents were blocked by the GABA(A)R antagonist gabazine and had fast decay kinetics, consistent with typical synaptic GABA(A)Rs. Very few layer II/III neurons showed a baseline current shift in response to gabazine, but almost all showed a current shift (15-25 pA) in response to picrotoxin. In addition to being a noncompetitive antagonist at GABA(A)Rs, picrotoxin also blocks homomeric glycine receptors (GlyRs). Application of the GlyR antagonist strychnine caused a modest but consistent shift (∼15 pA) in membrane current, without affecting spontaneous synaptic events, consistent with the tonic activation of GlyRs. Further investigation showed that these neurons respond in a concentration-dependent manner to glycine and taurine. Inhibition of glycine transporter 1 (GlyT1) with sarcosine resulted in an inward current and an increase of the strychnine-sensitive current. Our data demonstrate the existence of functional GlyRs in layer II/III of the mPFC and a role for these receptors in tonic inhibition that can have an important influence on mPFC excitability and signal processing. Copyright © 2014 the American Physiological Society.

  4. P1-5: Effect of Luminance Contrast on the Color Selective Responses in the Inferior Temporal Cortex Neurons of the Macaque Monkey

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    Tomoyuki Namima

    2012-10-01

    Full Text Available Although the relationship between color signal and luminance signal is an important problem in visual perception, relatively little is known about how the luminance contrast affects the responses of color selective neurons in the visual cortex. In this study, we examined this problem in the inferior temporal (IT of the awake monkey performing a visual fixation task. Single neuron activities were recorded from the anterior and posterior color selective regions in IT cortex (AITC and PITC identified in previous studies where color selective neurons are accumulated. Color stimuli consisted of 28 stimuli that evenly distribute across the gamut of the CRT display defined on the CIE- xychromaticity diagram at two different luminance levels (5 cd/m 2or 20 cd/m 2 and 2 stimuli at white points. The background was maintained at 10 cd/m 2gray. We found that the effect of luminance contrast on the color selectivity was markedly different between AITC and PITC. When we examined the correlation between the responses to the bright stimuli and those to the dark stimuli with the same chromaticity coordinates, most AITC neurons exhibited high correlation whereas many PITC neurons showed no correlation or only weak correlation. In PITC, the effect was specifically large for neutral colors (white, gray, black and for colors with low saturation. These results indicate that the effect of luminance contrast on the color selective responses differs across different areas and suggest that the separation between color signal and luminance signal involves a higher stage of the cortical color processing.

  5. Systems Biology Approaches to Discerning Striated Muscle Pathologies

    OpenAIRE

    Mukund, Kavitha

    2016-01-01

    The human muscular system represents nearly 75% of the body mass and encompasses two major muscle forms- striated and smooth. Striated muscle, composed broadly of myofibers, accompanying membrane systems, cytoskeletal networks together with the metabolic and regulatory machinery, have revealed complexities in composition, structure and function. A disruption to any component within this complex system of interactions lead to disorders of the muscle, typically characterized by muscle fiber los...

  6. Poorly Understood Aspects of Striated Muscle Contraction

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    Alf Månsson

    2015-01-01

    Full Text Available Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP. Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

  7. Chronic morphine selectively sensitizes the effect of D1 receptor agonist on presynaptic glutamate release in basolateral amygdala neurons that project to prelimbic cortex.

    Science.gov (United States)

    Song, Jiaojiao; Chen, Ming; Dong, Yi; Lai, Bin; Zheng, Ping

    2018-05-01

    Drug addiction is a brain disorder characterized by chronic, compulsive use of drugs. Previous studies have found a number of chronic morphine-induced changes in the brain at molecular levels. A study from our lab showed that chronic morphine-induced increase in the expression of presynaptic D1 receptors in basolateral amygdala (BLA) neurons played an important role in environmental cue-induced retrieval of morphine withdrawal memory. However, the downstream neurocircuitry of chronic morphine-induced increase presynaptic D1 receptors in the BLA remains to be elucidated. Using retrogradely labelling technique combined with whole-cell patch-clamp methods, our results showed that (1) chronic morphine sensitized the effect of D1 receptor agonist on presynaptic glutamate release in BLA neurons that projected to the prelimbic cortex (PrL), but had no influence on that in BLA neurons that projected to the nucleus accumbens (NAc) or the CA1 of the hippocampus; (2) chronic morphine sensitized the effect of D1 receptor agonist on action potential firing in BLA neurons that projected to the PrL, but without affecting the intrinsic excitability and the sensitivity of postsynaptic glutamate receptors to glutamate in BLA neurons that projected to the PrL. These results suggest that chronic morphine selectively sensitizes the effect of D1 receptor agonist on presynaptic glutamate release in BLA neurons that project to PrL and induces a sensitization of the effect of D1 receptor agonist on action potential firing in BLA neurons that project to the PrL. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Playing the electric light orchestra--how electrical stimulation of visual cortex elucidates the neural basis of perception.

    Science.gov (United States)

    Cicmil, Nela; Krug, Kristine

    2015-09-19

    Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the 'causal map' of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making.

  9. Playing the electric light orchestra—how electrical stimulation of visual cortex elucidates the neural basis of perception

    Science.gov (United States)

    Cicmil, Nela; Krug, Kristine

    2015-01-01

    Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the ‘causal map′ of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making. PMID:26240421

  10. Distribution and ultrastructure of neurons in opossum piriform cortex displaying immunoreactivity to GABA and GAD and high-affinity tritiated GABA uptake

    International Nuclear Information System (INIS)

    Haberly, L.B.; Hansen, D.J.; Feig, S.L.; Presto, S.

    1987-01-01

    GABAergic neurons have been identified in the piriform cortex of the opossum at light and electron microscopic levels by immunocytochemical localization of GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase and by autoradiographic visualization of high-affinity 3 H-GABA uptake. Four major neuron populations have been distinguished on the basis of soma size, shape, and segregation at specific depths and locations: large horizontal cells in layer Ia of the anterior piriform cortex, small globular cells with thin dendrites concentrated in layers Ib and II of the posterior piriform cortex, and multipolar and fusiform cells concentrated in the deep part of layer III in anterior and posterior parts of the piriform cortex and the subjacent endopiriform nucleus. All four populations were well visualized with both antisera, but the large layer Ia horizontal cells displayed only very light 3 H-GABA uptake, thus suggesting a lack of local axon collaterals or lack of high-affinity GABA uptake sites. The large, ultrastructurally distinctive somata of layer Ia horizontal cells receive a very small number of symmetrical synapses; the thin, axonlike dendrites of small globular cells are exclusively postsynaptic and receive large numbers of both symmetrical and asymmetrical synapses, in contrast to somata which receive a small number of both types; and the deep multipolar and fusiform cells receive a highly variable number of symmetrical and asymmetrical synapses on somata and proximal dendrites. Labeled puncta of axon terminal dimensions were found in large numbers in the neuropil surrounding pyramidal cell somata in layer II and in the endopiriform nucleus. Moderately large numbers of labeled puncta were found in layer I at the depth of pyramidal cell apical dendrites with greater numbers in layer Ia at the depth of distal apical segments than in layer Ib

  11. A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation.

    Science.gov (United States)

    Mazuel, Leslie; Blanc, Jordy; Repond, Cendrine; Bouchaud, Véronique; Raffard, Gérard; Déglon, Nicole; Bonvento, Gilles; Pellerin, Luc; Bouzier-Sore, Anne-Karine

    2017-01-01

    Although several in vitro and ex vivo evidence support the existence of lactate exchange between astrocytes and neurons, a direct demonstration in vivo is still lacking. In the present study, a lentiviral vector carrying a short hairpin RNA (shRNA) was used to downregulate the expression of the monocarboxylate transporter type 2 (MCT2) in neurons of the rat somatosensory cortex (called S1BF) by ~ 25%. After one hour of whisker stimulation, HRMAS 1H-NMR spectroscopy analysis of S1BF perchloric acid extracts showed that while an increase in lactate content is observed in both uninjected and shRNA-control injected extracts, such an effect was abrogated in shMCT2 injected rats. A 13C-incorporation analysis following [1-13C]glucose infusion during the stimulation confirmed that the elevated lactate observed during activation originates from newly synthesized [3-13C]lactate, with blood-derived [1-13C]glucose being the precursor. Moreover, the analysis of the 13C-labeling of glutamate in position C3 and C4 indicates that upon activation, there is an increase in TCA cycle velocity for control rats while a decrease is observed for MCT2 knockdown animals. Using in vivo localized 1H-NMR spectroscopy, an increase in lactate levels is observed in the S1BF area upon whisker stimulation for shRNA-control injected rats but not for MCT2 knockdown animals. Finally, while a robust BOLD fMRI response was evidenced in control rats, it was absent in MCT2 knockdown rats. These data not only demonstrate that glucose-derived lactate is locally produced following neuronal activation but also suggest that its use by neurons via MCT2 is probably essential to maintain synaptic activity within the barrel cortex.

  12. La Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp

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    Yanjiao Jin

    2015-01-01

    Full Text Available Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl 3 , a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl 3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl 3 is reversible. Furthermore, this effect is persistent and stable unless LaCl 3 is washed out. Washout of LaCl 3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain.

  13. Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals.

    Science.gov (United States)

    Wang, Dangui; Zhao, Jun; Gao, Zilong; Chen, Na; Wen, Bo; Lu, Wei; Lei, Zhuofan; Chen, Changfeng; Liu, Yahui; Feng, Jing; Wang, Jin-Hui

    2015-01-01

    Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology, and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals.

  14. Ketamine-induced apoptosis in the mouse cerebral cortex follows similar characteristic of physiological apoptosis and can be regulated by neuronal activity.

    Science.gov (United States)

    Wang, Qi; Shen, Feng-Yan; Zou, Rong; Zheng, Jing-Jing; Yu, Xiang; Wang, Ying-Wei

    2017-06-17

    The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry. To explore the effect of neural activity on ketamine-induced apoptosis, the approaches of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and an environmental enrichment (EE) were performed. Ketamine-induced apoptosis in S1 is most prominent at postnatal days 5 and 7 (P5 - P7), and becomes insignificant by P12. Physiological and ketamine-induced apoptosis follow similar developmental patterns, mostly comprised of layer V pyramidal neurons at P5 and shifting to mostly layer II to IV GABAergic neurons by P9. Changes in neuronal activity induced by the DREADD system bidirectionally regulated the pattern of ketamine-induced apoptosis, with reduced activity inducing increased apoptosis and shifting the lamination pattern to a more immature form. Importantly, rearing mice in an EE significantly reduced the magnitude of ketamine-induced apoptosis and shifted its developmental pattern to a more mature form. Together, these results demonstrate that lamination pattern and cell-type dependent vulnerability to ketamine-induced apoptosis follow the physiological apoptosis pattern and are age- and activity-dependent. Naturally elevating neuronal activity is a possible method for reducing the adverse effects of general anesthesia.

  15. Persistent neuronal firing in primary somatosensory cortex in the absence of working memory of trial-specific features of the sample stimuli in a haptic working memory task.

    Science.gov (United States)

    Wang, Liping; Li, Xianchun; Hsiao, Steven S; Bodner, Mark; Lenz, Fred; Zhou, Yong-Di

    2012-03-01

    Previous studies suggested that primary somatosensory (SI) neurons in well-trained monkeys participated in the haptic-haptic unimodal delayed matching-to-sample (DMS) task. In this study, 585 SI neurons were recorded in monkeys performing a task that was identical to that in the previous studies but without requiring discrimination and active memorization of specific features of a tactile or visual memorandum. A substantial number of those cells significantly changed their firing rate in the delay compared with the baseline, and some of them showed differential delay activity. These firing changes are similar to those recorded from monkeys engaged in active (working) memory. We conclude that the delay activity is not necessarily only observed as was generally thought in the situation of active memorization of different features between memoranda after those features have been actively discriminated. The delay activity observed in this study appears to be an intrinsic property of SI neurons and suggests that there exists a neural network in SI (the primary sensory cortex) for haptic working memory no matter whether the difference in features of memoranda needs to be memorized in the task or not. Over 400 SI neurons were also recorded in monkeys well-trained to discriminate two memoranda in the haptic-haptic DMS task for comparison of delay firing of SI neurons between the two different working memory tasks used in this study. The similarity observed in those two situations suggests that working memory uses already-existing memory apparatus by activating it temporarily. Our data also suggest that, through training (repetitive exposure to the stimulus), SI neurons may increase their involvement in the working memory of the memorandum.

  16. Developing a neuronal model for the pathophysiology of schizophrenia based on the nature of electrophysiological actions of dopamine in the prefrontal cortex.

    Science.gov (United States)

    Yang, C R; Seamans, J K; Gorelova, N

    1999-08-01

    This review covers some recent findings of the electrophysiological mechanisms through which mesocortical dopamine modulates prefrontal cortical neurons. Dopamine has been shown to modulate several ionic conductances located along the soma-dendritic axis of prefrontal cortical pyramidal neurons. These ionic currents include high-voltage-activated calcium currents and slowly inactivating Na+ and K+ currents. They contribute actively in processing functionally segregated inputs during synaptic integration. In addition, dopamine mainly depolarizes the fast-spiking subtype of local GABAergic interneurons that connect the pyramidal neurons. This latter action can indirectly control pyramidal cell excitability. These electrophysiological data indicate that the actions of dopamine are neither "excitatory" nor "inhibitory" in pyramidal prefrontal cortex neurons. Rather, the actions of dopamine are dependent on somadendritic loci, timing of the arrival of synaptic inputs, strength of synaptic inputs, as well as the membrane potential range at which the PFC neuron is operating at a given moment. Based on available electrophysiological findings, a neuronal model of the pathophysiology of schizophrenia is presented. This model proposes that episodic hypo- and hyperactivity of the PFC and the associated dysfunctional mesocortical dopamine system (and their interconnected brain regions) may coexist in the same schizophrenic patient in the course of the illness. We hypothesize that the dysfunctional mesocortical dopamine input to the PFC may lead to abnormal modulation of ionic channels distributed in the dendritic-somatic compartments of PFC pyramidal neurons that project to the ventral tegmental area and/or nucleus accumbens. In some schizophrenics, a reduction of mesocortical dopamine to below optimal levels and/or a loss of local GABAergic inputs may result in a dysfunctional integration of extrinsic associative inputs by Ca2+ channel activity in the distal dendrites of PFC

  17. Primary motor cortex neurons during individuated finger and wrist movements: correlation of spike firing rates with the motion of individual digits versus their principal components

    Directory of Open Access Journals (Sweden)

    Evan eKirsch

    2014-05-01

    Full Text Available The joints of the hand provide 24 mechanical degrees of freedom. Yet 2 to 7 principal components (PCs account for 80 to 95 % of the variance in hand joint motion during tasks that vary from grasping to finger spelling. Such findings have led to the hypothesis that the brain may simplify operation of the hand by preferentially controlling PCs. We tested this hypothesis using data recorded from the primary motor cortex (M1 during individuated finger and wrist movements. Principal component analysis (PCA of the simultaneous position of the 5 digits and the wrist showed relatively consistent kinematic synergies across recording sessions in two monkeys. The first 3 PCs typically accounted for 85% of the variance. Cross-correlations then were calculated between the firing rate of single neurons and the simultaneous flexion/extension motion of each of the 5 digits and the wrist, as well as with each of their 6 PCs. For each neuron, we then compared the maximal absolute value of the cross-correlations (MAXC achieved with the motion of any digit or the wrist to the MAXC achieved with motion along any PC axis. The MAXC with a digit and the MAXC with a PC were themselves highly correlated across neurons. A minority of neurons correlated more strongly with a principal component than with any digit. But for the populations of neurons sampled from each of two subjects, MAXCs with digits were slightly but significantly higher than those with PCs. We therefore reject the hypothesis that M1 neurons preferentially control PCs of hand motion. We cannot exclude the possibility that M1 neurons might control kinematic synergies identified using linear or non-linear methods other than PCA. We consider it more likely, however, that neurons in other centers of the motor system—such as the pontomedullary reticular formation and the spinal gray matter—drive synergies of movement and/or muscles, which M1 neurons act to fractionate in producing individuated finger and

  18. Involvement of neuronal and glial activities in control of the extracellular d-serine concentrations by the AMPA glutamate receptor in the mouse medial prefrontal cortex.

    Science.gov (United States)

    Ishiwata, Sayuri; Umino, Asami; Nishikawa, Toru

    2017-09-28

    It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner. The inhibitory influence by the AMPA receptor on the extracellular d-serine, however, contradicts the data obtained from in vitro experiments that the AMPA receptor stimulation leads to facilitation of the d-serine liberation. This discrepancy appears to be due to the different cell setups between the in vivo and in vitro preparations. From the viewpoints of the previous reports indicating (1) the neuronal presence of d-serine synthesizing enzyme, serine racemase, and d-serine-like immunoreactivity and (2) the same high tissue concentrations of d-serine in the glia-enriched white matter and in the neuron-enriched gray matter of the mammalian neocortex, we have now investigated in the mouse medial prefrontal cortex, the effects of attenuation of neuronal and glial activities, by tetrodotoxin or fluorocitrate, respectively, on the S-AMPA-induced downregulation of the extracellular d-serine contents. In vivo dialysis studies revealed that a local infusion of tetrodotoxin or fluorocitrate eliminated the ability of S-AMPA given intra-cortically to cause a significant decrease in the dialysate concentrations of d-serine without affecting the elevating effects of S-AMPA on those of glycine, another intrinsic coagonist for the NMDA receptor. These findings suggest that the control by the AMPA receptor of the extracellular d-serine levels could be modulated by the neuronal and glial activities in the prefrontal cortex. It cannot be excluded that

  19. The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

    Science.gov (United States)

    Maeng, Lisa Y; Shors, Tracey J

    2013-01-01

    Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life

  20. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

    Directory of Open Access Journals (Sweden)

    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  1. Hippocampus-mediated activation of superficial and deep layer neurons in the medial entorhinal cortex of the isolated guinea pig brain.

    Science.gov (United States)

    Gnatkovsky, Vadym; de Curtis, Marco

    2006-01-18

    The entorhinal cortex (EC) is regarded as the structure that regulates information flow to and from the hippocampus. It is commonly assumed that superficial and deep EC neurons project to and receive from the hippocampal formation, respectively. Anatomical evidences suggest that both the hippocampal output and deep EC neurons also project to superficial EC layers. To functionally characterize the interlaminar synaptic EC circuit entrained the by hippocampal output, we performed simultaneous intracellular recordings and laminar profile analysis in the medial EC (m-EC) of the in vitro isolated guinea pig brain after polysynaptic hippocampal activation by lateral olfactory tract (LOT) stimulation. Optical imaging of voltage-generated signals confirmed that the LOT-evoked hippocampus-mediated response is restricted to the m-EC. The hippocampal output generated an extracellular current sink in layers V-VI, coupled with an EPSP in deep neurons. Deep neuron firing was terminated by a biphasic IPSP. The earliest response observed in superficial layer neurons was characterized by a feedforward IPSP of circa 100 ms (-69 +/- 1.3 mV reversal potential) abolished by local application of 1 mm bicuculline. The feedforward IPSP was followed by a delayed EPSP blocked by AP-5 (100 microM), presumably mediated by deep-to-superficial m-EC connections. Our findings demonstrate that superficial m-EC cells are inhibited by the hippocampal output via a feedforward pathway that prevents activity reverberation in the hippocampal-EC-hippocampal loop. We propose that such inhibition could serve as a protective mechanism to prevent epileptic hyperexcitability.

  2. Shifts in developmental timing, and not increased levels of experience-dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

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    Ingrid Fetter-Pruneda

    Full Text Available Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the posteromedial subfield in the primary somatosensory cortex. Although the historical view maintains that barrel expansion is due to incremental increases in neuronal activity along the trigeminal pathway during postnatal development, recent evidence obtained in experimental models of intramodal plasticity challenges this view. Here, we re-evaluate the role of experience-dependent neuronal activity on barrel expansion in birth-enucleated rats by combining various anatomical methods and sensory deprivation paradigms. We show that barrels in birth-enucleated rats were already enlarged by the end of the first week of life and had levels of metabolic activity comparable to those in control rats at different ages. Dewhiskering after the postnatal period of barrel formation did not prevent barrel expansion in adult, birth-enucleated rats. Further, dark rearing and enucleation after barrel formation did not lead to expanded barrels in adult brains. Because incremental increases of somatosensory experience did not promote barrel expansion in birth-enucleated rats, we explored whether shifts of the developmental timing could better explain barrel expansion during the first week of life. Accordingly, birth-enucleated rats show earlier formation of barrels, accelerated growth of somatosensory thalamocortical afferents, and an earlier H4 deacetylation. Interestingly, when H4 deacetylation was prevented with a histone deacetylases inhibitor (valproic acid, barrel specification timing returned to normal and barrel expansion did not occur. Thus, we provide evidence supporting that shifts in developmental timing modulated through epigenetic mechanisms, and not increased levels of experience dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

  3. Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior

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    Ronald P Gaykema

    2014-07-01

    Full Text Available The medial prefrontal cortex (mPFC is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular (IL/DP and prelimbic/anterior cingulate (PL/AC subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that activation of select mPFC interneurons may be required to support high cognitive demand states while being dispensable during

  4. Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

    OpenAIRE

    García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis

    2016-01-01

    The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of hi...

  5. Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice

    Science.gov (United States)

    Urban, Alan; Rancillac, Armelle; Martinez, Lucie; Rossier, Jean

    2012-01-01

    Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF. PMID:22715327

  6. Enduring high-efficiency in vivo transfection of neurons with non-viral magnetoparticles in the rat visual cortex for optogenetic applications.

