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Sample records for pyramidal neuron number

  1. Pyramidal Neuron Number in Layer 3 of Primary Auditory Cortex of Subjects with Schizophrenia

    PubMed Central

    Dorph-Petersen, Karl-Anton; Delevich, Kristen M.; Marcsisin, Michael J.; Zhang, Wei; Sampson, Allan R.; Gundersen, Hans Jørgen G.; Lewis, David A.; Sweet, Robert A.

    2009-01-01

    Individuals with schizophrenia demonstrate impairments of sensory processing within primary auditory cortex. We have previously identified lower densities of dendritic spines and axon boutons, and smaller mean pyramidal neuron somal volume, in layer 3 of the primary auditory cortex in subjects with schizophrenia, all of which might reflect fewer layer 3 pyramidal neurons in schizophrenia. To examine this hypothesis, we developed a robust stereological method based upon unbiased principles for estimation of total volume and pyramidal neuron numbers for each layer of a cortical area. Our method generates both a systematic, uniformly random set of mapping sections as well as a set of randomly rotated sections cut orthogonal to the pial surface, within the region of interest. We applied our approach in twelve subjects with schizophrenia, each matched to a normal comparison subject. Primary auditory cortex volume was assessed using Cavalieri’s method. The relative and absolute volume of each cortical layer and, within layer 3, the number and density of pyramidal neurons was estimated using our novel approach. Subject groups did not differ in regional volume, layer volumes, or pyramidal neuron number, although pyramidal neuron density was significantly greater in subjects with schizophrenia. These findings suggest that previously observed lower densities of dendritic spines and axon boutons reflect fewer numbers per neuron, and contribute to greater neuronal density via a reduced neuropil. Our approach represents a powerful new method for stereologic estimation of features of interest within individual layers of cerebral cortex, with applications beyond the current study. PMID:19524554

  2. The mammalian neocortex new pyramidal neuron: a new conception

    PubMed Central

    Marín-Padilla, Miguel

    2014-01-01

    The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex subplate zone). From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating its developing motor activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface) without losing its original attachment to first layer or the location of its soma and, hence, retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs two pyramidal cell functional strata to carry out all its motor activities, the mouse 3, cat 4, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing and thinking as a premotor activity. Words used in language are the motor expression of thoughts and represent sounds produced by maneuvering the column of expiratory

  3. Chronic benzodiazepine treatment decreases spine density in cortical pyramidal neurons.

    PubMed

    Curto, Yasmina; Garcia-Mompo, Clara; Bueno-Fernandez, Clara; Nacher, Juan

    2016-02-01

    The adult brain retains a substantial capacity for synaptic reorganization, which includes a wide range of modifications from molecular to structural plasticity. Previous reports have demonstrated that the structural remodeling of excitatory neurons seems to occur in parallel to changes in GABAergic neurotransmission. The function of neuronal inhibitory networks can be modified through GABAA receptors, which have a binding site for benzodiazepines (BZ). Although BZs are among the most prescribed drugs, is not known whether they modify the structure and connectivity of pyramidal neurons. In the present study we wish to elucidate the impact of a chronic treatment of 21 days with diazepam (2mg/kg, ip), a BZ that acts as an agonist of GABAA receptors, on the structural plasticity of pyramidal neurons in the prefrontal cortex of adult mice. We have examined the density of dendritic spines and the density of axonal en passant boutons in the cingulate cortex. Although no significant changes were observed in their anxiety levels, animals treated with diazepam showed a decrease in the density of spines in the apical dendrites of pyramidal neurons. Most GFP-expressing en passant boutons in the upper layers of the cingulate cortex had an extracortical origin and no changes in their density were detected after diazepam treatment. These results indicate that the chronic potentiation of GABAergic synapses can induce the structural remodeling of postsynaptic elements in pyramidal neurons. PMID:26733301

  4. Multisynaptic activity in a pyramidal neuron model and neural code.

    PubMed

    Ventriglia, Francesco; Di Maio, Vito

    2006-01-01

    The highly irregular firing of mammalian cortical pyramidal neurons is one of the most striking observation of the brain activity. This result affects greatly the discussion on the neural code, i.e. how the brain codes information transmitted along the different cortical stages. In fact it seems to be in favor of one of the two main hypotheses about this issue, named the rate code. But the supporters of the contrasting hypothesis, the temporal code, consider this evidence inconclusive. We discuss here a leaky integrate-and-fire model of a hippocampal pyramidal neuron intended to be biologically sound to investigate the genesis of the irregular pyramidal firing and to give useful information about the coding problem. To this aim, the complete set of excitatory and inhibitory synapses impinging on such a neuron has been taken into account. The firing activity of the neuron model has been studied by computer simulation both in basic conditions and allowing brief periods of over-stimulation in specific regions of its synaptic constellation. Our results show neuronal firing conditions similar to those observed in experimental investigations on pyramidal cortical neurons. In particular, the variation coefficient (CV) computed from the inter-spike intervals (ISIs) in our simulations for basic conditions is close to the unity as that computed from experimental data. Our simulation shows also different behaviors in firing sequences for different frequencies of stimulation. PMID:16870323

  5. Input transformation by dendritic spines of pyramidal neurons

    PubMed Central

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike. PMID:25520626

  6. Input transformation by dendritic spines of pyramidal neurons.

    PubMed

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

    This work presents PyramidalExplorer, a new tool to interactively explore and reveal the detailed organization of the microanatomy of pyramidal neurons with functionally related models. It consists of a set of functionalities that allow possible regional differences in the pyramidal cell architecture to be interactively discovered by combining quantitative morphological information about the structure of the cell with implemented functional models. The key contribution of this tool is the morpho-functional oriented design that allows the user to navigate within the 3D dataset, filter and perform Content-Based Retrieval operations. As a case study, we present a human pyramidal neuron with over 9000 dendritic spines in its apical and basal dendritic trees. Using PyramidalExplorer, we were able to find unexpected differential morphological attributes of dendritic spines in particular compartments of the neuron, revealing new aspects of the morpho-functional organization of the pyramidal neuron. PMID:26778972

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

    PubMed

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

    2015-01-01

    This work presents PyramidalExplorer, a new tool to interactively explore and reveal the detailed organization of the microanatomy of pyramidal neurons with functionally related models. It consists of a set of functionalities that allow possible regional differences in the pyramidal cell architecture to be interactively discovered by combining quantitative morphological information about the structure of the cell with implemented functional models. The key contribution of this tool is the morpho-functional oriented design that allows the user to navigate within the 3D dataset, filter and perform Content-Based Retrieval operations. As a case study, we present a human pyramidal neuron with over 9000 dendritic spines in its apical and basal dendritic trees. Using PyramidalExplorer, we were able to find unexpected differential morphological attributes of dendritic spines in particular compartments of the neuron, revealing new aspects of the morpho-functional organization of the pyramidal neuron. PMID:26778972

  10. Physiological evidence that pyramidal neurons lack functional water channels.

    PubMed

    Andrew, R David; Labron, Mark W; Boehnke, Susan E; Carnduff, Lisa; Kirov, Sergei A

    2007-04-01

    The physiological conditions that swell mammalian neurons are clinically important but contentious. Distinguishing the neuronal component of brain swelling requires viewing intact neuronal cell bodies, dendrites, and axons and measuring their changing volume in real time. Cultured or dissociated neuronal somata swell within minutes under acutely overhydrated conditions and shrink when strongly dehydrated. But paradoxically, most central nervous system (CNS) neurons do not express aquaporins, the membrane channels that conduct osmotically driven water. Using 2-photon laser scanning microscopy (2PLSM), we monitored neuronal volume under osmotic stress in real time. Specifically, the volume of pyramidal neurons in cerebral cortex and axon terminals comprising cerebellar mossy fibers was measured deep within live brain slices. The expected swelling or shrinking of the gray matter was confirmed by recording altered light transmittance and by indirectly measuring extracellular resistance over a wide osmotic range of -80 to +80 milliOsmoles (mOsm). Neurons expressing green fluorescent protein were then imaged with 2PLSM between -40 and +80 mOsm over 20 min. Surprisingly, pyramidal somata, dendrites, and spines steadfastly maintained their volume, as did the cerebellar axon terminals. This precluded a need for the neurons to acutely regulate volume, preserved their intrinsic electrophysiological stability, and confirmed that these CNS nerve cells lack functional aquaporins. Thus, whereas water easily permeates the aquaporin-rich endothelia and glia driving osmotic brain swelling, neurons tenatiously maintain their volume. However, these same neurons then swell dramatically upon oxygen/glucose deprivation or [K+]0 elevation, so prolonged depolarization (as during stroke or seizure) apparently swells neurons by opening nonaquaporin channels to water. PMID:16723408

  11. A network of tufted layer 5 pyramidal neurons.

    PubMed

    Markram, H

    1997-09-01

    Tufted layer 5 (TL5) pyramidal neurons are important projection neurons from the cerebral cortex to subcortical areas. Recent and ongoing experiments aimed at understanding the computational analysis performed by a network of synaptically connected TL5 neurons are reviewed here. The experiments employed dual and triple whole-cell patch clamp recordings from visually identified and preselected neurons in brain slices of somatosensory cortex of young (14- to 16-day-old) rats. These studies suggest that a local network of TL5 neurons within a cortical module of diameter 300 microns consists of a few hundred neurons that are extensively inter-connected with reciprocal feedback from at least first-, second- and third-order target neurons. A statistical analysis of synaptic innervation suggests that this recurrent network is not randomly arranged and hence each neuron could be functionally unique. Synaptic transmission between these neurons is characterized by use-dependent synaptic depression which confers novel properties to this recurrent network of neurons. First, a range of rates of depression for different synaptic connections enable each TL5 neuron to receive a unique mixture of information about the average firing rates and the temporally correlated action potential (AP) activity in the population of presynaptic TL5 neurons. Second, each AP generated by any neuron in the network induces a change (defined as an iteration step) in the functional coupling of the neurons in the network (defined as network configuration). It is proposed that the network configuration is iterated during a stimulus to achieve an optimally orchestrated network response. Hebbian, anti-Hebbian and neuromodulatory-induced modifications of neurotransmitter release probability change the rates of synaptic depression and thereby alter the iteration step size. These data may be important to understand the dynamics of electrical activity within the network.

  12. Dendritic Spine Alterations in Neocortical Pyramidal Neurons following Postnatal Neuronal Nogo-A Knockdown

    PubMed Central

    Pradhan, A.D.; Case, A.M.; Farrer, R.G.; Tsai, S.Y.; Cheatwood, J.L.; Martin, J.L.; Kartje, G.L.

    2010-01-01

    The myelin-associated protein Nogo-A is a well-known inhibitor of axonal regeneration and compensatory plasticity, yet functions of neuronal Nogo-A are not as clear. The present study examined the effects of decreased levels of neuronal Nogo-A on dendritic spines of developing neocortical neurons. Decreased Nogo-A levels in these neurons resulted in lowered spine density and an increase in filopodial type protrusions. These results suggest a role for neuronal Nogo-A in maintaining a spine phenotype in neocortical pyramidal cells. PMID:20938157

  13. Comparative morphology of three types of projection-identified pyramidal neurons in the superficial layers of cat visual cortex.

    PubMed

    Matsubara, J A; Chase, R; Thejomayen, M

    1996-02-26

    The morphology and dendritic organization of corticocortical neurons in the superficial layers of area 18 that project to area 17 were studied by intracellular injection of lucifer yellow in the fixed-slice preparation. This corticocortical population contains primarily standard pyramidal cells, but occasional nonpyramidal, modified, fusiform, star, and inverted pyramidal cells were also seen. All cell types were present throughout layer 2 and in the upper and middle parts of layer 3. Standard pyramidal cells were found exclusively in lower layer 3. The mean somatic area of the area 17 projecting neurons was 251 microns 2. The width of basal dendritic fields was correlated to cell size for standard pyramidal cells but not for the other cell types. Next, the morphology and dendritic organization of the area 17 projecting neurons were compared to the pyramidal cells of the local horizontal patch networks and of the callosal system. The depth profile of the area 17 projecting and callosal pyramidal groups was virtually identical, peaking at 400 microns from the pial surface, whereas the local patch pyramidal group peaked at 281 microns. The local patch, area 17 projecting, and callosal pyramidal cells displayed increasingly larger mean somatic areas and basilar dendritic field width measurements. The number of basal dendritic branch points was greatest for callosal cells, and it was indistinguishable between local patch and area 17 projecting neurons. In the tangential plane, circular dendritic fields were observed on all callosal cells, but they were found on only approximately half of the local patch and area 17 projecting neurons. The remaining local patch and area 17 projecting neurons displayed mediolaterally and anteroposteriorly elongated basal dendritic fields, respectively. PMID:8866848

  14. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons.

    PubMed

    Silva, L R; Amitai, Y; Connors, B W

    1991-01-25

    Rhythmic activity in the neocortex varies with different behavioral and pathological states and in some cases may encode sensory information. However, the neural mechanisms of these oscillations are largely unknown. Many pyramidal neurons in layer 5 of the neocortex showed prolonged, 5- to 12-hertz rhythmic firing patterns at threshold. Rhythmic firing was due to intrinsic membrane properties, sodium conductances were essential for rhythmicity, and calcium-dependent conductances strongly modified rhythmicity. Isolated slices of neocortex generated epochs of 4- to 10-hertz synchronized activity when N-methyl-D-aspartate receptor-mediated channels were facilitated. Layer 5 was both necessary and sufficient to produce these synchronized oscillations. Thus, synaptic networks of intrinsically rhythmic neurons in layer 5 may generate or promote certain synchronized oscillations of the neocortex.

  15. Neurotoxic effects of methamphetamine on rat hippocampus pyramidal neurons.

    PubMed

    Hori, N; Kadota, M T; Watanabe, M; Ito, Y; Akaike, N; Carpenter, D O

    2010-08-01

    Methamphetamine (MAP) is known to alter behavior and cause deficits in learning and memory. While the major site of action of MAP is on mesolimbic dopaminergic pathways, the effects on learning and memory raise the possibility of important actions in the hippocampus. We have studied electrophysiologic and morphologic effects of MAP in the CA1 region of hippocampus from young male rats chronically exposed to MAP, male rats exposed during gestation only and the effects of bath perfusion of MAP onto brain slices from control rats. Pyramidal neurons in brain slices from chronically exposed rats had reduced membrane potential and membrane resistance. Long-term potentiation (LTP) was reduced as compared to control, but when MAP was acutely perfused over control slices the amplitude of LTP was increased. LTP in young adult animals that had been gestationally exposed to MAP showed reduced LTP as compared to controls. Morphologically CA1 pyramidal neurons in chronically exposed animals showed a high prevalence of extensive blebbing of dendrites. We conclude that the NMDA receptor and the process of LTP are also targets of MAP dysfunction, at least in the hippocampus.

  16. Changes in the axonal conduction velocity of pyramidal tract neurons in the aged cat.

    PubMed

    Xi, M C; Liu, R H; Engelhardt, J K; Morales, F R; Chase, M H

    1999-01-01

    The present study was undertaken to determine whether age-dependent changes in axonal conduction velocity occur in pyramidal tract neurons. A total of 260 and 254 pyramidal tract neurons were recorded extracellularly in the motor cortex of adult control and aged cats, respectively. These cells were activated antidromically by electrical stimulation of the medullary pyramidal tract. Fast- and slow-conducting neurons were identified according to their axonal conduction velocity in both control and aged cats. While 51% of pyramidal tract neurons recorded in the control cats were fast conducting (conduction velocity greater than 20 m/s), only 26% of pyramidal tract neurons in the aged cats were fast conducting. There was a 43% decrease in the median conduction velocity for the entire population of pyramidal tract neurons in aged cats when compared with that of pyramidal tract neurons in the control cats (P < 0.001, Mann-Whitney U-test). A linear relationship between the spike duration of pyramidal tract neurons and their antidromic latency was present in both control and aged cats. However, the regression slope was significantly reduced in aged cats. This reduction was due to the appearance of a group of pyramidal tract neurons with relatively shorter spike durations but slower axonal conduction velocities in the aged cat. Sample intracellular data confirmed the above results. These observations form the basis for the following conclusions: (i) there is a decrease in median conduction velocity of pyramidal tract neurons in aged cats; (ii) the reduction in the axonal conduction velocity of pyramidal tract neurons in aged cats is due, in part, to fibers that previously belonged to the fast-conducting group and now conduct at slower velocity. PMID:10392844

  17. Mechanisms underlying subunit independence in pyramidal neuron dendrites

    PubMed Central

    Behabadi, Bardia F.; Mel, Bartlett W.

    2014-01-01

    Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611

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

    PubMed

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

    2013-12-01

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

  19. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.

    PubMed

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-07-07

    Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity.

  20. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.

    PubMed

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-01-01

    Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity. PMID:26151674

  1. Pyramidal neurons in the septal and temporal CA1 field of the human and hedgehog tenrec hippocampus.

    PubMed

    Liagkouras, Ioannis; Michaloudi, Helen; Batzios, Christos; Psaroulis, Dimitrios; Georgiadis, Marios; Künzle, Heinz; Papadopoulos, Georgios C

    2008-07-01

    The present study examines comparatively the cellular density of disector-counted/Nissl-stained CA1 pyramidal neurons and the morphometric characteristics (dendritic number/length, spine number/density and Sholl-counted dendritic branch points/20 microm) of the basal and apical dendritic systems of Golgi-impregnated CA1 neurons, in the septal and temporal hippocampus of the human and hedgehog tenrec brain. The obtained results indicate that in both hippocampal parts the cellular density of the CA1 pyramidal neurons is lower in human than in tenrec. However, while the human pyramidal cell density is higher in the septal hippocampal part than in the temporal one, in the tenrec the density of these cells is higher in the temporal part. The dendritic tree of the CA1 pyramidal cells, more developed in the septal than in temporal hippocampus in both species studied, is in general more complex in the human hippocampus. The basal and the apical dendritic systems exhibit species related morphometric differences, while dendrites of different orders exhibit differences in their number and length, and in their spine density. Finally, in both species, as well as hippocampal parts and dendritic systems, changes of dendritic morphometric features along ascending dendritic orders fluctuate in a similar way, as do the number of dendritic branch points in relation to the distance from the neuron soma.

  2. Subthreshold voltage noise of rat neocortical pyramidal neurones.

    PubMed

    Jacobson, Gilad A; Diba, Kamran; Yaron-Jakoubovitch, Anat; Oz, Yasmin; Koch, Christof; Segev, Idan; Yarom, Yosef

    2005-04-01

    Neurones are noisy elements. Noise arises from both intrinsic and extrinsic sources, and manifests itself as fluctuations in the membrane potential. These fluctuations limit the accuracy of a neurone's output but have also been suggested to play a computational role. We present a detailed study of the amplitude and spectrum of voltage noise recorded at the soma of layer IV-V pyramidal neurones in slices taken from rat neocortex. The dependence of the noise on holding potential, synaptic activity and Na+ conductance is systematically analysed. We demonstrate that voltage noise increases non-linearly as the cell depolarizes (from a standard deviation (s.d.) of 0.19 mV at -75 mV to an s.d. of 0.54 mV at -55 mV). The increase in voltage noise is accompanied by an increase in the cell impedance, due to voltage dependence of Na+ conductance. The impedance increase accounts for the majority (70%) of the voltage noise increase. The increase in voltage noise and impedance is restricted to the low-frequency range (0.2-2 Hz). At the high frequency range (5-100 Hz) the voltage noise is dominated by synaptic activity. In our slice preparation, synaptic noise has little effect on the cell impedance. A minimal model reproduces qualitatively these data. Our results imply that ion channel noise contributes significantly to membrane voltage fluctuations at the subthreshold voltage range, and that Na+ conductance plays a key role in determining the amplitude of this noise by acting as a voltage-dependent amplifier of low-frequency transients. PMID:15695244

  3. Subthreshold voltage noise of rat neocortical pyramidal neurones

    PubMed Central

    Jacobson, Gilad A; Diba, Kamran; Yaron-Jakoubovitch, Anat; Oz, Yasmin; Koch, Christof; Segev, Idan; Yarom, Yosef

    2005-01-01

    Neurones are noisy elements. Noise arises from both intrinsic and extrinsic sources, and manifests itself as fluctuations in the membrane potential. These fluctuations limit the accuracy of a neurone's output but have also been suggested to play a computational role. We present a detailed study of the amplitude and spectrum of voltage noise recorded at the soma of layer IV–V pyramidal neurones in slices taken from rat neocortex. The dependence of the noise on holding potential, synaptic activity and Na+ conductance is systematically analysed. We demonstrate that voltage noise increases non-linearly as the cell depolarizes (from a standard deviation (s.d.) of 0.19 mV at −75 mV to an s.d. of 0.54 mV at −55 mV). The increase in voltage noise is accompanied by an increase in the cell impedance, due to voltage dependence of Na+ conductance. The impedance increase accounts for the majority (70%) of the voltage noise increase. The increase in voltage noise and impedance is restricted to the low-frequency range (0.2–2 Hz). At the high frequency range (5–100 Hz) the voltage noise is dominated by synaptic activity. In our slice preparation, synaptic noise has little effect on the cell impedance. A minimal model reproduces qualitatively these data. Our results imply that ion channel noise contributes significantly to membrane voltage fluctuations at the subthreshold voltage range, and that Na+ conductance plays a key role in determining the amplitude of this noise by acting as a voltage-dependent amplifier of low-frequency transients. PMID:15695244

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

    PubMed Central

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

    2013-01-01

    CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. PMID:22388958

  5. Location-Dependent Excitatory Synaptic Interactions in Pyramidal Neuron Dendrites

    PubMed Central

    Behabadi, Bardia F.; Polsky, Alon; Jadi, Monika; Schiller, Jackie; Mel, Bartlett W.

    2012-01-01

    Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors. PMID:22829759

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2016-01-01

    Study Objective: The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Methods: Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6–8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Results: Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Conclusions: Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. Citation: de Vivo L, Nelson AB, Bellesi M, Noguti J, Tononi G, Cirelli C. Loss of sleep affects the ultrastructure of pyramidal neurons in the adolescent mouse frontal cortex. SLEEP 2016;39(4):861–874. PMID:26715225

  8. Action potential initiation and propagation in rat neocortical pyramidal neurons.

    PubMed

    Stuart, G; Schiller, J; Sakmann, B

    1997-12-15

    1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to

  9. Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice

    PubMed Central

    Bjorefeldt, Andreas; Andreasson, Ulf; Daborg, Jonny; Riebe, Ilse; Wasling, Pontus; Zetterberg, Henrik; Hanse, Eric

    2015-01-01

    The composition of brain extracellular fluid is shaped by a continuous exchange of substances between the cerebrospinal fluid (CSF) and interstitial fluid. The CSF is known to contain a wide range of endogenous neuromodulatory substances, but their collective influence on neuronal activity has been poorly investigated. We show here that replacing artificial CSF (aCSF), routinely used for perfusion of brain slices in vitro, with human CSF (hCSF) powerfully boosts spontaneous firing of CA1, CA3 and layer 5 pyramidal neurons in the rat brain slice. CA1 pyramidal neurons in hCSF display lowered firing thresholds, more depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The increased excitability of CA1 pyramidal neurons was completely occluded by intracellular application of GTPγS, suggesting that endogenous neuromodulators in hCSF act on G-protein coupled receptors to enhance excitability. We found no increase in spontaneous inhibitory synaptic transmission by hCSF, indicating a differential effect on glutamatergic and GABAergic neurons. Our findings highlight a previously unknown function of the CSF in promoting spontaneous excitatory activity, and may help to explain differences observed in the activity of pyramidal neurons recorded in vivo and in vitro. PMID:25556798

  10. IK1 channels do not contribute to the slow afterhyperpolarization in pyramidal neurons

    PubMed Central

    Wang, Kang; Mateos-Aparicio, Pedro; Hönigsperger, Christoph; Raghuram, Vijeta; Wu, Wendy W; Ridder, Margreet C; Sah, Pankaj; Maylie, Jim; Storm, Johan F; Adelman, John P

    2016-01-01

    In pyramidal neurons such as hippocampal area CA1 and basolateral amygdala, a slow afterhyperpolarization (sAHP) follows a burst of action potentials, which is a powerful regulator of neuronal excitability. The sAHP amplitude increases with aging and may underlie age related memory decline. The sAHP is due to a Ca2+-dependent, voltage-independent K+ conductance, the molecular identity of which has remained elusive until a recent report suggested the Ca2+-activated K+ channel, IK1 (KCNN4) as the sAHP channel in CA1 pyramidal neurons. The signature pharmacology of IK1, blockade by TRAM-34, was reported for the sAHP and underlying current. We have examined the sAHP and find no evidence that TRAM-34 affects either the current underling the sAHP or excitability of CA1 or basolateral amygdala pyramidal neurons. In addition, CA1 pyramidal neurons from IK1 null mice exhibit a characteristic sAHP current. Our results indicate that IK1 channels do not mediate the sAHP in pyramidal neurons. DOI: http://dx.doi.org/10.7554/eLife.11206.001 PMID:26765773

  11. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state

    PubMed Central

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-01-01

    Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity. DOI: http://dx.doi.org/10.7554/eLife.07224.001 PMID:26151674

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

    PubMed

    Bopp, Rita; Maçarico da Costa, Nuno; Kampa, Björn M; Martin, Kevan A C; Roth, Morgane M

    2014-08-01

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

  13. Pyramidal Cells in Prefrontal Cortex of Primates: Marked Differences in Neuronal Structure Among Species

    PubMed Central

    Elston, Guy N.; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul R.; DeFelipe, Javier

    2010-01-01

    The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates. PMID:21347276

  14. Brief dopaminergic stimulations produce transient physiological changes in prefrontal pyramidal neurons.

    PubMed

    Moore, Anna R; Zhou, Wen-Liang; Potapenko, Evgeniy S; Kim, Eun-Ji; Antic, Srdjan D

    2011-01-25

    In response to food reward and other pertinent events, midbrain dopaminergic neurons fire short bursts of action potentials causing a phasic release of dopamine in the prefrontal cortex (rapid and transient increases in cortical dopamine concentration). Here we apply short (2s) iontophoretic pulses of glutamate, GABA, dopamine and dopaminergic agonists locally, onto layer 5 pyramidal neurons in brain slices of the rat medial prefrontal cortex (PFC). Unlike glutamate and GABA, brief dopaminergic pulses had negligible effects on the resting membrane potential. However, dopamine altered action potential firing in an extremely rapid (<1s) and transient (<5 min) manner, as every neuron returned to baseline in less than 5-min post-application. The physiological responses to dopamine differed markedly among individual neurons. Pyramidal neurons with a preponderance of D1-like receptor signaling respond to dopamine with a severe depression in action potential firing rate, while pyramidal neurons dominated by the D2 signaling pathway respond to dopamine with an instantaneous increase in spike production. Increasing levels of dopamine concentrations around the cell body resulted in a dose dependent response, which resembles an "inverted U curve" (Vijayraghavan S, Wang M, Birnbaum SG, Williams GV, Arnsten AF (2007) Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci 10:376-384), but this effect can easily be caused by an iontophoresis current artifact. Our present data imply that one population of PFC pyramidal neurons receiving direct synaptic contacts from midbrain dopaminergic neurons would stall during the 0.5s of the phasic dopamine burst. The spillover dopamine, on the other hand, would act as a positive stimulator of cortical excitability (30% increase) to all D2-receptor carrying pyramidal cells, for the next 40s.

  15. Hippocampal neuron number loss in rats exposed to ingested sulfite.

    PubMed

    Akdogan, Ilgaz; Kocamaz, Erdogan; Kucukatay, Vural; Yonguc, Nilufer Goksin; Ozdemir, Mehmet Bulent; Murk, William

    2011-10-01

    Sulfite, which is continuously formed in the body during metabolism of sulfur-containing amino acids, is commonly used in preservatives. It has been shown that there are toxic effects of sulfite on many cellular components. The aim of this study was to investigate the possible toxic effects of sulfite on pyramidal neurons by counting cell numbers in CA1 and CA2-CA3 subdivisions of the rat hippocampus. For this purpose, male albino rats were divided into a control group and a sulfite group (25 mg/kg). Sulfite was administered to the animals via drinking water for 8 weeks. At the end of the experimental period, brains were removed and neurons were estimated in total and in a known fraction of CA1 and CA2-CA3 subdivisions of the left hippocampus by using the optical fractionator method--a stereological method. Results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA2-CA3) in the sulfite group compared with the control group (p < 0.05, Mann Whitney U test). It was concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA2-CA3 subdivisions of the rat hippocampus.

  16. An unusual population of pyramidal neurons in the anterior cingulate cortex of hominids contains the calcium-binding protein calretinin.

    PubMed

    Hof, P R; Nimchinsky, E A; Perl, D P; Erwin, J M

    2001-07-20

    In the context of an on-going comparative analysis of primate neocortex evolution, we describe the occurrence and distribution of a previously unrecognized group of pyramidal neurons, restricted to the superficial part of layer V in the anterior cingulate cortex of hominids and characterized by immunoreactivity to the calcium-binding protein, calretinin. These neurons were rare in orangutans, more numerous in gorillas and common chimpanzees, while humans had the highest numbers. These calretinin-containing pyramidal cells were not observed in the cingulate cortex of any other primate or mammalian species. This finding, together with other recent observations on the hominoid cingulate cortex, is interesting when considering primate neocortical evolution, as it indicates possible adaptive and anatomical modifications in a cortical region critical for the integration of many aspects of autonomic function, vocalization, and cognitive processes.

  17. Brief Dopaminergic Stimulations Produce Transient Physiological Changes in Prefrontal Pyramidal Neurons

    PubMed Central

    Moore, Anna R.; Zhou, Wen-Liang; Potapenko, Evgeniy S.; Kim, Eun-Ji; Antic, Srdjan D.

    2010-01-01

    In response to food reward and other pertinent events, midbrain dopaminergic neurons fire short bursts of action potentials causing a phasic release of dopamine in the prefrontal cortex (rapid and transient increases in cortical dopamine concentration). Here we apply short (2 sec) iontophoretic pulses of glutamate, GABA, dopamine and dopaminergic agonists locally, onto layer 5 pyramidal neurons in brain slices of the rat medial prefrontal cortex (PFC). Unlike glutamate and GABA, brief dopaminergic pulses had negligible effects on the resting membrane potential. However, dopamine altered action potential firing in an extremely rapid (<1s) and transient (<5min) manner, as every neuron returned to baseline in less than 5-min post-application. The physiological responses to dopamine differed markedly among individual neurons. Pyramidal neurons with a preponderance of D1-like receptor signaling respond to dopamine with a severe depression in action potential firing rate, while pyramidal neurons dominated by the D2 signaling pathway respond to dopamine with an instantaneous increase in spike production. Increasing levels of dopamine concentrations around the cell body resulted in a dose dependent response, which resembles an “inverted U curve” (Vijayraghavan et al., 2007), but this effect can easily be caused by an iontophoresis current artifact. Our present data imply that one population of PFC pyramidal neurons receiving direct synaptic contacts from midbrain dopaminergic neurons would stall during the 0.5 sec of the phasic dopamine burst. The spillover dopamine, on the other hand, would act as a positive stimulator of cortical excitability (30% increase) to all D2-receptor carrying pyramidal cells, for the next 40 seconds. PMID:21059342

  18. Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation.

    PubMed

    Chua, Yansong; Morrison, Abigail

    2016-01-01

    The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be

  19. Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation

    PubMed Central

    Chua, Yansong; Morrison, Abigail

    2016-01-01

    The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be

  20. Cholecystokinin-immunoreactive cells form symmetrical synaptic contacts with pyramidal and nonpyramidal neurons in the hippocampus.

    PubMed

    Nunzi, M G; Gorio, A; Milan, F; Freund, T F; Somogyi, P; Smith, A D

    1985-07-22

    The ultrastructural features and synaptic relationships of cholecystokinin (CCK)-immunoreactive cells of rat and cat hippocampus were studied using the unlabeled antibody immunoperoxidase technique and correlated light and electron microscopy. CCK-positive perikarya of variable shape and size were distributed in all layers and were particularly concentrated in stratum pyramidale and radiatum: the CCK-immunoreactive neurons were nonpyramidal in shape and the three most common types had the morphological features of tufted, bipolar, and multipolar cells. Electron microscopic examination revealed that all the CCK-positive boutons established symmetrical (Gray's type II) synaptic contacts with perikarya and dendrites of pyramidal and nonpyramidal neurons. The origin of some of the boutons was established by tracing fine collaterals that arose from the main axon of two CCK-immunostained cells and terminated in the stratum pyramidale; these collaterals were then examined in the electron microscope. The axon of one such neuron exhibited a course parallel to the pyramidal layer and formed pericellular nets of synaptic boutons upon the perikarya of pyramidal neurons. This pattern of axonal arborization is very similar to that of some of the basket cells, previously suggested to be the anatomical correlate for pyramidal cell inhibition. Typical dendrites of pyramidal cells also received symmetrical synaptic contacts from CCK-immunoreactive boutons, and some of these boutons could be shown to originate from a local neuron in stratum radiatum. Many CCK-immunoreactive cells received CCK-labeled boutons upon their soma and dendritic shafts. Synaptic relationship, established by multiple "en passant" boutons, was observed between CCK-positive interneurons of the stratum lacunosum-moleculare and radiatum. The soma and dendrites of the CCK-immunostained neurons also received symmetrical and asymmetrical synapses from nonimmunoreactive boutons. These results indicate that the CCK

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

    PubMed Central

    Ramaswamy, Srikanth; Markram, Henry

    2015-01-01

    The thick-tufted layer 5 (TTL5) pyramidal neuron is one of the most extensively studied neuron types in the mammalian neocortex and has become a benchmark for understanding information processing in excitatory neurons. By virtue of having the widest local axonal and dendritic arborization, the TTL5 neuron encompasses various local neocortical neurons and thereby defines the dimensions of neocortical microcircuitry. The TTL5 neuron integrates input across all neocortical layers and is the principal output pathway funneling information flow to subcortical structures. Several studies over the past decades have investigated the anatomy, physiology, synaptology, and pathophysiology of the TTL5 neuron. This review summarizes key discoveries and identifies potential avenues of research to facilitate an integrated and unifying understanding on the role of a central neuron in the neocortex. PMID:26167146

  2. Suppressive Effects of Resveratrol Treatment on The Intrinsic Evoked Excitability of CA1 Pyramidal Neurons

    PubMed Central

    Meftahi, Gholamhossein; Ghotbedin, Zohreh; Eslamizade, Mohammad Javad; Hosseinmardi, Narges; Janahmadi, Mahyar

    2015-01-01

    Objective Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neu- ronal function, little effort, if any, has been made to investigate the cellular effect of res- veratrol treatment on intrinsic neuronal properties. Materials and Methods This experimental study was performed to examine the acute effects of resveratrol (100 µM) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp re- cording under current clamp conditions. Results Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity. PMID:26464825

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

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

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

    PubMed

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

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

  5. Dendritic integration in pyramidal neurons during network activity and disease.

    PubMed

    Palmer, Lucy M

    2014-04-01

    Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.

  6. Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons.

    PubMed

    Guan, D; Tkatch, T; Surmeier, D J; Armstrong, W E; Foehring, R C

    2007-06-15

    We determined the expression of Kv2 channel subunits in rat somatosensory and motor cortex and tested for the contributions of Kv2 subunits to slowly inactivating K+ currents in supragranular pyramidal neurons. Single cell RT-PCR showed that virtually all pyramidal cells expressed Kv2.1 mRNA and approximately 80% expressed Kv2.2 mRNA. Immunocytochemistry revealed striking differences in the distribution of Kv2.1 and Kv2.2 subunits. Kv2.1 subunits were clustered and located on somata and proximal dendrites of all pyramidal cells. Kv2.2 subunits were primarily distributed on large apical dendrites of a subset of pyramidal cells from deep layers. We used two methods for isolating currents through Kv2 channels after excluding contributions from Kv1 subunits: intracellular diffusion of Kv2.1 antibodies through the recording pipette and extracellular application of rStromatoxin-1 (ScTx). The Kv2.1 antibody specifically blocked the slowly inactivating K+ current by 25-50% (at 8 min), demonstrating that Kv2.1 subunits underlie much of this current in neocortical pyramidal neurons. ScTx (300 nM) also inhibited approximately 40% of the slowly inactivating K+ current. We observed occlusion between the actions of Kv2.1 antibody and ScTx. In addition, Kv2.1 antibody- and ScTx-sensitive currents demonstrated similar recovery from inactivation and voltage dependence and kinetics of activation and inactivation. These data indicate that both agents targeted the same channels. Considering the localization of Kv2.1 and 2.2 subunits, currents from truncated dissociated cells are probably dominated by Kv2.1 subunits. Compared with Kv2.1 currents in expression systems, the Kv2.1 current in neocortical pyramidal cells activated and inactivated at relatively negative potentials and was very sensitive to holding potential.

  7. Active summation of excitatory postsynaptic potentials in hippocampal CA3 pyramidal neurons

    PubMed Central

    Urban, Nathaniel N.; Barrionuevo, German

    1998-01-01

    The manner in which the thousands of synaptic inputs received by a pyramidal neuron are summed is critical both to our understanding of the computations that may be performed by single neurons and of the codes used by neurons to transmit information. Recent work on pyramidal cell dendrites has shown that subthreshold synaptic inputs are modulated by voltage-dependent channels, raising the possibility that summation of synaptic responses is influenced by the active properties of dendrites. Here, we use somatic and dendritic whole-cell recordings to show that pyramidal cells in hippocampal area CA3 sum distal and proximal excitatory postsynaptic potentials sublinearly and actively, that the degree of nonlinearity depends on the magnitude and timing of the excitatory postsynaptic potentials, and that blockade of transient potassium channels linearizes summation. Nonlinear summation of synaptic inputs could have important implications for the computations performed by single neurons and also for the role of the mossy fiber and perforant path inputs to hippocampal area CA3. PMID:9736757

  8. Tachykinins and bombesin excite non-pyramidal neurones in rat hippocampus.

    PubMed Central

    Dreifuss, J J; Raggenbass, M

    1986-01-01

    The effects of substance P, eledoisin and physalaemin--which are structurally similar and all belong to the tachykinin family--and of bombesin, a gastrin-releasing peptide, on non-pyramidal neurones were studied using unitary extracellular recordings from rat hippocampal slices. The peptides were added to the perifusion solution, or locally applied by pressure ejection from a micropipette, at concentrations ranging from 10(-8) to 10(-6) M. 104 out of 115 non-pyramidal neurones responded to tachykinins, and 26 out of 27 responded to bombesin, by a reversible, concentration-dependent increase in firing. The responsive neurones retained their sensitivity to the tachykinins and to bombesin under the condition of synaptic blockade. A synthetic peptide known to antagonize the effects of oxytocin on hippocampal non-pyramidal neurones did not affect the excitations induced by the tachykinins or bombesin. The action of the tachykinins was not blocked by the muscarinic antagonist, atropine. These results indicate that hippocampal non-pyramidal neurones--which were previously shown to possess oxytocin receptors and mu-type opiate receptors--bear receptors for peptides of the tachykinin and of the gastrin-releasing families. The hippocampal effects of tachykinins and of bombesin, however, were not blocked by synthetic structural analogues of substance P, known to antagonize the action of these peptides on some non-nervous tissues. The possibility must be considered that brain receptors for tachykinins and for gastrin-releasing peptides may be distinct from the peripheral receptors for these peptides. PMID:2435894

  9. Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

    PubMed

    Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

    2016-06-01

    Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex.

  10. Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

    PubMed

    Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

    2016-06-01

    Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. PMID:26762857

  11. Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex

    PubMed Central

    Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

    2016-01-01

    Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. PMID:26762857

  12. Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex

    PubMed Central

    Mohan, Hemanth; Verhoog, Matthijs B.; Doreswamy, Keerthi K.; Eyal, Guy; Aardse, Romy; Lodder, Brendan N.; Goriounova, Natalia A.; Asamoah, Boateng; B. Brakspear, A.B. Clementine; Groot, Colin; van der Sluis, Sophie; Testa-Silva, Guilherme; Obermayer, Joshua; Boudewijns, Zimbo S.R.M.; Narayanan, Rajeevan T.; Baayen, Johannes C.; Segev, Idan; Mansvelder, Huibert D.; de Kock, Christiaan P.J.

    2015-01-01

    The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on “full” human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of “full” human neuron morphologies and present direct evidence that human neurons are not “scaled-up” versions of rodent or macaque neurons, but have unique structural and functional properties. PMID:26318661

  13. Peripheral Neuropathy Induces HCN Channel Dysfunction in Pyramidal Neurons of the Medial Prefrontal Cortex.

    PubMed

    Cordeiro Matos, Steven; Zhang, Zizhen; Séguéla, Philippe

    2015-09-23

    Neuropathic pain is a debilitating condition for which the development of effective treatments has been limited by an incomplete understanding of its molecular basis. The cationic current Ih mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels plays an important role in pain by facilitating ectopic firing and hyperexcitability in DRG neurons, however little is known regarding the role of Ih in supraspinal pain pathways. The medial prefrontal cortex (mPFC), which is reported to be involved in the affective aspects of pain, exhibits high HCN channel expression. Using the spared nerve injury (SNI) model of neuropathic pain in Long-Evans rats and patch-clamp recordings in layer II/III pyramidal neurons of the contralateral mPFC, we observed a hyperpolarizing shift in the voltage-dependent activation of Ih in SNI neurons, whereas maximal Ih remained unchanged. Accordingly, SNI mPFC pyramidal neurons exhibited increased input resistance and excitability, as well as facilitated glutamatergic mGluR5-mediated persistent firing, compared with sham neurons. Moreover, intracellular application of bromo-cAMP abolished the hyperpolarizing shift in the voltage-dependent activation of Ih observed in SNI neurons, whereas protein kinase A (PKA) inhibition further promoted this shift in both SNI and sham neurons. Behaviorally, acute HCN channel blockade by local injection of ZD7288 in the mPFC of SNI rats induced a decrease in cold allodynia. These findings suggest that changes in the cAMP/PKA axis in mPFC neurons underlie alterations to HCN channel function, which can influence descending inhibition of pain pathways in neuropathic conditions. Significance statement: Recent studies investigating the role of the medial prefrontal cortex (mPFC) in neuropathic pain have led to an increased awareness of how affective and cognitive factors can influence pain perception. It is therefore imperative that we advance our understanding of the involvement of supraspinal

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

    SciTech Connect

    Donoso, J.A.; Norton, S.

    1982-07-01

    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.

  15. Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex.

    PubMed

    Tomassy, Giulio Srubek; Berger, Daniel R; Chen, Hsu-Hsin; Kasthuri, Narayanan; Hayworth, Kenneth J; Vercelli, Alessandro; Seung, H Sebastian; Lichtman, Jeff W; Arlotta, Paola

    2014-04-18

    Myelin is a defining feature of the vertebrate nervous system. Variability in the thickness of the myelin envelope is a structural feature affecting the conduction of neuronal signals. Conversely, the distribution of myelinated tracts along the length of axons has been assumed to be uniform. Here, we traced high-throughput electron microscopy reconstructions of single axons of pyramidal neurons in the mouse neocortex and built high-resolution maps of myelination. We find that individual neurons have distinct longitudinal distribution of myelin. Neurons in the superficial layers displayed the most diversified profiles, including a new pattern where myelinated segments are interspersed with long, unmyelinated tracts. Our data indicate that the profile of longitudinal distribution of myelin is an integral feature of neuronal identity and may have evolved as a strategy to modulate long-distance communication in the neocortex.

  16. Generation of glutamatergic neurons from postnatal and adult subventricular zone with pyramidal-like morphology.

    PubMed

    Sequerra, Eduardo B; Miyakoshi, Leo M; Fróes, Maira M; Menezes, João R L; Hedin-Pereira, Cecilia

    2010-11-01

    The mammalian subventricular zone (SVZ) contains progenitors derived from cerebral cortex radial glia cells, which give rise to glutamatergic pyramidal neurons during embryogenesis. However, during postnatal life, SVZ generates neurons that migrate and differentiate into olfactory bulb γ-aminobutyric acid (GABA)ergic interneurons. In this work, we tested if SVZ cells are able to produce glutamatergic neurons if confronted with the embryonic cortical ventricular zone environment. Different from typical SVZ chain migration, cells from P9-P11 SVZ explants migrate into embryonic cortical slices individually, many of which radially oriented. An average of 82.5% of green fluorescent protein-positive cells were immunolabeled for neuronal marker class III β-tubulin. Invading cells differentiate into multiple morphologies, including a pyramidal-like morphotype. A subset of these cells are GABAergic; however, about 28% of SVZ-derived cells are immunoreactive for glutamate. Adult SVZ explants also give rise to glutamatergic neurons in these conditions. Taken together, our results indicate that SVZ can be a source of glutamatergic cortical neurons when submitted to proper environmental cues.

  17. De novo expression of neurokinin-1 receptors by spinoparabrachial lamina I pyramidal neurons following a peripheral nerve lesion.

    PubMed

    Saeed, Abeer W; Ribeiro-da-Silva, Alfredo

    2013-06-01

    Lamina I of the spinal dorsal horn is a major site of integration and transmission to higher centers of nociceptive information from the periphery. One important primary afferent population that transmits such information to the spinal cord expresses substance P (SP). These fibers terminate in contact with lamina I projection neurons that express the SP receptor, also known as the neurokinin-1 receptor (NK-1r). Three types of lamina I projection neurons have been described: multipolar, fusiform, and pyramidal. Most neurons of the first two types are thought to be nociceptive and express the NK-1r, whereas most pyramidal neurons are nonnociceptive and do not express the NK-1r. In this immunocytochemical and behavioral study, we induced a neuropathic pain-like condition in the rat by means of a polyethylene cuff placed around in the sciatic nerve. We document that this lesion led to a de novo expression of NK-1r on pyramidal neurons as well as a significant increase in SP-immunoreactive innervation onto these neurons. These phenotypic changes were evident at the time of onset of neuropathic pain-related behavior. Additionally, we show that, after a noxious stimulus (intradermal capsaicin injection), these NK-1r on pyramidal neurons were internalized, providing evidence that these neurons become responsive to peripheral noxious stimulation. We suggest that the changes following nerve lesion in the phenotype and innervation pattern of pyramidal neurons are of significance for neuropathic pain and/or limb temperature regulation.

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

    PubMed

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

    2015-10-22

    Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (p<0.05) and the SHM-EG (p<0.05). In conclusion, our results suggest that pyramidal neuron loss and histopathological changes in the cornu ammonis of 8-week-old male rats may be due to the 900-MHz EMF exposure.

  19. Stress-induced remodeling of hippocampal CA3 pyramidal neurons.

    PubMed

    McEwen, Bruce S

    2016-08-15

    The discovery of steroid hormone receptors in brain regions that mediate virtually every aspect of brain function has broadened the definition of 'neuroendocrinology' to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as determining the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neurogenesis leading to neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. The two Brain Research papers noted in this review played an important role in triggering these advances. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID:26740399

  20. Suppression of ih contributes to propofol-induced inhibition of mouse cortical pyramidal neurons.

    PubMed

    Chen, Xiangdong; Shu, Shaofang; Bayliss, Douglas A

    2005-12-01

    The contributions of the hyperpolarization-activated current, I(h), to generation of rhythmic activities are well described for various central neurons, particularly in thalamocortical circuits. In the present study, we investigated effects of a general anesthetic, propofol, on native I(h) in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits. Whole cell voltage-clamp recordings from mouse brain slices identified neuronal I(h) currents with fast activation kinetics in neocortical pyramidal neurons and with slower kinetics in thalamocortical relay cells. Propofol inhibited the fast-activating I(h) in cortical neurons at a clinically relevant concentration (5 microM); inhibition of I(h) involved a hyperpolarizing shift in half-activation voltage (DeltaV1/2 approximately -9 mV) and a decrease in maximal available current (approximately 36% inhibition, measured at -120 mV). With the slower form of I(h) expressed in thalamocortical neurons, propofol had no effect on current activation or amplitude. In heterologous expression systems, 5 muM propofol caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1 and linked heteromeric HCN1-HCN2 channels, both of which activate with fast kinetics but did not affect V1/2 or current amplitude of slowly activating homomeric HCN2 channels. With GABA(A) and glycine receptor channels blocked, propofol caused membrane hyperpolarization and suppressed action potential discharge in cortical neurons; these effects were occluded by the I(h) blocker, ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN channels containing HCN1 subunits, such as those that mediate I(h) in cortical pyramidal neurons-and they suggest that anesthetic actions of propofol may involve inhibition of cortical neurons and perhaps other HCN1-expressing cells. PMID:16093340

  1. On learning time delays between the spikes from different input neurons in a biophysical model of a pyramidal neuron.

    PubMed

    Koutsou, Achilleas; Bugmann, Guido; Christodoulou, Chris

    2015-10-01

    Biological systems are able to recognise temporal sequences of stimuli or compute in the temporal domain. In this paper we are exploring whether a biophysical model of a pyramidal neuron can detect and learn systematic time delays between the spikes from different input neurons. In particular, we investigate whether it is possible to reinforce pairs of synapses separated by a dendritic propagation time delay corresponding to the arrival time difference of two spikes from two different input neurons. We examine two subthreshold learning approaches where the first relies on the backpropagation of EPSPs (excitatory postsynaptic potentials) and the second on the backpropagation of a somatic action potential, whose production is supported by a learning-enabling background current. The first approach does not provide a learning signal that sufficiently differentiates between synapses at different locations, while in the second approach, somatic spikes do not provide a reliable signal distinguishing arrival time differences of the order of the dendritic propagation time. It appears that the firing of pyramidal neurons shows little sensitivity to heterosynaptic spike arrival time differences of several milliseconds. This neuron is therefore unlikely to be able to learn to detect such differences.

  2. Basal Dendrites of Layer-III Pyramidal Neurons do not Scale with Changes in Cortical Magnification Factor in Macaque Primary Visual Cortex

    PubMed Central

    Oga, Tomofumi; Okamoto, Tsuguhisa; Fujita, Ichiro

    2016-01-01

    Neurons in the mammalian primary visual cortex (V1) are systematically arranged across the cortical surface according to the location of their receptive fields (RFs), forming a visuotopic (or retinotopic) map. Within this map, the foveal visual field is represented by a large cortical surface area, with increasingly peripheral visual fields gradually occupying smaller cortical areas. Although cellular organization in the retina, such as the spatial distribution of ganglion cells, can partially account for the eccentricity-dependent differences in the size of cortical representation, whether morphological differences exist across V1 neurons representing different eccentricities is unclear. In particular, morphological differences in dendritic field diameter might contribute to the magnified representation of the central visual field. Here, we addressed this question by measuring the basal dendritic arbors of pyramidal neurons of layer-IIIC and adjoining layer III sublayers (in the Hassler’s nomenclature) in macaque V1. We labeled layer-III pyramidal neurons at various retinotopic positions in V1 by injecting lightly fixed brain tissue with intracellular dye, and then compared dendritic morphology across regions in the retinotopic map representing 0–20° of eccentricity. The dendritic field area, total dendritic length, number of principal dendrites, branching complexity, spine density and total number of spines were all consistent across different retinotopic regions of V1. These results indicate that dendrites in layer-III pyramidal neurons are relatively homogeneous according to these morphometric parameters irrespective of their locations in this portion of the retinotopic map. The homogeneity of dendritic morphology in these neurons suggests that the emphasis of central visual field representation is not attributable to changes in the basal dendritic arbors of pyramidal neurons in layer III, but is likely the result of successive processes earlier in the

  3. Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease.

    PubMed

    Phipps, Andrew J; Vickers, James C; Taberlay, Phillippa C; Woodhouse, Adele

    2016-09-01

    There is increasing evidence that epigenetic alterations may play a role in Alzheimer's disease (AD); yet, there is little information regarding epigenetic modifications in specific cell types. We assessed DNA methylation (5-methylcytosine [5mC]) and hydroxymethylation (5-hydroxymethylcytosine [5hmC]) marks specifically in neuronal and glial cell types in the inferior temporal gyrus of human AD cases and age-matched controls. Interestingly, neurofilament (NF)-labeled pyramidal neurons that are vulnerable to AD pathology are deficient in extranuclear 5mC in AD cases compared with controls. We also found that fewer astrocytes exhibited nuclear 5mC and 5hmC marks in AD cases compared with controls. However, there were no alterations in 5mC and 5hmC in disease-resistant calretinin interneurons or microglia in AD, and there was no alteration in the density of 5mC- or 5hmC-labeled nuclei in near-plaque versus plaque-free regions in late-AD cases. 5mC and 5hmC were present in a high proportion of neurofibrillary tangles, suggesting no loss of DNA methylation marks in tangle bearing neurons. We provide evidence that epigenetic dysregulation may be occurring in astrocytes and NF-positive pyramidal neurons in AD. PMID:27459923

  4. CoREST/LSD1 control the development of pyramidal cortical neurons.

    PubMed

    Fuentes, Patricio; Cánovas, José; Berndt, F Andrés; Noctor, Stephen C; Kukuljan, Manuel

    2012-06-01

    The development of a neuron from a precursor cell comprises a complex set of steps ranging from regulation of the proliferative cycle through the acquisition of distinct morphology and functionality. How these processes are orchestrated is largely unknown. Using in utero manipulation of gene expression in the mouse embryonic cerebral cortex, we found that the transition between multipolar and bipolar stages of newborn cortical pyramidal neurons is markedly delayed by depletion of CoREST, a corepressor component of chromatin remodeling complexes. This profoundly affects the onset of their radial migration. The loss of CoREST function also perturbs the dynamics of neuronal precursor cell populations, transiently increasing the fraction of cells remaining in progenitor states, but not the acquisition of the neuronal glutamatergic fate of pyramidal cells. The function of CoREST in these processes appears to be independent of its best-known interactor, the RE-1 silencer of transcription/neural restrictive silencing factor, and requires the histone demethylase LSD1. This reveals the importance of epigenetic control in the execution of neural development programs, specifically in the cerebral cortex.

  5. Enhancement of an outwardly rectifying chloride channel in hippocampal pyramidal neurons after cerebral ischemia.

    PubMed

    Li, Jianguo; Chang, Quanzhong; Li, Xiaoming; Li, Xiawen; Qiao, Jiantian; Gao, Tianming

    2016-08-01

    Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats. The channel had a nonlinear current-voltage relationship with a conductance of 42.26±1.2pS in the positive voltage range and 18.23±0.96pS in the negative voltage range, indicating an outward rectification pattern. The channel is Cl(-) selective, and the open probability is voltage-dependent. It can be blocked by the classical Cl(-) channel blockers DIDS, SITS, NPPB and glibenclamide. We examined the different changes in ORCC activity in CA1 and CA3 pyramidal neurons at 6, 24 and 48h after transient forebrain ischemia. In the vulnerable CA1 neurons, ORCC activity was persistently enhanced after ischemic insult, whereas in the invulnerable CA3 neurons, no significant changes occurred. Further analysis of channel kinetics suggested that multiple openings are a major contributor to the increase in channel activity after ischemia. Pharmacological blockade of the ORCC partly attenuated cell death in the hippocampal neurons. We propose that the enhanced activity of ORCC might contribute to selective neuronal damage in the CA1 region after cerebral ischemia, and that ORCC may be a therapeutic target against ischemia-induced cell death. PMID:27181516

  6. Effects of Maternal Marginal Iodine Deficiency on Dendritic Morphology in the Hippocampal CA1 Pyramidal Neurons in Rat Offspring.

    PubMed

    Min, Hui; Wang, Yi; Dong, Jing; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

    2016-06-01

    Although the salt iodization programmes are taken to control iodine deficiency (ID), some regions are still suffering from marginal ID. During pregnancy, marginal ID frequently leads to subtle insufficiency of thyroid hormones, characterized as low serum T4 levels. Therefore, the present research was to explore the effects of maternal marginal ID exposure on dendritic arbor growth in the hippocampal CA1 region and the underlying mechanisms. We established Wistar rat models with ID diet during pregnancy and lactation. The overall daily iodine intakes of the rats were estimated as 7.0, 5.0 and 1.5 μg/day in the control, marginal ID and severe ID groups, respectively. To study the morphological alterations of pyramidal neurons, Golgi-Cox procedure was conducted in the hippocampus. Sholl analyses demonstrated a slight decrease in the total length and branching numbers of basal dendrites on postnatal day (PN) 7, PN14 and PN21 in marginal ID group relative to the controls. However, there was no overt morphological change observed in apical dendrites. Immunofluorescence and Western blot analysis indicated that phosphorylation of MAP2, stathmin and JNK1 was down-regulated in marginal ID group. We speculate that the pups treated with maternal marginal ID subjected to subtle changes in dendritic growth of CA1 pyramidal neurons, which may be associated with the dysregulation of MAP2 and stathmin in a JNK1-dependent manner. PMID:27017219

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

    PubMed

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

    2016-02-17

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

  8. In Vivo Monosynaptic Excitatory Transmission between Layer 2 Cortical Pyramidal Neurons

    PubMed Central

    Jouhanneau, Jean-Sébastien; Kremkow, Jens; Dorrn, Anja L.; Poulet, James F.A.

    2015-01-01

    Summary Little is known about the properties of monosynaptic connections between identified neurons in vivo. We made multiple (two to four) two-photon targeted whole-cell recordings from neighboring layer 2 mouse somatosensory barrel cortex pyramidal neurons in vivo to investigate excitatory monosynaptic transmission in the hyperpolarized downstate. We report that pyramidal neurons form a sparsely connected (6.7% connectivity) network with an overrepresentation of bidirectional connections. The majority of unitary excitatory postsynaptic potentials were small in amplitude (<0.5 mV), with a small minority >1 mV. The coefficient of variation (CV = 0.74) could largely be explained by the presence of synaptic failures (22%). Both the CV and failure rates were reduced with increasing amplitude. The mean paired-pulse ratio was 1.15 and positively correlated with the CV. Our approach will help bridge the gap between connectivity and function and allow investigations into the impact of brain state on monosynaptic transmission and integration. PMID:26670044

  9. Loss of Hippocampal CA3 Pyramidal Neurons in Mice Lacking STAM1

    PubMed Central

    Yamada, Mitsuhiro; Takeshita, Toshikazu; Miura, Shigeto; Murata, Kazuko; Kimura, Yutaka; Ishii, Naoto; Nose, Masato; Sakagami, Hiroyuki; Kondo, Hisatake; Tashiro, Fumi; Miyazaki, Jun-Ichi; Sasaki, Hidetada; Sugamura, Kazuo

    2001-01-01

    STAM1, a member of the STAM (signal transducing adapter molecule) family, has a unique structure containing a Src homology 3 domain and ITAM (immunoreceptor tyrosine-based activation motif). STAM1 was previously shown to be associated with the Jak2 and Jak3 tyrosine kinases and to be involved in the regulation of intracellular signal transduction mediated by interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Here we generated mice lacking STAM1 by using homologous recombination with embryonic stem cells. STAM1−/− mice were morphologically indistinguishable from their littermates at birth. However, growth retardation in the third week after birth was observed for the STAM1−/− mice. Unexpectedly, despite the absence of STAM1, hematopoietic cells, including T- and B-lymphocyte and other hematopoietic cell populations, developed normally and responded well to several cytokines, including IL-2 and GM-CSF. However, histological analyses revealed the disappearance of hippocampal CA3 pyramidal neurons in STAM1−/− mice. Furthermore, we observed that primary hippocampal neurons derived from STAM1−/− mice are vulnerable to cell death induced by excitotoxic amino acids or an NO donor. These data suggest that STAM1 is dispensable for cytokine-mediated signaling in lymphocytes but may be involved in the survival of hippocampal CA3 pyramidal neurons. PMID:11340172

  10. A Method for High Fidelity Optogenetic Control of Individual Pyramidal Neurons In vivo

    PubMed Central

    Cooper, Donald C.

    2013-01-01

    Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales. We first demonstrate a simple approach for adeno-associated virus-mediated delivery of ChR2 and NpHR transgenes to the dorsal subiculum and prelimbic region of the prefrontal cortex in rat. Because ChR2 and NpHR are genetically targetable, we describe the use of this technology to control the electrical activity of specific populations of neurons (i.e., pyramidal neurons) embedded in heterogeneous tissue with high temporal precision. We describe herein the hardware, custom software user interface, and procedures that allow for simultaneous light delivery and electrical recording from transduced pyramidal neurons in an anesthetized in vivo preparation. These light-responsive tools provide the opportunity for identifying the causal contributions of different cell types to information processing and behavior. PMID:24022017

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

    PubMed

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

    2015-05-01

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

  12. Persistent Sodium Current Drives Conditional Pacemaking in CA1 Pyramidal Neurons under Muscarinic Stimulation

    PubMed Central

    Yamada-Hanff, Jason

    2013-01-01

    Hippocampal CA1 pyramidal neurons are normally quiescent but can fire spontaneously when stimulated by muscarinic agonists. In brain slice recordings from mouse CA1 pyramidal neurons, we examined the ionic basis of this activity using interleaved current-clamp and voltage-clamp experiments. Both in control and after muscarinic stimulation, the steady-state current–voltage curve was dominated by inward TTX-sensitive persistent sodium current (INaP) that activated near −75 mV and increased steeply with depolarization. In control, total membrane current was net outward (hyperpolarizing) near −70 mV so that cells had a stable resting potential. Muscarinic stimulation activated a small nonselective cation current so that total membrane current near −70 mV shifted to become barely net inward (depolarizing). The small depolarization triggers regenerative activation of INaP, which then depolarizes the cell from −70 mV to spike threshold. We quantified the relative contributions of INaP, hyperpolarization-activated cation current (Ih), and calcium current to pacemaking by using the cell's own firing as a voltage command along with specific blockers. TTX-sensitive sodium current was substantial throughout the entire interspike interval, increasing as the membrane potential approached threshold, while both Ih and calcium current were minimal. Thus, spontaneous activity is driven primarily by activation of INaP in a positive feedback loop starting near −70 mV and providing increasing inward current to threshold. These results show that the pacemaking “engine” from INaP is an inherent property of CA1 pyramidal neurons that can be engaged or disengaged by small shifts in net membrane current near −70 mV, as by muscarinic stimulation. PMID:24048831

  13. Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons.

    PubMed

    Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

    2016-02-01

    The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter--describing somatic integration--and the spike-history filter--accounting for spike-frequency adaptation--dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations. PMID:26907675

  14. Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

    PubMed Central

    Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

    2016-01-01

    The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter—describing somatic integration—and the spike-history filter—accounting for spike-frequency adaptation—dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations. PMID:26907675

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

    PubMed Central

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

    2013-01-01

    Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans ∼25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3–5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages. PMID:23754422

  16. Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

    PubMed Central

    Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.

    2016-01-01

    De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin–Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability. SIGNIFICANCE STATEMENT Haploinsufficiency of ARID1B, a component of chromatin remodeling complex, causes intellectual disability. However, the role of ARID1B in brain development is unknown. Here, we demonstrate that ARID1B is required for neuronal differentiation in the developing brain, such as in dendritic arborization and synapse formation. Our findings suggest that ARID1B plays a critical role in the establishment of cognitive circuitry by regulating dendritic complexity. Thus, ARID1B deficiency may cause intellectual disability via abnormal brain wiring induced by the defective differentiation of cortical neurons. PMID:26937011

  17. Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons.

    PubMed

    Ashhad, Sufyan; Narayanan, Rishikesh

    2016-06-01

    An important consequence of gliotransmission, a signaling mechanism that involves glial release of active transmitter molecules, is its manifestation as N-methyl-d-aspartate receptor (NMDAR)-dependent slow inward currents in neurons. However, the intraneuronal spatial dynamics of these events or the role of active dendrites in regulating their amplitude and spatial spread have remained unexplored. Here, we used somatic and/or dendritic recordings from rat hippocampal pyramidal neurons and demonstrate that a majority of NMDAR-dependent spontaneous slow excitatory potentials (SEP) originate at dendritic locations and are significantly attenuated through their propagation across the neuronal arbor. We substantiated the astrocytic origin of SEPs through paired neuron-astrocyte recordings, where we found that specific infusion of inositol trisphosphate (InsP3) into either distal or proximal astrocytes enhanced the amplitude and frequency of neuronal SEPs. Importantly, SEPs recorded after InsP3 infusion into distal astrocytes exhibited significantly slower kinetics compared with those recorded after proximal infusion. Furthermore, using neuron-specific infusion of pharmacological agents and morphologically realistic conductance-based computational models, we demonstrate that dendritically expressed hyperpolarization-activated cyclic-nucleotide-gated (HCN) and transient potassium channels play critical roles in regulating the strength, kinetics, and compartmentalization of neuronal SEPs. Finally, through the application of subtype-specific receptor blockers during paired neuron-astrocyte recordings, we provide evidence that GluN2B- and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Our results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell

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

    PubMed

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

    2015-03-01

    Pyramidal neurons of the mammalian cerebral cortex have specific structure and pattern of organization that involves the presence of apical dendrite. Morphology of the apical dendrite is well-known, but quantification of its complexity still remains open. Fractal analysis has proved to be a valuable method for analyzing the complexity of dendrite morphology. The aim of this study was to establish the fractal dimension of apical dendrite arborization of pyramidal neurons in distinct neocortical laminae by using the modified box-counting method. A total of thirty, Golgi impregnated neurons from the rat brain were analyzed: 15 superficial (cell bodies located within lamina II-III), and 15 deep pyramidal neurons (cell bodies situated within lamina V-VI). Analysis of topological parameters of apical dendrite arborization showed no statistical differences except in total dendritic length (p=0.02), indicating considerable homogeneity between the two groups of neurons. On the other hand, average fractal dimension of apical dendrite was 1.33±0.06 for the superficial and 1.24±0.04 for the deep cortical neurons, showing statistically significant difference between these two groups (p<0.001). In conclusion, according to the fractal dimension values, apical dendrites of the superficial pyramidal neurons tend to show higher structural complexity compared to the deep ones.

  19. Ephrin-B1 controls the columnar distribution of cortical pyramidal neurons by restricting their tangential migration.

    PubMed

    Dimidschstein, Jordane; Passante, Lara; Dufour, Audrey; van den Ameele, Jelle; Tiberi, Luca; Hrechdakian, Tatyana; Adams, Ralf; Klein, Rüdiger; Lie, Dieter Chichung; Jossin, Yves; Vanderhaeghen, Pierre

    2013-09-18

    Neurons of the cerebral cortex are organized in layers and columns. Unlike laminar patterning, the mechanisms underlying columnar organization remain largely unexplored. Here, we show that ephrin-B1 plays a key role in this process through the control of nonradial steps of migration of pyramidal neurons. In vivo gain of function of ephrin-B1 resulted in a reduction of tangential motility of pyramidal neurons, leading to abnormal neuronal clustering. Conversely, following genetic disruption of ephrin-B1, cortical neurons displayed a wider lateral dispersion, resulting in enlarged ontogenic columns. Dynamic analyses revealed that ephrin-B1 controls the lateral spread of pyramidal neurons by limiting neurite extension and tangential migration during the multipolar phase. Furthermore, we identified P-Rex1, a guanine-exchange factor for Rac3, as a downstream ephrin-B1 effector required to control migration during the multipolar phase. Our results demonstrate that ephrin-B1 inhibits nonradial migration of pyramidal neurons, thereby controlling the pattern of cortical columns.

  20. Alterations of Neocortical Pyramidal Neurons: Turning Points in the Genesis of Mental Retardation

    PubMed Central

    Granato, Alberto; De Giorgio, Andrea

    2014-01-01

    Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions. PMID:25157343

  1. Dendritic spine density of prefrontal layer 6 pyramidal neurons in relation to apical dendrite sculpting by nicotinic acetylcholine receptors

    PubMed Central

    Kang, Lily; Tian, Michael K.; Bailey, Craig D. C.; Lambe, Evelyn K.

    2015-01-01

    Prefrontal layer 6 (L6) pyramidal neurons play an important role in the adult control of attention, facilitated by their strong activation by nicotinic acetylcholine receptors. These neurons in mouse association cortex are distinctive morphologically when compared to L6 neurons in primary cortical regions. Roughly equal proportions of the prefrontal L6 neurons have apical dendrites that are “long” (reaching to the pial surface) vs. “short” (terminating in the deep layers, as in primary cortical regions). This distinct prefrontal morphological pattern is established in the post-juvenile period and appears dependent on nicotinic receptors. Here, we examine dendritic spine densities in these two subgroups of prefrontal L6 pyramidal neurons under control conditions as well as after perturbation of nicotinic acetylcholine receptors. In control mice, the long neurons have significantly greater apical and basal dendritic spine density compared to the short neurons. Furthermore, manipulations of nicotinic receptors (chrna5 deletion or chronic developmental nicotine exposure) have distinct effects on these two subgroups of L6 neurons: apical spine density is significantly reduced in long neurons, and basal spine density is significantly increased in short neurons. These changes appear dependent on the α5 nicotinic subunit encoded by chrna5. Overall, the two subgroups of prefrontal L6 neurons appear positioned to integrate information either across cortex (long neurons) or within the deep layers (short neurons), and nicotinic perturbations differently alter spine density within each subgroup. PMID:26500498

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

    PubMed

    Elston, Guy N

    2003-11-01

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

  3. Properties of the pyramidal tract neuron system within the precentral wrist and hand area of primate motor cortex.

    PubMed

    Humphrey, D R; Corrie, W S; Rietz, R

    1978-01-01

    1. To obtain basic anatomical data that will be useful in interpreting the results of studies of primate pyramidal tract neurons (PTNs), extracellular, single-unit recording techniques were used to determine a number of the properties of the PTN population within the electrically defined, precentral wrist zone of the monkey's motor cortex. 2. Recordings were obtained from a total of 1,375 antidromically identified PT and corticospinal tract (CST) cells. A mathematical model was then used to correct the statistics of the sample for variations in the probability of unit detection, which arise from variations in neuronal size and extracellular field dimensions. 3. Both the experimentally observed and theoretically corrected results suggest that the PT projection from this cortical zone is derived principally from slowly conducting, and presumably small to medium-sized cells (an estimated 85% of the resident PTN population). 4. Both the fast and slow cell subpopulations were found to be concentrated within cortical layer V, where they tend to congregate in small, mixed clusters of 2 to 5 neurons. Estimates of the total packing density of PTNs within layer V of this cortical zone suggest that they account for only 10-20% of the neurons within this major efferent layer. 5. 70% of the slow and 82% of the fast PT neurons within this cortical area were found to send their axons into the contralateral, lateral corticospinal tract. Thus, in futur functional studies of PTNs in this cortical area, it can be assumed that three of every four neurons will in fact influence segmental cells of one category or another directly. 6. Extensive data are also presented on the incidence of axon collateral branching from PT and CST cells to the red nucleus, the medial medullary reticular formation and the cuneate nucleus. 7. Some general implications of these findings for the design of future functional studies of anatomically identified motor cortex cell systems are then discussed.