    Science.gov (United States)

    Soto-Sánchez, Cristina; Martínez-Navarrete, Gema; Humphreys, Lawrence; Puras, Gustavo; Zarate, Jon; Pedraz, José Luis; Fernández, Eduardo

    2015-05-01

    This work demonstrates the successful long-term transfection in vivo of a DNA plasmid vector in rat visual cortex neurons using the magnetofection technique. The transfection rates reached values of up to 97% of the neurons after 30days, comparable to those achieved by viral vectors. Immunohistochemical treatment with anti-EGFP antibodies enhanced the detection of the EYFP-channelrhodopsin expression throughout the dendritic trees and cell bodies. These results show that magnetic nanoparticles offer highly efficient and enduring in vivo high-rate transfection in identified neurons of an adult mammalian brain and suggest that the magnetotechnique facilitates the introduction of large functional genetic material like channelrhodopsin with safe non-viral vectors using minimally invasive approaches. Gene therapy may be one of the treatment modalities for neurological diseases in the future. The use of viral transfection remains a concern due to restrictions to the size limit of the genetic material able to be packed, as well as safety issues. In this work, the authors evaluated magnetoplexes as an alternative vehicle. The results showed very promising data in that these nanoparticles could offer high transfection efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Neurohypophyseal hormones: novel actors of striated muscle development and homeostasis

    Directory of Open Access Journals (Sweden)

    Alessandra Costa

    2014-09-01

    Full Text Available Since the 1980's, novel functional roles of the neurohypophyseal hormones vasopressin and oxytocin have emerged. Several studies have investigated the effects of these two neurohormones on striated muscle tissues, both in vitro and in vivo. The effects of vasopressin on skeletal myogenic cells, developing muscle and muscle homeostasis have been documented. Oxytocin appears to have a greater influence on cardiomyocite differentiation and heart homeostasis. This review summarizes the studies on these novel roles of the two neurohypophyseal hormones, and open the possibility of new therapeutic approaches for diseases affecting striated muscle.

  8. View-based encoding of actions in mirror neurons of area f5 in macaque premotor cortex.

    Science.gov (United States)

    Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Pomper, Joern K; Thier, Peter; Giese, Martin A; Casile, Antonino

    2011-01-25

    Converging experimental evidence indicates that mirror neurons in the monkey premotor area F5 encode the goals of observed motor acts [1-3]. However, it is unknown whether they also contribute to encoding the perspective from which the motor acts of others are seen. In order to address this issue, we recorded the visual responses of mirror neurons of monkey area F5 by using a novel experimental paradigm based on the presentation of movies showing grasping motor acts from different visual perspectives. We found that the majority of the tested mirror neurons (74%) exhibited view-dependent activity with responses tuned to specific points of view. A minority of the tested mirror neurons (26%) exhibited view-independent responses. We conclude that view-independent mirror neurons encode action goals irrespective of the details of the observed motor acts, whereas the view-dependent ones might either form an intermediate step in the formation of view independence or contribute to a modulation of view-dependent representations in higher-level visual areas, potentially linking the goals of observed motor acts with their pictorial aspects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    OpenAIRE

    Débora Jardim-Messeder; Kelly Lambert; Stephen Noctor; Fernanda M. Pestana; Maria E. de Castro Leal; Mads F. Bertelsen; Abdulaziz N. Alagaili; Osama B. Mohammad; Paul R. Manger; Suzana Herculano-Houzel; Suzana Herculano-Houzel; Suzana Herculano-Houzel

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constr...

  10. Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action.

    Science.gov (United States)

    Mocci, Giuseppe; Jiménez-Sánchez, Laura; Adell, Albert; Cortés, Roser; Artigas, Francesc

    2014-04-01

    The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neurons projecting to ventral tegmental area express 5-HT2A receptors suggesting that atypical antipsychotic drugs modulate dopaminergic activity distally, via 5-HT2A receptor (5-HT2A-R) blockade in PFC. Since the mPFC also projects heavily to NAc, we examined whether NAc-projecting pyramidal neurons also express 5-HT2A-R. Using a combination of retrograde tracing experiments and in situ hybridization we report that a substantial proportion of mPFC-NAc pyramidal neurons in rat brain express 5-HT2A-R mRNA in a layer- and area-specific manner (up to 68% in layer V of contralateral cingulate). The functional relevance of 5-HT2A-R to modulate mPFC-NAc projections was examined in dual-probe microdialysis experiments. The application of the preferential 5-HT2A-R agonist DOI into mPFC enhanced glutamate release locally (+66 ± 18%) and in NAc (+74 ± 12%) indicating that cortical 5-HT2A-R activation augments glutamatergic transmission in NAc. Since NAc integrates glutamatergic and dopaminergic inputs, blockade of 5-HT2A-R by atypical drugs may reduce cortical excitatory inputs onto GABAergic neurons of NAc, adding to dopamine D2 receptor blockade. Together with previous observations, the present results suggest that atypical antipsychotic drugs may control the activity of the mesolimbic pathway at cell body and terminal level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The evolutionary origin of bilaterian smooth and striated myocytes

    Science.gov (United States)

    Brunet, Thibaut; Fischer, Antje HL; Steinmetz, Patrick RH; Lauri, Antonella; Bertucci, Paola; Arendt, Detlev

    2016-01-01

    The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed and nervous control. Our data suggest that both visceral smooth and somatic striated myocytes were present in the protostome-deuterostome ancestor and that smooth myocytes later co-opted the striated contractile module repeatedly – for example, in vertebrate heart evolution. During these smooth-to-striated myocyte conversions, the core regulatory complex of transcription factors conveying myocyte identity remained unchanged, reflecting a general principle in cell type evolution. DOI: http://dx.doi.org/10.7554/eLife.19607.001 PMID:27906129

  12. Fiber types in the striated urethral and anal sphincters

    DEFF Research Database (Denmark)

    Schrøder, H D; Reske-Nielsen, E

    1983-01-01

    Seven normal human striated urethral and anal sphincters obtained by autopsy were examined using histochemical techniques. In both the urethral sphincter and the subcutaneous (s.c.) and superficial part of the anal sphincter a characteristic pattern with two populations of muscle fibers, abundant...

  13. Stem/progenitor cells in the cerebral cortex of the human preterm: a resource for an endogenous regenerative neuronal medicine?

    Directory of Open Access Journals (Sweden)

    Laura Vinci

    2016-04-01

    Full Text Available The development of the central nervous system represents a very delicate period of embryogenesis. Premature interruption of neurogenesis in human preterm newborns can lead to motor deficits, including cerebral palsy, and significant cognitive, behavioral or sensory deficits in childhood. Preterm infants also have a higher risk of developing neurodegenerative diseases later in life. In the last decade, great importance has been given to stem/progenitor cells and their possible role in the development and treatment of several neurological disorders. Several studies, mainly carried out on experimental models, evidenced that immunohistochemistry may allow the identification of different neural and glial precursors inside the developing cerebral cortex. However, only a few studies have been performed on markers of human stem cells in the embryonic period.This review aims at illustrating the importance of stem/progenitor cells in cerebral cortex during pre- and post-natal life. Defining the immunohistochemical markers of stem/progenitor cells in the human cerebral cortex during development may be important to develop an “endogenous” target therapy in the perinatal period. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  14. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

    Science.gov (United States)

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  15. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  16. The striated MR nephrogram, not a reflection of pathology

    Energy Technology Data Exchange (ETDEWEB)

    Trout, Andrew T.; Care, Marguerite M.; Towbin, Alexander J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology - MLC 5031, Cincinnati, OH (United States); Zhang, Bin [Cincinnati Children' s Hospital Medical Center, Division of Biostatistics and Epidemiology, Cincinnati, OH (United States)

    2015-10-15

    We have intermittently observed low signal striations in the kidneys on delayed post-contrast MR exams of the spine. While we suspected these striations were due to concentrated gadolinium, the clinical importance of this finding was uncertain. To describe the striated MR nephrogram (low signal striations in the kidney) and assess its clinical relevance. Retrospective review of delayed post-contrast MRIs of the spine (mean: 45 min after contrast administration). The presence of the striated MR nephrogram was correlated with imaging parameters (field strength, time since contrast), and findings (gadolinium in the bladder, inferior vena cava and aorta diameters) and with clinical factors (history of renal disease, laboratory values). Seven hundred seventy-three exams performed on 229 patients, 8.3 ± 5.3 years of age, were reviewed. The striated MR nephrogram was observed in 102/773 examinations (13.2%) and was present on at least one study in 54/229 patients (23.6%). The presence of striations was associated with the specific magnet on which the exam was performed (P < 0.01) but not with magnet field strength. Serum creatinine was minimally lower in patients with striations (0.43 ± 0.12 vs. 0.49 ± 0.18 mg/dL, P = 0.002), but no other clinical or historical data, including time from contrast administration (P = 0.54), fluid status (P = 0.17) and clinical history of renal disease (P = 0.14), were predictive of the presence of striations. The striated MR nephrogram was observed in 13% of delayed post-contrast MR exams of the spine. Precipitating factors are unclear, but the striated nephrogram does not appear to be a marker of clinically apparent renal dysfunction. (orig.)

  17. Targeted Inactivation of Bax Reveals a Subtype-Specific Mechanism of Cajal-Retzius Neuron Death in the Postnatal Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Fanny Ledonne

    2016-12-01

    Full Text Available Cajal-Retzius cells (CRs, the first-born neurons in the developing cerebral cortex, coordinate crucial steps in the construction of functional circuits. CRs are thought to be transient, as they disappear during early postnatal life in both mice and humans, where their abnormal persistence is associated with pathological conditions. Embryonic CRs comprise at least three molecularly and functionally distinct subtypes: septum, ventral pallium/pallial-subpallial boundary (PSB, and hem. However, whether subtype-specific features exist postnatally and through which mechanisms they disappear remain unknown. We report that CR subtypes display unique distributions and dynamics of death in the postnatal mouse cortex. Surprisingly, although all CR subtypes undergo cell death, septum, but not hem, CRs die in a Bax-dependent manner. Bax-inactivated rescued septum-CRs maintain immature electrophysiological properties. These results underlie the existence of an exquisitely refined control of developmental cell death and provide a model to test the effect of maintaining immature circuits in the adult neocortex.

  18. Running wheel exercise reduces renewal of extinguished instrumental behavior and alters medial prefrontal cortex neurons in adolescent, but not adult, rats.

    Science.gov (United States)

    Eddy, Meghan C; Green, John T

    2017-12-01

    Physical exercise in rodents has repeatedly been shown to trigger positive effects on brain function, including increased neurotrophic factors and improved learning and memory. However, most of this work has focused on the adult hippocampus and hippocampal-dependent behavior. Here we examined the effect of running wheel exercise in adult and adolescent male rats on ABA renewal of extinguished instrumental conditioning, in which acquisition occurs in Context A, extinction in Context B, and renewal testing occurs back in Context A. In the first experiment, rats were given unlocked (exercise) or locked (no exercise) running wheel access in their home cages beginning at postnatal Day 30 (adolescent) or postnatal Day 56 (adult). Rats underwent lever-press acquisition in Context A and extinction in Context B. ABA renewal testing took place 2 weeks after the start of running wheel exposure. Nonexercising adolescent rats showed greater ABA renewal than nonexercising adult rats and exercise reduced ABA renewal in adolescents but not adults. ABA renewal depends on medial prefrontal cortex function. In a second experiment, we compared adolescent and adult apical dendrite branch length, branch number, and spine density of medial prefrontal cortex pyramidal neurons after 2 weeks of unlocked or locked running wheel access. The results revealed a higher density of dendritic spines and a lower dendritic branch length in adolescent exercisers than adolescent nonexercisers. Adult exercisers and nonexercisers did not differ. Collectively, these experiments suggest that exercise may have particularly strong effects on adolescent medial prefrontal cortex function and structure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Top-Down Control of Motor Cortex Ensembles by Dorsomedial Prefrontal Cortex

    OpenAIRE

    Narayanan, Nandakumar S.; Laubach, Mark

    2006-01-01

    Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predi...

  20. Data file of a deep proteome analysis of the prefrontal cortex in aged mice with progranulin deficiency or neuronal overexpression of progranulin

    Directory of Open Access Journals (Sweden)

    Juliana Heidler

    2016-12-01

    Full Text Available Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13–15 months female progranulin-deficient mice (GRN−/− and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source. Full Scan MS-data were acquired using Xcalibur and raw files were analyzed using the proteomics software Max Quant. The mouse reference proteome set from uniprot (June 2015 was used to identify peptides and proteins. The DiB data file is a reduced MaxQuant output and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ values of each sample. Differences in protein expression in genotypes are presented in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  1. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Directory of Open Access Journals (Sweden)

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  2. VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for adult survival in caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Sung Min Han

    Full Text Available Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA, two motor neuron diseases that often include alterations in energy metabolism. We have shown that C. elegans and Drosophila neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein domain (vMSP. Secreted vMSPs signal through Roundabout and Lar-like receptors expressed on striated muscle. The muscle signaling pathway localizes mitochondria to myofilaments, alters their fission/fusion balance, and promotes energy production. Here, we show that neuronal loss of the C. elegans VAPB homolog triggers metabolic alterations that appear to compensate for muscle mitochondrial dysfunction. When vMSP levels drop, cytoskeletal or mitochondrial abnormalities in muscle induce elevated DAF-16, the Forkhead Box O (FoxO homolog, transcription factor activity. DAF-16 promotes muscle triacylglycerol accumulation, increases ATP levels in adults, and extends lifespan, despite reduced muscle mitochondria electron transport chain activity. Finally, Vapb knock-out mice exhibit abnormal muscular triacylglycerol levels and FoxO target gene transcriptional responses to fasting and refeeding. Our data indicate that impaired vMSP signaling to striated muscle alters FoxO activity, which affects energy metabolism. Abnormalities in energy metabolism of ALS patients may thus constitute a compensatory mechanism counterbalancing skeletal muscle mitochondrial dysfunction.

  3. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors

    OpenAIRE

    Borbély, S; Jocsak, Gergely; Moldovan, Kinga; Sedlak, Lucie; Preininger, Eva; Boldizsar, Imre; Toth, Attila; Atlason, Palmi T; Molnar, Elek; Vilagi, Ildiko

    2016-01-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) t...

  4. Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons

    Science.gov (United States)

    Park, Junchol

    2017-01-01

    Actions motivated by rewards are often associated with risk of punishment. Little is known about the neural representation of punishment risk during reward-seeking behavior. We modeled this circumstance in rats by designing a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during task performance simultaneously from VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and aversive behaviors. At the single unit level, we found that ensembles of putative dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship between action and punishment. At the network level, we found that coherent theta oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment probability, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions. PMID:29058673

  5. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

    Science.gov (United States)

    Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó

    2016-07-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Rapid dopaminergic and GABAergic modulation of calcium and voltage transients in dendrites of prefrontal cortex pyramidal neurons

    Science.gov (United States)

    Zhou, Wen-Liang; Antic, Srdjan D

    2012-01-01

    The physiological responses of dendrites to dopaminergic inputs are poorly understood and controversial. We applied dopamine on one dendritic branch while simultaneously monitoring action potentials (APs) from multiple dendrites using either calcium-sensitive dye, voltage-sensitive dye or both. Dopaminergic suppression of dendritic calcium transients was rapid (calcium signals, as determined by dual voltage and calcium imaging. The dopamine effects on dendritic calcium transients were fully mimicked by D1 agonists, partially reduced by D1 antagonist and completely insensitive to protein kinase blockade; consistent with a membrane delimited mechanism. This dopamine effect was unaltered in the presence of L-, R- and T-type calcium channel blockers. The somatic excitability (i.e. AP firing) was not affected by strong dopaminergic stimulation of dendrites. Dopamine and GABA were then sequentially applied on the same dendrite. In contrast to dopamine, the pulses of GABA prohibited AP backpropagation distally from the application site, even in neurons with natural Cl− concentration (patch pipette removed). Thus, the neocortex employs at least two distinct mechanisms (dopamine and GABA) for rapid modulation of dendritic calcium influx. The spatio-temporal pattern of dendritic calcium suppression described in this paper is expected to occur during phasic dopaminergic signalling, when midbrain dopaminergic neurons generate a transient (0.5 s) burst of APs in response to a salient event. PMID:22641784

  7. Autoradiographic analysis of protein regeneration in striated skeleton muscle

    International Nuclear Information System (INIS)

    Dadoune, J.P.

    1977-01-01

    An autoradiographic study was conducted of protein regeneration in striated muscles aimed at clarifying the contradictions in the literature: while some authors hold that the regeneration rate is identical for all types of myofibril proteins and the myofibril is thus regenerated as a whole, others claim that the regeneration rate differs depending on the type of the myofibril protein. Tritium-labelled leucine incorporation experiments showed the existence of at least 2 pools of newly formed proteins in striated muscles in both adult and young animals. One pool is regenerated in 1 to 2 weeks, the other roughly in a month. The regeneration of proteins is initially more significant in red fibres; thus the rate of myofibril protein regeneration is not uniform. In adult animals regeneration seems to be slower in filaments than in the sarcoplasm and in the mitochondria. (A.K.)

  8. Expression of various sarcomeric tropomyosin isoforms in equine striated muscles

    OpenAIRE

    Dube, Syamalima; Chionuma, Henry; Matoq, Amr; Alshiekh-Nasany, Ruham; Abbott, Lynn; Poiesz, Bernard J.; Dube, Dipak K.

    2017-01-01

    In order to better understand the training and athletic activity of horses, we must have complete understanding of the isoform diversity of various myofibrillar protein genes like tropomyosin. Tropomyosin (TPM), a coiled-coil dimeric protein, is a component of thin filament in striated muscles. In mammals, four TPM genes (TPM1, TPM2, TPM3, and TPM4) generate a multitude of TPM isoforms via alternate splicing and/or using different promoters. Unfortunately, our knowledge of TPM isoform diversi...

  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. [The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation].

    Science.gov (United States)

    Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente

    2015-01-06

    The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  11. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    International Nuclear Information System (INIS)

    Tsirulnikov, Kirill; Abuladze, Natalia; Bragin, Anatol; Faull, Kym; Cascio, Duilio; Damoiseaux, Robert; Schibler, Matthew J.; Pushkin, Alexander

    2012-01-01

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase. The enzymes of the GSH-conjugation pathway and β-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a β-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  12. Differential effects of swimming training on neuronal calcium sensor-1 expression in rat hippocampus/cortex and in object recognition memory tasks.

    Science.gov (United States)

    Drumond, Luciana Estefani; Mourão, Flávio Afonso Gonçalves; Leite, Hércules Ribeiro; Abreu, Renata Viana; Reis, Helton José; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Massensini, André Ricardo

    2012-07-01

    Physical activity has been proposed as a behavioral intervention that improves learning and memory; nevertheless, the mechanisms underlying these health benefits are still not well understood. Neuronal Calcium Sensor-1 (NCS-1) is a member of a superfamily of proteins that respond to local Ca(2+) changes shown to have an important role in learning and memory. The aim of the present study was to investigate the effects of swimming training on NCS-1 levels in the rat brain after accessing cognitive performance. Wistar rats were randomly assigned to sedentary (SG) or exercised groups (EG). The EG was subject to forced swimming activity, 30 min/day, 5 days/week, during 8 weeks. Progressive load trials were performed in the first and last week in order to access the efficiency of the training. After the 8 week training protocol, memory performance was evaluated by the novel object preference and object location tasks. NCS-1 levels were measured in the cortex and hippocampus using immunoblotting. The EG performed statistically better for the spatial short-term memory (0.73 ± 0.01) when compared to the SG (0.63 ± 0.02; P0.05). In addition, chronic exercise promoted a significant increase in hippocampal NCS-1 levels (1.8 ± 0.1) when compared to SG (1.17 ± 0.08; P0.05). Results suggest that physical exercise would modulate the state of the neural network regarding its potential for plastic changes: physical exercise could be modulating NCS-1 in an activity dependent manner, for specific neural substrates, thus enhancing the cellular/neuronal capability for plastic changes in these areas; which, in turn, would differentially effect ORM task performance for object recognition and displacement. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    Energy Technology Data Exchange (ETDEWEB)

    Tsirulnikov, Kirill; Abuladze, Natalia [Department of Medicine, University of California at Los Angeles, CA 90095 (United States); Bragin, Anatol [Department of Neurology, University of California at Los Angeles, CA 90095 (United States); Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Faull, Kym [Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095 (United States); Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 (United States); Cascio, Duilio [Institute of Genomics and Proteomics, University of California at Los Angeles, CA 90095 (United States); Damoiseaux, Robert; Schibler, Matthew J. [California NanoSystems Institute, University of California at Los Angeles, CA 90095 (United States); Pushkin, Alexander, E-mail: apushkin@mednet.ucla.edu [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)

    2012-09-15

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase. The enzymes of the GSH-conjugation pathway and β-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a β-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  14. Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency

    DEFF Research Database (Denmark)

    Castrop, H; Kammerl, M; Mann, Birgitte

    2000-01-01

    Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of n......NOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined...... with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day...

  15. Sensorimotor cortex as a critical component of an 'extended' mirror neuron system: Does it solve the development, correspondence, and control problems in mirroring?

    Science.gov (United States)

    Pineda, Jaime A

    2008-01-01

    from an anatomical, physiological, modeling, and functional perspectives that a critical component of the human mirror neuron system is sensorimotor cortex. Not only are sensorimotor transformations necessary for computing the patterns of muscle activation and kinematics during action observation but they provide potential answers to the development, correspondence and control problems. PMID:18928566

  16. Sensorimotor cortex as a critical component of an 'extended' mirror neuron system: Does it solve the development, correspondence, and control problems in mirroring?

    Directory of Open Access Journals (Sweden)

    Pineda Jaime A

    2008-10-01

    ?" In this review, we argue from an anatomical, physiological, modeling, and functional perspectives that a critical component of the human mirror neuron system is sensorimotor cortex. Not only are sensorimotor transformations necessary for computing the patterns of muscle activation and kinematics during action observation but they provide potential answers to the development, correspondence and control problems.

  17. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. Copyright © 2015 the American Physiological Society.

  18. Neuronal nicotinic receptors are crucial for tuning of E/I balance in prelimbic cortex and for decision-making processes

    Directory of Open Access Journals (Sweden)

    alexis Faure

    2016-10-01

    Full Text Available Rationale Decision-making is an essential component of our everyday life commonly disabled in a myriad of psychiatric conditions such as bipolar and impulsive control disorders, addiction and pathological gambling, or schizophrenia. A large cerebral network encompassing the prefrontal cortex -PFC- the amygdala and the nucleus accumbens is activated for efficient decision-making.Methods We developed a Mouse Gambling Task -MGT- well suited to investigate the influence of uncertainty and risk in decision-making and the role of neurobiological circuits and their monoaminergic inputs. Neuronal nicotinic acetylcholine receptors (nAChRs of the PFC are important for decision-making processes but their presumed roles in risk-taking and uncertainty management, as well as in cellular balance of excitation and inhibition (E/I need to be investigated. Results Using mice lacking nAChRs - β2-/- mice, we evidence for the first time the crucial role of nAChRs in the fine tuning of prefrontal E/I balance together with the PFC, insular, and hippocampal alterations in gambling behavior likely due to sensitivity to penalties and flexibility alterations. Risky behaviors and perseveration in extinction task were largely increased in β2-/- mice as compared to control mice, suggesting the important role of nAChRs in the ability to make appropriate choices adapted to the outcome.

  19. Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus.

    Directory of Open Access Journals (Sweden)

    Katrina E Furth

    Full Text Available Alterations in the function of the medial prefrontal cortex (mPFC and its major thalamic source of innervation, the mediodorsal (MD thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP activity in the rat mPFC and MD thalamus. Additionally, we investigated the ability of drugs targeting the dopamine D4 receptor (D4R to modify the effects of ketamine on gamma activity as a measure of potential cognitive therapeutic efficacy. Rats were trained to walk on a treadmill to reduce confounds related to hyperactivity after ketamine administration (10 mg/kg s.c. while recordings were obtained from electrodes chronically implanted in the mPFC and MD thalamus. Ketamine increased gamma LFP power in mPFC and MD thalamus in a similar frequency range, yet did not increase thalamocortical synchronization. Ketamine also increased firing rates and spike synchronization to gamma oscillations in the mPFC but decreased both measures in MD thalamus. Conversely, walking alone increased both firing rates and spike-gamma LFP correlations in both mPFC and MD thalamus. The D4R antagonist alone (L-745,870 had no effect on gamma LFP power during treadmill walking, although it reversed increases induced by the D4R agonist (A-412997 in both mPFC and MD thalamus. Neither drug altered ketamine-induced changes in gamma power or firing rates in the mPFC. However, in MD thalamus, the D4R agonist increased ketamine-induced gamma power and prevented ketamine's inhibitory effect on firing rates. Results provide new evidence that ketamine differentially modulates spiking and gamma power in MD thalamus and mPFC, supporting a potential role for both

  20. Forecasting Faces in the Cortex: Comment on 'High-Level Prediction Signals in a Low-Level Area of the Macaque Face-Processing Hierarchy', by Schwiedrzik and Freiwald, Neuron (2017).

    Science.gov (United States)

    Petro, Lucy S; Muckli, Lars

    2018-02-01

    Although theories of predictive coding in the brain abound, we lack key pieces of neuronal data to support these theories. Recently, Schwiedrzik and Freiwald found neurophysiological evidence for predictive codes throughout the face-processing hierarchy in macaque cortex. We highlight how these data enhance our knowledge of cortical information processing, and the impact of this more broadly. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Expression of various sarcomeric tropomyosin isoforms in equine striated muscles

    Directory of Open Access Journals (Sweden)

    Syamalima Dube

    2017-06-01

    Full Text Available In order to better understand the training and athletic activity of horses, we must have complete understanding of the isoform diversity of various myofibrillar protein genes like tropomyosin. Tropomyosin (TPM, a coiled-coil dimeric protein, is a component of thin filament in striated muscles. In mammals, four TPM genes (TPM1, TPM2, TPM3, and TPM4 generate a multitude of TPM isoforms via alternate splicing and/or using different promoters. Unfortunately, our knowledge of TPM isoform diversity in the horse is very limited. Hence, we undertook a comprehensive exploratory study of various TPM isoforms from horse heart and skeletal muscle. We have cloned and sequenced two sarcomeric isoforms of the TPM1 gene called TPM1α and TPM1κ, one sarcomeric isoform of the TPM2 and one of the TPM3 gene, TPM2α and TPM3α respectively. By qRT-PCR using both relative expression and copy number, we have shown that TPM1α expression compared to TPM1κ is very high in heart. On the other hand, the expression of TPM1α is higher in skeletal muscle compared to heart. Further, the expression of TPM2α and TPM3α are higher in skeletal muscle compared to heart. Using western blot analyses with CH1 monoclonal antibody we have shown the high expression levels of sarcomeric TPM proteins in cardiac and skeletal muscle. Due to the paucity of isoform specific antibodies we cannot specifically detect the expression of TPM1κ in horse striated muscle. To the best of our knowledge this is the very first report on the characterization of sarcmeric TPMs in horse striated muscle.

  2. Contracture of Slow Striated Muscle during Calcium Deprivation

    Science.gov (United States)

    Irwin, Richard L.; Hein, Manfred M.

    1963-01-01

    When deprived of calcium the slow striated muscle fibers of the frog develop reversible contractures in either hypertonic or isotonic solutions. While calcium deprivation continues because of a flowing calcium-free solution the muscles relax slowly and completely. Restoration of calcium during contracture relaxes the muscle promptly to initial tension. When relaxed during calcium lack the return of calcium does not change tension and the muscle stays relaxed. When contractures are induced by solutions containing small amounts of calcium relaxation does not occur or requires several hours. The rate of tension development depends upon the rate at which calcium moves outward since the contractures develop slower in low concentrations of calcium and are absent or greatly slowed in a stagnant calcium-free solution. Withdrawal of calcium prevents the contractile responses to ACh, KCl, or electrical stimulation through the nerve. Muscles return to their original excitability after calcium is restored. Origin of the contractures is unrelated to nerve activity since they are maximal during transmission failure from calcium lack, occur in denervated muscles, and are not blocked by high concentrations of d-tubocurarine, procaine, or atropine. The experiments also indicate that the contractures do not originate from repetitive activity of muscle membranes. The findings are most simply explained by relating the outward movement of calcium as a link for initiating contraction in slow type striated muscle. PMID:14065284

  3. Virtual and simulated striated toolmarks for forensic applications.

    Science.gov (United States)

    Baiker, Martin; Petraco, Nicholas D K; Gambino, Carol; Pieterman, René; Shenkin, Peter; Zoon, Peter

    2016-04-01

    Large numbers of experimental toolmarks of screwdrivers are often required in casework of toolmark examiners and in research environments alike, to be able to recover the angle of attack of a crime scene mark and to determine statistically meaningful properties of toolmarks respectively. However, in practice the number of marks is limited by the time needed to create them. In this article, we present an approach to predict how a striated mark of a particular tool would look like, using 3D surface datasets of screwdrivers. We compare these virtual toolmarks qualitatively and quantitatively with real experimental marks in wax and show that they are very similar. In addition we study toolmark similarity, dependent on the angle of attack, with a very high angular resolution of 1°. The results show that for the tested type of screwdriver, our toolmark comparison framework yields known match similarity scores that are above the mean known non-match similarity scores, even for known match differences in angle of attack of up to 40°. In addition we demonstrate an approach to automatically recover the angle of attack of an experimental toolmark and experiments yield high accuracy and precision of 0.618 ± 4.179°. Furthermore, we present a strategy to study the structural elements of striated toolmarks using wavelet analysis, and show how to use the results to simulate realistic toolmarks. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Corticospinal mirror neurons

    OpenAIRE

    Kraskov, A.; Philipp, R.; Waldert, S.; Vigneswaran, G.; Quallo, M. M.; Lemon, R. N.

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like p...

  5. Effect of feature-selective attention on neuronal responses in macaque area MT

    Science.gov (United States)

    Chen, X.; Hoffmann, K.-P.; Albright, T. D.

    2012-01-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

  6. Study of the striated nature of a glow discharge

    International Nuclear Information System (INIS)

    Hernandez A, M.

    1995-01-01

    In an investigation in progress here, plasma diagnostics and detection of standing and moving striations is being made in a discharge in Argon at pressures of 2 x 10 -1 to 9 x 10 -1 mb and currents of 2 to 9 m-amp inside an discharge tube. Measurement of the temperature of the electrons, the concentration of electrons and the plasma potential are obtained in different places of the discharge by the double probe method, together with the computation system reported in [1]. In similar way an experimental work of the striated column in a discharge plasma to find the regimen of appearance of the standing and moving striations show some properties of moving striations (frequency and velocity) and standing striations. Two different oscilations are observed in motion in contrary directions along the discharge tube with a photomultiplier. (Author)

  7. Early Monocular Defocus Disrupts the Normal Development of Receptive-Field Structure in V2 Neurons of Macaque Monkeys

    Science.gov (United States)

    Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L.; Nishimoto, Shinji; Ohzawa, Izumi

    2014-01-01

    Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. PMID:25297110

  8. Distinct timescales of population coding across cortex.

    Science.gov (United States)

    Runyan, Caroline A; Piasini, Eugenio; Panzeri, Stefano; Harvey, Christopher D

    2017-08-03

    The cortex represents information across widely varying timescales. For instance, sensory cortex encodes stimuli that fluctuate over few tens of milliseconds, whereas in association cortex behavioural choices can require the maintenance of information over seconds. However, it remains poorly understood whether diverse timescales result mostly from features intrinsic to individual neurons or from neuronal population activity. This question remains unanswered, because the timescales of coding in populations of neurons have not been studied extensively, and population codes have not been compared systematically across cortical regions. Here we show that population codes can be essential to achieve long coding timescales. Furthermore, we find that the properties of population codes differ between sensory and association cortices. We compared coding for sensory stimuli and behavioural choices in auditory cortex and posterior parietal cortex as mice performed a sound localization task. Auditory stimulus information was stronger in auditory cortex than in posterior parietal cortex, and both regions contained choice information. Although auditory cortex and posterior parietal cortex coded information by tiling in time neurons that were transiently informative for approximately 200 milliseconds, the areas had major differences in functional coupling between neurons, measured as activity correlations that could not be explained by task events. Coupling among posterior parietal cortex neurons was strong and extended over long time lags, whereas coupling among auditory cortex neurons was weak and short-lived. Stronger coupling in posterior parietal cortex led to a population code with long timescales and a representation of choice that remained consistent for approximately 1 second. In contrast, auditory cortex had a code with rapid fluctuations in stimulus and choice information over hundreds of milliseconds. Our results reveal that population codes differ across cortex

  9. ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex.

    Science.gov (United States)

    Hirota, Yuki; Kubo, Ken-Ichiro; Fujino, Takahiro; Yamamoto, Tokuo T; Nakajima, Kazunori

    2018-01-01

    Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yeo Cho Yoon

    2015-12-01

    Full Text Available Limonin, one of the major components in dictamni radicis cortex (DRC, has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

  11. Persistent Neuronal Firing in Primary Somatosensory Cortex in the Absence of Working Memory of Trial-Specific Features of the Sample Stimuli in a Haptic Working Memory Task

    Science.gov (United States)

    Wang, Liping; Li, Xianchun; Hsiao, Steven S.; Bodner, Mark; Lenz, Fred; Zhou, Yong-Di

    2012-01-01

    Previous studies suggested that primary somatosensory (SI) neurons in well-trained monkeys participated in the haptic-haptic unimodal delayed matching-to-sample (DMS) task. In this study, 585 SI neurons were recorded in monkeys performing a task that was identical to that in the previous studies but without requiring discrimination and active…

  12. Cre-expressing neurons in visual cortex of Ntsr1-Cre GN220 mice are corticothalamic and are depolarized by acetylcholine.

    Science.gov (United States)

    Sundberg, Sofie Charlotte; Lindström, Sarah Helen; Sanchez, Gonzalo Manuel; Granseth, Björn

    2018-01-01

    The Ntsr1-Cre GN220 mouse expresses Cre-recombinase in corticothalamic (CT) neurons in neocortical layer 6. It is not known if the other major types of pyramidal neurons in this layer also express this enzyme. By electrophysiological recordings in slices and histological analysis of the uptake of retrogradely transported beads we show that Cre-positive neurons are CT and not corticocortical or corticoclaustral types. Furthermore, we show that Ntsr1-Cre-positive cells are immuno-positive for the nuclear transcription factor Forkhead box protein P2 (FoxP2). We conclude that Cre-expression is limited to a specific type of pyramidal neuron: CT. However, it appears as not all CT neurons are Cre-expressing; there are indications that the penetrance of the gene is about 90%. We demonstrate the utility of assigning a specific identity to individual neurons by determining that the CT neurons are potently modulated by acetylcholine acting on both nicotinic and muscarinic acetylcholine receptors. These results corroborate the suggested function of these neurons in regulating the gain of thalamocortical transfer of sensory information depending on attentional demand and state of arousal. © 2017 Wiley Periodicals, Inc.

  13. Compositional studies of myofibrils from rabbit striated muscle

    Energy Technology Data Exchange (ETDEWEB)

    Etlinger, J.D.; Zak, R.; Fischman, D.A.

    1976-01-01

    The localization of high-molecular-weight (80,000-200,000-daltons) proteins in the sarcomere of striated muscle has been studied by coordinated electron-microscopic and sodium dodecyl sulfate (SDS) gel electrophoretic analysis of native myofilaments and extracted and digested myofibrils. Methods were developed for the isolation of thick and thin filaments and of uncontracted myofibrils which are devoid of endoproteases and membrane fragments. Treatment of crude myofibrils with 0.5% Triton X-100 results in the release of a 110,000-dalton component without affecting the myofibrillar structure. Extraction of uncontracted myofibrils with a relaxing solution of high ionic strength results in the complete disappearance of the A band and M line. In this extract, five other protein bands in addition to myosin are resolved on SDS gels: bands M 1 (190,000 daltons) and M 2 (170,000 daltons), which are suggested to be components of the M line; M 3 (150,000 daltons), a degradation product; and a doublet M 4, M 5 (140,000 daltons), thick-filament protein having the same mobility as C protein.

  14. Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

    Directory of Open Access Journals (Sweden)

    Park SY

    2017-06-01

    Full Text Available Sun Young Park,1 Seon Yeong Chae,1,2 Jin Oh Park,2 Kyu Jin Lee,2 Geuntae Park1,2 1Bio-IT Fusion Technology Research Institute, 2Department of Nanofusion Technology, Graduate School, Pusan National University, Busan, Republic of Korea Abstract: Recently, environment-friendly synthesis of gold nanoparticles (GNPs has been extensively explored by biologists and chemists. However, significant research is still required to determine whether “eco-friendly” GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs, prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen–glucose deprivation/reoxygenation (OGD/R-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet–visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm and zeta potential (-20.3±0.04 mV were determined by dynamic light scattering. The average diameter (41.07±3.05 nm was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O–H, C–C, and C–N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p

  15. Injection of Retrograde Beads into the Nucleus Accumbens (NAc) and Medial Prefronral Cortex (mPFC) to Isolate Projection-Specific Neurons in the Ventral Tegmental Area (VTA)

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Jessica Walsh, Allyson Friedman, Dipesh Chaudhury, Barbara Juarez, Stacy Ku & Ming-Hu Han ### Abstract Retrograde dyes, such as lumafluors, have been used as tracers to visualize neurons that project to a specific target region. Injection of these dyes provides an important method in being able to understand the functional role of projection-specific neurons. Lumafluors can be directly injected into a target brain region of a mouse and dye positive cells from the projection ...

  16. Optogenetic manipulation of Ventral Tegmental Area (VTA) Neurons that project to the Nucleus Accumbens (NAc) and medial Prefrontal Cortex (mPFC)

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Jessica Walsh, Dipesh Chaudhury, Allyson Friedman, Barbara Juarez, Stacy Ku, Mary Kay Lobo & Ming-Hu Han ### Abstract Optogenetics has evolved to be a critical technique used to manipulate the firing activity of specific subsets of neurons. Through the use of specific firing parameters, it has become possible to control the behavior of freely moving animals. Here we have established a system to control projection pathway-specific neurons from a particular brain region through...

  17. Layer-Dependent Short-Term Synaptic Plasticity Between Excitatory Neurons in the C2 Barrel Column of Mouse Primary Somatosensory Cortex.

    Science.gov (United States)

    Lefort, Sandrine; Petersen, Carl C H

    2017-07-01

    Neurons process information through spatiotemporal integration of synaptic input. Synaptic transmission between any given pair of neurons is typically a dynamic process with presynaptic action potentials (APs) evoking depressing or facilitating postsynaptic potentials when presynaptic APs occur within hundreds of milliseconds of each other. In order to understand neocortical function, it is therefore important to investigate such short-term synaptic plasticity at synapses between different types of neocortical neurons. Here, we examine short-term synaptic dynamics between excitatory neurons in different layers of the mouse C2 barrel column through in vitro whole-cell recordings. We find layer-dependent short-term plasticity, with depression being dominant at many synaptic connections. Interestingly, however, presynaptic layer 2 neurons predominantly give rise to facilitating excitatory synaptic output at short interspike intervals of 10 and 30 ms. Previous studies have found prominent burst firing of excitatory neurons in supragranular layers of awake mice. The facilitation we observed in the synaptic output of layer 2 may, therefore, be functionally relevant, possibly serving to enhance the postsynaptic impact of burst firing. © The Author 2017. Published by Oxford University Press.

  18. Neurons in the basal forebrain project to the cortex in a complex topographic organization that reflects corticocortical connectivity patterns: an experimental study based on retrograde tracing and 3D reconstruction.

    Science.gov (United States)

    Zaborszky, Laszlo; Csordas, Attila; Mosca, Kevin; Kim, Joseph; Gielow, Matthew R; Vadasz, Csaba; Nadasdy, Zoltan

    2015-01-01

    The most prominent feature of the Basal Forebrain (BF) is the collection of large cortically projecting neurons (basal nucleus of Meynert) that serve as the primary source of cholinergic input to the entire cortical mantle. Despite its broad involvement in cortical activation, attention, and memory, the functional details of the BF are not well understood due to the anatomical complexity of the region. This study tested the hypothesis that basalocortical connections reflect cortical connectivity patterns. Distinct retrograde tracers were deposited into various frontal and posterior cortical areas, and retrogradely labeled cholinergic and noncholinergic neurons were mapped in the BF. Concurrently, we mapped retrogradely labeled cells in posterior cortical areas that project to various frontal areas, and all cell populations were combined in the same coordinate system. Our studies suggest that the cholinergic and noncholinergic projections to the neocortex are not diffuse, but instead, are organized into segregated or overlapping pools of projection neurons. The extent of overlap between BF populations projecting to the cortex depends on the degree of connectivity between the cortical targets of these projection populations. We suggest that the organization of projections from the BF may enable parallel modulation of multiple groupings of interconnected yet nonadjacent cortical areas. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. A cable theory based biophysical model of resistance change in crab peripheral nerve and human cerebral cortex during neuronal depolarisation: implications for electrical impedance tomography of fast neural activity in the brain.

    Science.gov (United States)

    Liston, Adam; Bayford, Richard; Holder, David

    2012-05-01

    Electrical impedance tomography (EIT) is a medical imaging method with the potential to image resistance changes which occur during neuronal depolarisation in the brain with a resolution of milliseconds and millimetres. Most biomedical EIT is conducted with applied current over 10 kHz, as this reduces electrode impedance and so instrumentation artefact. However, impedance changes during neuronal depolarization are negligible at such frequencies. In order to estimate optimal recording frequency and specify instrumentation requirements, we have modelled their amplitude and frequency dependence during evoked activity using cable theory. Published values were used for the electrical properties and geometry of cell processes. The model was adjusted for the filtering effect of membrane capacitance and proportion of active neurons. At DC, resistance decreases by 2.8 % in crab nerve during the compound action potential and 0.6 % (range 0.06-1.7 %) locally in cerebral cortex during evoked physiological activity. Both predictions correlate well with independent experimental data. This encourages the view that true tomographic imaging of fast neural activity in the brain is possible, at least with epicortical electrodes in the first instance. It is essential to undertake this at low frequencies below about 100 Hz as above 1 kHz the signal becomes vanishingly small.

  20. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  1. 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

    NARCIS (Netherlands)

    den Boon, F.S.; Werkman, T.R.; Schaafsma-Zhao, Q.; Houthuijs, K.; Vitalis, T.; Kruse, C.G.; Wadman, W.J.; Chameau, P.

    2015-01-01

    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

  2. Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior and Neuronal Morphology in the Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    de Melo, Silvana Regina; de David Antoniazzi, Caren Tatiane; Hossain, Shakhawat; Kolb, Bryan

    2018-02-22

    The long-lasting effects of early stress on brain development have been well studied. Recent evidence indicates that males and females respond differently to the same stressor. We examined the chronic effects of daily maternal separation (MS) on behavior and cerebral morphology in both male and female rats. Cognitive and anxiety-like behaviors were evaluated, and neuroplastic changes in 2 subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in adult male and female rats. The animals were subjected to MS on postnatal day (P) 3-14 for 3 h per day. Cognitive and emotional behaviors were assessed in the object/context mismatch task, elevated plus maze, and locomotor activity test in early adulthood (P87-P95). Anatomical assessments were performed in the prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety-related behavior only in males, whereas locomotor activity was higher in females, with no effects on cognition. MS decreased spine density in the AID and increased spine density in the CA1 area in males. Females exhibited an increase in spine density in the Cg3. Our findings confirm previous work that found that MS causes long-term behavioral and anatomical effects, and these effects were dependent on sex and the duration of MS stress. © 2018 S. Karger AG, Basel.

  3. Effects of piracetam on the incorporation of 32P into the phospholipids of neurons and glial cells isolated from rabbit cerebral cortex

    International Nuclear Information System (INIS)

    Woelk, H.