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

    PubMed Central

    Ropireddy, Deepak; Ascoli, Giorgio A.

    2011-01-01

    Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g., with electron microscopy) or on regional connectivity (tract tracing). An individual pyramidal cell (PC) extends thousands of synapses over macroscopic distances (∼cm). The contrasting requirements of high-resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these “potential synapses” functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto PC dendrites from the axons of a dentate granule cell, three CA3 PCs, one CA2 PC, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g., CA3 vs. CA1), layer (e.g., oriens vs. radiatum), and septo-temporal location (e.g., dorsal vs. ventral). The overall ratio between the numbers of actual and potential synapses was ∼0.20 for the granule and CA3 PCs. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post-synaptic neurons. PMID:21779242

  5. An Augmented Two-Layer Model Captures Nonlinear Analog Spatial Integration Effects in Pyramidal Neuron Dendrites

    PubMed Central

    JADI, MONIKA P.; BEHABADI, BARDIA F.; POLEG-POLSKY, ALON; SCHILLER, JACKIE; MEL, BARTLETT W.

    2014-01-01

    In pursuit of the goal to understand and eventually reproduce the diverse functions of the brain, a key challenge lies in reverse engineering the peculiar biology-based “technology” that underlies the brain’s remarkable ability to process and store information. The basic building block of the nervous system is the nerve cell, or “neuron,” yet after more than 100 years of neurophysiological study and 60 years of modeling, the information processing functions of individual neurons, and the parameters that allow them to engage in so many different types of computation (sensory, motor, mnemonic, executive, etc.) remain poorly understood. In this paper, we review both historical and recent findings that have led to our current understanding of the analog spatial processing capabilities of dendrites, the major input structures of neurons, with a focus on the principal cell type of the neocortex and hippocampus, the pyramidal neuron (PN). We encapsulate our current understanding of PN dendritic integration in an abstract layered model whose spatially sensitive branch-subunits compute multidimensional sigmoidal functions. Unlike the 1-D sigmoids found in conventional neural network models, multidimensional sigmoids allow the cell to implement a rich spectrum of nonlinear modulation effects directly within their dendritic trees. PMID:25554708

  6. Simple Method for Evaluation of Planum Temporale Pyramidal Neurons Shrinkage in Postmortem Tissue of Alzheimer Disease Patients

    PubMed Central

    Kutová, Martina; Mrzílková, Jana; Kirdajová, Denisa; Řípová, Daniela; Zach, Petr

    2014-01-01

    We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls—in the transition into the Sylvian fissure—and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease group compared to the control group, (c) both right and left Heschl's gyrus transitions significantly shorter in the Alzheimer disease group compared to the control group, and (d) right Sylvian fissure transition significantly shorter in the Alzheimer disease group compared to the control group. This neuronal length measurement method could supplement already existing neuropathological criteria for postmortem Alzheimer disease diagnostics. PMID:24719875

  7. Simple method for evaluation of planum temporale pyramidal neurons shrinkage in postmortem tissue of Alzheimer disease patients.

    PubMed

    Kutová, Martina; Mrzílková, Jana; Kirdajová, Denisa; Řípová, Daniela; Zach, Petr

    2014-01-01

    We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls--in the transition into the Sylvian fissure--and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease group compared to the control group, (c) both right and left Heschl's gyrus transitions significantly shorter in the Alzheimer disease group compared to the control group, and (d) right Sylvian fissure transition significantly shorter in the Alzheimer disease group compared to the control group. This neuronal length measurement method could supplement already existing neuropathological criteria for postmortem Alzheimer disease diagnostics.

  8. Heterogeneity of spine density in pyramidal neurons of isocortex of mongoose, Herpestes edwardsii (É. Geoffroy Saint-Hilaire 1818).

    PubMed

    Srivastava, U C; Singh, Sippy; Chauhan, Prashant

    2013-08-01

    The characteristics of pyramidal neurons within six layers of Indian gray mongoose (Herpestes edwardsii) isocortex have been investigated using Golgi and Cresyl-Violet methods. Pyramidal neurons and the cytoarchitecture of isocortex of mongoose were photographed with the help of computer aided Nikon eclipse 80i microscope whereas the lucida drawings were made by simple light microscope equipped with camera lucida. The cortical neurons exhibit marked regional differences in phenotype. The differences occur in morphology and distribution of spines within the cortical neurons not only among different species but also within an animal's brain. The present investigation aims at studying the features of pyramidal neurons and to find out the differences if any in distribution of spines in different layers (II-VI) as well as regions (Frontal, Temporal, Parietal, and Occipital) of isocortex of mongoose, which will provide information regarding importance of different layer and region. This piece of work embarks the findings that spine density shows inter-regional as well as interlaminar variations within isocortex of mongoose indicating that pyramidal cells present in varied layer and region are not equally functional and there do exists differences in activity among layers and regions. Among regions, the Temporal region possessing highest spine density contributes more toward functioning of mongoose isocortex and might play significant role in predatory nature of mongoose because this region in mammals is associated with auditory, visual perception, and object recognition. PMID:23733533

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

    PubMed

    Yamada-Hanff, Jason; Bean, Bruce P

    2015-10-01

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

  10. Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide

    PubMed Central

    Scullion, Sarah; Brown, Jon T.; Randall, Andrew D.

    2015-01-01

    ABSTRACT Accumulation of beta‐amyloid (Aβ) peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ‐overexpressing transgenic mice indicates that increased brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study, we examined what changes in IE are produced in hippocampal CA1 pyramidal cells after 2–5 h treatment with an oligomeric preparation of synthetic human Aβ 1–42 peptide. Whole cell current clamp recordings were compared between Aβ‐(500 nM) and vehicle‐(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub‐threshold intrinsic properties, including membrane potential, input resistance, and hyperpolarization activated “sag”. Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra‐threshold stimuli. However, Aβ 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM depressed the after‐hyperpolarization that followed both a single AP or 50 Hz trains of a number of APs between 5 and 25. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models, the IE changes are toward hyperexcitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25515596

  11. Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide.

    PubMed

    Tamagnini, Francesco; Scullion, Sarah; Brown, Jon T; Randall, Andrew D

    2015-07-01

    Accumulation of beta-amyloid (Aβ) peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ-overexpressing transgenic mice indicates that increased brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study, we examined what changes in IE are produced in hippocampal CA1 pyramidal cells after 2-5 h treatment with an oligomeric preparation of synthetic human Aβ 1-42 peptide. Whole cell current clamp recordings were compared between Aβ-(500 nM) and vehicle-(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub-threshold intrinsic properties, including membrane potential, input resistance, and hyperpolarization activated "sag". Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra-threshold stimuli. However, Aβ 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM depressed the after-hyperpolarization that followed both a single AP or 50 Hz trains of a number of APs between 5 and 25. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models, the IE changes are toward hyperexcitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients.

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

    PubMed

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

    2015-10-22

    Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (p<0.05) and the SHM-EG (p<0.05). In conclusion, our results suggest that pyramidal neuron loss and histopathological changes in the cornu ammonis of 8-week-old male rats may be due to the 900-MHz EMF exposure. PMID:26239913

  13. Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-beta-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons.

    PubMed

    Hellstrom, Ian C; Danik, Marc; Luheshi, Giamal N; Williams, Sylvain

    2005-01-01

    Chronic inflammation has been reported to be a significant factor in the induction and progression of a number of chronic neurological disorders including Alzheimer's disease and Down syndrome. It is believed that inflammation may promote synaptic dysfunction, an effect that is mediated in part by pro-inflammatory cytokines such as interleukin-1beta (IL-1beta). However, the role of IL-1beta and other cytokines in synaptic transmission is still poorly understood. In this study, we have investigated how synaptic transmission and neuronal excitability in hippocampal pyramidal neurons are affected by chronic inflammation induced by exposing organotypic slices to the bacterial cell-wall product lipopolysaccharide (LPS). We report that CA1 pyramidal neurons recorded in whole cell from slices previously exposed to LPS for 7 days had resting membrane potential and action potential properties similar to those of the controls. However, they had significantly lower membrane resistance and a more elevated action potential threshold, and displayed a slower frequency of action potential discharge. Moreover, the amplitude of pharmacologically isolated postsynaptic gamma-aminobutyric acid (GABA)ergic potentials, but not excitatory glutamatergic postsynaptic potentials, was significantly larger following chronic LPS exposure. Interestingly, co-incubation of the IL-1 receptor antagonist (IL-1Ra) concurrently with LPS prevented the increase in GABAergic transmission, but not the reduction in intrinsic neuronal excitability. Finally, we confirmed that LPS dramatically increased IL-1beta, and IL-1beta-dependent IL-6 levels in the culture medium for 2 days before returning to baseline. We conclude that CA1 pyramidal neurons in slices chronically exposed to LPS show a persistent decrease in excitability due to a combined decrease in intrinsic membrane excitability and an enhancement in synaptic GABAergic input, the latter being dependent on IL-1beta. Therefore, chronic inflammation in

  14. A Transgenic Mouse Model Reveals Fast Nicotinic Transmission in Hippocampal Pyramidal Neurons

    PubMed Central

    Grybko, Michael J.; Hahm, Eu-teum; Perrine, Wesley; Parnes, Jason A.; Chick, Wallace S.; Sharma, Geeta; Finger, Thomas E.; Vijayaraghavan, Sukumar

    2011-01-01

    The relative contribution, to brain cholinergic signaling, by synaptic- and diffusion-based mechanisms remains to be elucidated. In this study, we examined the prevalence of fast nicotinic signaling in the hippocampus. We describe a mouse model where cholinergic axons are labeled with the tauGFP fusion protein driven by the choline acetyltransferase (ChAT) promoter. The model provides for the visualization of individual cholinergic axons at greater resolution than other available models and techniques, even in thick, live, slices. Combining calcium imaging and electrophysiology, we demonstrate that local stimulation of visualized cholinergic fibers results in rapid EPSCs mediated by the activation of α7-subunit containing nicotinic receptors (α7-nAChRs) on CA3 pyramidal neurons. These responses were blocked by the α7-nAChR antagonist methyllycaconitine (MLA) and potentiated by the receptor specific allosteric modulator 1-(5-chloro-2,4- dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea (PNU-120596). Our results suggest, for the first time, that synaptic nAChRs can modulate pyramidal cell plasticity and development. Fast nicotinic transmission might play a greater role in cholinergic signaling than previously assumed. We provide a model for the examination of synaptic properties of basal forebrain cholinergic innervation in the brain. PMID:21501254

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  16. PKC activators enhance GABAergic neurotransmission and paired-pulse facilitation in hippocampal CA1 pyramidal neurons.

    PubMed

    Xu, C; Liu, Q-Y; Alkon, D L

    2014-05-30

    Bryostatin-1, a potent agonist of protein kinase C (PKC), has recently been found to enhance spatial learning and long-term memory in rats, mice, rabbits and the nudibranch Hermissenda, and to exert profound neuroprotective effects on Alzheimer's disease (AD) in transgenic mice. However, details of the mechanistic effects of bryostatin on learning and memory remain unclear. To address this issue, whole-cell recording, a dual-recording approach and extracellular recording techniques were performed on young (2-4months) Brown-Norway rats. We found that bath-applied bryostatin-1 significantly increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). The firing rate of GABAergic interneurons significantly was also increased as recorded with a loosely-attached extracellular recording configuration. Simultaneous recordings from communicating cell pairs of interneuron and pyramidal neuron revealed unique activity-dependent properties of GABAergic synapses. Furthermore, the bryostatin-induced increase of the frequency and amplitude of IPSCs was blocked by methionine enkephalin which selectively suppressed the excitability of interneurons. Pretreatment with RO-32-0432, a relatively specific PKCα antagonist, blocked the effect of bryostatin on sIPSCs. Finally, bryostatin increased paired-pulse ratio of GABAergic synapses that lasted for at least 20min while pretreatment with RO-32-0432 significantly reduced the ratio. In addition, 8-[2-(2-pentyl-cyclopropylmethl)-cyclopropyl]-octanoic acid (DCP-LA), a selective PKCε activator, also increased the frequency and amplitude of sIPSCs. Taken together, these results suggest that bryostatin enhances GABAergic neurotransmission in pyramidal neurons by activating the PKCα & ε-dependent pathway and by a presynaptic mechanism with excitation of GABAergic interneurons. These effects of bryostatin on GABAergic transmissions and modifiability may contribute to the improvement of learning and memory

  17. Sex differences in GABABR-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex

    PubMed Central

    de Velasco, Ezequiel Marron Fernandez; Hearing, Matthew; Xia, Zhilian; Victoria, Nicole C.; Luján, Rafael; Wickman, Kevin

    2015-01-01

    The medial prefrontal cortex (mPFC) has been implicated in multiple disorders characterized by clear sex differences, including schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, and drug addiction. These sex differences likely represent underlying differences in connectivity and/or the balance of neuronal excitability within the mPFC. Recently, we demonstrated that signaling via the metabotropic γ-aminobutyric acid receptor (GABABR) and G proteingated inwardly-rectifying K+ (GIRK/Kir3) channels modulates the excitability of the key output neurons of the mPFC, the layer 5/6 pyramidal neurons. Here, we report a sex difference in the GABABR-GIRK signaling pathway in these neurons. Specifically, GABABR-dependent GIRK currents recorded in the prelimbic region of the mPFC were larger in adolescent male mice than in female counterparts. Interestingly, this sex difference was not observed in layer 5/6 pyramidal neurons of the adjacent infralimbic cortex, nor was it seen in young adult mice. The sex difference in GABABR-GIRK signaling is not attributable to different expression levels of signaling pathway components, but rather to a phosphorylation-dependent trafficking mechanism. Thus, sex differences related to some diseases associated with altered mPFC function may be explained in part by sex differences in GIRK-dependent signaling in mPFC pyramidal neurons. PMID:25843643

  18. The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

    PubMed

    Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

    2013-07-01

    With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the

  19. The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

    PubMed

    Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

    2013-07-01

    With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the

  20. Acute Seizures in Old Age Leads to a Greater Loss of CA1 Pyramidal Neurons, an Increased Propensity for Developing Chronic TLE and a Severe Cognitive Dysfunction.

    PubMed

    Hattiangady, Bharathi; Kuruba, Ramkumar; Shetty, Ashok K

    2011-02-01

    The aged population displays an enhanced risk for developing acute seizure (AS) activity. However, it is unclear whether AS activity in old age would result in a greater magnitude of hippocampal neurodegeneration and inflammation, and an increased predilection for developing chronic temporal lobe epilepsy (TLE) and cognitive dysfunction. Therefore, we addressed these issues in young-adult (5-months old) and aged (22-months old) F344 rats after three-hours of AS activity, induced through graded intraperitoneal injections of kainic acid (KA), and terminated through a diazepam injection. During the three-hours of AS activity, both young adult and aged groups exhibited similar numbers of stage-V motor seizures but the numbers of stage-IV motor seizures were greater in the aged group. In both age groups, three-hour AS activity induced degeneration of 50-55% of neurons in the dentate hilus, 22-32% of neurons in the granule cell layer and 49-52% neurons in the CA3 pyramidal cell layer without showing any interaction between the age and AS activity. However, degeneration of neurons in the CA1 pyramidal cell layer showed a clear interaction between the age and AS activity (12% in the young adult group and 56% in the aged group), suggesting that an advanced age makes the CA1 pyramidal neurons more susceptible to die with AS activity. The extent of inflammation measured through the numbers of activated microglial cells was similar between the two age groups. Interestingly, the predisposition for developing chronic TLE at 2-3 months after AS activity was 60% for young adult rats but 100% for aged rats. Moreover, both frequency & intensity of spontaneous recurrent seizures in the chronic phase after AS activity were 6-12 folds greater in aged rats than in young adult rats. Furthermore, aged rats lost their ability for spatial learning even in a scrupulous eleven-session water maze learning paradigm after AS activity, in divergence from young adult rats which retained the

  1. Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons

    PubMed Central

    Robinson, Hugh P. C.; Århem, Peter

    2014-01-01

    Several types of intrinsic dynamics have been identified in brain neurons. Type 1 excitability is characterized by a continuous frequency-stimulus relationship and, thus, an arbitrarily low frequency at threshold current. Conversely, Type 2 excitability is characterized by a discontinuous frequency-stimulus relationship and a nonzero threshold frequency. In previous theoretical work we showed that the density of Kv channels is a bifurcation parameter, such that increasing the Kv channel density in a neuron model transforms Type 1 excitability into Type 2 excitability. Here we test this finding experimentally, using the dynamic clamp technique on Type 1 pyramidal cells in rat cortex. We found that increasing the density of slow Kv channels leads to a shift from Type 1 to Type 2 threshold dynamics, i.e., a distinct onset frequency, subthreshold oscillations, and reduced latency to first spike. In addition, the action potential was resculptured, with a narrower spike width and more pronounced afterhyperpolarization. All changes could be captured with a two-dimensional model. It may seem paradoxical that an increase in slow K channel density can lead to a higher threshold firing frequency; however, this can be explained in terms of bifurcation theory. In contrast to previous work, we argue that an increased outward current leads to a change in dynamics in these neurons without a rectification of the current-voltage curve. These results demonstrate that the behavior of neurons is determined by the global interactions of their dynamical elements and not necessarily simply by individual types of ion channels. PMID:25339708

  2. Total number and volume of Von Economo neurons in the cerebral cortex of cetaceans.

    PubMed

    Butti, Camilla; Sherwood, Chet C; Hakeem, Atiya Y; Allman, John M; Hof, Patrick R

    2009-07-10

    Von Economo neurons (VENs) are a type of large, layer V spindle-shaped neurons that were previously described in humans, great apes, elephants, and some large-brained cetaceans. Here we report the presence of Von Economo neurons in the anterior cingulate (ACC), anterior insular (AI), and frontopolar (FP) cortices of small odontocetes, including the bottlenose dolphin (Tursiops truncatus), the Risso's dolphin (Grampus griseus), and the beluga whale (Delphinapterus leucas). The total number and volume of VENs and the volume of neighboring layer V pyramidal neurons and layer VI fusiform neurons were obtained by using a design-based stereologic approach. Two humpback whale (Megaptera novaeangliae) brains were investigated for comparative purposes as representatives of the suborder Mysticeti. Our results show that the distribution of VENs in these cetacean species is comparable to that reported in humans, great apes, and elephants. The number of VENs in these cetaceans is also comparable to data available from great apes, and stereologic estimates indicate that VEN volume follows in these cetacean species a pattern similar to that in hominids, the VENs being larger than neighboring layer V pyramidal cells and conspicuously larger than fusiform neurons of layer VI. The fact that VENs are found in species representative of both cetacean suborders in addition to hominids and elephants suggests that these particular neurons have appeared convergently in phylogenetically unrelated groups of mammals possibly under the influence of comparable selective pressures that influenced specifically the evolution of cortical domains involved in complex cognitive and social/emotional processes. PMID:19412956

  3. Synaptic Conductances during Interictal Discharges in Pyramidal Neurons of Rat Entorhinal Cortex

    PubMed Central

    Amakhin, Dmitry V.; Ergina, Julia L.; Chizhov, Anton V.; Zaitsev, Aleksey V.

    2016-01-01

    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 GABAA R-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 GABAA R channels with depolarized reversal potential. The second type of IID is determined by the interplay between excitation and inhibition, with early AMPAR and prolonged depolarized GABAA R 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. PMID:27790093

  4. Theoretical principles underlying optical stimulation of a channelrhodopsin-2 positive pyramidal neuron

    PubMed Central

    Foutz, Thomas J.; Arlow, Richard L.

    2012-01-01

    Optogenetics is an emerging field of neuromodulation that permits scaled, millisecond temporal control of the membrane dynamics of genetically targeted cells using light. Optogenetic technology has revolutionized neuroscience research; however, numerous biophysical questions remain on the optical and neuronal factors impacting the modulation of neural activity with photon-sensitive ion channels. To begin to address such questions, we developed a computational tool to explore the underlying principles of optogenetic neural stimulation. This “light-neuron” model consists of theoretical representations of the light dynamics generated by a fiber optic in brain tissue, coupled to a multicompartment cable model of a cortical pyramidal neuron embedded with channelrhodopsin-2 (ChR2) membrane dynamics. Simulations revealed that the large energies required to generate an action potential are primarily due to the limited conductivity of ChR2, and that the major determinants of stimulation threshold are the surface area of illuminated cell membrane and proximity to the light source. Our results predict that the activation threshold is sensitive to many of the properties of ChR2 (density, conductivity, and kinetics), tissue medium (scattering and absorbance), and the fiber-optic light source (diameter and numerical aperture). We also illustrate the impact of redistributing the ChR2 expression density (uniform vs. nonuniform) on the activation threshold. The model system developed in this study represents a scientific instrument to characterize the effects of optogenetic neuromodulation, as well as an engineering design tool to help guide future development of optogenetic technology. PMID:22442566

  5. An arithmetic rule for spatial summation of excitatory and inhibitory inputs in pyramidal neurons

    PubMed Central

    Hao, Jiang; Wang, Xu-dong; Dan, Yang; Poo, Mu-ming; Zhang, Xiao-hui

    2009-01-01

    Dendritic integration of excitatory and inhibitory inputs is critical for neuronal computation, but the underlying rules remain to be elucidated. Based on realistic modeling and experiments in rat hippocampal slices, we derived a simple arithmetic rule for spatial summation of concurrent excitatory glutamatergic inputs (E) and inhibitory GABAergic inputs (I). The somatic response can be well approximated as the sum of the excitatory postsynaptic potential (EPSP), the inhibitory postsynaptic potential (IPSP), and a nonlinear term proportional to their product (k*EPSP*IPSP), where the coefficient k reflects the strength of shunting effect. The k value shows a pronounced asymmetry in its dependence on E and I locations. For I on the dendritic trunk, k decays rapidly with E–I distance for proximal Es, but remains largely constant for distal Es, indicating a uniformly high shunting efficacy for all distal Es. For I on an oblique branch, the shunting effect is restricted mainly within the branch, with the same proximal/distal asymmetry. This asymmetry can be largely attributed to cable properties of the dendrite. Further modeling studies showed that this rule also applies to the integration of multiple coincident Es and Is. Thus, this arithmetic rule offers a simple analytical tool for studying E–I integration in pyramidal neurons that incorporates the location specificity of GABAergic shunting inhibition. PMID:19955407

  6. Comparison of activity of individual pyramidal tract neurons during balancing, locomotion, and scratching.

    PubMed

    Beloozerova, Irina N; Sirota, Mikhail G; Orlovsky, Grigori N; Deliagina, Tatiana G

    2006-04-25

    Neuronal mechanisms of the spinal cord, brainstem, and cerebellum play a key role in the control of complex automatic motor behaviors-postural corrections, stepping, and scratching, whereas the role of the motor cortex is less clear. To assess this role, we recorded fore and hind limb-related pyramidal tract neurons (PTNs) in the cat during postural corrections and during locomotion; hind limb PTNs were also tested during scratching. The activity of nearly all PTNs was modulated in the rhythm of each of these motor patterns. The discharge frequency, averaged over the PTN population, was similar in different motor tasks, whereas the degree of frequency modulation was larger during locomotion. In individual PTNs, a correlation between analogous discharge characteristics (frequency or its modulation) in different tasks was very low, suggesting that input signals to PTNs in these tasks have a substantially different origin. In about a half of PTNs, their activity in different tasks was timed to the analogous (flexor/extensor) parts of the cycle, suggesting that these PTNs perform similar functions in these tasks (e.g., control of the value of muscle activity). In another half of PTNs, their activity was timed to opposite parts of the cycle in different tasks. These PTNs seem to perform different motor functions in different tasks, or their targets are active in different parts of the cycle in these tasks, or their effects are not directly related to the control of motor output (e.g., they modulate transmission of afferent signals).

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

    PubMed Central

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

    2016-01-01

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

  8. Apoptosis of Hippocampal Pyramidal Neurons Is Virus Independent in a Mouse Model of Acute Neurovirulent Picornavirus Infection

    PubMed Central

    Buenz, Eric J.; Sauer, Brian M.; LaFrance-Corey, Reghann G.; Deb, Chandra; Denic, Aleksandar; German, Christopher L.; Howe, Charles L.

    2009-01-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler’s murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non–cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  9. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.

    PubMed

    Buenz, Eric J; Sauer, Brian M; Lafrance-Corey, Reghann G; Deb, Chandra; Denic, Aleksandar; German, Christopher L; Howe, Charles L

    2009-08-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

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

    PubMed

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

    2015-02-01

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

  11. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits.

    PubMed

    Oh, M Matthew; Simkin, Dina; Disterhoft, John F

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  12. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  13. Synaptic Conductance Estimates of the Connection Between Local Inhibitor Interneurons and Pyramidal Neurons in Layer 2/3 of a Cortical Column.

    PubMed

    Hoffmann, Jochen H O; Meyer, H S; Schmitt, Arno C; Straehle, Jakob; Weitbrecht, Trinh; Sakmann, Bert; Helmstaedter, Moritz

    2015-11-01

    Stimulation of a principal whisker yields sparse action potential (AP) spiking in layer 2/3 (L2/3) pyramidal neurons in a cortical column of rat barrel cortex. The low AP rates in pyramidal neurons could be explained by activation of interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3 interneurons classified as local inhibitors based on their axonal projection in the same column were reported to receive strong excitatory input from spiny neurons in L4, which are also the main source of the excitatory input to L2/3 pyramidal neurons. Here, we investigated the remaining synaptic connection in this intracolumnar microcircuit. We found strong and reliable inhibitory synaptic transmission between intracolumnar L2/3 local-inhibitor-to-L2/3 pyramidal neuron pairs [inhibitory postsynaptic potential (IPSP) amplitude -0.88 ± 0.67 mV]. On average, 6.2 ± 2 synaptic contacts were made by L2/3 local inhibitors onto L2/3 pyramidal neurons at 107 ± 64 µm path distance from the pyramidal neuron soma, thus overlapping with the distribution of synaptic contacts from L4 spiny neurons onto L2/3 pyramidal neurons (67 ± 34 µm). Finally, using compartmental simulations, we determined the synaptic conductance per synaptic contact to be 0.77 ± 0.4 nS. We conclude that the synaptic circuit from L4 to L2/3 can provide efficient shunting inhibition that is temporally and spatially aligned with the excitatory input from L4 to L2/3. PMID:25761638

  14. Patterns of axon collateralization of identified supragranular pyramidal neurons in the cat auditory cortex.

    PubMed

    Ojima, H; Honda, C N; Jones, E G

    1991-01-01

    Nine pyramidal neurons in layers II and III of cat primary auditory cortex (AI) were fully reconstructed after intracellular injections of horseradish peroxidase or biocytin. Each neuron was functionally characterized according to its position relative to an anteroposterior sequence of best frequency responses. All labeled somata were in layers II or III and gave rise to typical apical and basal dendritic arbors as well as to extensive systems of axon collaterals. The primary axon of all except 1 cell entered the white matter and was probably directed toward other cortical areas ipsi- or contralaterally. Two major intracortical collateral systems emerged from the main axon in AI, one ending in the vicinity of the cell and the second at a distance. (1) Many local and recurrent collaterals, given off in layers III and V, contributed terminal branches to the formation of a columnar pattern of terminations extending superficially and deeply into the soma. The column extended through layers I-V, with some constriction in the middle portion corresponding to layer IV. (2) The axon of each cell also gave rise to 2-5 thick, long-range collaterals in layers III and/or V. These ran parallel to the pial surface for several millimeters. At several points along these long horizontal collaterals, vertically directed branches emerged to form columnar terminations, again extending through layers I-V. These columns did not overlap with that formed in the vicinity of the cell, and were situated at distances 500-1200 microns from the cell body. When viewed in the tangential plane, horizontal collaterals were oriented, on the whole, dorsoventrally with respect to the surface of the cortex. This may correspond to the organization of isofrequency bands previously described in cats. The results suggest that the major spread of excitation in AI is mediated by horizontal collaterals of pyramidal cells and that it occurs along the lines of isofrequency domains. Within the latter the

  15. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex.

    PubMed

    Ohshima, Toshio; Hirasawa, Motoyuki; Tabata, Hidenori; Mutoh, Tetsuji; Adachi, Tomoko; Suzuki, Hiromi; Saruta, Keiko; Iwasato, Takuji; Itohara, Shigeyoshi; Hashimoto, Mistuhiro; Nakajima, Kazunori; Ogawa, Masaharu; Kulkarni, Ashok B; Mikoshiba, Katsuhiko

    2007-06-01

    The mammalian cerebral cortex consists of six layers that are generated via coordinated neuronal migration during the embryonic period. Recent studies identified specific phases of radial migration of cortical neurons. After the final division, neurons transform from a multipolar to a bipolar shape within the subventricular zone-intermediate zone (SVZ-IZ) and then migrate along radial glial fibres. Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal migration defects. When we introduced GFP into migrating neurons at E14.5 by in utero electroporation, we observed migrating neurons in wild-type but not in Cdk5(-/-) embryos after 3-4 days. Introduction of the dominant-negative form of Cdk5 into the wild-type migrating neurons confirmed specific impairment of the multipolar-to-bipolar transition within the SVZ-IZ in a cell-autonomous manner. Cortex-specific Cdk5 conditional knockout mice showed inverted layering of the cerebral cortex and the layer V and callosal neurons, but not layer VI neurons, had severely impaired dendritic morphology. The amount of the dendritic protein Map2 was decreased in the cerebral cortex of Cdk5-deficient mice, and the axonal trajectory of cortical neurons within the cortex was also abnormal. These results indicate that Cdk5 is required for proper multipolar-to-bipolar transition, and a deficiency of Cdk5 results in abnormal morphology of pyramidal neurons. In addition, proper radial neuronal migration generates an inside-out pattern of cerebral cortex formation and normal axonal trajectories of cortical pyramidal neurons.

  16. Characteristics of intracellularly injected infragranular pyramidal neurons in cat primary auditory cortex.

    PubMed

    Ojima, H; Honda, C N; Jones, E G

    1992-01-01

    Pyramidal neurons in layers V and VI of cat primary auditory cortex (AI) were intracellularly injected with biocytin after functional characterization according to a position relative to an anteroposterior sequence of best-frequency responses. A sample of 19 completely filled neurons was analyzed, and a preliminary classification was made on the basis of dendritic morphology and axon collateral distribution. Layer V cells could be divided into two types. Cells in the upper part of layer V and projecting toward the diencephalon had a large cell body and an apical dendrite with extensive branches in layer I. These cells had few recurrent axon collaterals, and no terminal axonal bushes were formed in the vicinity of the dendritic field. Long horizontal collaterals with many boutons, however, extended in various directions parallel to the cortical surface. By contrast, cells in the lower part of layer V and sending an axon into the putamen, or without an obvious subcortical axon, had a medium soma and an apical dendrite with few branches in layer I. These cells had a dense bush of recurrent collaterals extending into layers II and III and surrounding the dendritic field, but few or no horizontal collaterals. Layer VI injected neurons were more heterogeneous. All had a thin ascending dendrite with oblique branches both ending in layer III. Axon collateral distributions varied from cell to cell. Relatively small cells with an apical dendrite that branched frequently in layers III and IV had a dense network of recurrent collaterals in the dendritic field, but virtually no horizontal collaterals. This type projected toward the diencephalon. Cells with relatively long horizontal collaterals and a weak recurrent system confined to layers V and VI had a unique arborization pattern of basal dendrites. This type may have projected to the claustrum or other cortical areas. One cell with dendritic branches restricted to layer VI had horizontal collaterals predominantly in layer

  17. EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons123

    PubMed Central

    2016-01-01

    Abstract EPSPs occur when the neurotransmitter glutamate binds to postsynaptic receptors located on small pleomorphic membrane protrusions called dendritic spines. To transmit the synaptic signal, these potentials must travel through the spine neck and the dendritic tree to reach the soma. Due to their small size, the electrical behavior of spines and their ability to compartmentalize electrical signals has been very difficult to assess experimentally. In this study, we developed a method to perform simultaneous two-photon voltage-sensitive dye recording with two-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in single spines on the basal dendrites of L5 pyramidal neurons in acute brain slices from CD1 control mice. We were able to record uncaging-evoked spine potentials that resembled miniature EPSPs at the soma from a wide range of spine morphologies. In proximal spines, these potentials averaged 13.0 mV (range, 6.5–30.8 mV; N = 20) for an average somatic EPSP of 0.59 mV, whereas the mean attenuation ratio (spine/soma) was found to be 25.3. Durations of spine EPSP waveforms were found to be 11.7 ms on average. Modeling studies demonstrate the important role that spine neck resistance (Rneck) plays in spine EPSP amplitudes. Simulations used to estimate Rneck by fits to voltage-sensitive dye measurements produced a mean of 179 MΩ (range, 23–420 MΩ; N = 19). Independent measurements based on fluorescence recovery after photobleaching of a cytosolic dye from spines of the same population of neurons produced a mean Rneck estimate of 204 MΩ (range, 52–521 MΩ; N = 34). PMID:27257618

  18. Ethanol enhances neurosteroidogenesis in hippocampal pyramidal neurons by paradoxical NMDA receptor activation.

    PubMed

    Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F

    2011-07-01

    Using an antibody against 5α-reduced neurosteroids, predominantly allopregnanolone, we found that immunostaining in the CA1 region of rat hippocampal slices was confined to pyramidal neurons. This neurosteroid staining was increased following 15 min administration of 60 mm but not 20 mm ethanol, and the enhancement was blocked by finasteride and dutasteride, selective inhibitors of 5α-reductase, a key enzyme required for allopregnanolone synthesis. Consistent with a prior report indicating that N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation can promote steroid production, we observed that D-2-amino-5-phosphonovalerate (APV), a competitive NMDAR antagonist, blocked the effects of 60 mm ethanol on staining. We previously reported that 60 mm ethanol inhibits the induction of long-term potentiation (LTP), a cellular model for memory formation, in the CA1 region. In the present study, LTP inhibition by 60 mm ethanol was also overcome by both the 5α-reductase inhibitors and by APV. Furthermore, the effects of ethanol on neurosteroid production and LTP were mimicked by a low concentration of NMDA (1 μm), and the ability of NMDA to inhibit LTP and to enhance neurosteroid staining was reversed by finasteride and dutasteride, as well as by APV. These results indicate that ethanol paradoxically enhances GABAergic neurosteroid production by activation of unblocked NMDARs and that acute LTP inhibition by ethanol represents a form of NMDAR-mediated metaplasticity. PMID:21734282

  19. Combined chronic blockade of hyper-active L-type calcium channels and NMDA receptors ameliorates HIV-1 associated hyper-excitability of mPFC pyramidal neurons.