    1979-01-01

    In the search for the biochemical basis of the action of Piracetam, the effects of this encephalotropic substance on the neuronal and glial phospholipid metabolism was investigated. Piracetam increases the incorporation of 32 P into phosphatidylinositol and phosphatidyl choline of both glia and neuronal cell bodies. When taking the important role of phosphatidylinoitol in the processes of synaptic transmission and axonal conduction into consideration, the data obtained in the present work suggest that piracetam may stimulate excitatory neurons and may be involved in the process of synaptic transmission. The stimulatory effect of piracetam on the incorporation of 32 P into phosphatidylinositol and phosphatidyl choline appears to be mediated by norepinephrine or another neurotransmitter. (orig.) [de

  4. In vivo functional and morphological characterization of bone and striated muscle microcirculation in NSG mice.

    Directory of Open Access Journals (Sweden)

    Haider Mussawy

    Full Text Available Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG mice has not yet been reported. Here, we established either a dorsal skinfold chamber or femur window in NSG mice (n = 23, allowing direct analysis of microcirculatory parameters in vivo by intravital fluorescence microscopy at 7, 14, 21, and 28 days after chamber preparation. Organ-specific differences were observed. Bone had a significantly lower vessel density but a higher vessel diameter than striated muscle. Bone also showed higher effective vascular permeability than striated muscle. The centerline velocity values were similar in the femur window and dorsal skinfold chamber, with a higher volumetric blood flow in bone. Interestingly, bone and striated muscle showed similar tissue perfusion rates. Knowledge of physiological microhemodynamic values of bone and striated muscle in NSG mice makes it possible to analyze pathophysiological processes at these anatomic sites, such as tumor growth, tumor metastasis, and tumor microcirculation, as well as the response to therapeutic agents.

  5. High frequency action potential bursts (≥ 100 Hz) in L2/3 and L5B thick tufted neurons in anaesthetized and awake rat primary somatosensory cortex

    NARCIS (Netherlands)

    C.P.J. de Kock (Christiaan); B. Sakmann (Bert)

    2008-01-01

    textabstractHigh frequency (≥ 100 Hz) bursts of action potentials (APs) generated by neocortical neurons are thought to increase information content and, through back-propagation, to influence synaptic integration and efficacy in distal dendritic compartments. It was recently shown in acute slice

  6. Cultures of Cerebellar Granule Neurons

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Parizad M. Bilimoria and Azad Bonni1 Corresponding author ([]()) ### INTRODUCTION Primary cultures of granule neurons from the post-natal rat cerebellum provide an excellent model system for molecular and cell biological studies of neuronal development and function. The cerebellar cortex, with its highly organized structure and few neuronal subtypes, offers a well-characterized neural circuitry. Many fundamental insight...

  7. Lack of insulin results in reduced seladin-1 expression in primary cultured neurons and in cerebral cortex of STZ-induced diabetic rats.

    Science.gov (United States)

    Kazkayasi, Inci; Ismail, Muhammad-Al-Mustafa; Parrado-Fernandez, Cristina; Björkhem, Ingemar; Pekiner, Can; Uma, Serdar; Cedazo-Minguez, Angel; Burul-Bozkurt, Nihan

    2016-10-28

    Several studies demonstrated that Diabetes mellitus (DM) enhances the risk for Alzheimer's disease (AD). Although hyperglycemia and perturbed function of insulin signaling have been proposed to contribute to AD pathogenesis, the molecular mechanisms behind this association is not clear yet. Seladin-1 is an enzyme catalyzing the last step in cholesterol biosynthesis converting desmosterol to cholesterol. The neuroprotective function of seladin-1 has gained interest in AD research recently. Seladin-1 has anti-apoptotic properties and regulates the expression of β-secretase (BACE-1). Here we measured seladin-1 mRNA and protein expressions in rat primary cultured neurons under diabetic conditions and also in the brains of rats with streptozotocine (STZ)-induced diabetes. We show that constant lack of insulin for 5days decreased seladin-1 levels in cultured rat primary neurons. Similarly, a decrease in seladin-1 was found in the brains of rats with STZ-induced diabetes. However, if the lack of insulin and/or high glucose treatment was intermittent, neuronal seladin-1 levels were not affected in vitro. On the other hand, treatment of neurons with metformin resulted in a significant increase in seladin-1. Constant lack of insulin for 5days, as well as high glucose treatment, increased the neuronal expression of BACE-1 in vitro, but not in the in vivo model. Our study defines insulin as a regulator of seladin-1 expression for the first time. The relevance of these findings for the association of DM with AD is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus...... scarce in both muscle layers of the thoracic esophagus, while their number increased steeply toward the cardia in the striated portion of the intraabdominal esophagus. They did not form networks and had no relationship with intrinsic myenteric ganglia and motor end-plates. They were often close to nerve...... but absent in adult ICC-deficient KitW-lacZ/KitWv mice. Interstitial cells of Cajal were identified by electron microscopy by their ultrastructure in the striated muscle of the esophagus and exhibited Xgal labeling, while fibroblasts and muscle cells were unlabeled. Interstitial cells of Cajal are scattered...

  9. Disposition of the striated urethral sphincter and its relation to the prostate in human fetuses

    Directory of Open Access Journals (Sweden)

    Luciano A. Favorito

    2007-06-01

    Full Text Available OBJECTIVE: To describe the arrangement of the muscle fibers of the striated urethral sphincter and its relationship with the prostate during the fetal period in humans. MATERIALS AND METHODS: We analyzed 17 prostates from well preserved fresh human fetuses ranging in age from 10 to 31 weeks postconception (WPC. Transversal sections were obtained and stained with Gomori's trichrome and immunolabeled with anti alpha-actin antibody. RESULTS: We found that the urethral striated sphincter (rabdosphincter is located on the periphery of the smooth muscle and there was no merge between striated and smooth muscle fibers in any fetal period. In the prostate apex, the striated sphincter shows a circular arrangement and covers completely the urethra externally, whereas adjacent to verumontanum, it looks like a "horseshoe" and covers only the anterior and lateral surfaces of the urethra. Near the bladder neck, in fetuses younger than 20 WPC, we have found striated muscle fibers only at the anterior surface of the prostate, while in fetuses older than 20 WPC, the striated muscle covers the anterior and lateral surfaces of the prostate. CONCLUSIONS: The urethral sphincter muscle covers the anterior and lateral surfaces of the urethra in all fetuses older than 20 WPC, close to the bladder neck and at the distal prostate. In the region of the prostate apex, the urethral sphincter covers completely the urethra circularly. The knowledge of the normal anatomy of the urethral sphincter in fetuses could be important to understand its alterations in congenital anomalies involving the base of the bladder, the bladder neck and the proximal urethra.

  10. Human primary visual cortex topography imaged via positron tomography

    International Nuclear Information System (INIS)

    Schwartz, E.L.; Christman, D.R.; Wolf, A.P.

    1984-01-01

    The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18 F-labeled 2-deoxy-2-fluoro-D-glucose ([ 18 F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical 'checker-board' pattern of [ 18 F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [ 18 F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable 'signature' in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic 'signature' was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed. (Auth.)

  11. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

    Directory of Open Access Journals (Sweden)

    Tomonori eFurukawa

    2014-03-01

    Full Text Available γ-Aminobutyric acid (GABA depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose-response properties of cells labeled to detect GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67GFP/GFP mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidinoethanesulfonic acid (GES, and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl oxobutyric acid (DCPIB, as examined through high-performance liquid chromatography (HPLC. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the

  12. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus. Sec...

  13. Embracing change: striated-for-smooth muscle replacement in esophagus development.

    Science.gov (United States)

    Krauss, Robert S; Chihara, Daisuke; Romer, Anthony I

    2016-01-01

    The esophagus functions to transport food from the oropharyngeal region to the stomach via waves of peristalsis and transient relaxation of the lower esophageal sphincter. The gastrointestinal tract, including the esophagus, is ensheathed by the muscularis externa (ME). However, while the ME of the gastrointestinal tract distal to the esophagus is exclusively smooth muscle, the esophageal ME of many vertebrate species comprises a variable amount of striated muscle. The esophageal ME is initially composed only of smooth muscle, but its developmental maturation involves proximal-to-distal replacement of smooth muscle with striated muscle. This fascinating phenomenon raises two important questions: what is the developmental origin of the striated muscle precursor cells, and what are the cellular and morphogenetic mechanisms underlying the process? Studies addressing these questions have provided controversial answers. In this review, we discuss the development of ideas in this area and recent work that has shed light on these issues. A working model has emerged that should permit deeper understanding of the role of ME development and maturation in esophageal disorders and in the functional and evolutionary underpinnings of the variable degree of esophageal striated myogenesis in vertebrate species.

  14. Tachykinins are involved in local reflex modulation of vagally mediated striated muscle contractions in the rat esophagus via tachykinin NK1 receptors.

    Science.gov (United States)

    Shiina, T; Shimizu, Y; Boudaka, A; Wörl, J; Takewaki, T

    2006-05-12

    The objective of the present study was to investigate the hypothesis of the presence of a local neural reflex modulating the vagally mediated contractions of striated muscle in the rat esophagus and to determine the possible involvement of tachykinins in such a local neural reflex. Electrical stimulation of the vagus nerve evoked twitch contractile responses that were abolished by d-tubocurarine (5 microM). Capsaicin (1-100 microM) inhibited the vagally mediated twitch contractions o f the normal rat esophageal preparations concentration-dependently but not those of the neonatally capsaicin-treated ones. NG-nitro-L-arginine methyl ester (100 microM), a nitric oxide synthase inhibitor, blocked the inhibitory effect of capsaicin and exogenous application of a nitric oxide donor (1 mM) inhibited the vagally mediated twitch contractions. Capsaicin suppressed acetylcholine release from the normal rat esophageal segments evoked by vagus nerve stimulation but not that from the neonatally capsaicin-treated ones. A selective tachykinin NK1 receptor antagonist (0.1 or 1 microM) attenuated the inhibitory effect of capsaicin. However, antagonists of tachykinin NK2, tachykinin NK3 and calcitonin gene-related peptide receptors (1 microM) did not have any effect. A tachykinin NK1 receptor agonist (1 or 5 microM) inhibited the vagally mediated twitch contractions, which was prevented by NG-nitro-L-arginine methyl ester (100 microM). These data suggest that the rat esophagus might have a local neural reflex inhibiting the vagally mediated striated muscle motility, which consists of capsaicin-sensitive sensory neurons and myenteric nitrergic neurons, and that tachykinins might be involved in the neural reflex through tachykinin NK1 receptors.

  15. Distinct recruitment of the hippocampal, thalamic, and amygdalar neurons projecting to the prelimbic cortex in male and female rats during context-mediated renewal of responding to food cues.

    Science.gov (United States)

    Anderson, Lauren C; Petrovich, Gorica D

    2018-02-26

    Persistent responding to food cues may underlie the difficulty to resist palatable foods and to maintain healthy eating habits. Renewal of responding after extinction is a model of persistent food seeking that can be used to study the underlying neural mechanisms. In context-mediated renewal, a return to the context in which the initial cue-food learning occurred induces robust responding to the cues that were extinguished elsewhere. Previous work found sex differences in context-mediated renewal and in the recruitment of the ventromedial prefrontal cortex (vmPFC) during that behavior. Males exhibited renewal of responding to food cues and had higher Fos induction in the prelimbic area (PL) of the vmPFC, while females failed to exhibit renewal of responding and had lower Fos induction in the PL. The main aim of the current study was to determine key components of the PL circuitry mediating renewal. The focus was on inputs from three areas important in appetitive associative learning and contextual processing: the amygdala, ventral hippocampal formation, and the paraventricular nucleus of the thalamus. The goal was to determine whether neurons from these areas that send direct projections to the PL (identified with a retrograde tracer) are selectively activated (Fos induction) during renewal and whether they are differently recruited in males and females. The Fos induction patterns demonstrated that the PL-projecting neurons in each of these areas were recruited in a sex-specific way that corresponded to the behavioral differences between males and females. These pathways were selectively activated in the male experimental group-the only group that showed renewal behavior. The findings suggest the pathways from the ventral hippocampal formation, paraventricular nucleus of the thalamus, and basolateral amygdala to the PL mediate renewal in males. The lack of recruitment in females suggests that under activation of these pathways may underlie their lack of renewal

  16. [Role of functional state of neuronal mitochondria of cerebral cortex in mechanisms of nootropic activity of neuroprotectors in rats with alloxan hyperglycemia].

    Science.gov (United States)

    Zhiliuk, V I; Mamchur, V I; Pavlov, S V

    2015-01-01

    The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.

  17. The anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Pavlović D.M.

    2009-01-01

    Full Text Available The anterior cingulate cortex (ACC has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision. Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases.

  18. Camillo Golgi and Santiago Ramon y Cajal: the anatomical organization of the cortex of the cerebellum. Can the neuron doctrine still support our actual knowledge on the cerebellar structural arrangement?

    Science.gov (United States)

    Sotelo, Constantino

    2011-01-07

    Camillo Golgi and Santiago Ramón y Cajal were the two main investigators that revealed the morphological organization of the cerebellar cortex, although they never shared the same basic concepts. While for Golgi all axons fused into a large syncytium (the diffuse nerve network), for Cajal they had free endings and communication between neurons was done by contiguity not by continuity. The classical diagrammatic representation of the cerebellar circuitry shown by Cajal in his Croonian lecture (1894), although still valid, has drastically change by the accumulation of the great amount of data generated from 1894 to our days. The topic of this review is to briefly summarize this new knowledge, and to confront it with Cajal's concepts, to determine whether or not the added complexity to the circuit invalidates the Cajal's principles. Our conclusion is that although most of these principles are consolidated, the applicability of the law of dynamic polarization does not adapt to some of them. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Chemosensory Learning in the Cortex

    Directory of Open Access Journals (Sweden)

    Edmund eRolls

    2011-09-01

    Full Text Available Taste is a primary reinforcer. Olfactory-taste and visual-taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavour. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavour reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual / olfactory / taste / input as shown by devaluation experiments in which food is fed to satiety, and by correlations with the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety are implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention.

  20. Corticospinal mirror neurons.

    Science.gov (United States)

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  1. Embracing change: striated-for-smooth muscle replacement in esophagus development

    OpenAIRE

    Krauss, Robert S.; Chihara, Daisuke; Romer, Anthony I.

    2016-01-01

    The esophagus functions to transport food from the oropharyngeal region to the stomach via waves of peristalsis and transient relaxation of the lower esophageal sphincter. The gastrointestinal tract, including the esophagus, is ensheathed by the muscularis externa (ME). However, while the ME of the gastrointestinal tract distal to the esophagus is exclusively smooth muscle, the esophageal ME of many vertebrate species comprises a variable amount of striated muscle. The esophageal ME is initia...

  2. The gaseous plasmonic response of a one-dimensional photonic crystal composed of striated plasma layers

    Science.gov (United States)

    Wang, B.; Righetti, F.; Cappelli, M. A.

    2018-03-01

    We present simulations of the response of a one-dimensional striated plasma slab to incident electromagnetic waves that span regions both above and below the plasma frequency, ωp. Photonic bandgap modes are present throughout these regions, and volume and surface plasmon modes facilitate the response below ωp, where the dielectric constant, ɛp application of these structures as ultra-narrow tunable microwave transmission filters.

  3. Morphology of lesions in striated muscle fibres from the beige mouse

    DEFF Research Database (Denmark)

    Kirkeby, S

    1982-01-01

    Lesions in striated muscle fibres from the beige mouse are described at both the light- and electronmicroscopical levels. The muscles have two types of lesions, one is well defined cores in the fibres and the other is diffusely enlarged intermyofibrillar spaces (IMS). The cores can be filled...... with membrane-like structures or a fluffy unstructured material. In the areas with enlarged IMS comparatively few organelles are present and the muscle fibres seem to be fragmented....

  4. Muscle lim protein isoform negatively regulates striated muscle actin dynamics and differentiation.

    Science.gov (United States)

    Vafiadaki, Elizabeth; Arvanitis, Demetrios A; Papalouka, Vasiliki; Terzis, Gerasimos; Roumeliotis, Theodoros I; Spengos, Konstantinos; Garbis, Spiros D; Manta, Panagiota; Kranias, Evangelia G; Sanoudou, Despina

    2014-07-01

    Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including α-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity. © 2014 FEBS.

  5. Imitation, mirror neurons and autism

    OpenAIRE

    Williams, Justin H.G.; Whiten, Andrew; Suddendorf, Thomas; Perrett, David I.

    2001-01-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show ac...

  6. Corticospinal mirror neurons

    Science.gov (United States)

    Kraskov, A.; Philipp, R.; Waldert, S.; Vigneswaran, G.; Quallo, M. M.; Lemon, R. N.

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons’ discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited ‘classical’ mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation (‘suppression mirror-neurons’). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others. PMID:24778371

  7. Cortical cell and neuron density estimates in one chimpanzee hemisphere.

    Science.gov (United States)

    Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

    2016-01-19

    The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

  8. Auditory Connections and Functions of Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Bethany ePlakke

    2014-07-01

    Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

  9. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  10. Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

    Directory of Open Access Journals (Sweden)

    Nicolas Vignier

    Full Text Available Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD, limb-girdle muscular dystrophy type 2D (LGMD2D, limb-girdle muscular dystrophy type 2C (LGMD2C, Emery-Dreifuss muscular dystrophy (EDMD and hypertrophic cardiomyopathy (HCM. Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

  11. The Popeye Domain Containing Genes and Their Function in Striated Muscle

    Science.gov (United States)

    Schindler, Roland F. R.; Scotton, Chiara; French, Vanessa; Ferlini, Alessandra; Brand, Thomas

    2016-01-01

    The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the recent analysis of patients carrying a missense mutation in POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of interacting proteins. Furthermore, we will discuss the current catalogue of established protein-protein interactions. In recent years, the number of POPDC-interacting proteins has been rising and currently includes ion channels (TREK-1), sarcolemma-associated proteins serving functions in mechanical stability (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that POPDC proteins might also control the cellular level of the nuclear proto-oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins probably serves multiple roles in striated muscle. PMID:27347491

  12. Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.

    Science.gov (United States)

    Tsika, Richard W; Schramm, Christine; Simmer, Gretchen; Fitzsimons, Daniel P; Moss, Richard L; Ji, Juan

    2008-12-26

    TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (Vmax), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3alpha/beta and decreased nuclear beta-catenin and NFATc1/c3 protein. These effects could be reversed in vivo by mechanical overload, which decreased muscle creatine kinase-driven TEAD-1 transgene expression, and in cultured satellite cells by TEAD-1-specific small interfering RNA. These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression.

  13. Immunocytochemical electron microscopic study and western blot analysis of myosin, paramyosin and miniparamyosin in the striated muscle of the fruit fly Drosophila melanogaster and in obliquely striated and smooth muscles of the earthworm Eisenia foetida.

    Science.gov (United States)

    Royuela, M; Fraile, B; Cervera, M; Paniagua, R

    1997-04-01

    Miniparamyosin is a paramyosin isoform (55-60 kDa) that has been isolated in insects (Drosophila) and immunolocalized in several species of arthropods, molluscs, annelids and nematodes. In this study, the presence and distribution of this protein, in comparison with that of paramyosin and myosin, has been examined in the striated muscle (tergal depressor of trochanter) of Drosophila melanogaster, and the obliquely striated muscle (body wall) and the smooth muscle (outer layer of the pseudoheart) of the earthworm Eisenia foetida by means of immunocytochemical electron microscopic study and Western blot analysis miniparamyosin paramyosin and myosin antibodies from Drosophila. In the striated muscle of D. melanogaster, the three proteins were immunolocalized along the length of the thick filaments (A-bands). The distribution of immunogold particles along these filaments was uniform. The relative proportions miniparamyosin/paramyosin/myosin (calculated by counting the number of immunogold particles) were: 1/10/68. In the obliquely striated muscle of E. foetida, immunoreactions to the three proteins were also found in the thick filaments, and the relative proportions miniparamyosin/paramyosin/myosin were 1/2.4/6.9. However, whereas the distribution of both myosin and miniparamyosin along the thick filament length was uniform, paramyosin immunolabelling was more abundant in the extremes of thick filaments (the outer zones of A-bands in the obliquely striated muscle), where the thick filaments become thinner than in the centre (the central zone of A-bands), where these filaments are thicker. The relative proportions of paramyosin in the outer and of paramyosin in the central zones of A-bands were 4/1. This irregular distribution of paramyosin along the thick filament length might be actual but it may also be explained by the fusiform shape of thick filaments in the earthworm: assuming that paramyosin is covered by myosin, paramyosin antigens would be more exposed in the

  14. Acute pharmacogenetic activation of medial prefrontal cortex ...

    Indian Academy of Sciences (India)

    The medial prefrontal cortex (mPFC) is implicated in anxiety-like behaviour. In rodent models, perturbations of mPFCneuronal activity through pharmacological manipulations, optogenetic activation of mPFC neurons or cell-type specificpharmacogenetic inhibition of somatostatin interneurons indicate conflicting effects on ...

  15. Prelimbic and infralimbic prefrontal cortex interact during fast network oscillations.

    Directory of Open Access Journals (Sweden)

    Karlijn I van Aerde

    Full Text Available BACKGROUND: The medial prefrontal cortex has been implicated in a variety of cognitive and executive processes such as decision making and working memory. The medial prefrontal cortex of rodents consists of several areas including the prelimbic and infralimbic cortex that are thought to be involved in different aspects of cognitive performance. Despite the distinct roles in cognitive behavior that have been attributed to prelimbic and infralimbic cortex, little is known about neuronal network functioning of these areas, and whether these networks show any interaction during fast network oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that fast network oscillations in rat infralimbic cortex slices occur at higher frequencies and with higher power than oscillations in prelimbic cortex. The difference in oscillation frequency disappeared when prelimbic and infralimbic cortex were disconnected. CONCLUSIONS/SIGNIFICANCE: Our data indicate that neuronal networks of prelimbic and infralimbic cortex can sustain fast network oscillations independent of each other, but suggest that neuronal networks of prelimbic and infralimbic cortex are interacting during these oscillations.

  16. Isoform composition, gene expression and sarcomeric protein phosphorylation in striated muscle of mice after space flight

    Science.gov (United States)

    Vikhlyantsev, Ivan; Ulanova, Anna; Salmov, Nikolay; Gritsyna, Yulia; Bobylev, Alexandr; Rogachevsky, Vadim; Shenkman, Boris; Podlubnaya, Zoya

    Using RT-PCR and SDS-PAGE, changes in isoform composition, gene expression, titin and nebulin phosphorylation, as well as changes in isoform composition of myosin heavy chains in striated muscles of mice were studied after 30-day-long space flight onboard the Russian spacecraft “BION-M” No. 1. The muscle fibre-type shift from slow-to-fast was observed in m. gastrocnemius and m. tibialis anterior of animals from “Flight” group. A decrease in the content of the NT and N2A titin isoforms and nebulin in the skeletal muscles of animals from “Flight” group was found. Meanwhile, significant differences in gene expression of these proteins in skeletal muscles of mice from “Flight” and “Control” groups were not observed. Using Pro-Q Diamond stain, an increase in titin phosphorylation in m. gastrocnemius of mice from “Flight” group was detected. The content of the NT, N2BA and N2B titin isoforms in cardiac muscle of mice from “Flight” and “Control” groups did not differ, nevertheless an increase in titin gene expression in the myocardium of the “Flight” group animals was found. The observed changes will be discussed in the context of theirs role in contractile activity of striated muscles of mice in conditions of weightlessness. This work was supported by the Russian Foundation for Basic Research (grants No. 14-04-32240, 14-04-00112). Acknowledgement. We express our gratitude to the teams of Institute of Biomedical Problems RAS and “PROGRESS” Corporation involved in the preparation of the “BION-M” mission.

  17. Effect of distribution of striated laser hardening tracks on dry sliding wear resistance of biomimetic surface

    Science.gov (United States)

    Su, Wei; Zhou, Ti; Zhang, Peng; Zhou, Hong; Li, Hui

    2018-01-01

    Some biological surfaces were proved to have excellent anti-wear performance. Being inspired, Nd:YAG pulsed laser was used to create striated biomimetic laser hardening tracks on medium carbon steel samples. Dry sliding wear tests biomimetic samples were performed to investigate specific influence of distribution of laser hardening tracks on sliding wear resistance of biomimetic samples. After comparing wear weight loss of biomimetic samples, quenched sample and untreated sample, it can be suggested that the sample covered with dense laser tracks (3.5 mm spacing) has lower wear weight loss than the one covered with sparse laser tracks (4.5 mm spacing); samples distributed with only dense laser tracks or sparse laser tracks (even distribution) were proved to have better wear resistance than samples distributed with both dense and sparse tracks (uneven distribution). Wear mechanisms indicate that laser track and exposed substrate of biomimetic sample can be regarded as hard zone and soft zone respectively. Inconsecutive striated hard regions, on the one hand, can disperse load into small branches, on the other hand, will hinder sliding abrasives during wear. Soft regions with small range are beneficial in consuming mechanical energy and storing lubricative oxides, however, soft zone with large width (>0.5 mm) will be harmful to abrasion resistance of biomimetic sample because damages and material loss are more obvious on surface of soft phase. As for the reason why samples with even distributed bionic laser tracks have better wear resistance, it can be explained by the fact that even distributed laser hardening tracks can inhibit severe worn of local regions, thus sliding process can be more stable and wear extent can be alleviated as well.

  18. The Mirror Neuron System and Action Recognition

    Science.gov (United States)

    Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia

    2004-01-01

    Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…

  19. Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism

    NARCIS (Netherlands)

    Testa-Silva, G.; Loebel, A.; Giugliano, M.; de Kock, C.P.J.; Mansvelder, H.D.; Meredith, R.M.

    2012-01-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex

  20. Decoding sound level in the marmoset primary auditory cortex.

    Science.gov (United States)

    Sun, Wensheng; Marongelli, Ellisha N; Watkins, Paul V; Barbour, Dennis L

    2017-10-01

    Neurons that respond favorably to a particular sound level have been observed throughout the central auditory system, becoming steadily more common at higher processing areas. One theory about the role of these level-tuned or nonmonotonic neurons is the level-invariant encoding of sounds. To investigate this theory, we simulated various subpopulations of neurons by drawing from real primary auditory cortex (A1) neuron responses and surveyed their performance in forming different sound level representations. Pure nonmonotonic subpopulations did not provide the best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic neurons provided the most accurate decoding. For level-fidelity decoding, the inclusion of nonmonotonic neurons slightly improved or did not change decoding accuracy until they constituted a high proportion. These results indicate that nonmonotonic neurons fill an encoding role complementary to, rather than alternate to, monotonic neurons. NEW & NOTEWORTHY Neurons with nonmonotonic rate-level functions are unique to the central auditory system. These level-tuned neurons have been proposed to account for invariant sound perception across sound levels. Through systematic simulations based on real neuron responses, this study shows that neuron populations perform sound encoding optimally when containing both monotonic and nonmonotonic neurons. The results indicate that instead of working independently, nonmonotonic neurons complement the function of monotonic neurons in different sound-encoding contexts. Copyright © 2017 the American Physiological Society.

  1. Experience-dependent spatial expectations in mouse visual cortex

    DEFF Research Database (Denmark)

    Fiser, Aris; Mahringer, David; Oyibo, Hassana K.

    2016-01-01

    primary visual cortex (V1) becomes increasingly informative of spatial location. We found that a subset of V1 neurons exhibited responses that were predictive of the upcoming visual stimulus in a spatially dependent manner and that the omission of an expected stimulus drove strong responses in V1....... Stimulus-predictive responses also emerged in V1-projecting anterior cingulate cortex axons, suggesting that anterior cingulate cortex serves as a source of predictions of visual input to V1. These findings are consistent with the hypothesis that visual cortex forms an internal representation of the visual...

  2. 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.

  3. Origins of choice-related activity in mouse somatosensory cortex

    Science.gov (United States)

    Yang, Hongdian; Kwon, Sung E.; Severson, Kyle S.; O’Connor, Daniel H.

    2015-01-01

    During perceptual decisions about faint or ambiguous sensory stimuli, even identical stimuli can produce different choices. Spike trains from sensory cortex neurons can predict trial-to-trial variability in choice. Choice-related spiking is widely studied to link cortical activity to perception, but its origins remain unclear. Using imaging and electrophysiology, we found that mouse primary somatosensory cortex neurons showed robust choice-related activity during a tactile detection task. Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli. Spike trains from thalamic relay neurons showed highly transient, weak choice-related activity. Intracellular recordings in cortex revealed a prolonged choice-related depolarization in most neurons that was not accounted for by feedforward thalamic input. Top-down axons projecting from secondary to primary somatosensory cortex signaled choice. An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking. Our results reveal how choice-related spiking emerges across neural circuits and within single neurons. PMID:26642088

  4. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration

    Directory of Open Access Journals (Sweden)

    Juan Mendizabal-Zubiaga

    2016-10-01

    Full Text Available The cannabinoid type 1 (CB1 receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1, where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles. Immunoelectron microscopy for CB1 was used in skeletal muscles (gastrocnemius and rectus abdominis and myocardium from wild-type and CB1-KO mice. Functional assessments were performed in mitochondria purified from the heart of the mice and the mitochondrial oxygen consumption upon application of different acute delta-9-tetrahidrocannabinol (Δ9-THC concentrations (100 nM or 200 nM was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in the rectus abdominis and 17% in the myocardium expressed CB1. Furthermore, the proportion of mtCB1 versus total CB1 immunoparticles was about 60% in the gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium. Importantly, the CB1 immunolabeling pattern disappeared in muscles of CB1-KO mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased mitochondria coupled respiration between 12% and 15% in wild-type isolated mitochondria of myocardial muscles but no significant difference was noticed between THC treated and vehicle in mitochondria isolated from CB1-KO heart. Furthermore, gene expression of key enzymes involved in pyruvate synthesis, tricarboxylic acid (TCA cycle and mitochondrial respiratory chain was evaluated in the striated muscle of CB1-WT and CB1-KO. CB1-KO showed an increase in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased production of pyruvate. In contrast, no significant

  5. Encoding and retrieval of artificial visuoauditory memory traces in the auditory cortex requires the entorhinal cortex.

    Science.gov (United States)

    Chen, Xi; Guo, Yiping; Feng, Jingyu; Liao, Zhengli; Li, Xinjian; Wang, Haitao; Li, Xiao; He, Jufang

    2013-06-12

    Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

  6. Effects of striated laser tracks on thermal fatigue resistance of cast iron samples with biomimetic non-smooth surface

    International Nuclear Information System (INIS)

    Tong, Xin; Zhou, Hong; Liu, Min; Dai, Ming-jiang

    2011-01-01

    In order to enhance the thermal fatigue resistance of cast iron materials, the samples with biomimetic non-smooth surface were processed by Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser. With self-controlled thermal fatigue test method, the thermal fatigue resistance of smooth and non-smooth samples was investigated. The effects of striated laser tracks on thermal fatigue resistance were also studied. The results indicated that biomimetic non-smooth surface was benefit for improving thermal fatigue resistance of cast iron sample. The striated non-smooth units formed by laser tracks which were vertical with thermal cracks had the best propagation resistance. The mechanisms behind these influences were discussed, and some schematic drawings were introduced to describe them.

  7. Complete genome sequence of maize yellow striate virus, a new cytorhabdovirus infecting maize and wheat crops in Argentina.

    Science.gov (United States)

    Maurino, Fernanda; Dumón, Analía D; Llauger, Gabriela; Alemandri, Vanina; de Haro, Luis A; Mattio, M Fernanda; Del Vas, Mariana; Laguna, Irma Graciela; Giménez Pecci, María de la Paz

    2018-01-01

    A rhabdovirus infecting maize and wheat crops in Argentina was molecularly characterized. Through next-generation sequencing (NGS) of symptomatic leaf samples, the complete genome was obtained of two isolates of maize yellow striate virus (MYSV), a putative new rhabdovirus, differing by only 0.4% at the nucleotide level. The MYSV genome consists of 12,654 nucleotides for maize and wheat virus isolates, and shares 71% nucleotide sequence identity with the complete genome of barley yellow striate mosaic virus (BYSMV, NC028244). Ten open reading frames (ORFs) were predicted in the MYSV genome from the antigenomic strand and were compared with their BYSMV counterparts. The highest amino acid sequence identity of the MYSV and BYSMV proteins was 80% between the L proteins, and the lowest was 37% between the proteins 4. Phylogenetic analysis suggested that the MYSV isolates are new members of the genus Cytorhabdovirus, family Rhabdoviridae. Yellow striate, affecting maize and wheat crops in Argentina, is an emergent disease that presents a potential economic risk for these widely distributed crops.

  8. Detection of a troponin I-like protein in non-striated muscle of the tardigrades (water bears).

    Science.gov (United States)

    Obinata, Takashi; Ono, Kanako; Ono, Shoichiro

    2011-03-01

    Tardigrades, also known as water bears, have somatic muscle fibers that are responsible for movement of their body and legs. These muscle fibers contain thin and thick filaments in a non-striated pattern. However, the regulatory mechanism of muscle contraction in tardigrades is unknown. In the absence of extensive molecular and genomic information, we detected a protein of 31 kDa in whole lysates of tardigrades that cross-reacted with the antibody raised against nematode troponin I (TnI). TnI is a component of the troponin complex that regulates actin-myosin interaction in a Ca(2+)-dependent and actin-linked manner. This TnI-like protein was co-extracted with actin in a buffer containing ATP and EGTA, which is known to induce relaxation of a troponin-regulated contractile system. The TnI-like protein was specifically expressed in the somatic muscle fibers in adult animals and partially co-localized with actin filaments in a non-striated manner. Interestingly, the pharyngeal muscle did not express this protein. These observations suggest that the non-striated somatic muscle of tardigrades has an actin-linked and troponin-regulated system for muscle contraction.

  9. Revealing t-tubules in striated muscle with new optical super-resolution microscopy techniques

    Directory of Open Access Journals (Sweden)

    Isuru D. Jayasinghe

    2014-12-01

    Full Text Available The t-tubular system plays a central role in the synchronisation of calcium signalling and excitation-contraction coupling in most striated muscle cells. Light microscopy has been used for imaging t-tubules for well over 100 years and together with electron microscopy (EM, has revealed the three-dimensional complexities of the t-system topology within cardiomyocytes and skeletal muscle fibres from a range of species. The emerging super-resolution single molecule localisation microscopy (SMLM techniques are offering a near 10-fold improvement over the resolution of conventional fluorescence light microscopy methods, with the ability to spectrally resolve nanometre scale distributions of multiple molecular targets. In conjunction with the next generation of electron microscopy, SMLM has allowed the visualisation and quantification of intricate t-tubule morphologies within large areas of muscle cells at an unprecedented level of detail. In this paper, we review recent advancements in the t-tubule structural biology with the utility of various microscopy techniques. We outline the technical considerations in adapting SMLM to study t-tubules and its potential to further our understanding of the molecular processes that underlie the sub-micron scale structural alterations observed in a range of muscle pathologies.

  10. Splicing transitions of the anchoring protein ENH during striated muscle development.

    Science.gov (United States)

    Ito, Jumpei; Hashimoto, Taiki; Nakamura, Sho; Aita, Yusuke; Yamazaki, Tomoko; Schlegel, Werner; Takimoto, Koichi; Maturana, Andrés D

    2012-05-04

    The ENH (PDLIM5) protein acts as a scaffold to tether various functional proteins at subcellular sites via PDZ and three LIM domains. Splicing of the ENH primary transcript generates various products with different repertories of protein interaction modules. Three LIM-containing ENH predominates in neonatal cardiac tissue, whereas LIM-less ENHs are abundant in adult hearts, as well as skeletal muscles. Here we examine the timing of splicing transitions of ENH gene products during postnatal heart development and C2C12 myoblast differentiation. Real-time PCR analysis shows that LIM-containing ENH1 mRNA is gradually decreased during postnatal heart development, whereas transcripts with the short exon 5 appear in the late postnatal period and continues to increase until at least one month after birth. The splicing transition from LIM-containing ENH1 to LIM-less ENHs is also observed during the early period of C2C12 differentiation. This transition correlates with the emergence of ENH transcripts with the short exon 5, as well as the expression of myogenin mRNA. In contrast, the shift from the short exon 5 to the exon 7 occurs in the late differentiation period. The timing of this late event corresponds to the appearance of mRNA for the skeletal myosin heavy chain MYH4. Thus, coordinated and stepwise splicing transitions result in the production of specific ENH transcripts in mature striated muscles. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated Muscle

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    Casey Carlisle

    2017-12-01

    Full Text Available Protein folding factors (chaperones are required for many diverse cellular functions. In striated muscle, chaperones are required for contractile protein function, as well as the larger scale assembly of the basic unit of muscle, the sarcomere. The sarcomere is complex and composed of hundreds of proteins and the number of proteins and processes recognized to be regulated by chaperones has increased dramatically over the past decade. Research in the past ten years has begun to discover and characterize the chaperones involved in the assembly of the sarcomere at a rapid rate. Because of the dynamic nature of muscle, wear and tear damage is inevitable. Several systems, including chaperones and the ubiquitin proteasome system (UPS, have evolved to regulate protein turnover. Much of our knowledge of muscle development focuses on the formation of the sarcomere but recent work has begun to elucidate the requirement and role of chaperones and the UPS in sarcomere maintenance and disease. This review will cover the roles of chaperones in sarcomere assembly, the importance of chaperone homeostasis and the cooperation of chaperones and the UPS in sarcomere integrity and disease.

  12. Distribution of Myosin Attachment Times Predicted from Viscoelastic Mechanics of Striated Muscle

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    Bradley M. Palmer

    2011-01-01

    Full Text Available We demonstrate that viscoelastic mechanics of striated muscle, measured as elastic and viscous moduli, emerge directly from the myosin crossbridge attachment time, tatt, also called time-on. The distribution of tatt was modeled using a gamma distribution with shape parameter, p, and scale parameter, β. At 5 mM MgATP, β was similar between mouse α-MyHC (16.0±3.7 ms and β-MyHC (17.9±2.0 ms, and p was higher (P<0.05 for β-MyHC (5.6±0.4 no units compared to α-MyHC (3.2±0.9. At 1 mM MgATP, p approached a value of 10 in both isoforms, but β rose only in the β-MyHC (34.8±5.8 ms. The estimated mean tatt (i.e., pβ product was longer in the β-MyHC compared to α-MyHC, and became prolonged in both isoforms as MgATP was reduced as expected. The application of our viscoelastic model to these isoforms and varying MgATP conditions suggest that tatt is better modeled as a gamma distribution due to its representing multiple temporal events occurring within tatt compared to a single exponential distribution which assumes only one temporal event within tatt.

  13. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  14. A radial glia-specific role of RhoA in double cortex formation

    DEFF Research Database (Denmark)

    Cappello, Silvia; Böhringer, Christian R J; Bergami, Matteo

    2012-01-01

    The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational...... disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex......, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also...

  15. An Electron Microscopic Study of the Irradiation Effects on the Striated Duct Cells of the Submandibular Gland in Rats

    International Nuclear Information System (INIS)

    Lee, Kyu Chan; Lee, Sang Rae

    1990-01-01

    The purpose of this study was to investigate the effects of irradiation on the striated duct cells of the rat submandibular gland ductal tissues which control the characteristics of saliva. For this study, the experimental group was composed of 36 irradiated Sprague Dawley strain rats divided into 8 subgroups- 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours after irradiation. 4 non-irradiated rats were used as the control group. The experimental animals were singly irradiated with a dose of 18 Gy gamma ray to their head and neck region by the Co-6-teletherapy unit and sacrificed after each experimental duration. The specimens were examined with a light microscope with an H-E stain and with a transmission electron microscope. The results of this study were as follows. 1. In the light micrograph, a severe atrophic change occurred in the striated duct cells at 2 hours after irradiation and gradual recovery occurred from 6 hours after irradiation. 2. The nuclear chromosomes of the striated duct cells were changed granular at 2 hours after irradiation. Recovery was observed at 6 hours after irradiation. Nuclear bodies were also observed from 3 hours after irradiation. 3. The mitochondria of the striated duct cells had indistinct cristae at 2 hours after irradiation, and were degenerated or swollen at 3 hours after irradiation. They recovered, however, from 6 hours, with an increasing number at 48 hours a regular arrangement was observed at 72 hours after irradiation. 4. The microvilli showed atrophic changes at 2 hours after irradiation and were almost lost at 3 hours after irradiation. They were observed again from 48 hours after irradiation. 5. The rough endoplasmic reticulum and golgi body were not apparent at 1 hours after irradiation and were dilated with degeneration 2 hours after, but intact rough endoplasmic reticulum were observed from 3 hours after irradiation and developed well at 24 hours after irradiation. By the result of this

  16. Layer-specificity in the effects of attention and working memory on activity in primary visual cortex

    NARCIS (Netherlands)

    van Kerkoerle, Timo; Self, Matthew W.; Roelfsema, Pieter R.

    2017-01-01

    Neuronal activity in early visual cortex depends on attention shifts but the contribution to working memory has remained unclear. Here, we examine neuronal activity in the different layers of the primary visual cortex (V1) in an attention-demanding and a working memory task. A current-source density

  17. Representation of Reward Feedback in Primate Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Michael eBrosch

    2011-02-01

    Full Text Available It is well established that auditory cortex is plastic on different time scales and that this plasticity is driven by the reinforcement that is used to motivate subjects to learn or to perform an auditory task. Motivated by these findings, we study in detail properties of neuronal firing in auditory cortex that is related to reward feedback. We recorded from the auditory cortex of two monkeys while they were performing an auditory categorization task. Monkeys listened to a sequence of tones and had to signal when the frequency of adjacent tones stepped in downward direction, irrespective of the tone frequency and step size. Correct identifications were rewarded with either a large or a small amount of water. The size of reward depended on the monkeys' performance in the previous trial: it was large after a correct trial and small after an incorrect trial. The rewards served to maintain task performance. During task performance we found three successive periods of neuronal firing in auditory cortex that reflected (1 the reward expectancy for each trial, (2 the reward size received and (3 the mismatch between the expected and delivered reward. These results, together with control experiments suggest that auditory cortex receives reward feedback that could be used to adapt auditory cortex to task requirements. Additionally, the results presented here extend previous observations of non-auditory roles of auditory cortex and shows that auditory cortex is even more cognitively influenced than lately recognized.

  18. Synaptic vesicle morphology and recycling are altered in myenteric neurons of mice lacking dystrophin (mdx mice).

    Science.gov (United States)

    Vannucchi, Maria Giuliana; Corsani, Letizia; Faussone-Pellegrini, Maria-Simonetta

    2003-11-01

    Several dystrophin isoforms are known. The full-length isoform is present in striated and smooth muscles and neurons and its lack causes Duchenne Muscular Dystrophy, a progressive myopathy accompanied by mild cognitive deficits and gastrointestinal dismotility. An ultrastructural study was undertaken in the colon of mice lacking full-length dystrophin and maintaining shorter isoforms (mdx mice) to ascertain whether myenteric neurons have an altered morphology. Results showed a significant increase in the size of synaptic vesicle and in the number of recycling vesicles. An enlargement of endoplasmic reticulum cisternae in a subpopulation of neurons was also seen. Immunohistochemistry confirmed that the shorter isoforms were expressed in mdx mice myenteric neurons. These findings indicate the presence of a neuropathy at the myenteric plexus which might justify the defective neuronal control of gastrointestinal motility reported for these animals and which might be correlated with full-length dystrophin loss, since the shorter isoforms are present. Copyright 2003 Wiley-Liss, Inc.