    PubMed

    Khodr, Christina E; Chen, Lihua; Dave, Sonya; Al-Harthi, Lena; Hu, Xiu-Ti

    2016-10-01

    Human Immunodeficiency Virus type 1 (HIV-1) infection induces neurological and neuropsychological deficits, which are associated with dysregulation of the medial prefrontal cortex (mPFC) and other vulnerable brain regions. We evaluated the impact of HIV infection in the mPFC and the therapeutic potential of targeting over-active voltage-gated L-type Ca(2+) channels (L-channel) and NMDA receptors (NMDAR), as modeled in HIV-1 transgenic (Tg) rats. Whole-cell patch-clamp recording was used to assess the membrane properties and voltage-sensitive Ca(2+) potentials (Ca(2+) influx) in mPFC pyramidal neurons. Neurons from HIV-1 Tg rats displayed reduced rheobase, spike amplitude and inwardly-rectifying K(+) influx, increased numbers of action potentials, and a trend of aberrant firing compared to those from non-Tg control rats. Neuronal hyper-excitation was associated with abnormally-enhanced Ca(2+) influx (independent of NMDAR), which was eliminated by acute L-channel blockade. Combined chronic blockade of over-active L-channels and NMDARs with open-channel blockers abolished HIV effects on spiking, aberrant firing and Ca(2+) potential half-amplitude duration, though not the reduced inward rectification. In contrast, individual chronic blockade of over-active L-channels or NMDARs did not alleviate HIV-induced mPFC hyper-excitability. These studies demonstrate that HIV alters mPFC neuronal activity by dysregulating membrane excitability and Ca(2+) influx through the L-channels. This renders these neurons more susceptible and vulnerable to excitatory stimuli, and could contribute to HIV-associated neuropathogenesis. Combined targeting of over-active L-channels/NMDARs alleviates HIV-induced dysfunction of mPFC pyramidal neurons, emphasizing a potential novel therapeutic strategy that may effectively decrease HIV-induced Ca(2+) dysregulation in the mPFC.

  20. Combined chronic blockade of hyper-active L-type calcium channels and NMDA receptors ameliorates HIV-1 associated hyper-excitability of mPFC pyramidal neurons.

    PubMed

    Khodr, Christina E; Chen, Lihua; Dave, Sonya; Al-Harthi, Lena; Hu, Xiu-Ti

    2016-10-01

    Human Immunodeficiency Virus type 1 (HIV-1) infection induces neurological and neuropsychological deficits, which are associated with dysregulation of the medial prefrontal cortex (mPFC) and other vulnerable brain regions. We evaluated the impact of HIV infection in the mPFC and the therapeutic potential of targeting over-active voltage-gated L-type Ca(2+) channels (L-channel) and NMDA receptors (NMDAR), as modeled in HIV-1 transgenic (Tg) rats. Whole-cell patch-clamp recording was used to assess the membrane properties and voltage-sensitive Ca(2+) potentials (Ca(2+) influx) in mPFC pyramidal neurons. Neurons from HIV-1 Tg rats displayed reduced rheobase, spike amplitude and inwardly-rectifying K(+) influx, increased numbers of action potentials, and a trend of aberrant firing compared to those from non-Tg control rats. Neuronal hyper-excitation was associated with abnormally-enhanced Ca(2+) influx (independent of NMDAR), which was eliminated by acute L-channel blockade. Combined chronic blockade of over-active L-channels and NMDARs with open-channel blockers abolished HIV effects on spiking, aberrant firing and Ca(2+) potential half-amplitude duration, though not the reduced inward rectification. In contrast, individual chronic blockade of over-active L-channels or NMDARs did not alleviate HIV-induced mPFC hyper-excitability. These studies demonstrate that HIV alters mPFC neuronal activity by dysregulating membrane excitability and Ca(2+) influx through the L-channels. This renders these neurons more susceptible and vulnerable to excitatory stimuli, and could contribute to HIV-associated neuropathogenesis. Combined targeting of over-active L-channels/NMDARs alleviates HIV-induced dysfunction of mPFC pyramidal neurons, emphasizing a potential novel therapeutic strategy that may effectively decrease HIV-induced Ca(2+) dysregulation in the mPFC. PMID:27326669

  1. Hippocampal CA1 pyramidal neurons of Mecp2 mutant mice show a dendritic spine phenotype only in the presymptomatic stage.

    PubMed

    Chapleau, Christopher A; Boggio, Elena Maria; Calfa, Gaston; Percy, Alan K; Giustetto, Maurizio; Pozzo-Miller, Lucas

    2012-01-01

    Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations in MECP2, is the leading cause of intellectual disabilities in women. Neurons in Mecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus of Mecp2(tm1.1Jae) male mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1 stratum radiatum of symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomatic Mecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.

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

    PubMed

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

    2014-01-22

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

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

    PubMed

    Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

    2015-01-01

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

  4. Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons.

    PubMed

    Kwag, Jeehyun; Majid, Aman Shah Abdul; Kang, Kui Dong

    2011-01-01

    Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult. PMID:22040892

  5. Dysplastic neocortex and subcortical heterotopias in methylazoxymethanol-treated rats: an intracellular study of identified pyramidal neurones.

    PubMed

    Sancini, G; Franceschetti, S; Battaglia, G; Colacitti, C; Di Luca, M; Spreafico, R; Avanzini, G

    1998-05-01

    Intracellular recordings were obtained using biocytin-filled electrodes from 78 neurones located in both dysplastic neocortex and subcortical heterotopic aggregates in a model of neuronal migration disorder induced in rats by means of a double methylazoxymethanol injection given on embryonic day 15. Both regular spiking and intrinsically bursting pyramidal neurones were found in all of the examined structures and were synaptically activated by subcortical stimulation. In a neuronal subpopulation (22%) located in the neocortex as well as in the subcortical heterotopic aggregates, the injection of depolarising current pulses elicited aberrant firing patterns, consisting of repetitive bursts of APs that gradually increased in duration and eventually merged in a long-lasting discharge. The gradual development of this 'excessive' bursting behaviour suggests a progressive run-down of the slow components of the hyperpolarising afterpotential. PMID:9792622

  6. Stability and plasticity of intrinsic membrane properties in hippocampal CA1 pyramidal neurons: effects of internal anions

    PubMed Central

    Kaczorowski, Catherine Cook; Disterhoft, John; Spruston, Nelson

    2007-01-01

    CA1 pyramidal neurons from animals that have acquired hippocampal tasks show increased neuronal excitability, as evidenced by a reduction in the postburst afterhyperpolarization (AHP). Studies of AHP plasticity require stable long-term recordings, which are affected by the intracellular solutions potassium methylsulphate (KMeth) or potassium gluconate (KGluc). Here we show immediate and gradual effects of these intracellular solutions on measurement of the AHP and basic membrane properties, and on the induction of AHP plasticity in CA1 pyramidal neurons from rat hippocampal slices. The AHP measured immediately after establishing whole-cell recordings was larger with KMeth than with KGluc. In general, the AHP in KMeth was comparable to the AHP measured in the perforated-patch configuration. However, KMeth induced time-dependent changes in the intrinsic membrane properties of CA1 pyramidal neurons. Specifically, input resistance progressively increased by 70% after 50 min; correspondingly, the current required to trigger an action potential and the fast afterdepolarization following action potentials gradually decreased by about 50%. Conversely, these measures were stable in KGluc. We also demonstrate that activity-dependent plasticity of the AHP occurs with physiologically relevant stimuli in KGluc. AHPs triggered with theta-burst firing every 30 s were progressively reduced, whereas AHPs elicited every 150 s were stable. Blockade of the apamin-sensitive AHP current (IAHP) was insufficient to block AHP plasticity, suggesting that plasticity is manifested through changes in the apamin-insensitive slow AHP current (sIAHP). These changes were observed in the presence of synaptic blockers, and therefore reflect changes in the intrinsic properties of the neurons. However, no AHP plasticity was observed using KMeth. In summary, these data show that KMeth produces time-dependent changes in basic membrane properties and prevents or obscures activity-dependent reduction of

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

    PubMed

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

    2015-03-01

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

  8. Pyramidal tract neurons receptive to different forelimb joints act differently during locomotion

    PubMed Central

    Stout, Erik E.

    2012-01-01

    During locomotion, motor cortical neurons projecting to the pyramidal tract (PTNs) discharge in close relation to strides. How their discharges vary based on the part of the body they influence is not well understood. We addressed this question with regard to joints of the forelimb in the cat. During simple and ladder locomotion, we compared the activity of four groups of PTNs with somatosensory receptive fields involving different forelimb joints: 1) 45 PTNs receptive to movements of shoulder, 2) 30 PTNs receptive to movements of elbow, 3) 40 PTNs receptive to movements of wrist, and 4) 30 nonresponsive PTNs. In the motor cortex, a relationship exists between the location of the source of afferent input and the target for motor output. On the basis of this relationship, we inferred the forelimb joint that a PTN influences from its somatosensory receptive field. We found that different PTNs tended to discharge differently during locomotion. During simple locomotion shoulder-related PTNs were most active during late stance/early swing, and upon transition from simple to ladder locomotion they often increased activity and stride-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically did not change activity, modulation, or discharge duration on the ladder. Wrist-related PTNs were most active during swing and upon transition to the ladder often decreased activity and increased modulation while reducing discharge duration. These data suggest that during locomotion the motor cortex uses distinct mechanisms to control the shoulder, elbow, and wrist. PMID:22236716

  9. Activity of pyramidal tract neurons in the cat during standing and walking on an inclined plane.

    PubMed

    Karayannidou, A; Beloozerova, I N; Zelenin, P V; Stout, E E; Sirota, M G; Orlovsky, G N; Deliagina, T G

    2009-08-01

    To keep balance when standing or walking on a surface inclined in the roll plane, the cat modifies its body configuration so that the functional length of its right and left limbs becomes different. The aim of the present study was to assess the motor cortex participation in the generation of this left/right asymmetry. We recorded the activity of fore- and hindlimb-related pyramidal tract neurons (PTNs) during standing and walking on a treadmill. A difference in PTN activity at two tilted positions of the treadmill (+/- 15 deg) was considered a positional response to surface inclination. During standing, 47% of PTNs exhibited a positional response, increasing their activity with either the contra-tilt (20%) or the ipsi-tilt (27%). During walking, PTNs were modulated in the rhythm of stepping, and tilts of the supporting surface evoked positional responses in the form of changes to the magnitude of modulation in 58% of PTNs. The contra-tilt increased activity in 28% of PTNs, and ipsi-tilt increased activity in 30% of PTNs. We suggest that PTNs with positional responses contribute to the modifications of limb configuration that are necessary for adaptation to the inclined surface. By comparing the responses to tilts in individual PTNs during standing and walking, four groups of PTNs were revealed: responding in both tasks (30%); responding only during standing (16%); responding only during walking (30%); responding in none of the tasks (24%). This diversity suggests that common and separate cortical mechanisms are used for postural adaptation to tilts during standing and walking.

  10. Changes in Neuronal Excitability by Activated Microglia: Differential Na(+) Current Upregulation in Pyramid-Shaped and Bipolar Neurons by TNF-α and IL-18.

    PubMed

    Klapal, Lars; Igelhorst, Birte A; Dietzel-Meyer, Irmgard D

    2016-01-01

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

  11. Changes in Neuronal Excitability by Activated Microglia: Differential Na+ Current Upregulation in Pyramid-Shaped and Bipolar Neurons by TNF-α and IL-18

    PubMed Central

    Klapal, Lars; Igelhorst, Birte A.; Dietzel-Meyer, Irmgard D.

    2016-01-01

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

  12. Aging-Related Hyperexcitability in CA3 Pyramidal Neurons Is Mediated by Enhanced A-Type K+ Channel Function and Expression

    PubMed Central

    Simkin, Dina; Hattori, Shoai; Ybarra, Natividad; Musial, Timothy F.; Buss, Eric W.; Richter, Hannah; Oh, M. Matthew

    2015-01-01

    Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29–32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K+ channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K+ channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state. SIGNIFICANCE STATEMENT Age-related learning deficits have been attributed, in part, to altered hippocampal pyramidal neuronal function with normal aging. Much evidence has come from work on CA1 neurons, with CA3 neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing. Hence, we conducted a series of experiments to identify the cellular mechanisms that underlie the hyperexcitability reported in the CA3 region. Contrary to CA1 neurons, we demonstrate that postburst afterhyperpolarization is not altered with aging and that aged CA3 pyramidal neurons are able to fire significantly more action potentials and that this is associated with

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

    PubMed

    Sepehri, Hamid; Ganji, Farzaneh

    2016-07-01

    Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead+100mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons' somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl's analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (P<0.01) that was reversed by cotreatment with ascorbic acid. Sholl's analysis revealed a significant increase in apical dendritic branch points near cell body (P<0.05) and a decreased total dendritic length in both apical and basal dendritic trees of CA1 neurons (P<0.05). Ascorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.

  14. Calcium-activated afterhyperpolarizations regulate synchronization and timing of epileptiform bursts in hippocampal CA3 pyramidal neurons.

    PubMed

    Fernández de Sevilla, David; Garduño, Julieta; Galván, Emilio; Buño, Washington

    2006-12-01

    Calcium-activated potassium conductances regulate neuronal excitability, but their role in epileptogenesis remains elusive. We investigated in rat CA3 pyramidal neurons the contribution of the Ca(2+)-activated K(+)-mediated afterhyperpolarizations (AHPs) in the genesis and regulation of epileptiform activity induced in vitro by 4-aminopyridine (4-AP) in Mg(2+)-free Ringer. Recurring spike bursts terminated by prolonged AHPs were generated. Burst synchronization between CA3 pyramidal neurons in paired recordings typified this interictal-like activity. A downregulation of the medium afterhyperpolarization (mAHP) paralleled the emergence of the interictal-like activity. When the mAHP was reduced or enhanced by apamin and EBIO bursts induced by 4-AP were increased or blocked, respectively. Inhibition of the slow afterhyperpolarization (sAHP) with carbachol, t-ACPD, or isoproterenol increased bursting frequency and disrupted burst regularity and synchronization between pyramidal neuron pairs. In contrast, enhancing the sAHP by intracellular dialysis with KMeSO(4) reduced burst frequency. Block of GABA(A-B) inhibitions did not modify the abnormal activity. We describe novel cellular mechanisms where 1) the inhibition of the mAHP plays an essential role in the genesis and regulation of the bursting activity by reducing negative feedback, 2) the sAHP sets the interburst interval by decreasing excitability, and 3) bursting was synchronized by excitatory synaptic interactions that increased in advance and during bursts and decreased throughout the subsequent sAHP. These cellular mechanisms are active in the CA3 region, where epileptiform activity is initiated, and cooperatively regulate the timing of the synchronized rhythmic interictal-like network activity. PMID:16971683

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    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

  17. Enhancement of Synaptic Potentials in Rabbit CA1 Pyramidal Neurons Following Classical Conditioning

    NASA Astrophysics Data System (ADS)

    Loturco, Joseph J.; Coulter, Douglas A.; Alkon, Daniel L.

    1988-03-01

    A synaptic potential elicited by high-frequency stimulation of the Schaffer collaterals was enhanced in hippocampal CA1 pyramidal cells from rabbits that were classically conditioned relative to cells from control rabbits. In addition, confirming previous reports, the after-hyperpolarization was reduced in cells from conditioned animals. We suggest that reduced after-hyperpolarization and enhanced synaptic responsiveness in cells from conditioned animals work in concert to contribute to the functioning of hippocampal CA1 pyramidal cells during classical conditioning.

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

    PubMed Central

    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

  19. Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons

    PubMed Central

    Bishop, Hannah I.; Guan, Dongxu; Bocksteins, Elke; Parajuli, Laxmi Kumar; Murray, Karl D.; Cobb, Melanie M.; Misonou, Hiroaki; Zito, Karen; Foehring, Robert C.

    2015-01-01

    The Kv2 family of voltage-gated potassium channel α subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K+ current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell- and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylation-dependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex. SIGNIFICANCE STATEMENT Neurons within the neocortex are arranged in a laminar architecture and contribute to the input, processing, and/or output of sensory and motor signals in a cell- and layer-specific manner. Neurons of different

  20. Three-dimensional Quantification of Dendritic Spines from Pyramidal Neurons Derived from Human Induced Pluripotent Stem Cells.

    PubMed

    Gouder, Laura; Tinevez, Jean-Yves; Goubran-Botros, Hany; Benchoua, Alexandra; Bourgeron, Thomas; Cloëz-Tayarani, Isabelle

    2015-01-01

    Dendritic spines are small protrusions that correspond to the post-synaptic compartments of excitatory synapses in the central nervous system. They are distributed along the dendrites. Their morphology is largely dependent on neuronal activity, and they are dynamic. Dendritic spines express glutamatergic receptors (AMPA and NMDA receptors) on their surface and at the levels of postsynaptic densities. Each spine allows the neuron to control its state and local activity independently. Spine morphologies have been extensively studied in glutamatergic pyramidal cells of the brain cortex, using both in vivo approaches and neuronal cultures obtained from rodent tissues. Neuropathological conditions can be associated to altered spine induction and maturation, as shown in rodent cultured neurons and one-dimensional quantitative analysis (1). The present study describes a protocol for the 3D quantitative analysis of spine morphologies using human cortical neurons derived from neural stem cells (late cortical progenitors). These cells were initially obtained from induced pluripotent stem cells. This protocol allows the analysis of spine morphologies at different culture periods, and with possible comparison between induced pluripotent stem cells obtained from control individuals with those obtained from patients with psychiatric diseases. PMID:26484791

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

    PubMed Central

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

    2014-01-01

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

  2. Cerebral cortical hypoplasia with abnormal morphology of pyramidal neuron in growth-retarded mouse (grt/grt).

    PubMed

    Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Sato, Chika; Aoyama, Junya; Kobayashi, Tetsuya; Sawada, Kazuhiko

    2014-01-01

    The purpose of this study was to quantitatively characterize structural abnormalities of the cerebrum in a growth-retarded mouse (grt/grt) with a tyrosylprotein sulfotransferase 2 gene defect. Three-dimensional computed tomography (CT) images were obtained from fixed brains of male homogenous grt/grt (n=5) and heterozygous grt/+ (n=5) mice at 15 weeks of age, and volumes of representative cerebral regions were calculated on the basis of those images. Following CT measurements, cryosections of the brain were made, and immunohistochemistry for NeuN and SMI-32 was carried out. By CT-based volumetry, region-specific reductions in volumes were marked in the cerebral cortex and white matter, but not in other cerebral regions of grt/grt. When quantitatively evaluating the shape of the cerebral cortex, the frontooccipital length of the cortex was significantly smaller in grt/grt than in grt/+, whereas the cortical width was not altered in grt/grt. On the other hand, both cortical thickness and density of NeuN-immunopositive neurons in three distinctive cortical regions, i.e., the primary motor cortex, barrel field of primary somatosensory cortex and primary visual cortex, were not different between grt/grt and grt/+. By semi-quantitative immunohistochemical analysis, the intensity of SMI-32 immunostaining was significantly weaker in grt/grt than in grt/+ in the three cortical areas examined. SMI-32 staining was reduced, particularly in layer III pyramidal neurons in grt/grt, while it was sustained in multipolar neurons. The present results suggest that cerebral abnormalities in grt/grt mice are characterized by cortical hypoplasia at the frontooccipital axis with immature pyramidal neurons and insufficient development of callosal fibers.

  3. Early postnatal migration and development of layer II pyramidal neurons in the rodent cingulate/retrosplenial cortex.

    PubMed

    Zgraggen, Eloisa; Boitard, Michael; Roman, Inge; Kanemitsu, Michiko; Potter, Gael; Salmon, Patrick; Vutskits, Laszlo; Dayer, Alexandre G; Kiss, Jozsef Z

    2012-01-01

    The cingulate and retrosplenial regions are major components of the dorsomedial (dm) limbic cortex and have been implicated in a range of cognitive functions such as emotion, attention, and spatial memory. While the structure and connectivity of these cortices are well characterized, little is known about their development. Notably, the timing and mode of migration that govern the appropriate positioning of late-born neurons remain unknown. Here, we analyzed migratory events during the early postnatal period from ventricular/subventricular zone (VZ/SVZ) to the cerebral cortex by transducing neuronal precursors in the VZ/SVZ of newborn rats/mice with Tomato/green fluorescent protein-encoding lentivectors. We have identified a pool of postmitotic pyramidal precursors in the dm part of the neonatal VZ/SVZ that migrate into the medial limbic cortex during the first postnatal week. Time-lapse imaging demonstrates that these cells migrate on radial glial fibers by locomotion and display morphological and behavioral changes as they travel through the white matter and enter into the cortical gray matter. In the granular retrosplenial cortex, these cells give rise to a Satb2+ pyramidal subtype and develop dendritic bundles in layer I. Our observations provide the first insight into the patterns and dynamics of cell migration into the medial limbic cortex. PMID:21625013

  4. Properties of BK-type Ca(+) (+)-dependent K(+) channel currents in medial prefrontal cortex pyramidal neurons in rats of different ages.

    PubMed

    Książek, Aneta; Ladno, Wioletta; Szulczyk, Bartłomiej; Grzelka, Katarzyna; Szulczyk, Paweł

    2013-01-01

    The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca(+) (+) ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker - paxilline (10 μM) - irreversibly decreased the non-inactivating K(+) current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K(+) currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K(+) channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca(+) (+) concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K(+) channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC

  5. Properties of BK-type Ca++-dependent K+ channel currents in medial prefrontal cortex pyramidal neurons in rats of different ages

    PubMed Central

    Książek, Aneta; Ładno, Wioletta; Szulczyk, Bartłomiej; Grzelka, Katarzyna; Szulczyk, Paweł

    2013-01-01

    The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca++ ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker – paxilline (10 μM) – irreversibly decreased the non-inactivating K+ current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K+ currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K+ channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca++ concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K+ channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC pyramidal

  6. How cesium dialysis affects the passive properties of pyramidal neurons: implications for voltage clamp studies of persistent sodium current

    NASA Astrophysics Data System (ADS)

    Fleidervish, Ilya A.; Libman, Lior

    2008-03-01

    In order to accurately understand and model neuronal integration in the brain, we must know the biophysical properties of channels that are located far from the soma, in the axonal and dendritic membranes of central nerve cells. Reliable electrophysiological measurements in these regions are difficult to obtain, because the processes are too tiny to directly study with an electrode. One common strategy is to record with a somatic electrode that contains Cs+, to dialyze the intracellular space with this K+ channel blocker, and thereby to render the neuron electrotonically compact. Does this work? Here, we combine the experimental and modeling techniques to determine the extent to which a whole-cell voltage clamp, established with a Cs+-containing pipette in the soma of a cortical pyramidal cell, attains adequate voltage control of distal neuronal processes. We focus on the low-voltage-activated, slowly inactivating 'persistent' Na+ current (INaP), that plays a crucial role in determining neuronal excitability and synaptic integration.

  7. Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice

    PubMed Central

    2011-01-01

    Background Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions. PMID:21527022

  8. Automated evolutionary optimization of ion channel conductances and kinetics in models of young and aged rhesus monkey pyramidal neurons.

    PubMed

    Rumbell, Timothy H; Draguljić, Danel; Yadav, Aniruddha; Hof, Patrick R; Luebke, Jennifer I; Weaver, Christina M

    2016-08-01

    Conductance-based compartment modeling requires tuning of many parameters to fit the neuron model to target electrophysiological data. Automated parameter optimization via evolutionary algorithms (EAs) is a common approach to accomplish this task, using error functions to quantify differences between model and target. We present a three-stage EA optimization protocol for tuning ion channel conductances and kinetics in a generic neuron model with minimal manual intervention. We use the technique of Latin hypercube sampling in a new way, to choose weights for error functions automatically so that each function influences the parameter search to a similar degree. This protocol requires no specialized physiological data collection and is applicable to commonly-collected current clamp data and either single- or multi-objective optimization. We applied the protocol to two representative pyramidal neurons from layer 3 of the prefrontal cortex of rhesus monkeys, in which action potential firing rates are significantly higher in aged compared to young animals. Using an idealized dendritic topology and models with either 4 or 8 ion channels (10 or 23 free parameters respectively), we produced populations of parameter combinations fitting the target datasets in less than 80 hours of optimization each. Passive parameter differences between young and aged models were consistent with our prior results using simpler models and hand tuning. We analyzed parameter values among fits to a single neuron to facilitate refinement of the underlying model, and across fits to multiple neurons to show how our protocol will lead to predictions of parameter differences with aging in these neurons. PMID:27106692

  9. Induction of plasminogen in rat hippocampal pyramidal neurons by kainic acid.

    PubMed

    Matsuoka, Y; Kitamura, Y; Taniguchi, T

    1998-08-14

    Tissue plasminogen activator (tPA) is used to treat acute stroke, but tPA- and plasminogen-gene-deficient mice exhibit resistance to neurodegeneration. Thus, it is unclear whether the tPA-plasminogen system, an extracellular proteolytic cascade plays a helpful or harmful role, and whether plasminogen is induced by neurodegeneration. In the CA3, kainic acid (KA)-injection caused neuronal damage after 6 h, and almost all of the neurons were lost after 7 days. Plasminogen mRNA was strongly induced 6 h after injection, then gradually decreased, and was very weak at 2 days after injection. Plasminogen protein was expressed after 6 h and localized in abnormally shaped neurons. The in vivo expression of plasminogen was synchronous with morphological changes in neurons. These results suggest that the expression of plasminogen induced by KA-injection may disrupt of neuron-extracellular matrix interaction and thereby contribute to cell death in neurons in the hippocampus.

  10. Differential cycling rates of Kv4.2 channels in proximal and distal dendrites of hippocampal CA1 pyramidal neurons

    PubMed Central

    Nestor, Michael W.; Hoffman, Dax A.

    2010-01-01

    The heterogeneous expression of voltage-gated channels in dendrites suggests that neurons perform local microdomain computations at different regions. It has been shown that A-type K+ channels have a non-uniform distribution along the primary apical dendrite in CA1 pyramidal neurons, increasing with distance from the soma. Kv4.2 channels, which are responsible for the somatodendritic A-type K+ current in CA1 pyramidal neurons, shape local synaptic input and regulate the back-propagation of APs into dendrites. Experiments were performed to test the hypothesis that Kv4.2 channels are differentially trafficked at different regions along the apical dendrite during basal activity and upon stimulation in CA1 neurons. Proximal (50–150 µm from the soma, primary and oblique) and distal (>200 µm) apical dendrites were selected. The fluorescence recovery after photobleaching (FRAP) technique was used to measure basal cycling rates of EGFP-tagged Kv4.2 (Kv4.2g). We found that the cycling rate of Kv4.2 channels was one order of magnitude slower at both primary and oblique dendrites between 50–150 µm from the soma. Kv4.2 channel cycling increased significantly at 200–250 µm from the soma. Expression of a Kv4.2 mutant lacking a phosphorylation site for protein kinase-A (Kv4.2gS552A) abolished this distance-dependent change in channel cycling; demonstrating that phosphorylation by PKA underlies the increased mobility in distal dendrites. Neuronal stimulation by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) treatment increased cycling of Kv4.2 channels significantly at distal sites only. This activity-dependent increase in Kv4.2 cycling at distal dendrites was blocked by expression of Kv4.2gS552A. These results indicate that distance-dependent Kv4.2 mobility is regulated by activity-dependent phosphorylation of Kv4.2 by PKA. PMID:21472817

  11. Numbers, Neurons and Tides, Oh My!

    ERIC Educational Resources Information Center

    Ortiz, Mary Theresa

    2006-01-01

    Mathematical applications to biology are presented in Anatomy & Physiology, General and Marine Biology. Body measurements and anatomical terminology are integrated, and problems involving neuron conduction speed, red blood cells, hemoglobin and glomerular filtration presented. General Biology applications include trans-membrane potential and…

  12. Dynamic FoxG1 expression coordinates the integration of multipolar pyramidal neuron precursors into the cortical plate.

    PubMed

    Miyoshi, Goichi; Fishell, Gord

    2012-06-21

    Pyramidal cells of the cerebral cortex are born in the ventricular zone and migrate through the intermediate zone to enter into the cortical plate. In the intermediate zone, these migrating precursors move tangentially and initiate the extension of their axons by transiently adopting a characteristic multipolar morphology. We observe that expression of the forkhead transcription factor FoxG1 is dynamically regulated during this transitional period. By utilizing conditional genetic strategies, we show that the downregulation of FoxG1 at the beginning of the multipolar cell phase induces Unc5D expression, the timing of which ultimately determines the laminar identity of pyramidal neurons. In addition, we demonstrate that the re-expression of FoxG1 is required for cells to transit out of the multipolar cell phase and to enter into the cortical plate. Thus, the dynamic expression of FoxG1 during migration within the intermediate zone is essential for the proper assembly of the cerebral cortex.

  13. Sex differences in GABA(B)R-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex.

    PubMed

    Marron Fernandez de Velasco, Ezequiel; Hearing, Matthew; Xia, Zhilian; Victoria, Nicole C; Luján, Rafael; Wickman, Kevin

    2015-08-01

    The medial prefrontal cortex (mPFC) has been implicated in multiple disorders characterized by clear sex differences, including schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, and drug addiction. These sex differences likely represent underlying differences in connectivity and/or the balance of neuronal excitability within the mPFC. Recently, we demonstrated that signaling via the metabotropic γ-aminobutyric acid receptor (GABABR) and G protein-gated inwardly-rectifying K(+) (GIRK/Kir3) channels modulates the excitability of the key output neurons of the mPFC, the layer 5/6 pyramidal neurons. Here, we report a sex difference in the GABABR-GIRK signaling pathway in these neurons. Specifically, GABABR-dependent GIRK currents recorded in the prelimbic region of the mPFC were larger in adolescent male mice than in female counterparts. Interestingly, this sex difference was not observed in layer 5/6 pyramidal neurons of the adjacent infralimbic cortex, nor was it seen in young adult mice. The sex difference in GABABR-GIRK signaling is not attributable to different expression levels of signaling pathway components, but rather to a phosphorylation-dependent trafficking mechanism. Thus, sex differences related to some diseases associated with altered mPFC function may be explained in part by sex differences in GIRK-dependent signaling in mPFC pyramidal neurons. PMID:25843643

  14. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  15. Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment

    PubMed Central

    Su, Susan C.; Rudenko, Andrii; Cho, Sukhee; Tsai, Li-Huei

    2013-01-01

    Cyclin-dependent kinase 5 (Cdk5) is associated with synaptic plasticity and cognitive function. Previous reports have demonstrated that Cdk5 is necessary for memory formation, although others have reported Cdk5 conditional knockout mouse models exhibiting enhanced learning and memory. Furthermore, how Cdk5 acts in specific cell populations to affect behavior and cognitive outcomes remains unclear. Here we conduct a behavioral characterization of a forebrain-specific Cdk5 conditional knockout mouse model under the αCaMKII promoter, in which Cdk5 is ablated in excitatory pyramidal neurons of the forebrain. The Cdk5 conditional knockouts exhibit hyperactivitiy in the open field, reduced anxiety, and reduced behavioral despair. Moreover, the Cdk5 conditional knockouts also display impaired spatial learning in the Morris water maze and are severely impaired in contextual fear memory, which correspond to deficits in synaptic transmission. Remarkably, the hyperactivity of the Cdk5 conditional knockouts can be ameliorated by the administration of lithium chloride, an inhibitor of GSK3β signaling. Collectively, our data reveal that Cdk5 ablation from forebrain excitatory neurons results in deleterious effects on emotional and cognitive behavior and highlight a key role for Cdk5 in regulating the GSK3β signaling pathway. PMID:23850563

  16. ACTIVITY-DEPENDENT STRUCTURAL PLASTICITY AFTER AVERSIVE EXPERIENCES IN AMYGDALA AND AUDITORY CORTEX PYRAMIDAL NEURONS

    PubMed Central

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-01-01

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc− neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc− neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity. PMID:27155146

  17. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    PubMed

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity.

  18. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    PubMed

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity. PMID:27155146

  19. Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

    PubMed Central

    Hong, Zhiwen; Tian, Yujing; Qi, Mengwen; Li, Yingchun; Du, Yimei; Chen, Lei; Liu, Wentao; Chen, Ling

    2016-01-01

    The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (IGABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK) and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited IGABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K) agonist. GSK1016790A-induced inhibition of IGABA was also significantly attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation. PMID:27616980

  20. Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

    PubMed Central

    Hong, Zhiwen; Tian, Yujing; Qi, Mengwen; Li, Yingchun; Du, Yimei; Chen, Lei; Liu, Wentao; Chen, Ling

    2016-01-01

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

  1. Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons.

    PubMed

    Hong, Zhiwen; Tian, Yujing; Qi, Mengwen; Li, Yingchun; Du, Yimei; Chen, Lei; Liu, Wentao; Chen, Ling

    2016-01-01

    The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (I GABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK) and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited I GABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K) agonist. GSK1016790A-induced inhibition of I GABA was also significantly attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation. PMID:27616980

  2. Impaired Memory and Evidence of Histopathology in CA1 Pyramidal Neurons through Injection of Aβ1-42 Peptides into the Frontal Cortices of Rat

    PubMed Central

    Eslamizade, Mohammad Javad; Madjd, Zahra; Rasoolijazi, Homa; Saffarzadeh, Fatemeh; Pirhajati, Vahid; Aligholi, Hadi; Janahmadi, Mahyar; Mehdizadeh, Mehdi

    2016-01-01

    Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-β peptides (Aβ) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following Aβ injection. Furthermore, Nissl staining showed that Aβ neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Aβ treated rats. Moreover, higher NF-κB immunoreactive CA1 pyramidal neurons were remarkably observed in Aβ treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Aβ-induced increased NF-κB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of Aβ into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by Aβ. PMID:27303597

  3. Synaptic relationships between a multipolar stellate cell and a pyramidal neuron in the rat visual cortex. A combined Golgi-electron microscope study.

    PubMed

    Peters, A; Proskauer, C C

    1980-04-01

    Two synapsing and impregnated neurons in the rat visual cortex have been examined by a combined Golgi-electron microscope technique in which the Golgi precipitate is replaced by gold particles. One of the neurons is a stellate cell with smooth dendrites and a well impregnated axon, while the other is a layer III pyramidal neuron. Light microscopy showed some boutons from the axonal plexus of the stellate cell closely apposed to the soma and dendrites of the pyramid and it was predicted that synapses were present at these sites. An electron microscopic examination of serial thin sections, in which the profiles of the impregnated neurons are marked by their content of gold particles, showed most of these predicted synapses to exist. Indeed, axon terminals of the stellate cell formed five symmetric synapses with the cell body of the pyramid, one with the apical dendritic shaft and three with basal dendrites. Reasons are given for believing these synapses to be inhibitory. In addition, it was found that one of the axon terminals of the stellate cell synapsed with one of that cell's own dendrites. The significance of this finding is discussed.

  4. Postnatal maternal separation enhances tonic GABA current of cortical layer 5 pyramidal neurons in juvenile rats and promotes genesis of GABAergic neurons in neocortical molecular layer and subventricular zone in adult rats.

    PubMed

    Feng, Mei; Sheng, Guoxia; Li, Zhongxia; Wang, Jiangping; Ren, Keming; Jin, Xiaoming; Jiang, Kewen

    2014-03-01

    Postnatal maternal separation (PMS) has been shown to be associated with an increased vulnerability to psychiatric illnesses in adulthood. However, the underlying neurological mechanisms are not well understood. Here we evaluated its effects on neurogenesis and tonic GABA currents of cortical layer 5 (L5) pyramidal neurons. PMS not only increased cell proliferation in the subventricular zone, cortical layer 1 and hippocampal dentate gyrus in the adult brain, but also promoted the newly generated cells to differentiate into GABAergic neurons, and PMS adult brain maintained higher ratios of GABAergic neurons in the survival of newly generated cells within 5 days immediately post PMS. Additionally, PMS increased the tonic currents at P7-10 and P30-35 in cortical L5 pyramidal cells. Our results suggest that the newly generated GABAergic neurons and the low GABA concentration-activated tonic currents may be involved in the development of psychiatric disorders after PMS.

  5. Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons.

    PubMed

    Daoudal, Gael; Hanada, Yasuhiro; Debanne, Dominique

    2002-10-29

    Integration of synaptic excitation to generate an action potential (excitatory postsynaptic potential-spike coupling or E-S coupling) determines the neuronal output. Bidirectional synaptic plasticity is well established in the hippocampus, but whether active synaptic integration can display potentiation and depression remains unclear. We show here that synaptic depression is associated with an N-methyl-d-aspartate receptor-dependent and long-lasting depression of E-S coupling. E-S depression is input-specific and is expressed in the presence of gamma-aminobutyric acid type A and B receptor antagonists. In single neurons, E-S depression is observed without modification of postsynaptic passive properties. We conclude that a decrease in intrinsic excitability underlies E-S depression and is synergic with glutamatergic long-term depression.

  6. A Distinct Class of Slow (∼0.2–2 Hz) Intrinsically Bursting Layer 5 Pyramidal Neurons Determines UP/DOWN State Dynamics in the Neocortex

    PubMed Central

    Gunner, David; Bao, Ying; Connelly, William M.; Isaac, John T.R.; Hughes, Stuart W.; Crunelli, Vincenzo

    2015-01-01

    During sleep and anesthesia, neocortical neurons exhibit rhythmic UP/DOWN membrane potential states. Although UP states are maintained by synaptic activity, the mechanisms that underlie the initiation and robust rhythmicity of UP states are unknown. Using a physiologically validated model of UP/DOWN state generation in mouse neocortical slices whereby the cholinergic tone present in vivo is reinstated, we show that the regular initiation of UP states is driven by an electrophysiologically distinct subset of morphologically identified layer 5 neurons, which exhibit intrinsic rhythmic low-frequency burst firing at ∼0.2–2 Hz. This low-frequency bursting is resistant to block of glutamatergic and GABAergic transmission but is absent when slices are maintained in a low Ca2+ medium (an alternative, widely used model of cortical UP/DOWN states), thus explaining the lack of rhythmic UP states and abnormally prolonged DOWN states in this condition. We also characterized the activity of various other pyramidal and nonpyramidal neurons during UP/DOWN states and found that an electrophysiologically distinct subset of layer 5 regular spiking pyramidal neurons fires earlier during the onset of network oscillations compared with all other types of neurons recorded. This study, therefore, identifies an important role for cell-type-specific neuronal activity in driving neocortical UP states. PMID:25855163

  7. Activity-dependent bidirectional regulation of GABAA receptor channels by the 5-HT4 receptor-mediated signalling in rat prefrontal cortical pyramidal neurons

    PubMed Central

    Cai, Xiang; Flores-Hernandez, Jorge; Feng, Jian; Yan, Zhen

    2002-01-01

    Emerging evidence has implicated a potential role for 5-HT4 receptors in cognition and anxiolysis. One of the main target structures of 5-HT4 receptors on ‘cognitive and emotional’ pathways is the prefrontal cortex (PFC). As GABAergic signalling plays a key role in regulating PFC functions, we examined the effect of 5-HT4 receptors on GABAA receptor channels in PFC pyramidal neurons. Application of 5-HT4 receptor agonists produced either an enhancement or a reduction of GABA-evoked currents in PFC neurons, which are both mediated by anchored protein kinase A (PKA). Although PKA phosphorylation of GABAA receptor β3 or β1 subunits leads to current enhancement or reduction respectively in heterologous expression systems, we found that β3 and β1 subunits are co-expressed in PFC pyramidal neurons. Interestingly, altering PKA activation levels can change the direction of the dual effect, switching enhancement to reduction and vice versa. In addition, increased neuronal activity in PFC slices elevated the PKA activation level, changing the enhancing effect of 5-HT4 receptors on the amplitude of GABAergic inhibitory postsynaptic currents (IPSCs) to a reduction. These results suggest that 5-HT4 receptors can modulate GABAergic signalling bidirectionally, depending on the basal PKA activation levels that are determined by neuronal activity. This modulation provides a unique and flexible mechanism for 5-HT4 receptors to dynamically regulate synaptic transmission and neuronal excitability in the PFC network. PMID:11986365

  8. Coordinated scaling of cortical and cerebellar numbers of neurons.

    PubMed

    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.

  9. Coordinated Scaling of Cortical and Cerebellar Numbers of Neurons

    PubMed Central

    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

  10. Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

    PubMed Central

    Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

    2015-01-01

    Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

  11. Inhibitory control of linear and supralinear dendritic excitation in CA1 pyramidal neurons.

    PubMed

    Müller, Christina; Beck, Heinz; Coulter, Douglas; Remy, Stefan

    2012-09-01

    The transformation of dendritic excitatory synaptic inputs to axonal action potential output is the fundamental computation performed by all principal neurons. We show that in the hippocampus this transformation is potently controlled by recurrent inhibitory microcircuits. However, excitatory input on highly excitable dendritic branches could resist inhibitory control by generating strong dendritic spikes and trigger precisely timed action potential output. Furthermore, we show that inhibition-sensitive branches can be transformed into inhibition-resistant, strongly spiking branches by intrinsic plasticity of branch excitability. In addition, we demonstrate that the inhibitory control of spatially defined dendritic excitation is strongly regulated by network activity patterns. Our findings suggest that dendritic spikes may serve to transform correlated branch input into reliable and temporally precise output even in the presence of inhibition.

  12. Reduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer.

    PubMed Central

    Aiken, S. P.; Lampe, B. J.; Murphy, P. A.; Brown, B. S.

    1995-01-01

    1. Linopirdine (DuP 996) has been shown to enhance depolarization-induced release of several neurotransmitters in the CNS through a mechanism which may involve K+ channel blockade. The electrophysiological effects of linopirdine were therefore investigated directly, by use of conventional voltage recording and single electrode voltage-clamp. 2. Linopirdine (10 microM) reduced spike frequency adaptation (SFA) in rat hippocampal CA1 pyramidal neurones in vitro. The reduction of SFA comprised an increase in number of spikes and a reduction in inter-spike intervals after the first, but with no effect on time to first spike. Linopirdine also caused a voltage-dependent depolarization of resting membrane potential (RMP). 3. M-current (IM), a current known to underlie SFA and to set RMP, was blocked by linopirdine in a reversible, concentration-dependent manner (IC50 = 8.5 microM). This block was not reversed by atropine (10 microM). 4. Linopirdine did not affect IQ, the slow after-hyperpolarization following a spike train, or spike duration. 5. Linopirdine may represent a novel class of K+ blocker with relative selectivity for the M-current. This block of IM is consistent with the suggestion from a previous study that linopirdine may affect a tetraethylammonium-sensitive channel, and it could be speculated that IM blockade may be involved with the enhancement of neurotransmitter release by linopirdine. PMID:7582539

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2004-11-01

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

  15. Cell-attached single-channel recordings in intact prefrontal cortex pyramidal neurons reveal compartmentalized D1/D5 receptor modulation of the persistent sodium current

    PubMed Central

    Gorelova, Natalia; Seamans, Jeremy K.

    2015-01-01

    The persistent Na+ current (INap) is believed to be an important target of dopamine modulation in prefrontal cortex (PFC) neurons. While past studies have tested the effects of dopamine on INap, the results have been contradictory largely because of difficulties in measuring INap using somatic whole-cell recordings. To circumvent these confounds we used the cell-attached patch-clamp technique to record single Na+ channels from the soma, proximal dendrite (PD) or proximal axon (PA) of intact prefrontal layer V pyramidal neurons. Under baseline conditions, numerous well resolved Na+ channel openings were recorded that exhibited an extrapolated reversal potential of 73 mV, a slope conductance of 14–19 pS and were blocked by tetrodotoxin (TTX). While similar in most respects, the propensity to exhibit prolonged bursts lasting >40 ms was many fold greater in the axon than the soma or dendrite. Bath application of the D1/D5 receptor agonist SKF81297 shifted the ensemble current activation curve leftward and increased the number of late events recorded from the PD but not the soma or PA. However, the greatest effect was on prolonged bursting where the D1/D5 receptor agonist increased their occurrence 3 fold in the PD and nearly 7 fold in the soma, but not at all in the PA. As a result, D1/D5 receptor activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region. Therefore, D1/D5 receptor modulation appears to be targeted mainly to Na+ channels in the PD/soma and not the PA. By circumventing the pitfalls of previous attempts to study the D1/D5 receptor modulation of INap, we demonstrate conclusively that D1/D5 receptor activation can increase the INap generated proximally, however questions still remain as to how D1/D5 receptor modulates Na+ currents in the more distal initial segment where most of the INap is normally generated. PMID:25729354

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

    PubMed

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

    2015-07-01

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

  17. Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.

    PubMed Central

    Nishikawa, M; Kimura, S; Akaike, N

    1994-01-01

    1. The effect of docosahexaenoic acid (DHA) on N-methyl-D-aspartic acid (NMDA) responses in the presence of glycine was investigated in pyramidal neurons acutely dissociated from rat cerebral cortex in whole-cell and single channel configurations. 2. DHA potentiated the NMDA-induced response but reduced the non-NMDA (kainate-induced) response in a concentration-dependent manner at a holding potential of -60 mV under voltage-clamp conditions. 3. Arachidonic acid (AA) also potentiated the NMDA-induced response in a manner similar to DHA. Oleic acid caused a slight potentiation. However, other polyunsaturated and saturated fatty acids had no such effects. 4. The facilitatory action of DHA on the NMDA-induced response was not affected by adding inhibitors of cyclo-oxygenase, lipoxygenase or phospholipase A2, suggesting that DHA may exert its facilitatory effect directly on the NMDA receptor. 5. The facilitatory action of DHA was observed in the presence of a saturating dose of NMDA. Moreover, a detailed analysis of the NMDA receptor-operated single channel currents revealed that, in the presence of DHA, the open probability of the channel increased without changing the conductance, indicating that DHA may act by binding directly to a novel site on the NMDA receptor or by altering the lipid environment of the NMDA receptor and thereby potentiating the response to NMDA. 6. The results are discussed in terms of the possibility that DHA may play an important role in the genesis of long-term potentiation, at least that involving the activation of NMDA receptors. PMID:7514666

  18. Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome

    PubMed Central

    Wood, Lydia; Shepherd, Gordon M. G.

    2010-01-01

    Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here, we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in motor-frontal cortex of male hemizygous MeCP2-null mice at 3–4 weeks of age. We mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser scanning photostimulation, and compared synaptic input maps recorded from MeCP2-null and wild type (WT) mice. Local excitatory input was significantly reduced in the mutants. The strongest phenotype was observed for lateral (horizontal, intralaminar) inputs, that is, L2/3→2/3 inputs, which showed a large reduction in MeCP2−/y animals. Neither the amount of local inhibitory input to these L2/3 pyramidal neurons nor their intrinsic electrophysiological properties differed by genotype. Our findings provide further evidence that excitatory networks are selectively reduced in RTT. We discuss our findings in the context of recently published parallel studies using selective MeCP2 knockdown in individual L2/3 neurons. PMID:20138994

  19. Run-down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat.

    PubMed Central

    Harata, N; Wu, J; Ishibashi, H; Ono, K; Akaike, N

    1997-01-01

    1. The effect of experimental ischaemia on the response to gamma-aminobutyric acid (GABA) was assessed in acutely dissociated CA1 pyramidal neurones of rats, using the patch-clamp technique. 2. Rapid application of 3 x 10(-5) M GABA induced a bicuculline-sensitive inward Cl- current (IGABA) at a holding potential (Vh) of -44 mV. The peak amplitude of IGABA showed a time-dependent decrease (run-down) when it was recorded with the conventional whole-cell mode without internal ATP. The run-down was not observed when the intracellular ATP concentration ([ATP]i) was maintained by the nystatin-perforated recording with an intracellular Na+ concentration ([Na+]i) of 0 mM. 3. When [Na+]i was increased to more than 30 mM, the IGABA run-down was observed even with the nystatin-perforated recording. 4. The IGABA run-down observed at 60 mM [Na+]i with the nystatin method was further enhanced under experimental ischaemia without changes in the reversal potential of IGABA. The enhanced run-down was suppressed by application of the Na+,K(+)-ATPase inhibitors, ouabain and SPAI-1. 5. IGABA run-down during ischaemia was also accompanied by an outward holding current and a concomitant increase in intracellular free Ca2+ concentration ([Ca2+]i) in 48.5% of the neurones. The outward current was a Ca(2+)-activated K+ current, which was blocked by 3 x 10(-7) M charybdotoxin. 6. In the inside-out mode of the single-channel analysis, GABA activated three subconductance states with conductances of 33.4, 22.7 and 15.2 pS. Reduction of ATP concentration from 2 to 0 mM on the intracellular side suppressed the channel activities, while an increase in Ca2+ concentration from 0.7 x 10(-9) to 1.1 x 10(-6) M had no effect. 7. These results suggest that ischaemia induces the run-down of the postsynaptic GABA response at the GABAA receptor level, and that this run-down is triggered by a decrease in [ATP]i. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9161985

  20. Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

    PubMed

    Fogarty, Matthew J; Mu, Erica W H; Noakes, Peter G; Lavidis, Nickolas A; Bellingham, Mark C

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper (corticospinal) and lower motor neurons (MNs) with progressive muscle weakness. This incurable disease is clinically heterogeneous and its aetiology remains unknown. Increased excitability of corticospinal MNs has been observed prior to symptoms in human and rodent studies. Increased excitability has been correlated with structural changes in neuronal dendritic arbors and spines for decades. Here, using a modified Golgi-Cox staining method, we have made the first longitudinal study examining the dendrites of pyramidal neurons from the motor cortex, medial pre-frontal cortex, somatosensory cortex and entorhinal cortex of hSOD1(G93A) (SOD1) mice compared to wild-type (WT) littermate controls at postnatal (P) days 8-15, 28-35, 65-75 and 120. Progressive decreases in dendritic length and spine density commencing at pre-symptomatic ages (P8-15 or P28-35) were observed in layer V pyramidal neurons within the motor cortex and medial pre-frontal cortex of SOD1 mice compared to WT mice. Spine loss without concurrent dendritic pathology was present in the pyramidal neurons of the somatosensory cortex from disease-onset (P65-75). Our results from the SOD1 model suggest that dendritic and dendritic spine changes foreshadow and underpin the neuromotor phenotypes present in ALS and may contribute to the varied cognitive, executive function and extra-motor symptoms commonly seen in ALS patients. Determining if these phenomena are compensatory or maladaptive may help explain differential susceptibility of neurons to degeneration in ALS. PMID:27488828

  1. Voltage-clamp analysis of the potentiation of the slow Ca2+-activated K+ current in hippocampal pyramidal neurons.

    PubMed

    Borde, M; Bonansco, C; Fernández de Sevilla, D; Le Ray, D; Buño, W

    2000-01-01

    Exploring the principles that govern activity-dependent changes in excitability is an essential step to understand the function of the nervous system, because they act as a general postsynaptic control mechanism that modulates the flow of synaptic signals. We show an activity-dependent potentiation of the slow Ca2+-activated K+ current (sl(AHP)) which induces sustained decreases in the excitability in CA1 pyramidal neurons. We analyzed the sl(AHP) using the slice technique and voltage-clamp recordings with sharp or patch-electrodes. Using sharp electrodes-repeated activation with depolarizing pulses evoked a prolonged (8-min) potentiation of the amplitude (171%) and duration (208%) of the sl(AHP). Using patch electrodes, early after entering the whole-cell configuration (<20 min), responses were as those reported above. However, although the sl(AHP) remained unchanged, its potentiation was markedly reduced in later recordings, suggesting that the underlying mechanisms were rapidly eliminated by intracellular dialysis. Inhibition of L-type Ca2+ current by nifedipine (20 microM) markedly reduced the sl(AHP) (79%) and its potentiation (55%). Ryanodine (20 microM) that blocks the release of intracellular Ca2+ also reduced sl(AHP) (29%) and its potentiation (25%). The potentiation of the sl(AHP) induced a marked and prolonged (>50%; approximately equals 8 min) decrease in excitability. The results suggest that sl(AHP) is potentiated as a result of an increased intracellular Ca2+ concentration ([Ca2+]i) following activation of voltage-gated L-type Ca2+ channels, aided by the subsequent release of Ca2+ from intracellular stores. Another possibility is that repeated activation increases the Ca2+-binding capacity of the channels mediating the sl(AHP). This potentiation of the sl(AHP) could be relevant in hippocampal physiology, because the changes in excitability it causes may regulate the induction threshold of the long-term potentiation of synaptic efficacy. Moreover, the

  2. Pyramidal Neurons in Rat Prefrontal Cortex Projecting to Ventral Tegmental Area and Dorsal Raphe Nucleus Express 5-HT2A Receptors

    PubMed Central

    Vázquez-Borsetti, Pablo; Cortés, Roser

    2009-01-01

    The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotics modulate cortico-limbic circuits mainly through subcortical D2 receptor blockade, whereas second generation (atypical) antipsychotics preferentially target cortical 5-HT receptors. Anatomical and functional evidence supports a PFC-based control of the brainstem monoaminergic nuclei. Using a combination of retrograde tracing experiments and in situ hybridization we report that a substantial proportion of PFC pyramidal neurons projecting to the dorsal raphe (DR) and/or ventral tegmental area (VTA) express 5-HT2A receptors. Cholera-toxin B application into the DR and the VTA retrogradely labeled projection neurons in the medial PFC (mPFC) and in orbitofrontal cortex (OFC). In situ hybridization of 5-HT2A receptor mRNA in the same tissue sections labeled a large neuronal population in mPFC and OFC. The percentage of DR-projecting neurons expressing 5-HT2A receptor mRNA was ∼60% in mPFC and ∼75% in OFC (n = 3). Equivalent values for VTA-projecting neurons were ∼55% in both mPFC and ventral OFC. Thus, 5-HT2A receptor activation/blockade in PFC may have downstream effects on dopaminergic and serotonergic systems via direct descending pathways. Atypical antipsychotics may distally modulate monoaminergic cells through PFC 5-HT2A receptor blockade, presumably decreasing the activity of neurons receiving direct cortical inputs. PMID:19029064

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

    PubMed

    Malik, Ruchi; Chattarji, Sumantra

    2012-03-01

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

  4. Validation of optical voltage reporting by the genetically encoded voltage indicator VSFP-Butterfly from cortical layer 2/3 pyramidal neurons in mouse brain slices

    PubMed Central

    Empson, Ruth M; Goulton, Chelsea; Scholtz, David; Gallero-Salas, Yasir; Zeng, Hongkui; Knöpfel, Thomas

    2015-01-01

    Understanding how behavior emerges from brain electrical activity is one of the ultimate goals of neuroscience. To achieve this goal we require methods for large-scale recording of the electrical activity of specific neuronal circuits. A very promising approach is to use optical reporting of membrane voltage transients, particularly if the voltage reporter is genetically targeted to specific neuronal populations. Targeting in this way allows population signals to be recorded and interpreted without blindness to neuronal diversity. Here, we evaluated the voltage-sensitive fluorescent protein, VSFP Butterfly 2.1, a genetically encoded voltage indicator (GEVI), for monitoring electrical activity of layer 2/3 cortical pyramidal neurons in mouse brain slices. Standard widefield fluorescence and two-photon imaging revealed robust, high signal-to-noise ratio read-outs of membrane voltage transients that are predominantly synaptic in nature and can be resolved as discrete areas of synaptically connected layer 2/3 neurons. We find that targeted expression of this GEVI in the cortex provides a flexible and promising tool for the analysis of L2/3 cortical network function. PMID:26229003

  5. Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy

    PubMed Central

    Booth, Clair A.; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W.; Randall, Andrew D.

    2016-01-01

    The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. PMID:26758828

  6. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors.

    PubMed

    Caraiscos, Valerie B; Elliott, Erin M; You-Ten, Kong E; Cheng, Victor Y; Belelli, Delia; Newell, J Glen; Jackson, Michael F; Lambert, Jeremy J; Rosahl, Thomas W; Wafford, Keith A; MacDonald, John F; Orser, Beverley A

    2004-03-01

    The principal inhibitory neurotransmitter in the mammalian brain, gamma-aminobutyric acid (GABA), is thought to regulate memory processes by activating transient inhibitory postsynaptic currents. Here we describe a nonsynaptic, tonic form of inhibition in mouse CA1 pyramidal neurons that is generated by a distinct subpopulation of GABA type A receptors (GABA(A)Rs). This tonic inhibitory conductance is predominantly mediated by alpha5 subunit-containing GABA(A)Rs (alpha5GABA(A)Rs) that have different pharmacological and kinetic properties compared to postsynaptic receptors. GABA(A)Rs that mediate the tonic conductance are well suited to detect low, persistent, ambient concentrations of GABA in the extracellular space because they are highly sensitive to GABA and desensitize slowly. Moreover, the tonic current is highly sensitive to enhancement by amnestic drugs. Given the restricted expression of alpha5GABA(A)Rs to the hippocampus and the association between reduced alpha5GABA(A)R function and improved memory performance in behavioral studies, our results suggest that tonic inhibition mediated by alpha5GABA(A)Rs in hippocampal pyramidal neurons plays a key role in cognitive processes.

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

    PubMed Central

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

    2014-01-01

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

  8. Resolution of Nested Neuronal Representations Can Be Exponential in the Number of Neurons

    NASA Astrophysics Data System (ADS)

    Mathis, Alexander; Herz, Andreas V. M.; Stemmler, Martin B.

    2012-07-01

    Collective computation is typically polynomial in the number of computational elements, such as transistors or neurons, whether one considers the storage capacity of a memory device or the number of floating-point operations per second of a CPU. However, we show here that the capacity of a computational network to resolve real-valued signals of arbitrary dimensions can be exponential in N, even if the individual elements are noisy and unreliable. Nested, modular codes that achieve such high resolutions mirror the properties of grid cells in vertebrates, which underlie spatial navigation.

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

    PubMed

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

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. PMID:27568058

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

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID:22065958

  11. Direct and indirect interactions between cannabinoid CB1 receptor and group II metabotropic glutamate receptor signalling in layer V pyramidal neurons from the rat prefrontal cortex.

    PubMed

    Barbara, Jean-Gaël; Auclair, Nathalie; Roisin, Marie-Paule; Otani, Satoru; Valjent, Emmanuel; Caboche, Jocelyne; Soubrie, Philippe; Crepel, Francis

    2003-03-01

    At proximal synapses from layer V pyramidal neurons from the rat prefrontal cortex, activation of group II metabotropic glutamate receptors (group II mGlu) by (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine (DCG IV) induced a long-lasting depression of excitatory postsynaptic currents. Paired-pulse experiments suggested that the depression was expressed presynaptically. Activation of type 1 cannabinoid receptors (CB1) by WIN 55,212-2 occluded the DCG IV-induced depression in a mutually occlusive manner. At the postsynaptic level, WIN 55,212-2 and DCG IV were also occlusive for the activation of extracellular signal-regulated kinase. The postsynaptic localization of active extracellular signal-regulated kinase was confirmed by immunocytochemistry after activation of CB1 receptors. However, phosphorylation of extracellular signal-regulated kinase in layer V pyramidal neurons was dependent on the activation of N-methyl-d-aspartate receptors, consequently to a release of glutamate in the local network. Group II mGlu were also shown to be involved in long-term changes in synaptic plasticity induced by high frequency stimulations. The group II mGlu antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester (MSOPPE) favoured long-term depression. However, no interaction was found between MSOPPE, WIN 55,212-2 and the CB1 receptor antagonist SR 141716A on the modulation of long-term depression or long-term potentiation and the effects of these drugs were rather additive. We suggest that CB1 receptor and group II mGlu signalling may interact through a presynaptic mechanism in the induction of a DCG IV-induced depression. Postsynaptically, an indirect interaction occurs for activation of extracellular signal-regulated kinase. However, none of these interactions seem to play a role in synaptic plasticities induced with high frequency stimulations.

  12. Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake

    PubMed Central

    Warthen, Daniel M.; Lambeth, Philip S.; Ottolini, Matteo; Shi, Yingtang; Barker, Bryan Scot; Gaykema, Ronald P.; Newmyer, Brandon A.; Joy-Gaba, Jonathan; Ohmura, Yu; Perez-Reyes, Edward; Güler, Ali D.; Patel, Manoj K.; Scott, Michael M.

    2016-01-01

    The medial prefrontal cortex (mPFC) is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons (PN), which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting PN in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using designer receptors exclusively activated by designer drugs (DREADD) enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects on affect and food intake. Specifically, activation of mPFC PN enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC PN had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide (NO) synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control. PMID:27065827

  13. Neonatal alcohol exposure and the hippocampus in developing male rats: effects on behaviorally induced CA1 c-Fos expression, CA1 pyramidal cell number, and contextual fear conditioning

    PubMed Central

    Murawski, Nathen J.; Klintsova, Anna Y.; Stanton, Mark E.

    2012-01-01

    Rats exposed to a high binge-like dose of alcohol over postnatal days (PD) 4-9 show reductions in CA1 pyramidal cells and impairments on behavioral tasks that depend on the hippocampus. We first examined hippocampal c-Fos expression as a marker of neuronal activity in normally developing rats following different phases of the context preexposure facilitation effect (CPFE) paradigm (Exp. 1). During the CPFE, preexposure to the training context facilitates contextual conditioning to an immediate shock given on a subsequent occasion. We then examined the relationship between CPFE impairment, hippocampal cell loss and c-Fos expression in rats exposed to alcohol over PD 4-9 (Exp. 2). Normally developing (Exp. 1), sham-intubated control (SI), and PD 4-9 alcohol-exposed (4.00g and 5.25g/kg/day; Exp. 2) juvenile male rats were trained on the CPFE. The CPFE occurs over three phases separated by 24h. Starting on PD 31, rats were preexposed to Context A or Context B for five minutes. 24h later, all rats received an immediate, 1.5 mA foot shock in Context A. Finally, rats were tested for contextual conditioning in Context A on PD 33. Normally developing and SI rats preexposed to Context A showed enhanced contextual fear compared to those preexposed to Context B (Exp. 1) or alcohol-exposed rats preexposed to Context A (Exp. 2). Rats were sacrificed 2h following different phases of the CPFE and processed for c-Fos immunohistochemistry (Exp. 1 and 2) and CA1 pyramidal cell quantification (Exp. 2). In Exp. 1, c-Fos+ cells in the DG were consistently high among rats preexposed to Context A (Pre), Context B (No Pre), or sacrificed directly from their home cage (Home) and did not differ across CPFE phases. CA3 and CA1 c-Fos+ cells were highest during preexposure and decreased across training phases, with Group No Pre showing greater numbers of c-Fos+ cells during training than Group Pre and Controls. In Exp. 2, SI rats had greater numbers of CA1 c-Fos+ cells compared alcohol

  14. Specific Targeting of the Basolateral Amygdala to Projectionally Defined Pyramidal Neurons in Prelimbic and Infralimbic Cortex123

    PubMed Central

    Ferreira, Ashley N.

    2016-01-01

    Abstract Adjacent prelimbic (PL) and infralimbic (IL) regions in the medial prefrontal cortex have distinct roles in emotional learning. A complete mechanistic understanding underlying this dichotomy remains unclear. Here we explored targeting of specific PL and IL neurons by the basolateral amygdala (BLA), a limbic structure pivotal in pain and fear processing. In mice, we used retrograde labeling, brain-slice recordings, and adenoviral optogenetics to dissect connectivity of ascending BLA input onto PL and IL neurons projecting to the periaqueductal gray (PAG) or the amygdala. We found differential targeting of BLA projections to PL and IL cortex. Activating BLA projections evoked excitatory and inhibitory responses in cortico-PAG (CP) neurons in layer 5 (L5) of both PL and IL cortex. However, all inhibitory responses were polysynaptic and monosynaptic BLA input was stronger to CP neurons in IL cortex. Conversely, the BLA preferentially targeted corticoamygdalar (CA) neurons in layer 2 (L2) of PL over IL cortex. We also reveal that BLA input is projection specific by showing preferential targeting of L5 CP neurons over neighboring L3/5 CA neurons in IL cortex. We conclude by showing that BLA input is laminar-specific by producing stronger excitatory responses CA neurons in L3/5 compared with L2 in IL cortex. Collectively, this study reveals differential targeting of the BLA to PL and IL cortex, which depends both on laminar location and projection target of cortical neurons. Overall, our findings should have important implications for understanding the processing of pain and fear input by the PL and IL cortex. PMID:27022632

  15. The reduction of EPSC amplitude in CA1 pyramidal neurons by the peroxynitrite donor SIN-1 requires Ca2+ influx via postsynaptic non-L-type voltage gated calcium channels.

    PubMed

    Zhaowei, Liu; Yongling, Xie; Jiajia, Yang; Zhuo, Yang

    2014-02-01

    The peroxynitrite free radical (ONOO(-)) modulation of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) was investigated in rat CA1 pyramidal neurons using the whole-cell patch clamp technique. SIN-1(3-morpholino-sydnonimine), which can lead the simultaneous generation of superoxide anion and nitric oxide, and then form the highly reactive species ONOO(-), induced dose-dependent inhibition in amplitudes of both mEPSCs and sEPSCs. The SIN-1 action on mEPSC amplitude was completely blocked by U0126, a selective MEK inhibitor, suggesting that MEK contributed to the action of ONOO(-) on mEPSCs. The effect of SIN-1 was completely occluded either in the presence of the calcium chelator EGTA or the non-selective calcium channel antagonist Cd(2+). Furthermore, the application of nifedipine (20 μM), the L-type calcium channel blocker, had no effect on the ONOO(-)-induced decrease in mEPSC amplitude, excluding a role for L-type voltage-gated Ca(2+) channels in this process. SIN-1 inhibited the frequency of sEPSCs but had no effect on mEPSC frequency, which suggested a presynaptic action potential-dependent the action of ONOO(-) at CA1 pyramidal neuron synapses. The best-known glutamatergic input to CA1 pyramidal neurons is via Schaffer collaterals from CA3 area. However, no changes were observed in slices treated with SIN-1 on the spontaneous firing rates of CA3 pyramidal neurons. These findings suggested that SIN-1 inhibited glutamatergic synaptic transmission of CA1 pyramidal neurons by a postsynaptic non-L-type voltage gated calcium channel-dependent mechanism.

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

    PubMed

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

    2015-11-01

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

  17. Histamine H3 receptor activation decreases kainate-induced hippocampal gamma oscillations in vitro by action potential desynchronization in pyramidal neurons

    PubMed Central

    Andersson, Richard; Lindskog, Maria; Fisahn, André

    2010-01-01

    The study of rhythmic electrical activity in slice preparations has generated important insights into neural network function. While the synaptic mechanisms involved in the generation of in vitro network oscillations have been studied widely, little is known about the modulatory influence exerted on rhythmic activity in neuronal networks by neuropeptides and biogenic amines. Gamma oscillations play an important role in cognitive processes and are altered or disrupted in disorders such as Alzheimer's disease (AD) and schizophrenia. Given the importance of gamma oscillations for learning, memory and cognition processes as well as the recent interest in histamine H3 receptors in the development of pro-cognitive drugs to treat disorders such as AD and schizophrenia, it is relevant to study the impact of histaminergic mechanisms on network gamma oscillations. Here we show for the first time a modulation of gamma oscillation by histaminergic mechanisms. Selective activation of the H3 receptor by R-α-methylhistamine significantly reduces the power of kainate-induced gamma oscillations, but not carbachol-induced gamma oscillations, in the rat hippocampal slice preparation without affecting oscillation frequency. This effect is neither caused by a decrease in excitatory or inhibitory postsynaptic currents, nor a decrease in cellular excitability. Instead, we find that the decrease in oscillation power following H3 receptor activation results from a desynchronization of pyramidal neuron action potential firing with regard to the local field potential oscillation cycle. Our data provide a possible mechanism of action for histamine in regulating gamma oscillations in the hippocampal network. PMID:20156850

  18. Decreased Lin7b Expression in Layer 5 Pyramidal Neurons May Contribute to Impaired Corticostriatal Connectivity in Huntington Disease

    PubMed Central

    Zucker, Birgit; Kama, Jibrin A.; Kuhn, Alexandre; Thu, Doris; Orlando, Lianna R.; Dunah, Anthone W.; Gokce, Ozgun; Taylor, David M.; Lambeck, Johann; Friedrich, Bernd; Lindenberg, Katrin S.; Faull, Richard L.M.; Weiller, Cornelius; Young, Anne B.; Luthi-Carter, Ruth

    2010-01-01

    Motor dysfunction, cognitive impairment and regional cortical atrophy indicate cerebral cortical involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations in cortical gene expression, we isolated layer 5 cortical neurons by laser-capture microdissection and analyzed transcriptome-wide mRNA changes in them. Enrichment of transcription factor mRNAs including foxp2, tbr1, and neuroD6, and neurotransmission- and plasticity-related RNAs including sema5A, pclo, ntrk2, cntn1 and lin7b were observed. Layer 5 motor cortex neurons of transgenic R6/2 HD mice also demonstrated numerous transcriptomic changes, including decreased expression of mRNAs encoding the lin7 homolog b, (lin7b, also known as veli-2 and mals2). Decreases in LIN7B and CNTN1 RNAs were also detected in human HD layer 5 motor cortex neurons. lin7b, a scaffold protein implicated in synaptic plasticity, neurite outgrowth and cellular polarity, was decreased at the protein level in layer 5 cortical neurons in R6/2 mice and human HD brains. Decreases in Lin7b and Lin7a mRNAs were detected in R6/2 cortex as early as 6 weeks of age, suggesting that this is an early pathogenetic event. Thus, decreased cortical LIN7 expression may contribute to abnormal corticostriatal connectivity in HD. PMID:20720508

  19. Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors.

    PubMed

    Xu, Changqing; Cui, Changhai; Alkon, Daniel L

    2009-08-01

    Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. PMID:19123252

  20. Short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents in pyramidal neurons of rat neocortex.

    PubMed

    Sickmann, Thomas; Alzheimer, Christian

    2003-10-01

    Whole cell recordings from acutely isolated rat neocortical pyramidal cells were performed to study the kinetics and the mechanisms of short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents during prolonged application (5 min) of baclofen, adenosine, or serotonin. Most commonly, desensitization of GIRK currents was characterized by a biphasic time course with average time constants for fast and slow desensitization in the range of 8 and 120 s, respectively. The time constants were independent of the agonist used to evoke the current. The biphasic time course was preserved in perforated-patch recordings, indicating that neither component of desensitization is attributable to cell dialysis. Desensitization of GIRK currents displayed a strong heterologous component in that application of a second agonist substantially reduced the responsiveness to a test agonist. Fast desensitization, but not slow desensitization, was lost in cells loaded with GDP, suggesting that the hydrolysis cycle of G proteins might underlie the initial, rapid current decline. Hydrolysis of phosphatidylinositol biphosphate is an unlikely candidate underlying short-term desensitization, because both components of desensitization were preserved in the presence of the phospholipase C inhibitor U73122. We conclude that short-term desensitization does neither result from receptor downregulation nor from altered channel gating but might involve modifications of the G-protein-dependent pathway that serves to translate receptor activation into channel opening.