  19. Mirror neurons in a New World monkey, common marmoset

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    Wataru eSuzuki

    2015-12-01

    Full Text Available Mirror neurons respond when executing a motor act and when observing others’ similar act. So far, mirror neurons have been found only in macaques, humans and songbirds. To investigate the degree of phylogenetic specialization of mirror neurons during the course of their evolution, we determined whether mirror neurons with similar properties to macaques occur in a New World monkey, the common marmoset (Callithrix jacchus. The ventral premotor cortex (PMv, where mirror neurons have been reported in macaques, is difficult to identify in marmosets, since no sulcal landmarks exist in the frontal cortex. We addressed this problem using in vivo connection imaging methods. That is, we first identified cells responsive to others’ grasping action in a clear landmark, the superior temporal sulcus (STS, under anesthesia, and injected fluorescent tracers into the region. By fluorescence stereomicroscopy, we identified clusters of labelled cells in the ventrolateral frontal cortex, which were confirmed to be within the ventrolateral frontal cortex including PMv after sacrifice. We next implanted electrodes into the ventrolateral frontal cortex and STS and recorded single/multi-units under an awake condition. As a result, we found neurons in the ventrolateral frontal cortex with characteristic mirror properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution.

  20. Mirror Neurons in a New World Monkey, Common Marmoset.

    Science.gov (United States)

    Suzuki, Wataru; Banno, Taku; Miyakawa, Naohisa; Abe, Hiroshi; Goda, Naokazu; Ichinohe, Noritaka

    2015-01-01

    Mirror neurons respond when executing a motor act and when observing others' similar act. So far, mirror neurons have been found only in macaques, humans, and songbirds. To investigate the degree of phylogenetic specialization of mirror neurons during the course of their evolution, we determined whether mirror neurons with similar properties to macaques occur in a New World monkey, the common marmoset (Callithrix jacchus). The ventral premotor cortex (PMv), where mirror neurons have been reported in macaques, is difficult to identify in marmosets, since no sulcal landmarks exist in the frontal cortex. We addressed this problem using "in vivo" connection imaging methods. That is, we first identified cells responsive to others' grasping action in a clear landmark, the superior temporal sulcus (STS), under anesthesia, and injected fluorescent tracers into the region. By fluorescence stereomicroscopy, we identified clusters of labeled cells in the ventrolateral frontal cortex, which were confirmed to be within the ventrolateral frontal cortex including PMv after sacrifice. We next implanted electrodes into the ventrolateral frontal cortex and STS and recorded single/multi-units under an awake condition. As a result, we found neurons in the ventrolateral frontal cortex with characteristic "mirror" properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution.

  1. Identification and Characterization of Wheat Yellow Striate Virus, a Novel Leafhopper-Transmitted Nucleorhabdovirus Infecting Wheat

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-03-01

    Full Text Available A new wheat viral disease was found in China. Bullet-shaped viral particles within the nucleus of the infected wheat leave cells, which possessed 180–210 nm length and 35–40 nm width, were observed under transmission electron microscopy. A putative wheat-infecting rhabdovirus vectored by the leafhopper Psammotettix alienus was identified and tentatively named wheat yellow striate virus (WYSV. The full-length nucleotide sequence of WYSV was determined using transcriptome sequencing and RACE analysis of both wheat samples and leafhoppers P. alienus. The negative-sense RNA genome of WYSV contains 14,486 nucleotides (nt and seven open reading frames (ORFs encode deduced proteins in the order N-P-P3-M-P6-G-L on the antisense strand. In addition, WYSV genome has a 76-nt 3′ leader RNA and a 258-nt 5′ trailer, and the ORFs are separated by conserved intergenic sequences. The entire genome sequence shares 58.1 and 57.7% nucleotide sequence identity with two strains of rice yellow stunt virus (RYSV-A and RYSV-B genomes, respectively. The highest amino acid sequence identity was 63.8% between the L proteins of the WYSV and RYSV-B, but the lowest was 29.5% between the P6 proteins of these viruses. Phylogenetic analysis firmly established WYSV as a new member of the genus Nucleorhabdovirus. Collectively, this study provided evidence that WYSV is likely the first nucleorhabdovirus described infecting wheat via leafhopper P. alienus transmission.

  2. The Intriguing Dual Lattices of the Myosin Filaments in Vertebrate Striated Muscles: Evolution and Advantage

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    Pradeep K. Luther

    2014-12-01

    Full Text Available Myosin filaments in vertebrate striated muscle have a long roughly cylindrical backbone with cross-bridge projections on the surfaces of both halves except for a short central bare zone. In the middle of this central region the filaments are cross-linked by the M-band which holds them in a well-defined hexagonal lattice in the muscle A-band. During muscular contraction the M-band-defined rotation of the myosin filaments around their long axes influences the interactions that the cross-bridges can make with the neighbouring actin filaments. We can visualise this filament rotation by electron microscopy of thin cross-sections in the bare-region immediately adjacent to the M-band where the filament profiles are distinctly triangular. In the muscles of teleost fishes, the thick filament triangular profiles have a single orientation giving what we call the simple lattice. In other vertebrates, for example all the tetrapods, the thick filaments have one of two orientations where the triangles point in opposite directions (they are rotated by 60° or 180° according to set rules. Such a distribution cannot be developed in an ordered fashion across a large 2D lattice, but there are small domains of superlattice such that the next-nearest neighbouring thick filaments often have the same orientation. We believe that this difference in the lattice forms can lead to different contractile behaviours. Here we provide a historical review, and when appropriate cite recent work related to the emergence of the simple and superlattice forms by examining the muscles of several species ranging back to primitive vertebrates and we discuss the functional differences that the two lattice forms may have.

  3. Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

    Directory of Open Access Journals (Sweden)

    Robert Jarosch

    2008-12-01

    Full Text Available This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit. Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation. Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with forceregulating sites for Ca2+ binding, the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

  4. Sparse representation of sounds in the unanesthetized auditory cortex.

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    Tomás Hromádka

    2008-01-01

    Full Text Available How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second. At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons.

  5. Surround suppression maps in the cat primary visual cortex

    OpenAIRE

    Vanni, Matthieu P.; Casanova, Christian

    2013-01-01

    In the primary visual cortex and higher-order areas, it is well known that the stimulation of areas surrounding the classical receptive field of a neuron can inhibit its responses. In the primate area middle temporal (MT), this surround suppression was shown to be spatially organized into high and low suppression modules. However, such an organization has not been demonstrated yet in the primary visual cortex. Here, we used optical imaging of intrinsic signals to spatially evaluate surround s...

  6. Neural Dynamics and Information Representation in Microcircuits of Motor Cortex

    Directory of Open Access Journals (Sweden)

    Yasuhiro eTsubo

    2013-05-01

    Full Text Available The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs, in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

  7. Representation of Numerosity in Posterior Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Jamie D Roitman

    2012-05-01

    Full Text Available Humans and animals appear to share a similar representation of number as an analog magnitude on an internal, subjective scale. Neurological and neurophysiological data suggest that posterior parietal cortex (PPC is a critical component of the circuits that form the basis of numerical abilities in humans. Patients with parietal lesions are impaired in their ability to access the deep meaning of numbers. Acalculiac patients with inferior parietal damage often have difficulty performing arithmetic (2+4? or number bisection (what is between 3 and 5? tasks, but are able to recite multiplication tables and read or write numerals. Functional imaging studies of neurologically intact humans performing subtraction, number comparison, and nonverbal magnitude comparison tasks show activity in areas within the intraparietal sulcus. Taken together, clinical cases and imaging studies support a critical role for parietal cortex in the mental manipulation of numerical quantities. Further, responses of single PPC neurons in non-human primates are sensitive to the numerosity of visual stimuli independent of low-level stimulus qualities. When monkeys are trained to make explicit judgments about the numerical value of such stimuli, PPC neurons encode their cardinal numerical value; without such training PPC neurons appear to encode numerical magnitude in an analog fashion. Here we suggest that the spatial and integrative properties of PPC neurons contribute to their critical role in numerical cognition.

  8. Cognitive Control Signals in Posterior Cingulate Cortex

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-12-01

    Full Text Available Efficiently shifting between tasks is a central function of cognitive control. The role of the default network—a constellation of areas with high baseline activity that declines during task performance—in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing towards the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the CGp. To test this idea, we recorded the activity of single neurons in posterior cingulate cortex (CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex (LIP, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain..

  9. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    Science.gov (United States)

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  10. Higher Order Spike Synchrony in Prefrontal Cortex during visual memory

    Directory of Open Access Journals (Sweden)

    Gordon ePipa

    2011-06-01

    Full Text Available Precise temporal synchrony of spike firing has been postulated as an important neuronal mechanism for signal integration and the induction of plasticity in neocortex. As prefrontal cortex plays an important role in organizing memory and executive functions, the convergence of multiple visual pathways onto PFC predicts that neurons should preferentially synchronize their spiking when stimulus information is processed. Furthermore, synchronous spike firing should intensify if memory processes require the induction of neuronal plasticity, even if this is only for short-term. Here we show with multiple simultaneously recorded units in ventral prefrontal cortex that neurons participate in 3 ms precise synchronous discharges distributed across multiple sites separated by at least 500 µm. The frequency of synchronous firing is modulated by behavioral performance and is specific for the memorized visual stimuli. In particular, during the memory period in which activity is not stimulus driven, larger groups of up to 7 sites exhibit performance dependent modulation of their spike synchronization.

  11. Auditory cortex of newborn bats is prewired for echolocation.

    Science.gov (United States)

    Kössl, Manfred; Voss, Cornelia; Mora, Emanuel C; Macias, Silvio; Foeller, Elisabeth; Vater, Marianne

    2012-04-10

    Neuronal computation of object distance from echo delay is an essential task that echolocating bats must master for spatial orientation and the capture of prey. In the dorsal auditory cortex of bats, neurons specifically respond to combinations of short frequency-modulated components of emitted call and delayed echo. These delay-tuned neurons are thought to serve in target range calculation. It is unknown whether neuronal correlates of active space perception are established by experience-dependent plasticity or by innate mechanisms. Here we demonstrate that in the first postnatal week, before onset of echolocation and flight, dorsal auditory cortex already contains functional circuits that calculate distance from the temporal separation of a simulated pulse and echo. This innate cortical implementation of a purely computational processing mechanism for sonar ranging should enhance survival of juvenile bats when they first engage in active echolocation behaviour and flight.

  12. A comparative study of various electrodes in electromyography of the striated urethral and anal sphincter in children

    DEFF Research Database (Denmark)

    Nielsen, K K; Kristensen, E S; Qvist, N

    1985-01-01

    The series comprised 41 children aged 6 to 14 years consecutively referred with recurrent urinary tract infection and/or enuresis. Carbon dioxide cystometry was carried out in the supine and the erect position and combined with simultaneous electromyography (EMG). The external urethral sphincter...... was examined with a ring electrode mounted on a urethral catheter, while recordings from the striated anal sphincter were based on an anal plug electrode and perianal electrocardiographic (ECG) skin electrodes: 211 EMG and cystometric examinations were performed and all three methods gave satisfactory results...

  13. Preparing E18 Cortical Rat Neurons for Compartmentalization in a Microfluidic Device

    OpenAIRE

    Harris, Joseph; Lee, Hyuna; Tu, Christina Tu; Cribbs, David; Cotman, Carl; Jeon, Noo Li

    2007-01-01

    In this video, we demonstrate the preparation of E18 cortical rat neurons. E18 cortical rat neurons are obtained from E18 fetal rat cortex previously dissected and prepared. The E18 cortex is, upon dissection, immediately dissociated into individual neurons. It is possible to store E18 cortex in Hibernate E buffer containing B27 at 4°C for up to a week before the dissociation is performed. However, there will be a drop in cell viability. Typically we obtain our E18 Cortex fresh. It is tra...

  14. Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

    OpenAIRE

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

  15. Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice.

    Science.gov (United States)

    Devine, Raymond D; Bicer, Sabahattin; Reiser, Peter J; Wold, Loren E

    2017-06-01

    that occur during cancer cachexia. NEW & NOTEWORTHY We used proteomics and metadata analysis software to identify contributors to metabolic changes in striated muscle during cancer cachexia. We found increased expression of hypoxia-inducible factor-1α in the heart and skeletal muscle, suggesting a potential target for the therapeutic treatment of cancer cachexia. Copyright © 2017 the American Physiological Society.

  16. Frequency-specific attentional modulation in human primary auditory cortex and midbrain

    NARCIS (Netherlands)

    Riecke, Lars; Peters, Judith C.; Valente, Giancarlo; Poser, Benedikt A.; Kemper, Valentin G.; Formisano, Elia; Sorger, Bettina

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning,

  17. Sleep disordered breathing in motor neurone disease

    OpenAIRE

    D’Cruz, Rebecca F.; Murphy, Patrick B.; Kaltsakas, Georgios

    2018-01-01

    Motor neurone disease (MND) is a neurodegenerative disease defined by axonal loss and gliosis of upper and lower motor neurones in the motor cortex, lower brainstem nuclei and ventral horn of the spinal cord. MND is currently incurable and has a poor prognosis, with death typically occurring 3 to 5 years after disease onset. The disease is characterised by rapidly progressive weakness leading to paralysis, fasciculations, bulbar symptoms (including dysarthria and dysphagia) and respiratory co...

  18. Morphological Neuron Classification Using Machine Learning

    Science.gov (United States)

    Vasques, Xavier; Vanel, Laurent; Villette, Guillaume; Cif, Laura

    2016-01-01

    Classification and quantitative characterization of neuronal morphologies from histological neuronal reconstruction is challenging since it is still unclear how to delineate a neuronal cell class and which are the best features to define them by. The morphological neuron characterization represents a primary source to address anatomical comparisons, morphometric analysis of cells, or brain modeling. The objectives of this paper are (i) to develop and integrate a pipeline that goes from morphological feature extraction to classification and (ii) to assess and compare the accuracy of machine learning algorithms to classify neuron morphologies. The algorithms were trained on 430 digitally reconstructed neurons subjectively classified into layers and/or m-types using young and/or adult development state population of the somatosensory cortex in rats. For supervised algorithms, linear discriminant analysis provided better classification results in comparison with others. For unsupervised algorithms, the affinity propagation and the Ward algorithms provided slightly better results. PMID:27847467

  19. Hibernation induces pentobarbital insensitivity in medulla but not cortex

    Science.gov (United States)

    Hengen, Keith B.; Behan, Mary; Carey, Hannah V.; Jones, Mathew V.

    2009-01-01

    The 13-lined ground squirrel (Ictidomys tridecemlineatus), a hibernating species, is a natural model of physiological adaption to an extreme environment. During torpor, body temperature drops to 0–4°C, and the cortex is electrically silent, yet the brain stem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain during torpor are not known. To test whether altered GABAergic function is involved in regional and seasonal differences in neuronal activity, cortical and medullary slices from summer-active (SA) and interbout aroused (IBA) squirrels were placed in a standard in vitro recording chamber. Silicon multichannel electrodes were placed in cortex, ventral respiratory column (VRC), and nucleus tractus solitarius (NTS) to record spontaneous neuronal activity. In slices from IBA squirrels, bath-applied pentobarbital sodium (300 μM) nearly abolished cortical neuronal activity, but VRC and NTS neuronal activity was unaltered. In contrast, pentobarbital sodium (300 μM) nearly abolished all spontaneous cortical, VRC, and NTS neuronal activity in slices from SA squirrels. Muscimol (20 μM; GABAA receptor agonist) abolished all neuronal activity in cortical and medullary slices from both IBA and SA squirrels, thereby demonstrating the presence of functional GABAA receptors. Pretreatment of cortical slices from IBA squirrels with bicuculline (100 μM; GABAA receptor antagonist) blocked pentobarbital-dependent inhibition of spontaneous neuronal activity. We hypothesize that GABAA receptors undergo a seasonal modification in subunit composition, such that cardiorespiratory neurons are uniquely unaffected by surges of an endogenous positive allosteric modulator. PMID:19675281

  20. Noisy Neurons

    Indian Academy of Sciences (India)

    IAS Admin

    Nerves are fibres that conduct electrical signals and hence pass on information from and to the brain. Nerves are made of nerve cells called neurons (Figure 1). Instructions in our body are sent via electrical signals that present themselves as variations in the potential across neuronal membranes. These potential differences ...

  1. Striated nephrogram as an incidental finding in MRI examination of children; Streifiges Nephrogramm als Zufallsbefund nach Kontrastmittelgabe bei Kindern in der MRT

    Energy Technology Data Exchange (ETDEWEB)

    Strocka, S.; Sorge, I.; Ritter, L.; Hirsch, F.W. [Leipzig Univ. (Germany). Dept. of Pediatric Radiology

    2016-01-15

    A highly striated contrast pattern of the kidneys occasionally appears in abdominal MRI examinations of children following the administration of gadolinium. As this phenomenon is well known but has not yet been explicitly described in literature, we investigated how frequently and in which clinical context this occurred. 855 abdominal MRI examinations with contrast media of 362 children between 2006 and 2014 were analysed retrospectively. A striated renal parenchyma was found in a total of nine children and eleven examinations (1.3 % of examinations) and did only occur at a field strength of 3 Tesla. Of these children, seven had previously had tumors and chemotherapy. In two children there was no evidence of a previously serious condition with medications or a kidney disease. All of them had a normal renal function. A noticeably striated nephrogram in the later phase of an MRI examination following administration of gadolinium may appear as an incidental finding in examinations at 3 Tesla without pathological relevance.

  2. Processing of Natural Sounds: Characterization of Multipeak Spectral Tuning in Human Auditory Cortex

    OpenAIRE

    Moerel, Michelle; De Martino, Federico; Santoro, Roberta; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

    2013-01-01

    We examine the mechanisms by which the human auditory cortex processes the frequency content of natural sounds. Through mathematical modeling of ultra-high field (7 T) functional magnetic resonance imaging responses to natural sounds, we derive frequency-tuning curves of cortical neuronal populations. With a data-driven analysis, we divide the auditory cortex into five spatially distributed clusters, each characterized by a spectral tuning profile. Beyond neuronal populations with simple sing...

  3. Contracture Coupling of Slow Striated Muscle in Non-Ionic Solutions and Replacement of Calcium, Sodium, and Potassium

    Science.gov (United States)

    Irwin, Richard L.; Hein, Manfred M.

    1964-01-01

    The development of contracture related to changes of ionic environment (ionic contracture coupling) has been studied in the slowly responding fibers of frog skeletal muscle. When deprived of external ions for 30 minutes by use of solutions of sucrose, mannitol, or glucose, the slow skeletal muscle fibers, but not the fast, develop pronounced and easily reversible contractures. Partial replacement of the non-ionic substance with calcium or sodium reduces the development of the contractures but replacement by potassium does not. The concentration of calcium necessary to prevent contracture induced by a non-ionic solution is greater than that needed to maintain relaxation in ionic solutions. To suppress the non-ionic-induced contractures to the same extent as does calcium requires several fold higher concentrations of sodium. Two types of ionic contracture coupling occur in slow type striated muscle fibers: (a) a calcium deprivation type which develops maximally at full physiological concentration of external sodium, shows a flow rate dependency for the calcium-depriving fluid, and is lessened when the sodium concentration is decreased by replacement with sucrose; (b) a sodium deprivation type which occurs maximally without external sodium, is lessened by increasing the sodium concentration, and has no flow rate dependency for ion deprivation. Both types of contracture are largely prevented by the presence of sufficient calcium. There thus seem to be calcium- and sodium-linked processes at work in the ionic contracture coupling of slow striated muscle. PMID:14127603

  4. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham 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 dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  5. Functionally Specific Oscillatory Activity Correlates between Visual and Auditory Cortex in the Blind

    Science.gov (United States)

    Schepers, Inga M.; Hipp, Joerg F.; Schneider, Till R.; Roder, Brigitte; Engel, Andreas K.

    2012-01-01

    Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a…

  6. Zooming Out of Single Neurons Reveals Structure in Mnemonic Representations.

    Science.gov (United States)

    Jazayeri, Mehrdad

    2017-12-20

    In this issue of Neuron, Rossi-Pool et al. (2017) show that the complex and heterogeneous response profiles of individual neurons in the dorsal premotor cortex during comparison of tactile temporal patterns can be understood in terms of two robust activity patterns that emerge across the population. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Neocortical Neuronal Loss in Patients with Multiple System Atrophy

    DEFF Research Database (Denmark)

    Salvesen, Lisette; Winge, Kristian; Brudek, Tomasz

    2017-01-01

    To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients...... with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly...

  8. Characterization of auditory synaptic inputs to gerbil perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Vibhakar C Kotak

    2015-08-01

    Full Text Available The representation of acoustic cues involves regions downstream from the auditory cortex (ACx. One such area, the perirhinal cortex (PRh, processes sensory signals containing mnemonic information. Therefore, our goal was to assess whether PRh receives auditory inputs from the auditory thalamus (MG and ACx in an auditory thalamocortical brain slice preparation and characterize these afferent-driven synaptic properties. When the MG or ACx was electrically stimulated, synaptic responses were recorded from the PRh neurons. Blockade of GABA-A receptors dramatically increased the amplitude of evoked excitatory potentials. Stimulation of the MG or ACx also evoked calcium transients in most PRh neurons. Separately, when fluoro ruby was injected in ACx in vivo, anterogradely labeled axons and terminals were observed in the PRh. Collectively, these data show that the PRh integrates auditory information from the MG and ACx and that auditory driven inhibition dominates the postsynaptic responses in a non-sensory cortical region downstream from the auditory cortex.

  9. The Harmonic Organization of Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Xiaoqin eWang

    2013-12-01

    Full Text Available A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds.