  1. Activation of 5‐HT2A receptors by TCB‐2 induces recurrent oscillatory burst discharge in layer 5 pyramidal neurons of the mPFC in vitro

    PubMed Central

    Spindle, Michael S.; Thomas, Mark P.

    2014-01-01

    Abstract The medial prefrontal cortex (mPFC) is a region of neocortex that plays an integral role in several cognitive processes which are abnormal in schizophrenic patients. As with other cortical regions, large‐bodied layer 5 pyramidal neurons serve as the principle subcortical output of microcircuits of the mPFC. The coexpression of both inhibitory serotonin 5‐HT1A receptors on the axon initial segments, and excitatory 5‐HT2A receptors throughout the somatodendritic compartments, by layer 5 pyramidal neurons allows serotonin to provide potent top–down regulation of input–output relationships within cortical microcircuits. Application of 5‐HT2A agonists has previously been shown to enhance synaptic input to layer 5 pyramidal neurons, as well as increase the gain in neuronal firing rate in response to increasing depolarizing current steps. Using whole‐cell patch‐clamp recordings obtained from layer 5 pyramidal neurons of the mPFC of C57/bl6 mice, the aim of our present study was to investigate the modulation of long‐term spike trains by the selective 5‐HT2A agonist TCB‐2. We found that in the presence of synaptic blockers, TCB‐2 induced recurrent oscillatory bursting (ROB) after 15–20 sec of tonic spiking in 7 of the 14 cells. In those seven cells, ROB discharge was accurately predicted by the presence of a voltage sag in response to a hyperpolarizing current injection. This effect was reversed by 5–10 min of drug washout and ROB discharge was inhibited by both synaptic activity and coapplication of the 5‐HT2A/2C antagonist ketanserin. While the full implications of this work are not yet understood, it may provide important insight into serotonergic modulation of cortical networks. PMID:24844635

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

    PubMed

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

    2008-10-22

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

  3. NMDA-induced glutamate and aspartate release from rat cortical pyramidal neurones: evidence for modulation by a 5-HT1A antagonist.

    PubMed Central

    Dijk, S. N.; Francis, P. T.; Stratmann, G. C.; Bowen, D. M.

    1995-01-01

    1. We have investigated an aspect of the regulation of cortical pyramidal neurone activity. Microdialysis was used to assess whether topical application of drugs (in 10 microliter) to fill a burr hole over the frontal cortex, where part of the corticostriatal pathway originates, would change concentrations of the excitatory amino acids glutamate and aspartate in the striatum of the anaesthetized rat. 2. Topical application of N-methyl-D-aspartate (NMDA, 2 and 20 mM) dose-dependently increased glutamate and aspartate concentrations in the striatum. Coapplication of tetrodotoxin (10 microM) blocked the NMDA-evoked rise in these amino acids. A calcium-free medium, perfused through the probe also blocked the rise, indicating that it was due to an exocytotic mechanism in the striatum. 3. It was hypothesized that the rise observed was due to an increase in the activity of the corticostriatal pathway. As 5-hydroxytryptamine1A (5-HT1A) receptors are enriched on cell bodies of corticostriatal neurones, a selective 5-HT1A-antagonist (WAY 100135) was coapplied with the lower dose of NMDA. Compared to NMDA alone, coapplication of 50 microM WAY 100135 significantly increased glutamate release. This effect was sensitive to tetrodotoxin and calcium-dependent. Application of 50 microM WAY 100135 alone significantly enhanced glutamate release above baseline; this was also tested at 100 microM (not significant). 4. Compared to NMDA alone, coapplication of WAY 100135 (20 microM) significantly enhanced aspartate release; the mean value was also increased (not significantly) with 50 microM. This rise was calcium-dependent, but not tetrodotoxin-sensitive. WAY 100135 (100 microM) reduced NMDA-induced aspartate release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582540

  4. Effect of dopaminergic D1 receptors on plasticity is dependent of serotoninergic 5-HT1A receptors in L5-pyramidal neurons of the prefrontal cortex.

    PubMed

    Meunier, Claire Nicole Jeanne; Callebert, Jacques; Cancela, José-Manuel; Fossier, Philippe

    2015-01-01

    Major depression and schizophrenia are associated with dysfunctions of serotoninergic and dopaminergic systems mainly in the prefrontal cortex (PFC). Both serotonin and dopamine are known to modulate synaptic plasticity. 5-HT1A receptors (5-HT1ARs) and dopaminergic type D1 receptors are highly represented on dendritic spines of layer 5 pyramidal neurons (L5PyNs) in PFC. How these receptors interact to tune plasticity is poorly understood. Here we show that D1-like receptors (D1Rs) activation requires functional 5HT1ARs to facilitate LTP induction at the expense of LTD. Using 129/Sv and 5-HT1AR-KO mice, we recorded post-synaptic currents evoked by electrical stimulation in layer 2/3 after activation or inhibition of D1Rs. High frequency stimulation resulted in the induction of LTP, LTD or no plasticity. The D1 agonist markedly enhanced the NMDA current in 129/Sv mice and the percentage of L5PyNs displaying LTP was enhanced whereas LTD was reduced. In 5-HT1AR-KO mice, the D1 agonist failed to increase the NMDA current and orientated the plasticity towards L5PyNs displaying LTD, thus revealing a prominent role of 5-HT1ARs in dopamine-induced modulation of plasticity. Our data suggest that in pathological situation where 5-HT1ARs expression varies, dopaminergic treatment used for its ability to increase LTP could turn to be less and less effective. PMID:25775449

  5. Effect of Dopaminergic D1 Receptors on Plasticity Is Dependent of Serotoninergic 5-HT1A Receptors in L5-Pyramidal Neurons of the Prefrontal Cortex

    PubMed Central

    Meunier, Claire Nicole Jeanne; Callebert, Jacques; Cancela, José-Manuel; Fossier, Philippe

    2015-01-01

    Major depression and schizophrenia are associated with dysfunctions of serotoninergic and dopaminergic systems mainly in the prefrontal cortex (PFC). Both serotonin and dopamine are known to modulate synaptic plasticity. 5-HT1A receptors (5-HT1ARs) and dopaminergic type D1 receptors are highly represented on dendritic spines of layer 5 pyramidal neurons (L5PyNs) in PFC. How these receptors interact to tune plasticity is poorly understood. Here we show that D1-like receptors (D1Rs) activation requires functional 5HT1ARs to facilitate LTP induction at the expense of LTD. Using 129/Sv and 5-HT1AR-KO mice, we recorded post-synaptic currents evoked by electrical stimulation in layer 2/3 after activation or inhibition of D1Rs. High frequency stimulation resulted in the induction of LTP, LTD or no plasticity. The D1 agonist markedly enhanced the NMDA current in 129/Sv mice and the percentage of L5PyNs displaying LTP was enhanced whereas LTD was reduced. In 5-HT1AR-KO mice, the D1 agonist failed to increase the NMDA current and orientated the plasticity towards L5PyNs displaying LTD, thus revealing a prominent role of 5-HT1ARs in dopamine-induced modulation of plasticity. Our data suggest that in pathological situation where 5-HT1ARs expression varies, dopaminergic treatment used for its ability to increase LTP could turn to be less and less effective. PMID:25775449

  6. Somatic and dendritic perforated-patch recordings reveal b-adrenergic receptor-induced depolarization in medial prefrontal cortex pyramidal neurons.

    PubMed

    Szulczyk, Bartłomiej

    2016-01-01

    The aim of this perforated-patch study was to test the effect of isoproterenol on the membrane potential in mPFC (medial prefrontal cortex) pyramidal neurons. Isoproterenol depolarized the membrane potential recorded from the soma. This effect was absent in the presence of metoprolol, suggesting the involvement of beta1-adrenergic receptors. The adenylate cyclase activator forskolin also depolarized the membrane potential. Moreover, the effect of isoproterenol was abolished by the adenylate cyclase inhibitor SQ 22536. This suggested that adenylate cyclase was involved in mediating the effect of the beta-adrenergic receptor agonist. The isoproterenol-induced depolarization persisted after inhibition of protein kinase A with H-89. The effect of beta-adrenergic receptor activation on the membrane potential was dependent on Ih channels because it was abolished in the presence of the Ih channel inhibitor ZD 7288. Dendritic recordings were also performed. In the dendritic segments between 100 microm and 150 microm from the soma and between 200 microm and 250 microm from the soma, isoproterenol also depolarized the membrane potential. The magnitude of the beta-adrenergic receptor-stimulated depolarization was the same in the soma and in both dendritic localizations. The depolarization exerted by isoproterenol may influence PFC cognitive functions. PMID:27373953

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

    PubMed Central

    Ashhad, Sufyan; Johnston, Daniel

    2014-01-01

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

  8. pH modulation of currents that contribute to the medium and slow afterhyperpolarizations in rat CA1 pyramidal neurones

    PubMed Central

    Kelly, Tony; Church, John

    2004-01-01

    We examined the effects of changes in pHo and pHi on currents contributing to the medium and slow afterhyperpolarizations (mIAHP and sIAHP, respectively) in rat CA1 neurones. Reducing pHo from 7.4 to 6.7 inhibited mIAHP and sIAHP whereas increasing pHo to 7.7 augmented mIAHP and, to a greater extent, sIAHP. The ability of changes in pHo to modulate mIAHP reflected changes in the Ca2+-activated K+ current, IAHP, and a Co2+- and XE991-resistant component of mIAHP, but not the muscarine-sensitive current, IM. In the presence of 1 μm TTX and 5 mm TEA, low pHo-evoked reductions in sIAHP were associated with reductions in Ca2+-dependent depolarizing potentials; because neither effect was attenuated when internal H+ buffering power was raised by including 100 mm tricine in the patch pipette, the actions of reductions in pHo to inhibit sIAHP and, possibly, IAHP in large part appear to reflect a low pHo-dependent decrease in Ca2+ influx. In contrast, the effects of high pHo to augment mIAHP and sIAHP were associated with relatively small increases in Ca2+ potentials but were significantly attenuated by 100 mm internal tricine, indicating that a rise in pHi consequent upon the rise in pHo was largely responsible. The possibility that changes in pHi could act to modulate mIAHP and sIAHP, independently of changes in Ca2+ influx, was also suggested by experiments in which pHi was lowered at a constant pHo by the external application of propionate or by the withdrawal of HCO3− from the perfusing medium. Lowering pHi at a constant pHo had little effect on Ca2+ potentials but inhibited mIAHP and, to a greater extent, sIAHP, effects that were attenuated by 100 mm internal tricine. Together, the results indicate that changes in pHo and pHi modulate mIAHP and sIAHP in rat CA1 neurones and suggest that, depending on the direction of the pHo change, the sensitivities of the underlying currents to changes in Ca2+ influx and/or pHi may contribute to the effects of changes in pHo to

  9. Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex

    PubMed Central

    Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

    2016-01-01

    Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID:27193420

  10. Characterization of L-type Voltage-Gated Ca2+ Channel Expression and Function in Developing CA3 Pyramidal Neurons

    PubMed Central

    Morton, Russell A.; Norlin, Mackenzie S.; Vollmer, Cyndel C.; Valenzuela, C. Fernando

    2013-01-01

    Voltage gated calcium channels (VGCCs) play a major role during the development of the central nervous system (CNS). Ca2+ influx via VGCCs regulates axonal growth and neuronal migration as well as synaptic plasticity. Specifically, L-type VGCCs have been well characterized to be involved in the formation and refinement of the connections within the CA3 region of the hippocampus. The majority of the growth, formation, and refinement in the CNS occurs during the human third trimester. An equivalent developmental time period in rodents occurs during the first two weeks of post-natal life, and the expression pattern of L-type VGCCs during this time period has not been well characterized. In this study, we show that Cav1.2 channels are more highly expressed during this developmental period compared to adolescence (post-natal day 30) and that L-type VGCCs significantly contribute to the overall Ca2+ currents. These findings suggest that L-type VGCCs are functionally expressed during the crucial developmental period. PMID:23415785

  11. A microfluidic device to investigate axon targeting by limited numbers of purified cortical projection neuron subtypes

    PubMed Central

    Tharin, Suzanne; Kothapalli, Chandrasekhar R.; Ozdinler, Pembe Hande; Pasquina, Lincoln; Chung, Seok; Varner, Johanna; DeValence, Sarra; Kamm, Roger; Macklis, Jeffrey D.

    2012-01-01

    While much is known about general controls over axon guidance of broad classes of projection neurons (those with long-distance axonal connections), molecular controls over specific axon targeting by distinct neuron subtypes are poorly understood. Corticospinal motor neurons (CSMN) are prototypical and clinically important cerebral cortex projection neurons; they are the brain neurons that degenerate in amyotrophic lateral sclerosis (ALS) and related motor neuron diseases, and their injury is central to the loss of motor function in spinal cord injury. Primary culture of purified immature murine CSMN has been recently established, using either fluorescence-activated cell sorting (FACS) or immunopanning, enabling a previously unattainable level of subtype-specific investigation, but the resulting number of CSMN is quite limiting for standard approaches to study axon guidance. We developed a microfluidic system specifically designed to investigate axon targeting of limited numbers of purified CSMN and other projection neurons in culture. The system contains two chambers for culturing target tissue explants, allowing for biologically revealing axonal growth “choice” experiments. This device will be uniquely enabling for investigation of controls over axon growth and neuronal survival of many types of neurons, particularly those available only in limited numbers. PMID:23034677

  12. Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release evoked by metabotropic agonists and backpropagating action potentials in hippocampal CA1 pyramidal neurons.

    PubMed

    Nakamura, T; Nakamura, K; Lasser-Ross, N; Barbara, J G; Sandler, V M; Ross, W N

    2000-11-15

    We examined the properties of [Ca(2+)](i) changes that were evoked by backpropagating action potentials in pyramidal neurons in hippocampal slices from the rat. In the presence of the metabotropic glutamate receptor (mGluR) agonists t-ACPD, DHPG, or CHPG, spikes caused Ca(2+) waves that initiated in the proximal apical dendrites and spread over this region and in the soma. Consistent with previously described synaptic responses (Nakamura et al., 1999a), pharmacological experiments established that the waves were attributable to Ca(2+) release from internal stores mediated by the synergistic effect of receptor-mobilized inositol 1,4, 5-trisphosphate (IP(3)) and spike-evoked Ca(2+). The amplitude of the changes reached several micromoles per liter when detected with the low-affinity indicators fura-6F, fura-2-FF, or furaptra. Repetitive brief spike trains at 30-60 sec intervals generated increases of constant amplitude. However, trains at intervals of 10-20 sec evoked smaller increases, suggesting that the stores take 20-30 sec to refill. Release evoked by mGluR agonists was blocked by MCPG, AIDA, 4-CPG, MPEP, and LY367385, a profile consistent with the primacy of group I receptors. At threshold agonist concentrations the release was evoked only in the dendrites; threshold antagonist concentrations were effective only in the soma. Carbachol and 5-HT evoked release with the same spatial distribution as t-ACPD, suggesting that the distribution of neurotransmitter receptors was not responsible for the restricted range of regenerative release. Intracellular BAPTA and EGTA were approximately equally effective in blocking release. Extracellular Cd(2+) blocked release, but no single selective Ca(2+) channel blocker prevented release. These results suggest that IP(3) receptors are not associated closely with specific Ca(2+) channels and are not close to each other.

  13. Galantamine prevents long-lasting suppression of excitatory synaptic transmission in CA1 pyramidal neurons of soman-challenged guinea pigs.

    PubMed

    Alexandrova, E A; Alkondon, M; Aracava, Y; Pereira, E F R; Albuquerque, E X

    2014-09-01

    Galantamine, a drug currently approved for the treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1h, 24h, or 6-9 days after guinea pigs were injected with: (i) 1×LD50 soman (26.3μg/kg, s.c.); (ii) galantamine (8mg/kg, i.m.) followed 30min later by 1×LD50 soman, (iii) galantamine (8mg/kg, i.m.), or (iv) saline (0.5ml/kg, i.m.). In soman-injected guinea pigs that were not pretreated with galantamine, the frequency of EPSCs was significantly lower than that recorded from saline-injected animals. There was no correlation between the severity of soman-induced acute toxicity and the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with galantamine prevented the reduction of EPSC frequency observed at 6-9 days after the soman challenge. Prevention of soman-induced long-lasting reduction of hippocampal glutamatergic synaptic transmission may be an important determinant of the ability of galantamine to counter cognitive deficits that develop long after an acute exposure to the nerve agent. PMID:25064080

  14. Differential emotional experience induces elevated spine densities on basal dendrites of pyramidal neurons in the anterior cingulate cortex of Octodon degus.

    PubMed

    Helmeke, C; Poeggel, G; Braun, K

    2001-01-01

    It appears likely that, in analogy to the synaptic development of sensory and motor cortices, which critically depends on sensory or motor stimulation (Rosenzweig and Bennett, 1996), the synaptic development of limbic cortical regions are modulated by early postnatal cognitive and emotional experiences. The very first postnatal experience, which takes place in a confined and stable familial environment, is the interaction of the newborn individual with the parents and siblings (Gray, 1958). The aim of this quantitative morphological study was to analyze the impact of different degrees of juvenile emotional experience on the synaptic development in a limbic cortical area, the dorsal anterior cingulate cortex, a region which is involved in the perception and regulation of emotions. We study the precocious trumpet-tailed rat (Octodon degus) as the animal model, because, like human babies, this species is born with functional visual and acoustic systems and the pups are therefore capable of detecting even subtle environmental changes immediately after birth (Reynolds and Wright, 1979; Poeggel and Braun, 1996; Braun et al., 2000; Ovtscharoff and Braun, 2001). The results demonstrate that already a subtle disturbance of the familial environment such as handling induced significantly elevated spine densities on the basal dendrites of layer III cortical pyramidal neurons. More severe disturbances of the emotional environment, such as periodic parental deprivation with or without subsequent chronic social isolation, resulted in an elevation of spine densities of similar magnitude as seen after handling and in addition, altered spine densities confined to specific dendritic segments were observed in these groups. These observations unveil the remarkable sensitivity of the dorsal anterior cingulate cortex towards environmental influences and behavioral experiences during phases of postnatal development. The behavioral consequences of these experience-induced synaptic changes

  15. Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1

    PubMed Central

    Booth, Clair A; Brown, Jonathan T; Randall, Andrew D

    2014-01-01

    A t(1;11) balanced chromosomal translocation transects the Disc1 gene in a large Scottish family and produces genome-wide linkage to schizophrenia and recurrent major depressive disorder. This study describes our in vitro investigations into neurophysiological function in hippocampal area CA1 of a transgenic mouse (DISC1tr) that expresses a truncated version of DISC1 designed to reproduce aspects of the genetic situation in the Scottish t(1;11) pedigree. We employed both patch-clamp and extracellular recording methods in vitro to compare intrinsic properties and synaptic function and plasticity between DISC1tr animals and wild-type littermates. Patch-clamp analysis of CA1 pyramidal neurons (CA1-PNs) revealed no genotype dependence in multiple subthreshold parameters, including resting potential, input resistance, hyperpolarization-activated ‘sag’ and resonance properties. Suprathreshold stimuli revealed no alteration to action potential (AP) waveform, although the initial rate of AP production was higher in DISC1tr mice. No difference was observed in afterhyperpolarizing potentials following trains of 5–25 APs at 50 Hz. Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio. Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input–output and short-term plasticity were also unaltered in the temporoammonic (TA) input. However, in DISC1tr mice theta burst-induced long-term potentiation was enhanced in the SC pathway but completely lost in the TA pathway. These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity. PMID:24712988

  16. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.

    PubMed Central

    Rapp, P R; Gallagher, M

    1996-01-01

    Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence challenging these long-standing concepts. The status of hippocampal-dependent spatial learning was evaluated in young and aged Long-Evans rats using the Morris water maze, and the total number of neurons in the principal cell layers of the dentate gyrus and hippocampus was quantified according to the optical fractionator technique. For each of the hippocampal fields, neuron number was preserved in the aged subjects as a group and in aged individuals with documented learning and memory deficits indicative of hippocampal dysfunction. The findings demonstrate that hippocampal neuronal degeneration is not an inevitable consequence of normal aging and that a loss of principal neurons in the hippocampus fails to account for age-related learning and memory impairment. The observed preservation of neuron number represents an essential foundation for identifying the neurobiological effects of hippocampal aging that account for cognitive decline. Images Fig. 2 PMID:8790433

  17. Neurons selective to the number of visual items in the corvid songbird endbrain

    PubMed Central

    Ditz, Helen M.; Nieder, Andreas

    2015-01-01

    It is unknown whether anatomical specializations in the endbrains of different vertebrates determine the neuronal code to represent numerical quantity. Therefore, we recorded single-neuron activity from the endbrain of crows trained to judge the number of items in displays. Many neurons were tuned for numerosities irrespective of the physical appearance of the items, and their activity correlated with performance outcome. Comparison of both behavioral and neuronal representations of numerosity revealed that the data are best described by a logarithmically compressed scaling of numerical information, as postulated by the Weber–Fechner law. The behavioral and neuronal numerosity representations in the crow reflect surprisingly well those found in the primate association cortex. This finding suggests that distantly related vertebrates with independently developed endbrains adopted similar neuronal solutions to process quantity. PMID:26056278

  18. Age-Dependent Neurogenesis and Neuron Numbers within the Olfactory Bulb and Hippocampus of Homing Pigeons

    PubMed Central

    Meskenaite, Virginia; Krackow, Sven; Lipp, Hans-Peter

    2016-01-01

    Many birds are supreme long-distance navigators that develop their navigational ability in the first months after fledgling but update the memorized environmental information needed for navigation also later in life. We studied the extent of juvenile and adult neurogenesis that could provide such age-related plasticity in brain regions known to mediate different mechanisms of pigeon homing: the olfactory bulb (OB), and the triangular area of the hippocampal formation (HP tr). Newly generated neurons (visualized by doublecortin, DCX) and mature neurons were counted stereologically in 35 pigeon brains ranging from 1 to 168 months of age. At the age of 1 month, both areas showed maximal proportions of DCX positive neurons, which rapidly declined during the first year of life. In the OB, the number of DCX-positive periglomerular neurons declined further over time, but the number of mature periglomerular cells appeared unchanged. In the hippocampus, the proportion of DCX-positive neurons showed a similar decline yet to a lesser extent. Remarkably, in the triangular area of the hippocampus, the oldest birds showed nearly twice the number of neurons as compared to young adult pigeons, suggesting that adult born neurons in these regions expanded the local circuitry even in aged birds. This increase might reflect navigational experience and, possibly, expanded spatial memory. On the other hand, the decrease of juvenile neurons in the aging OB without adding new circuitry might be related to the improved attachment to the loft characterizing adult and old pigeons. PMID:27445724

  19. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    SciTech Connect

    Shi Lei Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-06-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of {sup 137}Cs {gamma} rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus.

  20. Differences in Number of Midbrain Dopamine Neurons Associated with Summer and Winter Photoperiods in Humans

    PubMed Central

    Aumann, Tim D.; Raabus, Mai; Tomas, Doris; Prijanto, Agustinus; Churilov, Leonid; Spitzer, Nicholas C.; Horne, Malcolm K.

    2016-01-01

    Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or down-regulation of expression of genes and proteins that are important for dopamine (DA) synthesis in extant neurons (‘DA neurotransmitter switching’). If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) and DA transporter (DAT) immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5) versus winter (short-day photoperiod, n = 5). TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+) neurons was significantly (~6-fold) higher whereas the density of TH immunonegative (TH-) neurons was significantly (~2.5-fold) lower in summer compared with winter. The density of total neurons (TH+ and TH- combined) was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells), and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod) and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association. PMID:27428306

  1. Carbon monoxide improves neuronal differentiation and yield by increasing the functioning and number of mitochondria.

    PubMed

    Almeida, Ana S; Sonnewald, Ursula; Alves, Paula M; Vieira, Helena L A

    2016-08-01

    The process of cell differentiation goes hand-in-hand with metabolic adaptations, which are needed to provide energy and new metabolites. Carbon monoxide (CO) is an endogenous cytoprotective molecule able to inhibit cell death and improve mitochondrial metabolism. Neuronal differentiation processes were studied using the NT2 cell line, which is derived from human testicular embryonic teratocarcinoma and differentiates into post-mitotic neurons upon retinoic acid treatment. CO-releasing molecule A1 (CORM-A1) was used do deliver CO into cell culture. CO treatment improved NT2 neuronal differentiation and yield, since there were more neurons and the total cell number increased following the differentiation process. CO supplementation enhanced the mitochondrial population in post-mitotic neurons derived from NT2 cells, as indicated by an increase in mitochondrial DNA. CO treatment during neuronal differentiation increased the extent of the classical metabolic change that occurs during neuronal differentiation, from glycolytic to more oxidative metabolism, by decreasing the ratio of lactate production and glucose consumption. The expression of pyruvate and lactate dehydrogenases was higher, indicating an augmented oxidative metabolism. Moreover, these findings were corroborated by an increased percentage of (13) C incorporation from [U-(13) C]glucose into the tricarboxylic acid cycle metabolites malate and citrate, and also glutamate and aspartate in CO-treated cells. Finally, under low levels of oxygen (5%), which enhances glycolytic metabolism, some of the enhancing effects of CO on mitochondria were not observed. In conclusion, our data show that CO improves neuronal and mitochondrial yield by stimulation of tricarboxylic acid cycle activity, and thus oxidative metabolism of NT2 cells during the process of neuronal differentiation. The process of cell differentiation is coupled with metabolic adaptations. Carbon monoxide (CO) is an endogenous cytoprotective

  2. Daily exercise normalizes the number of diaphorase (NOS) positive neurons in the hypothalamus of hypertensive rats.

    PubMed

    DiCarlo, Stephen E; Zheng, H; Collins, Heidi L; Rodenbaugh, David W; Patel, Kaushik P

    2002-11-15

    It is well known that nitric oxide (NO), within the paraventricular nucleus (PVN) of the hypothalamus, mediates sympatho-inhibition via an inhibitory GABA-ergic mechanism. Furthermore, the inhibitory GABA-ergic mechanism is impaired in the spontaneously hypertensive rat (SHR). These data suggest that the NO system, within the PVN, may also be impaired in the SHR. In addition, previous studies have documented that daily exercise attenuates the development of tachycardia, hypertension and blood pressure related cardiovascular disease risk factors in SHR. These data suggest that daily exercise enhances the inhibitory GABA-ergic and/or NO systems. Therefore, this study was designed to test the hypothesis that hypertension, in the SHR, is associated with a lower number of NADPH-diaphorase (a commonly used marker for neuronal NOS activity) positive neurons within the PVN and that daily exercise increases the number of NOS positive neurons. Using a standard histochemical protocol, NOS positive neurons were measured in the PVN, supraoptic nucleus, median preoptic area, lateral hypothalamus, nucleus of the tractus solitarius and rostral ventrolateral medulla. Results document that SHR have significantly fewer NOS-positive neurons in the PVN than their genetic control, the Wistar-Kyoto (WKY) rats (110+/-11 versus 139+/-17). Furthermore, daily exercise increased the number of NOS positive neurons in the SHR to levels seen in the WKY rats. These data demonstrate that hypertension, in the SHR, is associated with a lower number of NOS positive neurons within the PVN and that daily exercise increases the number of NOS positive neurons within the PVN.

  3. Effect of sex steroid hormones on the number of serotonergic neurons in rat dorsal raphe nucleus.

    PubMed

    Kunimura, Yuyu; Iwata, Kinuyo; Iijima, Norio; Kobayashi, Makito; Ozawa, Hitoshi

    2015-05-01

    Disorders caused by the malfunction of the serotonergic system in the central nervous system show sex-specific prevalence. Many studies have reported a relationship between sex steroid hormones and the brain serotonergic system; however, the interaction between sex steroid hormones and the number of brain neurons expressing serotonin has not yet been elucidated. In the present study, we determined whether sex steroid hormones altered the number of serotonergic neurons in the dorsal raphe nucleus (DR) of adult rat brains. Animals were divided into five groups: ovariectomized (OVX), OVX+low estradiol (E2), OVX+high E2, castrated males, and intact males. Antibodies against 5-hydroxytryptamine (5-HT, serotonin) and tryptophan hydroxylase (Tph), an enzyme for 5-HT synthesis, were used as markers of 5-HT neurons, and the number of 5-HT-immunoreactive (ir) or Tph-ir cells was counted. We detected no significant differences in the number of 5-HT-ir or Tph-ir cells in the DR among the five groups. By contrast, the intensity of 5-HT-ir showed significant sex differences in specific subregions of the DR independent of sex steroid levels, suggesting that the manipulation of sex steroid hormones after maturation does not affect the number and intensive immunostaining of serotonergic neurons in rat brain. Our results suggest that, the sexual dimorphism observed in the serotonergic system is due to factors such as 5-HT synthesis, transportation, and degradation but not to the number of serotonergic neurons.

  4. Stereological Analysis of Neuron, Glial and Endothelial Cell Numbers in the Human Amygdaloid Complex

    PubMed Central

    García-Amado, María; Prensa, Lucía

    2012-01-01

    Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm3 and mean cell numbers (x106) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals’ age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions. PMID:22719923

  5. Environmental modulations of the number of midbrain dopamine neurons in adult mice.

    PubMed

    Tomas, Doris; Prijanto, Augustinus H; Burrows, Emma L; Hannan, Anthony J; Horne, Malcolm K; Aumann, Tim D

    2015-01-01

    Long-lasting changes in the brain or 'brain plasticity' underlie adaptive behavior and brain repair following disease or injury. Furthermore, interactions with our environment can induce brain plasticity. Increasingly, research is trying to identify which environments stimulate brain plasticity beneficial for treating brain and behavioral disorders. Two environmental manipulations are described which increase or decrease the number of tyrosine hydroxylase immunopositive (TH+, the rate-limiting enzyme in dopamine (DA) synthesis) neurons in the adult mouse midbrain. The first comprises pairing male and female mice together continuously for 1 week, which increases midbrain TH+ neurons by approximately 12% in males, but decreases midbrain TH+ neurons by approximately 12% in females. The second comprises housing mice continuously for 2 weeks in 'enriched environments' (EE) containing running wheels, toys, ropes, nesting material, etc., which increases midbrain TH+ neurons by approximately 14% in males. Additionally, a protocol is described for concurrently infusing drugs directly into the midbrain during these environmental manipulations to help identify mechanisms underlying environmentally-induced brain plasticity. For example, EE-induction of more midbrain TH+ neurons is abolished by concurrent blockade of synaptic input onto midbrain neurons. Together, these data indicate that information about the environment is relayed via synaptic input to midbrain neurons to switch on or off expression of 'DA' genes. Thus, appropriate environmental stimulation, or drug targeting of the underlying mechanisms, might be helpful for treating brain and behavioral disorders associated with imbalances in midbrain DA (e.g. Parkinson's disease, attention deficit and hyperactivity disorder, schizophrenia, and drug addiction).

  6. Birds have primate-like numbers of neurons in the forebrain

    PubMed Central

    Olkowicz, Seweryn; Kocourek, Martin; Lučan, Radek K.; Porteš, Michal; Fitch, W. Tecumseh; Herculano-Houzel, Suzana; Němec, Pavel

    2016-01-01

    Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence. PMID:27298365

  7. Birds have primate-like numbers of neurons in the forebrain.

    PubMed

    Olkowicz, Seweryn; Kocourek, Martin; Lučan, Radek K; Porteš, Michal; Fitch, W Tecumseh; Herculano-Houzel, Suzana; Němec, Pavel

    2016-06-28

    Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence. PMID:27298365

  8. No relative expansion of the number of prefrontal neurons in primate and human evolution

    PubMed Central

    Gabi, Mariana; Neves, Kleber; Masseron, Carolinne; Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Torres, Laila; Mota, Bruno; Kaas, Jon H.; Herculano-Houzel, Suzana

    2016-01-01

    Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume. PMID:27503881

  9. No relative expansion of the number of prefrontal neurons in primate and human evolution.

    PubMed

    Gabi, Mariana; Neves, Kleber; Masseron, Carolinne; Ribeiro, Pedro F M; Ventura-Antunes, Lissa; Torres, Laila; Mota, Bruno; Kaas, Jon H; Herculano-Houzel, Suzana

    2016-08-23

    Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume. PMID:27503881

  10. Early-life environmental intervention may increase the number of neurons, astrocytes, and cellular proliferation in the hippocampus of rats.

    PubMed

    Winkelmann-Duarte, Elisa C; Padilha-Hoffmann, Camila B; Martins, Daniel F; Schuh, Artur F S; Fernandes, Marilda C; Santin, Ricardo; Merlo, Suelen; Sanvitto, Gilberto L; Lucion, Aldo B

    2011-11-01

    Neonatal handling reduces the stress response in adulthood due to a feedback mechanism. The present study analyzed the effects of repeated neonatal environmental intervention (daily handling during the first 10 days after birth) on neuron-, astroglial cell density, and cellular proliferation of the hippocampal (CA1, CA2, and CA3) pyramidal cell layers in female rats. Pups were divided into two groups, nonhandled and handled, which were submitted to repeated handling sessions between postnatal days 1 and 10. Histological and immunohistochemical procedures were used to determine changes in neuron density, astroglial cell density, and cellular proliferation. We found an increase in neuron density in each pyramidal cell layer of the hippocampus (CA1, CA2, and CA3) in female rats (11 and 90 day old) that were handled during the neonatal period. Furthermore, we found an increase in astroglial cell density in both hemispheres of the brain in the handled group. Finally, we observed an increase in cellular proliferation in both hippocampi (CA1, CA2, and CA3) of the brain in female pups (11 days old) handled during the neonatal period. This study demonstrates that an early-life environmental intervention may induce morphological changes in a structure involved with several functions, including the stress response. The results of the current study suggest that neonatal handling may influence the animals' responses to environmental adversities later in life.

  11. Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters.

    PubMed

    Sundvik, Maria; Panula, Pertti

    2012-12-01

    Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

  12. Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.

    PubMed

    Rodríguez-Martín, Teresa; Pooler, Amy M; Lau, Dawn H W; Mórotz, Gábor M; De Vos, Kurt J; Gilley, Jonathan; Coleman, Michael P; Hanger, Diane P

    2016-01-01

    Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies.

  13. Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism

    ERIC Educational Resources Information Center

    Vaccarino, Flora M.; Grigorenko, Elena L.; Smith, Karen Muller; Stevens, Hanna E.