  10. Coordinated Scaling of Cortical and Cerebellar Numbers of Neurons

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2010-01-01

    While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of four different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora), Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble. PMID:20300467

  11. Coordinated scaling of cortical and cerebellar numbers of neurons

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2010-03-01

    Full Text Available While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of 4 different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora, Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

  12. The representation of social facial touch in rat barrel cortex.

    Science.gov (United States)

    Bobrov, Evgeny; Wolfe, Jason; Rao, Rajnish P; Brecht, Michael

    2014-01-06

    Controlled presentation of stimuli to anesthetized [1] or awake [2] animals suggested that neurons in sensory cortices respond to elementary features [3, 4], but we know little about neuronal responses evoked by social interactions. Here we investigate processing in the barrel cortex of rats engaging in social facial touch [5, 6]. Sensory stimulation by conspecifics differs from classic whisker stimuli such as deflections, contact poles [7, 8], or textures [9, 10]. A large fraction of barrel cortex neurons responded to facial touch. Social touch responses peaked when animals aligned their faces and contacted each other by multiple whiskers with small, irregular whisker movements. Object touch was associated with larger, more regular whisker movements, and object responses were weaker than social responses. Whisker trimming abolished responses. During social touch, neurons in males increased their firing on average by 44%, while neurons in females increased their firing by only 19%. In females, socially evoked and ongoing firing rates were more than 1.5-fold higher in nonestrus than in estrus. Barrel cortex represented socially different contacts by distinct firing rates, and the variation of activity with sex and sexual status could contribute to the generation of gender-specific neural constructs of conspecifics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. An FPGA-Based Massively Parallel Neuromorphic Cortex Simulator

    Directory of Open Access Journals (Sweden)

    Runchun M. Wang

    2018-04-01

    Full Text Available This paper presents a massively parallel and scalable neuromorphic cortex simulator designed for simulating large and structurally connected spiking neural networks, such as complex models of various areas of the cortex. The main novelty of this work is the abstraction of a neuromorphic architecture into clusters represented by minicolumns and hypercolumns, analogously to the fundamental structural units observed in neurobiology. Without this approach, simulating large-scale fully connected networks needs prohibitively large memory to store look-up tables for point-to-point connections. Instead, we use a novel architecture, based on the structural connectivity in the neocortex, such that all the required parameters and connections can be stored in on-chip memory. The cortex simulator can be easily reconfigured for simulating different neural networks without any change in hardware structure by programming the memory. A hierarchical communication scheme allows one neuron to have a fan-out of up to 200 k neurons. As a proof-of-concept, an implementation on one Altera Stratix V FPGA was able to simulate 20 million to 2.6 billion leaky-integrate-and-fire (LIF neurons in real time. We verified the system by emulating a simplified auditory cortex (with 100 million neurons. This cortex simulator achieved a low power dissipation of 1.62 μW per neuron. With the advent of commercially available FPGA boards, our system offers an accessible and scalable tool for the design, real-time simulation, and analysis of large-scale spiking neural networks.

  14. Reduced synchronization in the visual cortex of cats with strabismic amblyopia

    NARCIS (Netherlands)

    Roelfsema, P. R.; König, P.; Engel, A. K.; Sireteanu, R.; Singer, W.

    1994-01-01

    Synchronous firing of spatially separate neurons was studied with multi-electrode recordings in area 17 of the visual cortex of strabismic cats which had developed behaviourally verified amblyopia of the deviated eye. Responses of neurons were evoked with moving light bars or gratings of different

  15. Population coding in mouse visual cortex : Response reliability and dissociability of stimulus tuning and noise correlation

    NARCIS (Netherlands)

    Montijn, J.S.; Vinck, M.; Pennartz, C.M.A.

    2014-01-01

    The primary visual cortex is an excellent model system for investigating how neuronal populations encode information, because of well-documented relationships between stimulus characteristics and neuronal activation patterns. We used two-photon calcium imaging data to relate the performance of

  16. Prefrontal cortex activity related to abstract response strategies.

    Science.gov (United States)

    Genovesio, Aldo; Brasted, Peter J; Mitz, Andrew R; Wise, Steven P

    2005-07-21

    Many monkeys adopt abstract response strategies as they learn to map visual symbols to responses by trial and error. According to the repeat-stay strategy, if a symbol repeats from a previous, successful trial, the monkeys should stay with their most recent response choice. According to the change-shift strategy, if the symbol changes, the monkeys should shift to a different choice. We recorded the activity of prefrontal cortex neurons while monkeys chose responses according to these two strategies. Many neurons had activity selective for the strategy used. In a subsequent block of trials, the monkeys learned fixed stimulus-response mappings with the same stimuli. Some neurons had activity selective for choosing responses based on fixed mappings, others for choosing based on abstract strategies. These findings indicate that the prefrontal cortex contributes to the implementation of the abstract response strategies that monkeys use during trial-and-error learning.

  17. Mirror neurons: their implications for group psychotherapy.

    Science.gov (United States)

    Schermer, Victor L

    2010-10-01

    Recently discovered mirror neurons in the motor cortex of the brain register the actions and intentions of both the organism and others in the environment. As such, they may play a significant role in social behavior and groups. This paper considers the potential implications of mirror neurons and related neural networks for group therapists, proposing that mirror neurons and mirror systems provide "hard-wired" support for the group therapist's belief in the centrality of relationships in the treatment process and exploring their value in accounting for group-as-a-whole phenomena. Mirror neurons further confirm the holistic, social nature of perception, action, and intention as distinct from a stimulus-response behaviorism. The implications of mirror neurons and mirroring processes for the group therapist role, interventions, and training are also discussed.

  18. Working Memory in the Prefrontal Cortex.

    Science.gov (United States)

    Funahashi, Shintaro

    2017-04-27

    The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley's working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified.

  19. Working Memory in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Shintaro Funahashi

    2017-04-01

    Full Text Available The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified.

  20. Striated muscle fiber size, composition and capillary density in diabetes in relation to neuropathy and muscle strength

    DEFF Research Database (Denmark)

    Andreassen, Christer Swan; Jensen, Jacob Malte; Jakobsen, Johannes

    2014-01-01

    OBJECTIVE: Diabetic polyneuropathy (DPN) leads to progressive loss of muscle strength in the lower extremities due to muscular atrophy. Changes in vascularization occur in diabetic striated muscle; however, the relationship between these changes and DPN is as yet unexplored. The aim of the present...... study was to evaluate histologic properties and capillarization of diabetic skeletal muscle in relation to DPN and muscle strength. METHODS: Twenty type 1 and 20 type 2 diabetic (T1D and T2D, respectively) patients underwent biopsy of the gastrocnemic muscle, isokinetic dynamometry at the ankle......, electrophysiological studies, clinical examination, and quantitative sensory examinations. Muscle biopsies were stained immunohistochemically and muscle fiber diameter, fiber type distribution, and capillary density determined. Twenty control subjects were also included in the study. RESULTS: No relationship was found...

  1. Visual Interhemispheric and Striate-Extrastriate Cortical Connections in the Rabbit: A Multiple Tracer Study

    Directory of Open Access Journals (Sweden)

    Adrian K. Andelin

    2015-01-01

    Full Text Available Previous studies in rabbits identified an array of extrastriate cortical areas anatomically connected with V1 but did not describe their internal topography. To address this issue, we injected multiple anatomical tracers into different regions in V1 of the same animal and analyzed the topography of resulting extrastriate labeled fields with reference to the patterns of callosal connections and myeloarchitecture revealed in tangential sections of the flattened cortex. Our results extend previous studies and provide further evidence that rabbit extrastriate areas resemble the visual areas in rats and mice not only in their general location with respect to V1 but also in their internal topography. Moreover, extrastriate areas in the rabbit maintain a constant relationship with myeloarchitectonic borders and features of the callosal pattern. These findings highlight the rabbit as an alternative model to rats and mice for advancing our understanding of cortical visual processing in mammals, especially for projects benefiting from a larger brain.

  2. DNA turnover in rat cerebral cortex.

    Science.gov (United States)

    Perrone-Capano, C; D'Onofrio, G; Giuditta, A

    1982-01-01

    After the intracranial injection of [methyl-3H]thymidine the specific activity of rat cortical DNA increases rapidly, reaching a maximum at about 5 h. More than half of the radioactive DNA disappears from the tissue in the following few hours. During the same period of time the concentration of radioactive DNA in liver remains essentially constant. Minor variations occur in both organs after 41 h. An apparent rapid turnover of DNA is also present in a fraction of purified neuronal perikarya prepared from the cerebral cortex.

  3. Reflections on agranular architecture: predictive coding in the motor cortex.

    Science.gov (United States)

    Shipp, Stewart; Adams, Rick A; Friston, Karl J

    2013-12-01

    The agranular architecture of motor cortex lacks a functional interpretation. Here, we consider a 'predictive coding' account of this unique feature based on asymmetries in hierarchical cortical connections. In sensory cortex, layer 4 (the granular layer) is the target of ascending pathways. We theorise that the operation of predictive coding in the motor system (a process termed 'active inference') provides a principled rationale for the apparent recession of the ascending pathway in motor cortex. The extension of this theory to interlaminar circuitry also accounts for a sub-class of 'mirror neuron' in motor cortex--whose activity is suppressed when observing an action--explaining how predictive coding can gate hierarchical processing to switch between perception and action. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  5. Construction of Direction Selectivity through Local Energy Computations in Primary Visual Cortex

    OpenAIRE

    Lochmann, Timm; Blanche, Timothy J.; Butts, Daniel A.

    2013-01-01

    Despite detailed knowledge about the anatomy and physiology of neurons in primary visual cortex (V1), the large numbers of inputs onto a given V1 neuron make it difficult to relate them to the neuron's functional properties. For example, models of direction selectivity (DS), such as the Energy Model, can successfully describe the computation of phase-invariant DS at a conceptual level, while leaving it unclear how such computations are implemented by cortical circuits. Here, we use statistica...

  6. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    Full Text Available It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans. The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum. These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  7. Circuit changes in motor cortex during motor skill learning.

    Science.gov (United States)

    Papale, Andrew E; Hooks, Bryan M

    2018-01-01

    Motor cortex is important for motor skill learning, particularly the dexterous skills necessary for our favorite sports and careers. We are especially interested in understanding how plasticity in motor cortex contributes to skill learning. Although human studies have been helpful in understanding the importance of motor cortex in learning skilled tasks, animal models are necessary for achieving a detailed understanding of the circuitry underlying these behaviors and the changes that occur during training. We review data from these models to try to identify sites of plasticity in motor cortex, focusing on rodents asa model system. Rodent neocortex contains well-differentiated motor and sensory regions, as well as neurons expressing similar genetic markers to many of the same circuit components in human cortex. Furthermore, rodents have circuit mapping tools for labeling, targeting, and manipulating these cell types as circuit nodes. Crucially, the projection from rodent primary somatosensory cortex to primary motor cortex is a well-studied corticocortical projection and a model of sensorimotor integration. We first summarize some of the descending pathways involved in making dexterous movements, including reaching. We then describe local and long-range circuitry in mouse motor cortex, summarizing structural and functional changes associated with motor skill acquisition. We then address which specific connections might be responsible for plasticity. For insight into the range of plasticity mechanisms employed by cortex, we review plasticity in sensory systems. The similarities and differences between motor cortex plasticity and critical periods of plasticity in sensory systems are discussed. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  9. A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

    Science.gov (United States)

    Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

    2016-11-21

    In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

  10. Neuronal replacement therapy: previous achievements and challenges ahead

    Science.gov (United States)

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  11. Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.

    Science.gov (United States)

    Sparks, Daniel W; Tian, Michael K; Sargin, Derya; Venkatesan, Sridevi; Intson, Katheron; Lambe, Evelyn K

    2017-01-01

    Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

  12. Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex.

    Science.gov (United States)

    Wagener, Robin J; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F

    2016-02-01

    Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory "barrel" cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. © The Author 2015. Published by Oxford University Press.

  13. Noisy Neurons

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 1. Noisy Neurons: Hodgkin-Huxley Model and Stochastic Variants. Shurti Paranjape. General Article Volume 20 Issue 1 January 2015 pp 34-43. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. Representation of Behavioral Tactics and Tactics-Action Transformation in the Primate Medial Prefrontal Cortex.

    Science.gov (United States)

    Matsuzaka, Yoshiya; Tanji, Jun; Mushiake, Hajime

    2016-06-01

    To expedite the selection of action under a structured behavioral context, we develop an expedient to promote its efficiency: tactics for action selection. Setting up a behavioral condition for subhuman primates (Macaca fuscata) that induced the development of a behavioral tactics, we explored neuronal representation of tactics in the medial frontal cortex. Here we show that neurons in the posterior medial prefrontal cortex, but not much in the medial premotor cortex, exhibit activity representing the behavioral tactics, in advance of action-selective activity. Such activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its implementation for the achievement of action selection. At a population level, posterior medial prefrontal cortex neurons take part in transforming the tactics information into the information representing action selection. The tactics representation revealed an aspect of neural mechanisms for an adaptive behavioral control, taking place in the medial prefrontal cortex. We studied behavioral significance of neuronal activity in the posterior medial prefrontal cortex (pmPFC) and found the representation of behavioral tactics defined as specific and efficient ways to achieve objectives of actions. Neuronal activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its use preceding the achievement of action selection. We found further that pmPFC neurons take part in transforming the tactics information into the information representing action selection. A majority of individual neurons was recruited during a limited period in each behavioral epoch, constituting, as a whole, a temporal cascade of activity. Such dynamics found in behavioral-tactics specific activity characterize the participation of pmPFC neurons in executive control of purposeful behavior. Copyright © 2016 the authors 0270-6474/16/365974-14$15.00/0.

  15. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit...... alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength...... of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions...

  16. Increased Cell Fusion in Cerebral Cortex May Contribute to Poststroke Regeneration

    Directory of Open Access Journals (Sweden)

    Alexander Paltsyn

    2013-01-01

    Full Text Available In this study, we used a model of a hemorrhagic stroke in a motor zone of the cortex in rats at the age of 3 months The report shows that cortical neurons can fuse with oligodendrocytes. In formed binuclear cells, the nucleus of an oligodendrocyte undergoes neuron specific reprogramming. It can be confirmed by changes in chromatin structure and in size of the second nucleus, by expression of specific neuronal markers and increasing total transcription rate. The nucleus of an oligodendrocyte likely transforms into a second neuronal nucleus. The number of binuclear neurons was validated with quantitative analysis. Fusion of neurons with oligodendrocytes might be a regenerative process in general and specifically following a stroke. The appearance of additional neuronal nuclei increases the functional outcome of the population of neurons. Participation of a certain number of binuclear cells in neuronal function might compensate for a functional deficit that arises from the death of a subset of neurons. After a stroke, the number of binuclear neurons increased in cortex around the lesion zone. In this case, the rate of recovery of stroke-damaged locomotor behavior also increased, which indicates the regenerative role of fusion.

  17. Preparatory attention in visual cortex.

    Science.gov (United States)

    Battistoni, Elisa; Stein, Timo; Peelen, Marius V

    2017-05-01

    Top-down attention is the mechanism that allows us to selectively process goal-relevant aspects of a scene while ignoring irrelevant aspects. A large body of research has characterized the effects of attention on neural activity evoked by a visual stimulus. However, attention also includes a preparatory phase before stimulus onset in which the attended dimension is internally represented. Here, we review neurophysiological, functional magnetic resonance imaging, magnetoencephalography, electroencephalography, and transcranial magnetic stimulation (TMS) studies investigating the neural basis of preparatory attention, both when attention is directed to a location in space and when it is directed to nonspatial stimulus attributes (content-based attention) ranging from low-level features to object categories. Results show that both spatial and content-based attention lead to increased baseline activity in neural populations that selectively code for the attended attribute. TMS studies provide evidence that this preparatory activity is causally related to subsequent attentional selection and behavioral performance. Attention thus acts by preactivating selective neurons in the visual cortex before stimulus onset. This appears to be a general mechanism that can operate on multiple levels of representation. We discuss the functional relevance of this mechanism, its limitations, and its relation to working memory, imagery, and expectation. We conclude by outlining open questions and future directions. © 2017 New York Academy of Sciences.

  18. Neural correlates of memory retrieval in the prefrontal cortex.

    Science.gov (United States)

    Nácher, Verónica; Ojeda, Sabiela; Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Acuña, Carlos

    2006-08-01

    Working memory includes short-term representations of information that were recently experienced or retrieved from long-term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long-term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters--the orientation--of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short-term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.

  19. High-Degree Neurons Feed Cortical Computations.

    Directory of Open Access Journals (Sweden)

    Nicholas M Timme

    2016-05-01

    Full Text Available Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree or sends out (out-degree. To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to

  20. The logic of single-cell projections from visual cortex.

    Science.gov (United States)

    Han, Yunyun; Kebschull, Justus M; Campbell, Robert A A; Cowan, Devon; Imhof, Fabia; Zador, Anthony M; Mrsic-Flogel, Thomas D

    2018-04-05

    Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.

  1. Plasticity in the prefrontal cortex of adult rats

    Science.gov (United States)

    Kolb, Bryan; Gibb, Robbin

    2015-01-01

    We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density) in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions. PMID:25691857

  2. Plasticity in the Prefrontal Cortex of Adult Rats

    Directory of Open Access Journals (Sweden)

    Bryan eKolb

    2015-02-01

    Full Text Available We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.

  3. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

    Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

    2013-04-12

    Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2009-05-01

    Full Text Available Abstract Functional human brain imaging studies have indicated the essential role of cortical regions, such as the anterior cingulate cortex (ACC, in romantic love and sex. However, the neurobiological basis of how the ACC neurons are activated and engaged in sexual attraction remains unknown. Using transgenic mice in which the expression of green fluorescent protein (GFP is controlled by the promoter of the activity-dependent gene c-fos, we found that ACC pyramidal neurons are activated by sexual attraction. The presynaptic glutamate release to the activated neurons is increased and pharmacological inhibition of neuronal activities in the ACC reduced the interest of male mice to female mice. Our results present direct evidence of the critical role of the ACC in sexual attraction, and long-term increases in glutamate mediated excitatory transmission may contribute to sexual attraction between male and female mice.

  5. Preparing e18 cortical rat neurons for compartmentalization in a microfluidic device.

    Science.gov (United States)

    Harris, Joseph; Lee, Hyuna; Tu, Christina Tu; Cribbs, David; Cotman, Carl; Jeon, Noo Li

    2007-01-01

    In this video, we demonstrate the preparation of E18 cortical rat neurons. E18 cortical rat neurons are obtained from E18 fetal rat cortex previously dissected and prepared. The E18 cortex is, upon dissection, immediately dissociated into individual neurons. It is possible to store E18 cortex in Hibernate E buffer containing B27 at 4 degrees C for up to a week before the dissociation is performed. However, there will be a drop in cell viability. Typically we obtain our E18 Cortex fresh. It is transported to the lab in ice cold Calcium free Magnesium free dissection buffer (CMFM). Upon arrival, trypsin is added to the cortex to a final concentration of 0.125%. The cortex is then incubated at 37 degrees C for 8 minutes. DMEM containing 10% FBS is added to the cortex to stop the reaction. The cortex is then centrifuged at 2500 rpm for 2 minutes. The supernatant is removed and 2 ml of Neural Basal Media (NBM) containing 2% B27 (vol/vol) and 0.25% Glutamax (vol/vol) is added to the cortex which is then re-suspended by pipetting up and down. Next, the cortex is triturated with previously fire polished glass pipettes, each with a successive smaller opening. After triturating, the cortex is once again centrifuged at 2500 rpm for 2 minutes. The supernatant is then removed and the cortex pellet re-suspended with 2 ml of NBM containing B27 and Glutamax. The cell suspension is then passed through a 40 um nylon cell strainer. Next the cells are counted. The neurons are now ready for loading into the neuron microfluidic device.

  6. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  7. Signals from the ventrolateral thalamus to the motor cortex during locomotion

    Science.gov (United States)

    Marlinski, Vladimir; Nilaweera, Wijitha U.; Zelenin, Pavel V.; Sirota, Mikhail G.

    2012-01-01

    The activity of the motor cortex during locomotion is profoundly modulated in the rhythm of strides. The source of modulation is not known. In this study we examined the activity of one of the major sources of afferent input to the motor cortex, the ventrolateral thalamus (VL). Experiments were conducted in chronically implanted cats with an extracellular single-neuron recording technique. VL neurons projecting to the motor cortex were identified by antidromic responses. During locomotion, the activity of 92% of neurons was modulated in the rhythm of strides; 67% of cells discharged one activity burst per stride, a pattern typical for the motor cortex. The characteristics of these discharges in most VL neurons appeared to be well suited to contribute to the locomotion-related activity of the motor cortex. In addition to simple locomotion, we examined VL activity during walking on a horizontal ladder, a task that requires vision for correct foot placement. Upon transition from simple to ladder locomotion, the activity of most VL neurons exhibited the same changes that have been reported for the motor cortex, i.e., an increase in the strength of stride-related modulation and shortening of the discharge duration. Five modes of integration of simple and ladder locomotion-related information were recognized in the VL. We suggest that, in addition to contributing to the locomotion-related activity in the motor cortex during simple locomotion, the VL integrates and transmits signals needed for correct foot placement on a complex terrain to the motor cortex. PMID:21994259

  8. Alterations in apical dendrite bundling in the somatosensory cortex of 5-HT3A receptor knockout mice.

    NARCIS (Netherlands)

    Smit-Rigter, L.A.; Wadman, W.J.; van Hooft, J.A.