    2009-01-01

    Increased brain size is common in children with autism spectrum disorders. Here we propose that an increased number of cortical excitatory neurons may underlie the increased brain volume, minicolumn pathology and excessive network excitability, leading to sensory hyper-reactivity and seizures, which are often found in autism. We suggest that…

  14. Orexinergic neuron numbers in three species of African mole rats with rhythmic and arrhythmic chronotypes.

    PubMed

    Bhagwandin, A; Gravett, N; Hemingway, J; Oosthuizen, M K; Bennett, N C; Siegel, J M; Manger, P R

    2011-12-29

    In the present study, orexinergic cell bodies within the brains of rhythmic and arrhythmic circadian chronotypes from three species of African mole rat (Highveld mole rat-Cryptomys hottentotus pretoriae, Ansell's mole rat--Fukomys anselli and the Damaraland mole rat--Fukomys damarensis) were identified using immunohistochemistry for orexin-A. Immunopositive orexinergic (Orx+) cell bodies were stereologically assessed and absolute numbers of orexinergic cell bodies were determined for the distinct circadian chronotypes of each species of mole rat examined. The aim of the study was to investigate whether the absolute numbers of identified orexinergic neurons differs between distinct circadian chronotypes with the hypothesis of elevated hypothalamic orexinergic neurons in the arrhythmic chronotypes compared with the rhythmic chronotypes. We found statistically significant differences between the circadian chronotypes ofF. anselli, where the arrhythmic group had higher mean numbers of hypothalamic orexin neurons compared with the rhythmic group. These differences were observed when the raw data was compared and when the raw data was corrected for body mass (M(b)) and brain mass (M(br)). For the two other species investigated, no significant differences were noted between the chronotypes, although a statistically significant difference was noted between all rhythmic and arrhythmic individuals of the current study when the counts of orexin neurons were corrected for M(b)--the arrhythmic individuals had larger numbers of orexin cells.

  15. Mossy cells and different subpopulations of pyramidal neurons are immunoreactive for cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation of non-human primates and tree shrew (Tupaia belangeri).

    PubMed

    Abrahám, H; Czéh, B; Fuchs, E; Seress, L

    2005-01-01

    Cocaine- and amphetamine-regulated transcript peptide mRNA was discovered in the rat striatum following cocaine and amphetamine administration. Since both psychostimulants elicit memory-related effects, localization of cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation may have functional importance. Previous studies demonstrated different cellular localizations of cocaine- and amphetamine-regulated transcript peptide in humans and in rodents. Mossy cells were cocaine- and amphetamine-regulated transcript-positive in the human dentate gyrus, whereas granule cells contained this peptide in the rat. In the present study, the localization of cocaine- and amphetamine-regulated transcript peptide was examined using immunohistochemistry in the hippocampal formation of the rhesus monkey (Macaca mulatta), the common marmoset monkey (Callithrix jacchus) and in the tree shrew (Tupaia belangeri). In these species principal neurons of the hippocampal formation were cocaine- and amphetamine-regulated transcript-immunoreactive. In both monkeys and tree shrews, mossy cells of the hilus were cocaine- and amphetamine-regulated transcript-positive whereas granule cells of the dentate gyrus were cocaine- and amphetamine-regulated transcript-negative. The dense cocaine- and amphetamine-regulated transcript-immunoreactive axonal plexus of the associational pathway outlined the inner one-third of the dentate molecular layer. In the hippocampus of the tree shrew and marmoset monkey, a subset of CA3 pyramidal cells were cocaine- and amphetamine-regulated transcript-immunoreactive. In the marmoset monkey, cocaine- and amphetamine-regulated transcript labeling was found only in layer V pyramidal cells of the entorhinal cortex, while in the rhesus monkey, pyramidal cells of layers II and III were cocaine- and amphetamine-regulated transcript-immunopositive. Our results show that cocaine- and amphetamine-regulated transcript positive neurons in the dentate

  16. Putting the Pyramid into Practice. Science Topics.

    ERIC Educational Resources Information Center

    Texas Child Care, 1994

    1994-01-01

    Explains the new U.S. Department of Agriculture (USDA) Food Guide Pyramid, which can help children and adults visualize the basics of sound nutrition. The pyramid chart places five food groups from top to bottom in inverse proportion to the number of servings that should be consumed. Special symbols are used to indicate fat content and added…

  17. Urban Public Health: Is There a Pyramid?

    PubMed Central

    Su, Meirong; Chen, Bin; Yang, Zhifeng; Cai, Yanpeng; Wang, Jiao

    2013-01-01

    Early ecologists identified a pyramidal trophic structure in terms of number, biomass and energy transfer. In 1943, the psychologist Maslow put forward a pyramid model to describe layers of human needs. It is indicated that the pyramid principle is universally applicable in natural, humanistic and social disciplines. Here, we report that a pyramid structure also exists in urban public health (UPH). Based on 18 indicators, the UPH states of four cities (Beijing, Tokyo, New York, and London) are compared from the point of view of five aspects, namely physical health, living conditions, social security, environmental quality, and education and culture. A pyramid structure was found in each city when focusing on 2000–2009 data. The pyramid of Beijing is relatively similar to that of Tokyo, and the pyramids of New York and London are similar to each other. A general development trend in UPH is proposed and represented by different pyramid modes. As a basic conjecture, the UPH pyramid model can be verified and developed with data of more cities over a longer period, and be used to promote healthy urban development. PMID:23358233

  18. Urban public health: is there a pyramid?

    PubMed

    Su, Meirong; Chen, Bin; Yang, Zhifeng; Cai, Yanpeng; Wang, Jiao

    2013-01-28

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

  19. Urban public health: is there a pyramid?

    PubMed

    Su, Meirong; Chen, Bin; Yang, Zhifeng; Cai, Yanpeng; Wang, Jiao

    2013-02-01

    Early ecologists identified a pyramidal trophic structure in terms of number, biomass and energy transfer. In 1943, the psychologist Maslow put forward a pyramid model to describe layers of human needs. It is indicated that the pyramid principle is universally applicable in natural, humanistic and social disciplines. Here, we report that a pyramid structure also exists in urban public health (UPH). Based on 18 indicators, the UPH states of four cities (Beijing, Tokyo, New York, and London) are compared from the point of view of five aspects, namely physical health, living conditions, social security, environmental quality, and education and culture. A pyramid structure was found in each city when focusing on 2000-2009 data. The pyramid of Beijing is relatively similar to that of Tokyo, and the pyramids of New York and London are similar to each other. A general development trend in UPH is proposed and represented by different pyramid modes. As a basic conjecture, the UPH pyramid model can be verified and developed with data of more cities over a longer period, and be used to promote healthy urban development. PMID:23358233

  20. Estimate of size and total number of neurons in superior cervical ganglion of rat, capybara and horse.

    PubMed

    Ribeiro, Antonio Augusto Coppi Maciel; Davis, Christine; Gabella, Giorgio

    2004-08-01

    The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats, capybaras and horses, respectively. The average neuronal size (area of the largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras and horses, respectively. When comparing the three species (average body weight: 200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in line with the variation of body weight. However, the average neuronal size in the capybara deviates from this pattern in being larger than that of in the horse. The rat presented great interindividual variability in all the neuronal parameters. From the data in the literature and our new findings in the capybara and horse, we conclude that some correlations exist between average size of neurons and body size and between total number of neurons and body size. However, these correlations are only approximate and are based on averaged parameters for large populations of neurons: they are less likely to be valid if one considers a single quantitative parameter. Several quantitative features of the nervous tissue have to be taken into account together, rather than individually, when evolutionary trends related to size are considered.

  1. Blockade by ifenprodil of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N-methyl-D-aspartate receptor antagonist actions.

    PubMed Central

    Church, J; Fletcher, E J; Baxter, K; MacDonald, J F

    1994-01-01

    1. The block by ifenprodil of voltage-activated Ca2+ channels was investigated in intracellular free calcium concentration ([Ca2+]i) evoked by 50 mM K+ (high-[K+]o) in Fura-2-loaded rat hippocampal pyramidal neurones in culture and on currents carried by Ba2+ ions (IBa) through Ca2+ channels in mouse cultured hippocampal neurones under whole-cell voltage-clamp. The effects of ifenprodil on voltage-activated Ca2+ channels were compared with its antagonist actions on N-methyl-D-aspartate- (NMDA) evoked responses in the same neuronal preparations. 2. Rises in [Ca2+]i evoked by transient exposure to high-[K+]o in our preparation of rat cultured hippocampal pyramidal neurones are mediated predominantly by Ca2+ flux through nifedipine-sensitive Ca2+ channels, with smaller contributions from nifedipine-resistant, omega-conotoxin GVIA-sensitive Ca2+ channels and Ca2+ channels sensitive to crude funnel-web spider venom (Church et al., 1994). Ifenprodil (0.1-200 microM) reversibly attenuated high-[K+]o-evoked rises in [Ca2+]i with an IC50 value of 17 +/- 3 microM, compared with an IC50 value of 0.7 +/- 0.1 microM for the reduction of rises in [Ca2+]i evoked by 20 microM NMDA. Tested in the presence of nifedipine 10 microM, ifenprodil (1-50 microM) produced a concentration-dependent reduction of the dihydropyridine-resistant high-[K+]o-evoked rise in [Ca2+]i with an IC50 value of 13 +/- 4 microM. The results suggest that ifenprodil blocks Ca2+ flux through multiple subtypes of high voltage-activated Ca2+ channels. 3. Application of the polyamine, spermine (0.25-5 mM), produced a concentration-dependent reduction of rises in [Ca2+]i evoked by high-[K+]o.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834201

  2. Relationship between seizure frequency and number of neuronal and non-neuronal cells in the hippocampus throughout the life of rats with epilepsy.

    PubMed

    Lopim, Glauber Menezes; Vannucci Campos, Diego; Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Lent, Roberto; Cavalheiro, Esper Abrão; Arida, Ricardo Mario

    2016-03-01

    The relationship between seizure frequency and cell death has been a subject of controversy. To tackle this issue, we determined the frequency of seizures and the total number of hippocampal cells throughout the life of rats with epilepsy using the pilocarpine model. Seizure frequency varied in animals with epilepsy according to which period of life they were in, with a progressive increase in the number of seizures until 180 days (sixth months) of epileptic life followed by a decrease (330 days-eleventh month) and subsequently stabilization of seizures. Cell counts by means of isotropic fractionation showed a reduction in the number of hippocampal neuronal cells following 30, 90, 180 and 360 days of spontaneous recurrent seizures (SRS) in rats compared to their controls (about 25%-30% of neuronal cell reduction). In addition, animals with 360 days of SRS showed a reduction in the number of neuronal cells when compared with animals with 90 and 180 days of seizures. The total number of hippocampal non-neuronal cells was reduced in rats with epilepsy after 30 days of SRS, but no significant alteration was observed on the 90th, 180th and 360th days. The total number of neuronal cells was negatively correlated with seizure frequency, indicating an association between occurrence of epileptic seizures throughout life and neuronal loss. In sum, our results add novel data to the literature concerning the time-course of SRS and hippocampal cell number throughout epileptic life.

  3. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis.

    PubMed

    Scharfman, H E; Goodman, J H; Sollas, A L

    2000-08-15

    A group of neurons with the characteristics of dentate gyrus granule cells was found at the hilar/CA3 border several weeks after pilocarpine- or kainic acid-induced status epilepticus. Intracellular recordings from pilocarpine-treated rats showed that these "granule-like" neurons were similar to normal granule cells (i. e., those in the granule cell layer) in membrane properties, firing behavior, morphology, and their mossy fiber axon. However, in contrast to normal granule cells, they were synchronized with spontaneous, rhythmic bursts of area CA3 pyramidal cells that survived status epilepticus. Saline-treated controls lacked the population of granule-like cells at the hilar/CA3 border and CA3 bursts. In rats that were injected after status epilepticus with bromodeoxyuridine (BrdU) to label newly born cells, and also labeled for calbindin D(28K) (because it normally stains granule cells), many double-labeled neurons were located at the hilar/CA3 border. Many BrdU-labeled cells at the hilar/CA3 border also were double-labeled with a neuronal marker (NeuN). Taken together with the recent evidence that granule cells that are born after seizures can migrate into the hilus, the results suggest that some newly born granule cells migrate as far as the CA3 cell layer, where they become integrated abnormally into the CA3 network, yet they retain granule cell intrinsic properties. The results provide insight into the physiological properties of newly born granule cells in the adult brain and suggest that relatively rigid developmental programs set the membrane properties of newly born cells, but substantial plasticity is present to influence their place in pre-existing circuitry.

  4. Axospinous synaptic subtype-specific differences in structure, size, ionotropic receptor expression, and connectivity in apical dendritic regions of rat hippocampal CA1 pyramidal neurons

    PubMed Central

    Nicholson, Daniel A.; Geinisman, Yuri

    2008-01-01

    The morphology of axospinous synapses and their parent spines varies widely. Additionally, many of these synapses are contacted by multiple synapse boutons (MSBs) and show substantial variability in receptor expression. The two major axospinous synaptic subtypes are perforated and nonperforated, but there are several subcategories within these two classes. The present study used serial section electron microscopy to determine whether perforated and nonperforated synaptic subtypes differed with regard to their distribution, size, receptor expression, and connectivity to MSBs in three apical dendritic regions of rat hippocampal area CA1: the proximal and distal thirds of stratum radiatum, and stratum lacunosum-moleculare. All synaptic subtypes were present throughout the apical dendritic regions, but there were several subclass-specific differences. First, segmented, completely partitioned synapses changed in number, proportion, and AMPA receptor expression with distance from the soma beyond that found within other perforated synaptic subtypes. Second, atypically large nonperforated synapses showed NMDA receptor immunoreactivity identical to perforated synapses, levels of AMPA receptor expression intermediate to nonperforated and perforated synapses, and perforated synapse-like changes in structure with distance from the soma. Finally, MSB connectivity was highest in proximal stratum radiatum, but only for those MSBs comprised of nonperforated synapses. The immunogold data suggest that most MSBs would not generate simultaneous depolarizations in multiple neurons or spines, however, because the vast majority of MSBs are comprised of two synapses with abnormally low levels of receptor expression, or involve one synapse with a high level of receptor expression and another with only a low level. PMID:19006199

  5. Deletion of the L-type Calcium Channel CaV1.3 but not CaV1.2 Results in a Diminished sAHP in Mouse CA1 Pyramidal Neurons

    PubMed Central

    Gamelli, Amy E.; McKinney, Brandon C.; White, Jessica A.; Murphy, Geoffrey G.

    2009-01-01

    Trains of action potentials in CA1 pyramidal neurons are followed by a prolonged calcium-dependent post-burst afterhyperpolarization (AHP) that serves to limit further firing to a sustained depolarizing input. A reduction in the AHP accompanies acquisition of several types of learning and increases in the AHP are correlated with age-related cognitive impairment. The AHP develops primarily as the result of activation of outward calcium-activated potassium currents; however the precise source of calcium for activation of the AHP remains unclear. There is substantial experimental evidence suggesting that calcium influx via voltage-gated L-type calcium channels (L-VGCCs) contributes to the generation of the AHP. Two L-VGCC subtypes are predominately expressed in the hippocampus, CaV1.2 and CaV1.3, however it is not known which L-VGCC subtype is involved in generation of the AHP. This ambiguity is due in large part to the fact that at present there are no subunit-specific agonists or antagonists. Therefore, using mice in which the gene encoding CaV1.2 or CaV1.3 was deleted, we sought to determine the impact of alterations in levels of these two L-VCGG subtypes on neuronal excitability. No differences in any AHP measure were seen between neurons from CaV1.2 knockout mice and controls. However, the total area of the AHP was significantly smaller in neurons from CaV1.3 knockout mice as compared to neurons from wildtype controls. A significant reduction in the amplitude of the AHP was also seen at the 1 sec time point in neurons from CaV1.3 knockout mice as compared to those from controls. Reductions in both the area and 1 sec amplitude suggest the involvement of calcium influx via CaV1.3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that deletion of CaV1.3, but not CaV1.2, significantly impacts the generation of the sAHP. PMID:20014384

  6. Pyramid beam splitter

    DOEpatents

    McKeown, Mark H.; Beason, Steven C.; Fairer, George

    1992-01-01

    The apparatus of the present invention provides means for obtaining accurate, dependable, measurement of bearings and directions for geologic mapping in subterranean shafts, such as, for example, nuclear waste storage investigations. In operation, a laser beam is projected along a reference bearing. A pyramid is mounted such that the laser beam is parallel to the pyramid axis and can impinge on the apex of the pyramid thus splitting the beam several ways into several beams at right angles to each other and at right angles to the reference beam. The pyramid is also translatable and rotatable in a plane perpendicular to the reference beam.

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

    PubMed Central

    Loucif, Alexandre J. C.; Schubert, Dirk; Möck, Martin

    2016-01-01

    Layer Vb pyramidal cells are the major output neurons of the neocortex and transmit the outcome of cortical columnar signal processing to distant target areas. At the same time they contribute to local tactile information processing by emitting recurrent axonal collaterals into the columnar microcircuitry. It is, however, not known how exactly the two types of pyramidal cells, called slender-tufted and thick-tufted, contribute to the local circuitry. Here, we investigated in the rat barrel cortex the detailed quantitative morphology of biocytin-filled layer Vb pyramidal cells in vitro, which were characterized for their intrinsic electrophysiology with special emphasis on their action potential firing pattern. Since we stained the same slices for cytochrome oxidase, we could also perform layer- and column-related analyses. Our results suggest that in layer Vb the unambiguous action potential firing patterns "regular spiking (RS)" and "repetitive burst spiking (RB)" (previously called intrinsically burst spiking) correlate well with a distinct morphology. RS pyramidal cells are somatodendritically of the slender-tufted type and possess numerous local intralaminar and intracolumnar axonal collaterals, mostly reaching layer I. By contrast, their transcolumnar projections are less well developed. The RB pyramidal cells are somatodendritically of the thick-tufted type and show only relatively sparse local axonal collaterals, which are preferentially emitted as long horizontal or oblique infragranular collaterals. However, contrary to many previous slice studies, a substantial number of these neurons also showed axonal collaterals reaching layer I. Thus, electrophysiologically defined pyramidal cells of layer Vb show an input and output pattern which suggests RS cells to be more "locally segregating" signal processors whereas RB cells seem to act more on a "global integrative" scale. PMID:27706253

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

    NASA Technical Reports Server (NTRS)

    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.

  9. Rebuilding the Food Pyramid.

    ERIC Educational Resources Information Center

    Willet, Walter C.; Stampfer, Meir J.

    2003-01-01

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

  10. 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid stimulates GABA release from interneurons projecting to CA1 pyramidal neurons in the rat hippocampus via pre-synaptic alpha7 acetylcholine receptors.

    PubMed

    Kanno, Takeshi; Yaguchi, Takahiro; Yamamoto, Satoshi; Yamamoto, Hideyuki; Fujikawa, Hirokazu; Nagata, Tetsu; Tanaka, Akito; Nishizaki, Tomoyuki

    2005-11-01

    Nicotinic acetylcholine (ACh) receptors, such as alpha7, alpha3beta4 and alpha4beta2 receptors in the hippocampus, are suggested to modulate neurotransmitter release. 8-[2-(2-Pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (100 nM), a linoleic acid derivative, potentiated responses of alpha7, alpha3beta4 and alpha4beta2 ACh receptors expressed in Xenopus oocytes that are blocked by 3-(1-[dimethylaminopropyl] indol-3-yl)-4-[indol-3-yl] maleimide (GF109203X), a selective inhibitor of protein kinase C (PKC), except for alpha3beta4 ACh receptors. DCP-LA enhanced the nicotine-triggered release of GABA from rat hippocampal slices in the presence of tetrodotoxin in a bell-shaped dose-dependent manner at concentrations ranging from 10 nM to 10 microM, although DCP-LA by itself had no effect on GABA release. The DCP-LA action was inhibited by GF109203X or alpha-bungarotoxin, an inhibitor of alpha7 ACh receptors, but not by mecamylamine or dihydro-beta-erithroidine, an inhibitor of alpha3beta4 and alpha4beta2 ACh receptors. A similar effect on GABA release was obtained with 12-O-tetradecanoylphorbol 13-acetate, a PKC activator. DCP-LA (100 nM) also enhanced GABA release triggered by choline, an agonist of alpha7 ACh receptors, but not 3-[2(s)-azetidinylmethoxy] pyridine, an agonist of alpha4beta2 ACh receptors. In addition, DCP-LA (100 nM) increased the rate of nicotine-triggered GABA(A) receptor-mediated miniature inhibitory post-synaptic currents, monitored from CA1 pyramidal neurons of rat hippocampal slices, and the effect was also inhibited by GF109203X or alpha-bungarotoxin but not by mecamylamine. Thus, the results of the present study indicate that DCP-LA stimulates GABA release by enhancing activity of pre-synaptic alpha7 ACh receptors present on the GABAergic terminals of interneurons that transmit to CA1 pyramidal neurons via a PKC pathway. PMID:16248884

  11. Submillisecond precision of the input-output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons.

    PubMed

    Ariav, Gal; Polsky, Alon; Schiller, Jackie

    2003-08-27

    The ability of cortical neurons to perform temporally accurate computations has been shown to be important for encoding of information in the cortex; however, cortical neurons are expected to be imprecise temporal encoders because of the stochastic nature of synaptic transmission and ion channel gating, dendritic filtering, and background synaptic noise. Here we show for the first time that fast local spikes in basal dendrites can serve to improve the temporal precision of neuronal output. Integration of coactivated, spatially distributed synaptic inputs produces temporally imprecise output action potentials within a time window of several milliseconds. In contrast, integration of closely spaced basal inputs initiates local dendritic spikes that amplify and sharpen the summed somatic potential. In turn, these fast basal spikes allow precise timing of output action potentials with submillisecond temporal jitter over a wide range of activation intensities and background synaptic noise. Our findings indicate that fast spikes initiated in individual basal dendrites can serve as precise "timers" of output action potentials in various network activity states and thus may contribute to temporal coding in the cortex.

  12. Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression.

    PubMed

    Chen, Fenghua; Madsen, Torsten M; Wegener, Gregers; Nyengaard, Jens R

    2010-12-01

    The aim was to investigate treatment effects of the antidepressant imipramine on the markers of neuronal plasticity. We investigated changes in neuron and synapse numbers in a rat strain that displays a genetic susceptibility to depressive behavior, the Flinders Sensitive and Resistant Lines (FSL/FRL). All rats were treated with imipramine (15 mg/kg) or saline (i.p) once daily for 25 days. The volume, neuron and synapse numbers in the hippocampus were estimated using design-based stereological methods. Under untreated conditions, the volume and the number of neurons and synapses were significantly smaller in the FSL saline group (untreated "depressed" rats) compared with the FRL saline group (normal rats), showing correlation to the observed decreased immobility in the forced swim test. Imipramine treatment significantly increased the number of neurons in the granule cell layer (GCL) and spine synapses in the CA1 in the FSL imipramine group (treated "depressed" rats) compared with the FSL saline group. The neuron numbers in the GCL and Hilus showed no differences in the FSL imipramine group compared to the FRL saline group. In conclusion, baseline levels of the volume and the number of neurons and spine synapses in hippocampus were significantly smaller in the untreated FSL rats. Our findings indicate that chronic imipramine treatment reverses the suppression of neurogenesis and synaptogenesis in the hippocampus of the "depressed" FSL rats, and this occurs in correlation with behavioral effects. Our results support the neuronal plasticity hypothesis that depressive disorders may be related to impairments of structural plasticity and neuronal viability in hippocampus, furthermore, antidepressant treatment counteracts the structural impairments.

  13. A synaptic organizing principle for cortical neuronal groups

    PubMed Central

    Perin, Rodrigo; Berger, Thomas K.; Markram, Henry

    2011-01-01

    Neuronal circuitry is often considered a clean slate that can be dynamically and arbitrarily molded by experience. However, when we investigated synaptic connectivity in groups of pyramidal neurons in the neocortex, we found that both connectivity and synaptic weights were surprisingly predictable. Synaptic weights follow very closely the number of connections in a group of neurons, saturating after only 20% of possible connections are formed between neurons in a group. When we examined the network topology of connectivity between neurons, we found that the neurons cluster into small world networks that are not scale-free, with less than 2 degrees of separation. We found a simple clustering rule where connectivity is directly proportional to the number of common neighbors, which accounts for these small world networks and accurately predicts the connection probability between any two neurons. This pyramidal neuron network clusters into multiple groups of a few dozen neurons each. The neurons composing each group are surprisingly distributed, typically more than 100 μm apart, allowing for multiple groups to be interlaced in the same space. In summary, we discovered a synaptic organizing principle that groups neurons in a manner that is common across animals and hence, independent of individual experiences. We speculate that these elementary neuronal groups are prescribed Lego-like building blocks of perception and that acquired memory relies more on combining these elementary assemblies into higher-order constructs. PMID:21383177

  14. Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain

    PubMed Central

    Trujillo-Paredes, Niurka; Valencia, Concepción; Guerrero-Flores, Gilda; Arzate, Dulce-María; Baizabal, José-Manuel; Guerra-Crespo, Magdalena; Fuentes-Hernández, Ayari; Zea-Armenta, Iván; Covarrubias, Luis

    2016-01-01

    ABSTRACT Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+). These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons. PMID:26912775

  15. The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer's Disease.

    PubMed

    Hansen, Henrik H; Fabricius, Katrine; Barkholt, Pernille; Niehoff, Michael L; Morley, John E; Jelsing, Jacob; Pyke, Charles; Knudsen, Lotte Bjerre; Farr, Susan A; Vrang, Niels

    2015-01-01

    Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of amyloid-β plaques or hyperphosphorylated tau, indicating the onset of cognitive deficits prior to deposition of amyloid plaques and neurofibrillary tangles in this AD model. Liraglutide significantly increased memory retention and total hippocampal CA1 pyramidal neuron numbers in SAMP8 mice, as compared to age-matched vehicle-dosed SAMP8 mice. In conclusion, liraglutide delayed or partially halted the progressive decline in memory function associated with hippocampal neuronal loss in a mouse model of pathological aging with characteristics of neurobehavioral and neuropathological impairments observed in early-stage sporadic AD.

  16. The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer’s Disease

    PubMed Central

    Hansen, Henrik H.; Fabricius, Katrine; Barkholt, Pernille; Niehoff, Michael L.; Morley, John E.; Jelsing, Jacob; Pyke, Charles; Knudsen, Lotte Bjerre; Farr, Susan A.; Vrang, Niels

    2015-01-01

    Abstract Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer’s disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of amyloid-β plaques or hyperphosphorylated tau, indicating the onset of cognitive deficits prior to deposition of amyloid plaques and neurofibrillary tangles in this AD model. Liraglutide significantly increased memory retention and total hippocampal CA1 pyramidal neuron numbers in SAMP8 mice, as compared to age-matched vehicle-dosed SAMP8 mice. In conclusion, liraglutide delayed or partially halted the progressive decline in memory function associated with hippocampal neuronal loss in a mouse model of pathological aging with characteristics of neurobehavioral and neuropathological impairments observed in early-stage sporadic AD. PMID:25869785

  17. Isotropic fractionator: a simple, rapid method for the quantification of total cell and neuron numbers in the brain.

    PubMed

    Herculano-Houzel, Suzana; Lent, Roberto

    2005-03-01

    Stereological techniques that estimate cell numbers must be restricted to well defined structures of isotropic architecture and therefore do not apply to the whole brain or to large neural regions. We developed a novel, fast, and inexpensive method to quantify total numbers of neuronal and non-neuronal cells in the brain or any dissectable regions thereof. It consists of transforming highly anisotropic brain structures into homogeneous, isotropic suspensions of cell nuclei, which can be counted and identified immunocytochemically as neuronal or non-neuronal. Estimates of total cell, neuronal, and non-neuronal numbers can be obtained in 24 h and vary by <10% among animals. Because the estimates obtained are independent of brain volume, they can be used in comparative studies of brain-volume variation among species and in studies of phylogenesis, development, adult neurogenesis, and pathology. Applying this method to the adult rat brain, we show, for example, that it contains approximately 330 million cells, of which 200 million are neurons, and almost 70% of these are located in the cerebellum alone. Moreover, contrary to what is commonly assumed in the literature, we show that glial cells are not the majority in the rat brain.

  18. The lathyrus toxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid

    SciTech Connect

    Chase, L.A. . E-mail: chase@hope.edu; Peterson, N.L. . E-mail: nlpeterson@noctrl.edu; Koerner, J.F. . E-mail: koern003@umn.edu

    2007-02-15

    A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the endogenous compound, L-cystine. This phenomenon has been termed QUIS sensitization. A mechanism similar to that previously described for QUIS neurotoxicity has been proposed to describe QUIS sensitization. Specifically, QUIS has been shown to be sequestered into GABAergic interneurons by the System x{sub c} {sup -} and subsequently released by heteroexchange with cystine or L-AP6, resulting in activation of non-NMDA receptors. We now report two additional neurotoxins, the Lathyrus excitotoxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and the endogenous compound, L-homocysteic acid (HCA), sensitize CA1 hippocampal neurons > 50-fold to L-AP6 and > 10-fold to cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP- or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA agonist that induces phosphonate or cystine sensitization. Like QUIS sensitization, the sensitization evoked by either ODAP or HCA can be reversed by a subsequent exposure to 2 mM {alpha}-aminoadipic acid. Finally, we have demonstrated that there is a correlation between the potency of inducers for triggering phosphonate or cystine sensitivity and their affinities for System x{sub c} {sup -} and either the non-NMDA or NMDA receptor. Thus, the results of this study support our previous model of QUIS sensitization and have important implications for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.

  19. Distinct mechanisms of spike timing‐dependent LTD at vertical and horizontal inputs onto L2/3 pyramidal neurons in mouse barrel cortex

    PubMed Central

    Banerjee, Abhishek; González‐Rueda, Ana; Sampaio‐Baptista, Cassandra; Paulsen, Ole; Rodríguez‐Moreno, Antonio

    2014-01-01

    Abstract Spike timing‐dependent plasticity (STDP) is an attractive candidate to mediate the synaptic changes that support circuit plasticity in sensory cortices during development. STDP is prevalent at excitatory synapses, but it is not known whether the underlying mechanisms are universal, or whether distinct mechanisms underpin STDP at different synapses. Here, we set out to compare and contrast STDP at vertical layer 4 and horizontal layer 2/3 inputs onto postsynaptic layer 2/3 neurons in the mouse barrel cortex. We find that both vertical and horizontal inputs show STDP, but that they display different time windows for induction of timing‐dependent long‐term depression (t‐LTD). Moreover, whereas t‐LTD at vertical inputs requires presynaptic NMDA receptors and is expressed presynaptically, using paired recordings we find that t‐LTD at horizontal inputs requires postsynaptic NMDA receptors and is expressed postsynaptically. These results demonstrate that similar forms of plasticity on the same postsynaptic neuron can be mediated by distinct mechanisms, and suggest that these forms of plasticity may enable these two types of cortical synapses to support different functions. PMID:24760524

  20. Motor neuron disease with pyramidal tract dysfunction involves the cortical generators of the early somatosensory evoked potential to tibial nerve stimulation.

    PubMed

    Zanette, G; Tinazzi, M; Polo, A; Rizzuto, N

    1996-10-01

    We evaluated somatosensory evoked potentials (SEPs) to tibial nerve stimulation in 39 patients with sporadic motor neuron disease using multiple scalp derivations (earlobe reference). SEPs were altered in 22 of 29 amyotrophic lateral sclerosis (ALS) patients, whereas they were unaffected in 10 progressive muscular atrophy (PMA) patients. The main changes involved the amplitude and the field distribution of the early P40 and N37 cortical potentials with different modalities varying from a selective loss of the P40 potential (33% of tested sides) to absence of all early cortical SEPs (22% of tested sides). The later components following N50 were generally spared. The commonly used Cz-Fz montage was inadequate for detecting these alterations. Central afferent conduction was slightly affected. The selective loss of cortical SEPs and their close correlation with clinicoelectrophysiologic evidence of central motor system involvement strongly support a cortical origin of the SEP alterations in ALS. We suggest that neuronal loss in the somatosensory cortex may selectively affect the generator sites of the cortical SEPs to lower limb stimulation. PMID:8857722

  1. A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia.

    PubMed

    Sapin, Emilie; Bérod, Anne; Léger, Lucienne; Herman, Paul A; Luppi, Pierre-Hervé; Peyron, Christelle

    2010-07-26

    We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67) mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67)in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+), Fos-ir/MCH(+), and GAD(+)/MCH(+) double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+) neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.

  2. No Reduction of Spindle Neuron Number in Frontoinsular Cortex in Autism

    ERIC Educational Resources Information Center

    Kennedy, Daniel P.; Semendeferi, Katerina; Courchesne, Eric

    2007-01-01

    It has been suggested that spindle neurons, an evolutionarily unique type of neuron, might be involved in higher-order social, emotional, and cognitive functions. As such, it was hypothesized that these neurons may be particularly important to the pathophysiology of autism, a disease characterized in part by disruption of higher-order social and…

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-01

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

  5. Evidence for a postnatal doubling of neuron number in the developing human cerebral cortex between 15 months and 6 years.

    PubMed

    Shankle, W R; Landing, B H; Rafii, M S; Schiano, A; Chen, J M; Hara, J

    1998-03-21

    The generalization of the finding of no postnatal neurogenesis in non-human primates to humans may be incorrect because: (1) rhesus macaques belong to a superfamily that diverged more than 25 million years ago from the superfamily including the genus Homo; (2) the pulse thymidine labeling method, which demonstrates DNA synthesis rather than mitosis per se, is less reliable than some have assumed. This study examines changes in the number of neurons in a column underneath a cortical surface area of 1 mm2, extending through all cortical layers (mm2-column) for 35 gyri (representing about 73% of the human cerebral cortex) based on the data of J.L. Conel (1939 to 1967). We corrected these data, derived from his measures of cortical neuronal packing density, somal breadth and height, and cortical layer thickness at postnatal ages 0, 1, 3, 6, 15, 24, 48, and 72 months, for shrinkage and stereological errors. In all 35 gyri, neuron number/mm2-column: (1) initially declines (mu = 46% decline, sigma = 8%), 95% of which is due to surface area expansion (mean age of nadir value = 15.8 months); (2) then increases to age 72 months by 70% (mu = 1.7-fold increase, (mu rate = 1.1% per month). Because of a a concomitant 1.3-fold increase in cortical surface from 15 to 72 months, total cortical neuron number increases 2.2-fold. The close agreement between neuron number/mm2-column for Conel's age 72-month data to the corresponding values reported by others for adult human and primate cortex using more modern methods suggests the finding is not an artifact. Neuronal proliferative fate-determining factors provide at least four mechanisms for increasing cortical neuron number postnatally, with or without DNA synthesis. PMID:9631564

  6. Protein tyrosine phosphatase σ regulates the synapse number of zebrafish olfactory sensory neurons.

    PubMed

    Chen, Xigui; Yoshida, Tomoyuki; Sagara, Hiroshi; Mikami, Yoshinori; Mishina, Masayoshi

    2011-11-01

    The formation and refinement of synaptic connections are key steps of neural development to establish elaborate brain networks. To investigate the functional role of protein tyrosine phosphatase (PTP) σ, we employed an olfactory sensory neuron (OSN)-specific gene manipulation system in combination with in vivo imaging of transparent zebrafish embryos. Knockdown of PTPσ enhanced the accumulation of synaptic vesicles in the axon terminals of OSNs. The exaggerated accumulation of synaptic vesicles was restored to the normal level by the OSN-specific expression of PTPσ, indicating that presynaptic PTPσ is responsible for the regulation of synaptic vesicle accumulation. Consistently, transient expression of a dominant-negative form of PTPσ in OSNs enhanced the accumulation of synaptic vesicles. The exaggerated accumulation of synaptic vesicles was reproduced in transgenic zebrafish lines carrying an OSN-specific expression vector of the dominant-negative PTPσ. By electron microscopic analysis of the transgenic line, we found the significant increase of the number of OSN-mitral cell synapses in the central zone of the olfactory bulb. The density of docked vesicles at the active zone was also increased significantly. Our results suggest that presynaptic PTPσ controls the number of OSN-mitral cell synapses by suppressing their excessive increase.