    2011-01-01

    In various species and areas of the cerebral cortex, apical dendrites of pyramidal neurons form clusters which extend through several layers of the cortex also known as dendritic bundles. Previously, it has been shown that 5-HT3A receptor knockout mice show hypercomplex apical dendrites of cortical

  9. Behavioral effects of chronically elevated corticosterone in subregions of the medial prefrontal cortex.

    Science.gov (United States)

    Croteau, Joshua D; Schulkin, Jay; Shepard, Jack D

    2017-01-01

    The medial prefrontal cortex is a key mediator of behavioral aspects of the defense response. Since chronic exposure to elevated glucocorticoids alters the dendritic structure of neurons in the medial prefrontal cortex, such exposure may alter behavioral responses to danger as well. We examined the effects of chronically elevated corticosterone in discrete regions of the medial prefrontal cortex on exploration of the elevated plus-maze. Chronically elevated corticosterone in the prelimbic or infralimbic cortices reduced open arm exploration. This effect was specific to the ventral regions of the medial prefrontal cortex as corticosterone had no effect on plus-maze exploration when administered into the anterior cingulate cortex. Taken together, these findings demonstrate clear regional differences for the effects of corticosterone in the medial prefrontal cortex. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Optimal compensation for neuron loss

    Science.gov (United States)

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  11. A striated, far travelled clast of rhyolitic tuff from Thames river deposits at Ardleigh, Essex, England : evidence for early Middle Pleistocene glaciation in the Thames catchment

    OpenAIRE

    Rose, J.; Carney, J.N.; Silva, B.N.; Booth, S.J.

    2010-01-01

    This paper reports the discovery of an in-situ striated, far-travelled, oversized clast in the Ardleigh Gravels of the Kesgrave Sands and Gravels of the River Thames at Ardleigh, east of Colchester in Essex, eastern England. The morphology, petrography and geochemistry of the clast, and the sedimentology of the host deposit are described. The striations are interpreted, on the basis of their sub-parallelism and the shape and subroundedness of the clast, as glacial and the clast is pr...

  12. Functional diversity of supragranular GABAergic neurons in the barrel cortex.

    NARCIS (Netherlands)

    Gentet, L.J.

    2012-01-01

    Although the neocortex forms a distributed system comprised of several functional areas, its vertical columnar organization is largely conserved across areas and species, suggesting the existence of a canonical neocortical microcircuit. In order to elucidate the principles governing the organization

  13. Geologic continuous casting below continental and deep-sea detachment faults and at the striated extrusion of Sacsayhuaman, Peru

    Science.gov (United States)

    Spencer, J.E.

    1999-01-01

    In the common type of industrial continuous casting, partially molten metal is extruded from a vessel through a shaped orifice called a mold in which the metal assumes the cross-sectional form of the mold as it cools and solidifies. Continuous casting can be sustained as long as molten metal is supplied and thermal conditions are maintained. I propose that a similar process produced parallel sets of grooves in three geologic settings, as follows: (1) corrugated metamorphic core complexes where mylonized mid-crustal rocks were exhumed by movement along low-angle normal faults known as detachment faults; (2) corrugated submarine surfaces where ultramafic and mafic rocks were exhumed by normal faulting within oceanic spreading centers; and (3) striated magma extrusions exemplified by the famous grooved outcrops at the Inca fortress of Sacsayhuaman in Peru. In each case, rocks inferred to have overlain the corrugated surface during corrugation genesis molded and shaped a plastic to partially molten rock mass as it was extruded from a moderate- to high-temperature reservoir.

  14. Impaired contractility of the circular striated urethral sphincter muscle may contribute to stress urinary incontinence in female zucker fatty rats.

    Science.gov (United States)

    Lee, Yung-Chin; Lin, Guiting; Wang, Guifang; Reed-Maldonado, Amanda; Lu, Zhihua; Wang, Lin; Banie, Lia; Lue, Tom F

    2017-08-01

    Obesity has been an independent risk factor for female stress urinary incontinence (SUI), the mechanism of this association remains unknown. The aim of this study is to validate the hypothesis that urethral dysfunction is a possible contributor to SUI in obese women. Ten Zucker Fatty (ZF) (ZUC-Lepr fa 185) and 10 Zucker Lean (ZL) (ZUC-Lepr fa 186) female rats at 12-week-old were used in this experiment. The urethral sphincter rings were harvested from the bladder neck through to the most proximal 2/3 regions. In the organ bath study, single pulses of electrical field stimulation (EFS) were applied. For the fatiguing stimulation, repeated multi-pulse EFS with 70 mA were applied at frequency of 5 Hz for 5 min. Caffeine-containing Krebs' solution was administrated to contract the urethra until the contraction began to reach a plateau for 10 min. We performed immunofluorescence staining of the urethra after the experiment was finished. Compared to ZL controls, ZF rats had significantly impaired muscle contractile activity (MCA) (P female rats had significantly impaired contractile properties of striated urethral sphincter, suggesting urethral dysfunction could be an important contributor to SUI in obesity. © 2016 Wiley Periodicals, Inc.

  15. Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.

    Science.gov (United States)

    Wallace, Marita A; Della Gatta, Paul A; Ahmad Mir, Bilal; Kowalski, Greg M; Kloehn, Joachim; McConville, Malcom J; Russell, Aaron P; Lamon, Séverine

    2016-01-01

    Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. These findings position STARS as an important regulator of skeletal muscle growth and regeneration.

  16. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

    Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

  17. Cognitive and neuronal correlates of videogaming

    OpenAIRE

    Schlüter, Kim-John

    2016-01-01

    BACKGROUND: Within the past few decades video gaming has become a popular recreational activity all over the world and throughout all social classes. Nevertheless distinct scientific conclusions about potential harm or more importantly benefits of video gaming are lacking. However, recent studies point to possible improvements of some cognitive abilities through the high mental demands of modern games. The prefrontal cortex is the essential neuronal correlate of cognitive processing. Scientif...

  18. A switch from inter-ocular to inter-hemispheric suppression following monocular deprivation in the rat visual cortex

    NARCIS (Netherlands)

    Pietrasanta, M.; Restani, L.; Cerri, C.; Olcese, U.; Medini, P.; Caleo, M.

    2014-01-01

    Binocularity is a key property of primary visual cortex (V1) neurons that is widely used to study synaptic integration in the brain and plastic mechanisms following an altered visual experience. However, it is not clear how the inputs from the two eyes converge onto binocular neurons, and how their

  19. DNA repair in mammalian nerve cells. 1. DNA synthesis in cerebral cortex induced by γ-irradiation of rats

    International Nuclear Information System (INIS)

    Ivanov, V.A.; Terpilovskaya, O.N.; Kulikov, A.V.; Tret'yak, T.M.

    1987-01-01

    A study was made of the DNA synthesis in cerebral cortex of rats, aged 14 and 60 days, after gamma-irradiation in vivo in a dose of 7 Gy, the 3 H-thymidine incorporation into DNA being determined. 137 Cs-radiation induces additional DNA synthesis in the neocortex tissue and in neurons. In the cortex of 14 day-old rats, the induced DNA synthesis stops 2 hours after irradiation, whereas in the cortex of 60 day-old rats and in neurons of rats of both the age groups DNA synthesis is proceeding for 3-35 hours. Specificity of DNA reparation, processes in nondividing cells is discussed

  20. Network activity of mirror neurons depends on experience.

    Science.gov (United States)

    Ushakov, Vadim L; Kartashov, Sergey I; Zavyalova, Victoria V; Bezverhiy, Denis D; Posichanyuk, Vladimir I; Terentev, Vasliliy N; Anokhin, Konstantin V

    2013-03-01

    In this work, the investigation of network activity of mirror neurons systems in animal brains depending on experience (existence or absence performance of the shown actions) was carried out. It carried out the research of mirror neurons network in the C57/BL6 line mice in the supervision task of swimming mice-demonstrators in Morris water maze. It showed the presence of mirror neurons systems in the motor cortex M1, M2, cingular cortex, hippocampus in mice groups, having experience of the swimming and without it. The conclusion is drawn about the possibility of the new functional network systems formation by means of mirror neurons systems and the acquisition of new knowledge through supervision by the animals in non-specific tasks.

  1. Remodeling of inhibitory synaptic connections in developing ferret visual cortex

    Directory of Open Access Journals (Sweden)

    Dalva Matthew B

    2010-02-01

    Full Text Available Abstract Background In the visual cortex, as in many other regions of the developing brain, excitatory synaptic connections undergo substantial remodeling during development. While evidence suggests that local inhibitory synapses may behave similarly, the extent and mechanisms that mediate remodeling of inhibitory connections are not well understood. Results Using scanning laser photostimulation in slices of developing ferret visual cortex, we assessed the overall patterns of developing inhibitory and excitatory synaptic connections converging onto individual neurons. Inhibitory synaptic inputs onto pyramidal neurons in cortical layers 2 and 3 were already present as early as postnatal day 20, well before eye opening, and originated from regions close to the recorded neurons. During the ensuing 2 weeks, the numbers of synaptic inputs increased, with the numbers of inhibitory (and excitatory synaptic inputs peaking near the time of eye opening. The pattern of inhibitory inputs refined rapidly prior to the refinement of excitatory inputs. By uncaging the neurotransmtter GABA in brain slices from animals of different ages, we find that this rapid refinement correlated with a loss of excitatory activity by GABA. Conclusion Inhibitory synapses, like excitatory synapses, undergo significant postnatal remodeling. The time course of the remodeling of inhibitory connections correlates with the emergence of orientation tuning in the visual cortex, implicating these rearrangements in the genesis of adult cortical response properties.

  2. Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

    Science.gov (United States)

    Scott, Brian H; Malone, Brian J; Semple, Malcolm N

    2009-04-01

    Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

  3. Predicting oculomotor behaviour from correlated populations of posterior parietal neurons.

    Science.gov (United States)

    Graf, Arnulf B A; Andersen, Richard A

    2015-01-23

    Oculomotor function critically depends on how signals representing saccade direction and eye position are combined across neurons in the lateral intraparietal (LIP) area of the posterior parietal cortex. Here we show that populations of parietal neurons exhibit correlated variability, and that using these interneuronal correlations yields oculomotor predictions that are more accurate and also less uncertain. The structure of LIP population responses is therefore essential for reliable read-out of oculomotor behaviour.

  4. The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex

    OpenAIRE

    Chavez, Candice M.; McGaugh, James L.; Weinberger, Norman M.

    2008-01-01

    Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cor...

  5. [Two-nuclear neurons: sincitial fusion or amitotic division].

    Science.gov (United States)

    Sotnikov, O S; Frumkina, L E; Lactionova, A A; Paramonova, N M; Novakovskaia, S A

    2011-01-01

    In the review the history of research two-nuclear neurons is stated and two hypotheses about mechanisms of their formation are analysed: by sincitial fusion or amytotic divisions. The facts of discrepancy of the former orthodox cellular theory categorically denying possibility sincitial of communications in nervous system and of sincitial fusion neurons are mentioned. As an example results of ultrastructural researches of occurrence sincitium in a cortex of the big brain of rats, in autonomic ganglions, in hypocampus and a cerebellum of adult animals are presented. The video data of the sincitial fusion of live neurons and the mechanism of formation multinuclear neurons in tissue culture are analyzed. Existing data about amytotic a way of formation two-nuclear neurons are critically considered. The conclusion becomes, that the mechanism of formation two-nuclear neurons is cellular fusion. Simultaneously the review confirms our representations about existence in nervous system sincitial interneural communications.

  6. Revisiting the role of neurons in neurovascular coupling

    Directory of Open Access Journals (Sweden)

    Bruno Cauli

    2010-06-01

    Full Text Available In this article, we will review molecular, anatomical, physiological and pharmacological data in an attempt to better understand how excitatory and inhibitory neurons recruited by distinct afferent inputs to the cerebral cortex contribute to the coupled hemodynamic response, and how astrocytes can act as intermediaries to these neuronal populations. We aim at providing the pros and cons to the following statements that, depending on the nature of the afferent input to the neocortex, (i different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes, (ii some recruited neurons release messengers that directly alter blood vessel tone, (iii others act by modulating neuronal and astroglial activity, and (iv astrocytes act as intermediaries for both excitatory and inhibitory neurotransmitters. We will stress that a given afferent signal activates a precise neuronal circuitry that determines the mediators of the hemodynamic response as well as the level of interaction with surrounding astrocytes.

  7. NEUROD1 Instructs Neuronal Conversion in Non-Reactive Astrocytes.

    Science.gov (United States)

    Brulet, Rebecca; Matsuda, Taito; Zhang, Ling; Miranda, Carlos; Giacca, Mauro; Kaspar, Brian K; Nakashima, Kinichi; Hsieh, Jenny

    2017-06-06

    Currently, all methods for converting non-neuronal cells into neurons involve injury to the brain; however, whether neuronal transdifferentiation can occur long after the period of insult remains largely unknown. Here, we use the transcription factor NEUROD1, previously shown to convert reactive glial cells to neurons in the cortex, to determine whether astrocyte-to-neuron transdifferentiation can occur under physiological conditions. We utilized adeno-associated virus 9 (AAV9), which crosses the blood-brain barrier without injury, to deliver NEUROD1 to astrocytes through an intravascular route. Interestingly, we found that a small, but significant number of non-reactive astrocytes converted to neurons in the striatum, but not the cortex. Moreover, astrocytes cultured to minimize their proliferative potential also exhibited limited neuronal transdifferentiation with NEUROD1 expression. Our results show that a single transcription factor can induce astrocyte-to-neuron conversion under physiological conditions, potentially facilitating future clinical approaches long after the acute injury phase. Published by Elsevier Inc.

  8. The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs.

    Directory of Open Access Journals (Sweden)

    Bing Ye

    Full Text Available Cross-modal plasticity is characterized as the hypersensitivity of remaining modalities after a sensory function is lost in rodents, which ensures their awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain unclear. We aim to study the role of different types of neurons in cross-modal plasticity.In addition to behavioral tasks in mice, whole-cell recordings at the excitatory and inhibitory neurons, and their two-photon imaging, were conducted in piriform cortex. We produced a mouse model of cross-modal sensory plasticity that olfactory function was upregulated by trimming whiskers to deprive their sensory inputs. In the meantime of olfactory hypersensitivity, pyramidal neurons and excitatory synapses were functionally upregulated, as well as GABAergic cells and inhibitory synapses were downregulated in piriform cortex from the mice of cross-modal sensory plasticity, compared with controls. A crosswire connection between barrel cortex and piriform cortex was established in cross-modal plasticity.An upregulation of pyramidal neurons and a downregulation of GABAergic neurons strengthen the activities of neuronal networks in piriform cortex, which may be responsible for olfactory hypersensitivity after a loss of whisker tactile input. This finding provides the clues for developing therapeutic strategies to promote sensory recovery and substitution.

  9. (−)-EPICATECHIN IMPROVES MITOCHONDRIAL RELATED PROTEIN LEVELS AND AMELIORATES OXIDATIVE STRESS IN DYSTROPHIC DELTA SARCOGLYCAN NULL MOUSE STRIATED MUSCLE

    Science.gov (United States)

    Ramirez-Sanchez, Israel; De los Santos, Sergio; Gonzalez-Basurto, Silvia; Canto, Patricia; Mendoza-Lorenzo, Patricia; Palma-Flores, Carlos; Ceballos-Reyes, Guillermo; Villarreal, Francisco; Zentella-Dehesa, Alejandro; Coral-Vazquez, Ramon

    2014-01-01

    Muscular dystrophies (MD) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD and likely represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (−)-epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice. Wild type or δ-SG null 2.5 month old male mice were treated via oral gavage with either water (control animals) or Epi (1 mg/kg, twice/day) for 2 weeks. Results evidence a significant normalization of total protein carbonylation, recovery of reduced/oxidized glutathione (GSH/GSSG ratio) and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in protein levels for thiolredoxin, glutathione peroxidase, superoxide dismutase 2, catalase and mitochondrial endpoints. Furthermore, we evidence decreases in heart and skeletal muscle fibrosis, accompanied with an improvement in skeletal muscle function with treatment. These results warrant the further investigation of Epi as a potential therapeutic agent to mitigate MD associated muscle degeneration. PMID:25284161

  10. Impact of a nickel-reduced stainless steel implant on striated muscle microcirculation: a comparative in vivo study.

    Science.gov (United States)

    Kraft, C N; Burian, B; Perlick, L; Wimmer, M A; Wallny, T; Schmitt, O; Diedrich, O

    2001-12-05

    The impairment of skeletal muscle microcirculation by a biomaterial may have profound consequences. With moderately good physical and corrosion characteristics, implant-quality stainless steel is particularly popular in orthopedic surgery. However, due to the presence of a considerable amount of nickel in the alloy, concern has been voiced in respect to local tissue responses. More recently a stainless steel alloy with a significant reduction of nickel has become commercially available. We, therefore, studied in vivo nutritive perfusion and leukocytic response of striated muscle to this nickel-reduced alloy, and compared these results with those of the materials conventional stainless steel and titanium. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, we could demonstrate that reduction of the nickel quantity in a stainless steel implant has a positive effect on local microvascular parameters. Although the implantation of a conventional stainless steel sample led to a distinct and persistent activation of leukocytes combined with disruption of the microvascular endothelial integrity, marked leukocyte extravasation, and considerable venular dilation, animals with a nickel-reduced stainless steel implant showed only a moderate increase of these parameters, with a clear tendency of recuperation. Titanium implants merely caused a transient increase of leukocyte-endothelial cell interaction within the first 120 min, and no significant change in macromolecular leakage, leukocyte extravasation, or venular diameter. Pending biomechanical and corrosion testing, nickel-reduced stainless steel may be a viable alternative to conventional implant-quality stainless steel for biomedical applications. Concerning tolerance by the local vascular system, titanium currently remains unsurpassed. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 57: 404-412, 2001

  11. Protein Kinase CK2 Regulates Leukocyte-Endothelial Cell Interactions during Ischemia and Reperfusion in Striated Skin Muscle.

    Science.gov (United States)

    Ampofo, Emmanuel; Widmaier, Daniela; Montenarh, Mathias; Menger, Michael D; Laschke, Matthias W

    2016-01-01

    Ischemia and reperfusion (I/R) causes tissue injury by inflammatory processes. This involves the upregulation of endothelial surface proteins by phospho-regulated signaling pathways, resulting in enhanced interactions of leukocytes with endothelial cells. Recently, we found that protein kinase CK2 is a crucial regulator of leukocyte-mediated inflammation. Therefore, in this study we investigated the involvement of CK2 in leukocyte-endothelial cell interactions during I/R injury. We first analyzed the inhibitory action of (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA) and CX-4945 on CK2 kinase activity and the viability of human dermal microvascular endothelial cells (HDMEC). To mimic I/R conditions in vitro, HDMEC were exposed to hypoxia and reoxygenation and the expression of adhesion molecules was analyzed by flow cytometry. Moreover, we analyzed in vivo the effect of CK2 inhibition on leukocyte-endothelial cell interactions in the dorsal skinfold chamber model of I/R injury by means of repetitive intravital fluorescence microscopy and immunohistochemistry. We found that TBCA and CX-4945 suppressed the activity of CK2 in HDMEC without affecting cell viability. This was associated with a significant downregulation of E-selectin and intercellular adhesion molecule (ICAM)-1 after in vitro hypoxia and reoxygenation. In vivo, CX-4945 treatment significantly decreased the numbers of adherent and transmigrated leukocytes in striated muscle tissue exposed to I/R. Our findings indicate that CK2 is involved in the regulation of leukocyte-endothelial cell interactions during I/R by mediating the expression of E-selectin and ICAM-1. © 2016 S. Karger AG, Basel.

  12. Cell division in Apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella.

    Directory of Open Access Journals (Sweden)

    Maria E Francia

    Full Text Available Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis. During host cell infection new parasites are formed through a budding process that parcels out nuclei and organelles into multiple daughters. Budding is remarkably flexible in output and can produce two to thousands of progeny cells. How genomes and daughters are counted and coordinated is unknown. Apicomplexa evolved from single celled flagellated algae, but with the exception of the gametes, lack flagella. Here we demonstrate that a structure that in the algal ancestor served as the rootlet of the flagellar basal bodies is required for parasite cell division. Parasite striated fiber assemblins (SFA polymerize into a dynamic fiber that emerges from the centrosomes immediately after their duplication. The fiber grows in a polarized fashion and daughter cells form at its distal tip. As the daughter cell is further elaborated it remains physically tethered at its apical end, the conoid and polar ring. Genetic experiments in Toxoplasma gondii demonstrate two essential components of the fiber, TgSFA2 and 3. In the absence of either of these proteins cytokinesis is blocked at its earliest point, the initiation of the daughter microtubule organizing center (MTOC. Mitosis remains unimpeded and mutant cells accumulate numerous nuclei but fail to form daughter cells. The SFA fiber provides a robust spatial and temporal organizer of parasite cell division, a process that appears hard-wired to the centrosome by multiple tethers. Our findings have broader evolutionary implications. We propose that Apicomplexa abandoned flagella for most stages yet retained the organizing principle of the flagellar MTOC. Instead of ensuring appropriate numbers of flagella, the system now positions the apical invasion complexes. This suggests that elements of the invasion apparatus may be derived from flagella or flagellum associated structures.

  13. Development of Trichosomoides nasalis (Nematoda: Trichinelloidea) in the murid host: evidence for larval growth in striated muscle fibres

    Science.gov (United States)

    Fall, E.H.; Diagne, M.; Junker, K.; Duplantier, J.M.; Ba, K.; Vallée, I.; Bain, O.

    2012-01-01

    Trichosomoides nasalis (Trichinelloidea) is a parasite of Arvicanthis niloticus (Muridae) in Senegal. Female worms that harbour dwarf males in their uteri, occur in the epithelium of the nasal mucosa. Young laboratory-bred A. niloticus were either fed females containing larvated eggs or intraperitoneally injected with motile first-stage larvae recovered from female uteri. Both resulted in successful infection. Organs examined during rodent necropsy were blood and lymphatic circulatory systems (heart, large vessels, lymphnodes), lungs, liver, kidneys, thoracic and abdominal cavities, thoracic and abdominal muscular walls, diaphragm, tongue, and nasal mucosa. Development to adult nasal stages took three weeks. Recovery of newly hatched larvae from the peritoneal fluid at four-eight hours after oral infection suggests