  7. Decreased Oligodendrocyte and Neuron Number in Anterior Hippocampal Areas and the Entire Hippocampus in Schizophrenia: A Stereological Postmortem Study.

    PubMed

    Falkai, Peter; Malchow, Berend; Wetzestein, Katharina; Nowastowski, Verena; Bernstein, Hans-Gert; Steiner, Johann; Schneider-Axmann, Thomas; Kraus, Theo; Hasan, Alkomiet; Bogerts, Bernhard; Schmitz, Christoph; Schmitt, Andrea

    2016-07-01

    The hippocampus is involved in cognition as well as emotion, with deficits in both domains consistently described in schizophrenia. Moreover, the whole volumes of both the anterior and posterior region have been reported to be decreased in schizophrenia patients. While fewer oligodendrocyte numbers in the left and right cornu ammonis CA4 subregion of the posterior part of the hippocampus have been reported, the aim of this stereological study was to investigate cell numbers in either the dentate gyrus (DG) or subregions of the anterior hippocampus. In this design-based stereological study of the anterior part of the hippocampus comparing 10 patients with schizophrenia to 10 age- and gender-matched healthy controls were examined. Patients showed a decreased number of oligodendrocytes in the left CA4, fewer neurons in the left DG and smaller volumes in both the left CA4 and DG, which correlated with oligodendrocyte and neuron numbers, respectively. When exploring the total hippocampus, keeping previously published own results from the posterior part of the same brains in mind, both decreased oligodendrocyte numbers in the left CA4 and reduced volume remained significant. The decreased oligodendrocyte number speaks for a deficit in myelination and connectivity in schizophrenia which may originate from disturbed maturational processes. The reduced neuron number of the DG in the anterior hippocampus may well point to a reduced capacity of this region to produce new neurons up to adulthood. Both mechanisms may be involved in cognitive dysfunction in schizophrenia patients. PMID:27460617

  8. Potentiation by sevoflurane of the gamma-aminobutyric acid-induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus.

    PubMed Central

    Wu, J.; Harata, N.; Akaike, N.

    1996-01-01

    1. The effects of a new kind of volatile anaesthetic, sevoflurane (Sev), on gamma-aminobutyric acid (GABA)-gated chloride current (Icl) in single neurones dissociated from the rat hippocampal CA1 area were examined using the nystatin perforated patch recording configuration under the voltage-clamp condition. All drugs were applied with a rapid perfusion system, termed the "Y-tube' method. 2. When the concentrations were higher than 3 x 10(-4) M, Sev, itself, induced an inward current (ISev) at a holding potential (VH) of -40 mV. The concentration-response curve of ISev was bell-shaped, with a suppressed peak and plateau currents at high concentrations (above 2 x 10(-3) M). The reversal potential of ISev (ESev) was close to the theoretical Cl- equilibrium potential, indicating that ISev was carried mainly by Cl-. 3. ISev was reversibly blocked by bicuculline (Bic), an antagonist of the GABAA receptor, in a concentration-dependent manner with a half-inhibitory concentration (IC50) of 7.2 x 10(-7) M. But ISev was insensitive to strychnine (Str), an antagonist of the glycine receptor. 4. At low concentrations (between 3 x 10(-4) and 10(-3) M), Sev markedly enhanced the 10(-6) M GABA induced current (IGABA) but reduced the IGABA with accelerating desensitization accompanied by a "hump' current after washout at high concentrations (higher than 2 x 10(-3) M). 5. Sev, 10(-3) M potentiated the current induced by low concentrations of GABA (between 10(-7) and 3 x 10(-6) M) but reduced the current induced by high concentrations (higher than 10(-5) M) of GABA with a clear acceleration of IGABA desensitization. 6. Sev, like pentobarbitone (PB), pregnanolone (PGN) or diazepam (DZP), potentiated the 10(-6) M GABA-induced response without shifting the reversal potential of IGABA. 7. ISev was augmented by PB, PGN, or DZP at concentrations that maximally potentiated IGABA, suggesting that Sev enhanced IGABA at a binding site distinct from that for PB, PGN, or DZP. 8. It is concluded

  9. Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

    PubMed Central

    Iacono, Diego; Geraci-Erck, Maria; Peng, Hui; Rabin, Marcie L.; Kurlan, Roger

    2015-01-01

    Background Dystonias (Dys) represent the third most common movement disorder after essential tremor (ET) and Parkinson's disease (PD). While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG), and specifically in the substantia nigra (SN). Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia) have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age-matched control subjects (C). Results We observed a significant reduction (∼20%) of pigmented neurons in the SN of Dys compared to C (p<0.01). Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co-occurring SN pathologies including Lewy pathology, tau-neurofibrillary tangles, β-amyloid deposits, ubiquitin (ubiq), and phosphorylated-TAR DNA-binding protein 43 (pTDP43)-positive inclusions. Discussion A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN. PMID:26069855

  10. beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects.

    PubMed

    Procter, A W; Francis, P T; Holmes, C; Webster, M T; Qume, M; Stratmann, G C; Doshi, R; Mann, D M; Harrison, P J; Pearson, R C

    1994-01-01

    Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity. PMID:7879601

  11. Pyramid image codes

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.

    1990-01-01

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

  12. Decreasing sleep requirement with increasing numbers of neurons as a driver for bigger brains and bodies in mammalian evolution

    PubMed Central

    Herculano-Houzel, Suzana

    2015-01-01

    Mammals sleep between 3 and 20 h d−1, but what regulates daily sleep requirement is unknown. While mammalian evolution has been characterized by a tendency towards larger bodies and brains, sustaining larger bodies and brains requires increasing hours of feeding per day, which is incompatible with a large sleep requirement. Mammalian evolution, therefore, must involve mechanisms that tie increasing body and brain size to decreasing sleep requirements. Here I show that daily sleep requirement decreases across mammalian species and in rat postnatal development with a decreasing ratio between cortical neuronal density and surface area, which presumably causes sleep-inducing metabolites to accumulate more slowly in the parenchyma. Because addition of neurons to the non-primate cortex in mammalian evolution decreases this ratio, I propose that increasing numbers of cortical neurons led to decreased sleep requirement in evolution that allowed for more hours of feeding and increased body mass, which would then facilitate further increases in numbers of brain neurons through a larger caloric intake per hour. Coupling of increasing numbers of neurons to decreasing sleep requirement and increasing hours of feeding thus may have not only allowed but also driven the trend of increasing brain and body mass in mammalian evolution. PMID:26400745

  13. Decreasing sleep requirement with increasing numbers of neurons as a driver for bigger brains and bodies in mammalian evolution.

    PubMed

    Herculano-Houzel, Suzana

    2015-10-01

    Mammals sleep between 3 and 20 h d(-1), but what regulates daily sleep requirement is unknown. While mammalian evolution has been characterized by a tendency towards larger bodies and brains, sustaining larger bodies and brains requires increasing hours of feeding per day, which is incompatible with a large sleep requirement. Mammalian evolution, therefore, must involve mechanisms that tie increasing body and brain size to decreasing sleep requirements. Here I show that daily sleep requirement decreases across mammalian species and in rat postnatal development with a decreasing ratio between cortical neuronal density and surface area, which presumably causes sleep-inducing metabolites to accumulate more slowly in the parenchyma. Because addition of neurons to the non-primate cortex in mammalian evolution decreases this ratio, I propose that increasing numbers of cortical neurons led to decreased sleep requirement in evolution that allowed for more hours of feeding and increased body mass, which would then facilitate further increases in numbers of brain neurons through a larger caloric intake per hour. Coupling of increasing numbers of neurons to decreasing sleep requirement and increasing hours of feeding thus may have not only allowed but also driven the trend of increasing brain and body mass in mammalian evolution.

  14. Neuronal number and volume alterations in the neocortex of HIV infected individuals.

    PubMed Central

    Everall, I P; Luthert, P J; Lantos, P L

    1993-01-01

    Substantial neuronal loss in the superior frontal gyrus in patients who have died of AIDS have been reported previously. This investigation examined the distribution of neuronal loss in three other neocortical areas and, alteration in neuronal volume in four neocortical areas. This was carried out using two stereological probes, the "disector" and the "nucleator". These recently developed methods provide estimations, regardless of size and shape, in real three-dimensional space, and are more efficient than conventional quantitation. The study was performed on 12 HIV infected individuals and nine controls. The HIV group had no neuropathological evidence of opportunistic infections or neoplasms, five had HIV encephalitis and the remaining seven had only minimal pathology. There was significant neuronal loss of 30% (p = 0.018) in the calcarine cortex (primary visual area), and loss of 18% in the superior parietal lobule which just failed to reach significance. This loss was not related to the presence of HIV encephalitis. The mean neuronal volume was increased in the occipital area by 29% (p = 0.028) and the frequency of large neurons (over 2000 microns 3) doubled in the frontal (p < 0.05) and parietal (p < 0.02) areas. The results confirm the hypothesis that HIV infection is associated with neuronal injury and death, and suggest that increase in neuronal size may be a feature of the cytopathology of this condition. PMID:8505639

  15. Numbers And Gains Of Neurons In Winner-Take-All Networks

    NASA Technical Reports Server (NTRS)

    Brown, Timothy X.

    1993-01-01

    Report presents theoretical study of gains required in neurons to implement winner-take-all electronic neural network of given size and related question of maximum size of winner-take-all network in which neurons have specified sigmoid transfer or response function with specified gain.

  16. Morphological characterization of slow and fast pyramidal tract cells in the cat.

    PubMed

    Deschênes, M; Labelle, A; Landry, P

    1979-12-14

    In adult cats the morphology of slow and fast pyramidal tract (Pt) neurons was studied following intracellular HRP injections and Golgi impregnation. Both types of neurons are pyramidal cells and their soma are all located in the fifth layer of the motor area. As a rule, fast Pt neurons have large somata and their basal and apical dendrites occupy a larger territory in the tangential plane. In layer I, terminal apical dendrites of fast Pt neurons are smooth and divide poorly while those of slow Pt neurons bear a moderate amount of spines and branch profusely. Midway between the pia and layer V, in the third layer, the apical shafts of both types of Pt cells run upward with little branching. These shafts are more numerous in fast Pt cells (7 to 16) and they are almost devoid of spines. Those of slow Pt cells in layer III number between 5 and 9 and are densely covered with spines. Oblique and horizontal branches of slow and fast Pt neurons extend in layer V and some of them invade the lower part of layer III. It is suggested that this zone corresponds to a true fourth layer in the motor area. In both types of cells oblique and lateral branches bear numerous spines. Within the basal dendritic territory of Pt cells, one has to distinguish two dendritic systems: a short and a long one. The former spreads downward obliquely and appears to remain within layer V. The latter is made up of long descending vertical (antiapical) and oblique dendrites (tap root). While both types of cells may have long antiapical dendrites that run down radially to the lower part of layer VI, tap root dendrites which expand laterally below the cell body for considerable distances are a distinctive feature of fast Pt neurons. Though basal dendrites of all Pt cells bear spines, their number, distribution and shape are very variable in fast Pt cells.

  17. Comparing Volumes of Prisms and Pyramids

    ERIC Educational Resources Information Center

    Vinogradova, Natalya

    2012-01-01

    Students' experience in using formulas for volumes is often limited to substituting numbers into given formulas. An activity presented in this article may help students make connections between the formulas for volumes of prisms and volumes of pyramids. In addition, some interesting facts from number theory arise, demonstrating strong connections…

  18. Clusters of synaptic inputs on dendrites of layer 5 pyramidal cells in mouse visual cortex

    PubMed Central

    Gökçe, Onur; Bonhoeffer, Tobias; Scheuss, Volker

    2016-01-01

    The spatial organization of synaptic inputs on the dendritic tree of cortical neurons plays a major role for dendritic integration and neural computations, yet, remarkably little is known about it. We mapped the spatial organization of glutamatergic synapses between layer 5 pyramidal cells by combining optogenetics and 2-photon calcium imaging in mouse neocortical slices. To mathematically characterize the organization of inputs we developed an approach based on combinatorial analysis of the likelihoods of specific synapse arrangements. We found that the synapses of intralaminar inputs form clusters on the basal dendrites of layer 5 pyramidal cells. These clusters contain 4 to 14 synapses within ≤30 µm of dendrite. According to the spatiotemporal characteristics of synaptic summation, these numbers suggest that there will be non-linear dendritic integration of synaptic inputs during synchronous activation. DOI: http://dx.doi.org/10.7554/eLife.09222.001 PMID:27431612

  19. Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

    PubMed

    González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

    2016-02-01

    The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training.

  20. Mnemonic Functions for Nonlinear Dendritic Integration in Hippocampal Pyramidal Circuits.

    PubMed

    Kaifosh, Patrick; Losonczy, Attila

    2016-05-01

    We present a model for neural circuit mechanisms underlying hippocampal memory. Central to this model are nonlinear interactions between anatomically and functionally segregated inputs onto dendrites of pyramidal cells in hippocampal areas CA3 and CA1. We study the consequences of such interactions using model neurons in which somatic burst-firing and synaptic plasticity are controlled by conjunctive processing of these separately integrated input pathways. We find that nonlinear dendritic input processing enhances the model's capacity to store and retrieve large numbers of similar memories. During memory encoding, CA3 stores heavily decorrelated engrams to prevent interference between similar memories, while CA1 pairs these engrams with information-rich memory representations that will later provide meaningful output signals during memory recall. While maintaining mathematical tractability, this model brings theoretical study of memory operations closer to the hippocampal circuit's anatomical and physiological properties, thus providing a framework for future experimental and theoretical study of hippocampal function. PMID:27146266

  1. GABAergic Somatostatin-immunoreactive Neurons in the Amygdala Project to the Entorhinal Cortex

    PubMed Central

    McDonald, Alexander J.; Zaric, Violeta

    2015-01-01

    The entorhinal cortex and other hippocampal and parahippocampal cortices are interconnected by a small number of GABAergic nonpyramidal neurons in addition to glutamatergic pyramidal cells. Since the cortical and basolateral amygdalar nuclei have cortex-like cell types and have robust projections to the entorhinal cortex, we hypothesized that a small number of amygdalar GABAergic nonpyramidal neurons might participate in amygdalo-entorhinal projections. To test this hypothesis we combined Fluorogold (FG) retrograde tract tracing with immunohistochemistry for the amygdalar nonpyramidal cell markers glutamic acid decarboxylase (GAD), parvalbumin (PV), somatostatin (SOM), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and the m2 muscarinic cholinergic receptor (M2R). Injections of FG into the rat entorhinal cortex labeled numerous neurons that were mainly located in the cortical and basolateral nuclei of the amygdala. Although most of these amygdalar FG+ neurons labeled by entorhinal injections were large pyramidal cells, 1–5% were smaller long-range nonpyramidal neurons (LRNP neurons) that expressed SOM, or both SOM and NPY. No amygdalar FG+ neurons in these cases were PV+ or VIP+. Cell counts revealed that LRNP neurons labeled by injections into the entorhinal cortex constituted about 10–20% of the total SOM+ population, and 20–40% of the total NPY population in portions of the lateral amygdalar nucleus that exhibited a high density of FG+ neurons. Sixty-two percent of amygdalar FG+/SOM+ neurons were GAD+, and 51% were M2R+. Since GABAergic projection neurons typically have low perikaryal levels of GABAergic markers, it is actually possible that most or all of the amygdalar LRNP neurons are GABAergic. Like GABAergic LRNP neurons in hippocampal/parahippocampal regions, amygdalar LRNP neurons that project to the entorhinal cortex are most likely involved in synchronizing oscillatory activity between the two regions. These oscillations could entrain

  2. Inverting the Achievement Pyramid

    ERIC Educational Resources Information Center

    White-Hood, Marian; Shindel, Melissa

    2006-01-01

    Attempting to invert the pyramid to improve student achievement and increase all students' chances for success is not a new endeavor. For decades, educators have strategized, formed think tanks, and developed school improvement teams to find better ways to improve the achievement of all students. Currently, the No Child Left Behind Act (NCLB) is…

  3. Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis.

    PubMed

    Nirgudkar, Pranita; Taylor, Devin H; Yanagawa, Yuchio; Valenzuela, C Fernando

    2016-10-01

    Cerebellar alterations are a hallmark of Fetal Alcohol Spectrum Disorders and are thought to be responsible for deficits in fine motor control, motor learning, balance, and higher cognitive functions. These deficits are, in part, a consequence of dysfunction of cerebellar circuits. Although the effect of developmental ethanol exposure on Purkinje and granule cells has been previously characterized, its actions on other cerebellar neuronal populations are not fully understood. Here, we assessed the impact of repeated ethanol exposure on the number of inhibitory neurons in the cerebellar vermis. We exposed pregnant mice to ethanol in vapor inhalation chambers during gestational days 12-19 and offspring during postnatal days 2-9. We used transgenic mice expressing the fluorescent protein, Venus, in GABAergic/glycinergic neurons. Using unbiased stereology techniques, we detected a reduction in Venus positive neurons in the molecular and granule cell layers of lobule II in the ethanol exposed group at postnatal day 16. In contrast, ethanol produced a more widespread reduction in Purkinje cell numbers that involved lobules II, IV-V and IX. We also found a reduction in the volume of lobules II, IV-V, VI-VII, IX and X in ethanol-exposed pups. These findings indicate that second and third trimester-equivalent ethanol exposure has a greater impact on Purkinje cells than interneurons in the developing cerebellar vermis. The decrease in the volume of most lobules could be a consequence of a reduction in cell numbers, dendritic arborizations, or axonal projections.

  4. Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis.

    PubMed

    Nirgudkar, Pranita; Taylor, Devin H; Yanagawa, Yuchio; Valenzuela, C Fernando

    2016-10-01

    Cerebellar alterations are a hallmark of Fetal Alcohol Spectrum Disorders and are thought to be responsible for deficits in fine motor control, motor learning, balance, and higher cognitive functions. These deficits are, in part, a consequence of dysfunction of cerebellar circuits. Although the effect of developmental ethanol exposure on Purkinje and granule cells has been previously characterized, its actions on other cerebellar neuronal populations are not fully understood. Here, we assessed the impact of repeated ethanol exposure on the number of inhibitory neurons in the cerebellar vermis. We exposed pregnant mice to ethanol in vapor inhalation chambers during gestational days 12-19 and offspring during postnatal days 2-9. We used transgenic mice expressing the fluorescent protein, Venus, in GABAergic/glycinergic neurons. Using unbiased stereology techniques, we detected a reduction in Venus positive neurons in the molecular and granule cell layers of lobule II in the ethanol exposed group at postnatal day 16. In contrast, ethanol produced a more widespread reduction in Purkinje cell numbers that involved lobules II, IV-V and IX. We also found a reduction in the volume of lobules II, IV-V, VI-VII, IX and X in ethanol-exposed pups. These findings indicate that second and third trimester-equivalent ethanol exposure has a greater impact on Purkinje cells than interneurons in the developing cerebellar vermis. The decrease in the volume of most lobules could be a consequence of a reduction in cell numbers, dendritic arborizations, or axonal projections. PMID:27565053

  5. Development and application of an optogenetic platform for controlling and imaging a large number of individual neurons

    NASA Astrophysics Data System (ADS)

    Mohammed, Ali Ibrahim Ali

    The understanding and treatment of brain disorders as well as the development of intelligent machines is hampered by the lack of knowledge of how the brain fundamentally functions. Over the past century, we have learned much about how individual neurons and neural networks behave, however new tools are critically needed to interrogate how neural networks give rise to complex brain processes and disease conditions. Recent innovations in molecular techniques, such as optogenetics, have enabled neuroscientists unprecedented precision to excite, inhibit and record defined neurons. The impressive sensitivity of currently available optogenetic sensors and actuators has now enabled the possibility of analyzing a large number of individual neurons in the brains of behaving animals. To promote the use of these optogenetic tools, this thesis integrates cutting edge optogenetic molecular sensors which is ultrasensitive for imaging neuronal activity with custom wide field optical microscope to analyze a large number of individual neurons in living brains. Wide-field microscopy provides a large field of view and better spatial resolution approaching the Abbe diffraction limit of fluorescent microscope. To demonstrate the advantages of this optical platform, we imaged a deep brain structure, the Hippocampus, and tracked hundreds of neurons over time while mouse was performing a memory task to investigate how those individual neurons related to behavior. In addition, we tested our optical platform in investigating transient neural network changes upon mechanical perturbation related to blast injuries. In this experiment, all blasted mice show a consistent change in neural network. A small portion of neurons showed a sustained calcium increase for an extended period of time, whereas the majority lost their activities. Finally, using optogenetic silencer to control selective motor cortex neurons, we examined their contributions to the network pathology of basal ganglia related to

  6. The Number of Alphaherpesvirus Particles Infecting Axons and the Axonal Protein Repertoire Determines the Outcome of Neuronal Infection

    PubMed Central

    Koyuncu, Orkide O.; Song, Ren; Greco, Todd M.; Cristea, Ileana M.

    2015-01-01

    ABSTRACT Infection by alphaherpesviruses invariably results in invasion of the peripheral nervous system (PNS) and establishment of either a latent or productive infection. Infection begins with long-distance retrograde transport of viral capsids and tegument proteins in axons toward the neuronal nuclei. Initial steps of axonal entry, retrograde transport, and replication in neuronal nuclei are poorly understood. To better understand how the mode of infection in the PNS is determined, we utilized a compartmented neuron culturing system where distal axons of PNS neurons are physically separated from cell bodies. We infected isolated axons with fluorescent-protein-tagged pseudorabies virus (PRV) particles and monitored viral entry and transport in axons and replication in cell bodies during low and high multiplicities of infection (MOIs of 0.01 to 100). We found a threshold for efficient retrograde transport in axons between MOIs of 1 and 10 and a threshold for productive infection in the neuronal cell bodies between MOIs of 1 and 0.1. Below an MOI of 0.1, the viral genomes that moved to neuronal nuclei were silenced. These genomes can be reactivated after superinfection by a nonreplicating virus, but not by a replicating virus. We further showed that viral particles at high-MOI infections compete for axonal proteins and that this competition determines the number of viral particles reaching the nuclei. Using mass spectrometry, we identified axonal proteins that are differentially regulated by PRV infection. Our results demonstrate the impact of the multiplicity of infection and the axonal milieu on the establishment of neuronal infection initiated from axons. PMID:25805728

  7. Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability.

    PubMed

    Murase, Sachiko; Lantz, Crystal L; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A; Quinlan, Elizabeth M

    2016-07-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth, and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here, we demonstrate that deletion of the extracellular proteinase matrix metalloproteinase-9 (MMP-9) affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons but decreases dendritic length and complexity. Parallel changes in neuronal morphology are observed in primary visual cortex and persist into adulthood. Individual CA1 neurons in MMP-9(-/-) mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significantly increases spontaneous neuronal activity in awake MMP-9(-/-) mice and enhances response to acute challenge by the excitotoxin kainate. Our data document a novel role for MMP-9-dependent proteolysis: the regulation of several aspects of circuit maturation to constrain excitability throughout life.

  8. Matrix Metalloproteinase-9 regulates neuronal circuit development and excitability

    PubMed Central

    Murase, Sachiko; Lantz, Crystal; Kim, Eunyoung; Gupta, Nitin; Higgins, Richard; Stopfer, Mark; Hoffman, Dax A.; Quinlan, Elizabeth M.

    2015-01-01

    In early postnatal development, naturally occurring cell death, dendritic outgrowth and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here we demonstrate that deletion of the extracellular proteinase MMP-9 affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons, but decreases dendritic length and complexity while dendritic spine density is unchanged. Parallel changes in neuronal morphology are observed in primary visual cortex, and persist into adulthood. Individual CA1 neurons in MMP-9−/− mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significant increases spontaneous neuronal activity in awake MMP-9−/− mice and enhances response to acute challenge by the excitotoxin kainate. Thus MMP-9-dependent proteolysis regulates several aspects of circuit maturation to constrain excitability throughout life. PMID:26093382

  9. Abeta(1-42) reduces synapse number and inhibits neurite outgrowth in primary cortical and hippocampal neurons: a quantitative analysis.

    PubMed

    Evans, Nicholas A; Facci, Laura; Owen, Davina E; Soden, Peter E; Burbidge, Stephen A; Prinjha, Rab K; Richardson, Jill C; Skaper, Stephen D

    2008-10-30

    Synaptic loss represents one of the earliest signs of neuronal damage and is observed within both Alzheimer's disease patients and transgenic mouse models of the disease. We have developed a novel in vitro assay using high content screening technology to measure changes in a number of cell physiological parameters simultaneously within a neuronal population. Using Hoechst-33342 to label nuclei, betaIII-tubulin as a neuron-specific marker, and synapsin-I as an indicator of pre-synaptic sites, we have designed software to interrogate triple-labelled images, counting only those synaptic puncta associated with tubulin-positive structures. Here we demonstrate that addition of amyloid beta peptide (Abeta(1-42)), to either primary hippocampal or cortical neurons for 4 days in vitro has deleterious effects upon synapse formation, neurite outgrowth and arborisation in a concentration-dependent manner. Control reverse peptide showed no effect over the same concentration range. The effects of Abeta(1-42) were inhibited by D-KLVFFA, which contains residues 16-20 of Abeta that function as a self-recognition element during Abeta assembly and bind to the homologous region of Abeta and block its oligomerisation. These effects of Abeta(1-42) on synapse number and neurite outgrowth are similar to those described within AD patient pathology and transgenic mouse models.

  10. Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains

    PubMed Central

    Bushman, Diane M; Kaeser, Gwendolyn E; Siddoway, Benjamin; Westra, Jurgen W; Rivera, Richard R; Rehen, Stevens K; Yung, Yun C; Chun, Jerold

    2015-01-01

    Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function. In this study, we report altered genomic mosaicism in single, sporadic Alzheimer's disease (AD) neurons characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average DNA content increases of ∼8% over non-diseased controls that were unrelated to trisomy 21. Two independent single-cell copy number analyses identified amplifications at the APP locus. The use of single-cell qPCR identified up to 12 copies of APP in sampled neurons. Peptide nucleic acid (PNA) probes targeting APP, combined with super-resolution microscopy detected primarily single fluorescent signals of variable intensity that paralleled single-cell qPCR analyses. These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS. DOI: http://dx.doi.org/10.7554/eLife.05116.001 PMID:25650802

  11. Effects of elevated magnesium and substrate on neuronal numbers and neurite outgrowth of neural stem/progenitor cells in vitro.

    PubMed

    Vennemeyer, John J; Hopkins, Tracy; Kuhlmann, Julia; Heineman, William R; Pixley, Sarah K

    2014-07-01

    Because a potential treatment for brain injuries could be elevating magnesium ions (Mg(2+)) intracerebrally, we characterized the effects of elevating external Mg(2+) in cultures of neonatal murine brain-derived neural stem/progenitor cells (NSCs). Using a crystal violet assay, which avoids interference of Mg(2+) in the assay, it was determined that substrate influenced Mg(2+) effects on cell numbers. On uncoated plastic, elevating Mg(2+) levels to between 2.5 and 10mM above basal increased NSC numbers, and at higher concentrations numbers decreased to control or lower levels. Similar biphasic curves were observed with different plating densities, treatment durations and length of time in culture. When cells were plated on laminin-coated plastic, NSC numbers were higher even in basal medium and no further effects were observed with Mg(2+). NSC differentiation into neurons was not altered by either substrate or Mg(2+) supplementation. Some parameters of neurite outgrowth were increased by elevated Mg(2+) when NSCs differentiated into neurons on uncoated plastic. Differentiation on laminin resulted in increased neurites even in basal medium and no further effects were seen when Mg(2+) was elevated. This system can now be used to study the multiple mechanisms by which Mg(2+) influences neuronal biology. PMID:24815060

  12. PYRAMID ROADLESS AREA, CALIFORNIA.

    USGS Publications Warehouse

    Armstrong, Augustus K.; Scott, Douglas F.

    1984-01-01

    A geologic and mineral survey was conducted in the Pyramid Roadless Area, California. The area contains mineral showings, but no mineral-resource potential was identified during our studies. Three granodiorite samples on the west side of the roadless area contained weakly anomalous concentrations of uranium. Two samples of roof-pendant rocks, one metasedimentary rock and one metavolcanic rock, contain low concentrations of copper, and of copper and molybdenum, respectively. Although none was identified, the geologic terrane is permissive for mineral occurrences and large-scale, detailed geologic mapping of the areas of metasedimentary and metavolcanic roof pendants in the Pyramid Roadless Area could define a mineral-resource potential for tungsten and precious metals.

  13. Pyramidal structures on Mars

    NASA Technical Reports Server (NTRS)

    Gipson, M., Jr.; Ablordeppey, V. K.

    1974-01-01

    Triangular and polygonal pyramid like structures have been observed on the Martian surface. Located in the east central portion of Elysium Quadrangle (MC-15), these features are visible on the Mariner 9 photographs. B frames MTVS 4205-3 DAS 07794853 and MTVS 4296-24 DAS 12985882. The structures cast triangular and polygonal shadows. Steep-sided volcanic cones and impact craters occur only a few kilometers away. The mean diameter of the triangular pyramidal structures at the base is approximately 3.0 km, and the mean diameter of the polygonal structures is approximately 6.0 km. The observed Martian structures tend to line up suggesting joint or fault control. However, they do not appear to be controlled by the visible faults. The structures appear to be either wind-faceted volcanic cones and blocks or solidified blocks which have been rotated in semiconsolidated lava.

  14. Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort.

    PubMed

    Qu, Yu-jin; Ge, Xiu-shan; Bai, Jin-li; Wang, Li-wen; Cao, Yan-yan; Lu, Yan-yu; Jin, Yu-wei; Wang, Hong; Song, Fang

    2015-03-01

    We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP. PMID:25330799

  15. Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort.

    PubMed

    Qu, Yu-jin; Ge, Xiu-shan; Bai, Jin-li; Wang, Li-wen; Cao, Yan-yan; Lu, Yan-yu; Jin, Yu-wei; Wang, Hong; Song, Fang

    2015-03-01

    We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.

  16. When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals

    PubMed Central

    Herculano-Houzel, Suzana; Messeder, Débora J.; Fonseca-Azevedo, Karina; Pantoja, Nilma A.

    2015-01-01

    There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease. PMID:26082686

  17. Seasonal changes in neuron numbers in the hippocampal formation of a food-hoarding bird: the black-capped chickadee.

    PubMed

    Smulders, T V; Shiflett, M W; Sperling, A J; DeVoogd, T J

    2000-09-15

    The volume of the hippocampal formation (HF) in black-capped chickadees (Poecile atricapillus) varies across the seasons, in parallel with the seasonal cycle in food hoarding. In this study, we estimate cell density and total cell number in the HF across seasons in both juveniles and adults. We find that the seasonal variation in volume is due to an increase in the number of small and large cells (principally neurons) in the fall. Adults also have lower neuron densities than juveniles. Both juveniles and adults show an increase in cell density in the rostral part of the HF in August and a subsequent decrease toward October. This suggests that the net cell addition to the HF may already start in August. We discuss the implications of this early start with respect to the possibility that the seasonal change in HF volume is driven by the experience of food hoarding. We also speculate on the functional significance of the addition of neurons to the HF in the fall.

  18. Human Immunodeficiency Virus-1 Tat Protein Increases the Number of Inhibitory Synapses between Hippocampal Neurons in Culture

    PubMed Central

    Hargus, Nicholas J.

    2013-01-01

    Synaptodendritic damage correlates with cognitive decline in many neurodegenerative diseases, including human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorders (HAND). Because HIV-1 does not infect neurons, viral-mediated toxicity is indirect, resulting from released neurotoxins such as the HIV-1 protein transactivator of transcription (Tat). We compared the effects of Tat on inhibitory and excitatory synaptic connections between rat hippocampal neurons using an imaging-based assay that quantified clusters of the scaffolding proteins gephyrin or PSD95 fused to GFP. Tat (24 h) increased the number of GFP–gephyrin puncta and decreased the number of PSD95–GFP puncta. The effects of Tat on inhibitory and excitatory synapse number were mediated via the low-density lipoprotein receptor-related protein and subsequent Ca2+ influx through GluN2A-containing NMDA receptors (NMDARs). The effects of Tat on synapse number required cell-autonomous activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). Ca2+ buffering experiments suggested that loss of excitatory synapses required activation of CaMKII in close apposition to the NMDAR, whereas the increase in inhibitory synapses required Ca2+ diffusion to a more distal site. The increase in inhibitory synapses was prevented by inhibiting the insertion of GABAA receptors into the membrane. Synaptic changes induced by Tat (16 h) were reversed by blocking either GluN2B-containing NMDARs or neuronal nitric oxide synthase, indicating changing roles for pathways activated by NMDAR subtypes during the neurotoxic process. Compensatory changes in the number of inhibitory and excitatory synapses may serve as a novel mechanism to reduce network excitability in the presence of HIV-1 neurotoxins; these changes may inform the development of treatments for HAND. PMID:24198379

  19. Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases

    PubMed Central

    Butchbach, Matthew E. R.

    2016-01-01

    Proximal spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an early-onset, autosomal recessive neurodegenerative disease characterized by the loss of spinal α-motor neurons. This loss of α-motor neurons is associated with muscle weakness and atrophy. SMA can be classified into five clinical grades based on age of onset and severity of the disease. Regardless of clinical grade, proximal SMA results from the loss or mutation of SMN1 (survival motor neuron 1) on chromosome 5q13. In humans a large tandem chromosomal duplication has lead to a second copy of the SMN gene locus known as SMN2. SMN2 is distinguishable from SMN1 by a single nucleotide difference that disrupts an exonic splice enhancer in exon 7. As a result, most of SMN2 mRNAs lack exon 7 (SMNΔ7) and produce a protein that is both unstable and less than fully functional. Although only 10–20% of the SMN2 gene product is fully functional, increased genomic copies of SMN2 inversely correlates with disease severity among individuals with SMA. Because SMN2 copy number influences disease severity in SMA, there is prognostic value in accurate measurement of SMN2 copy number from patients being evaluated for SMA. This prognostic value is especially important given that SMN2 copy number is now being used as an inclusion criterion for SMA clinical trials. In addition to SMA, copy number variations (CNVs) in the SMN genes can affect the clinical severity of other neurological disorders including amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). This review will discuss how SMN1 and SMN2 CNVs are detected and why accurate measurement of SMN1 and SMN2 copy numbers is relevant for SMA and other neurodegenerative diseases. PMID:27014701

  20. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc.

  1. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. PMID:26850576

  2. Projection neurons in the cortex and hippocampus: differential effects of chronic khat and ethanol exposure in adult male rats

    PubMed Central

    Alele, Paul E; Matovu, Daniel; Imanirampa, Lawrence; Ajayi, Abayomi M; Kasule, Gyaviira T

    2016-01-01

    Background Recent evidence suggests that many individuals who chew khat recreationally also drink ethanol to offset the stimulating effect of khat. The objective of this study was to describe the separate and interactive effects of chronic ethanol and khat exposure on key projection neurons in the cortex and hippocampus of young adult male rats. Methods Young adult male Sprague Dawley rats were divided into six treatment groups: 2 g/kg khat, 4 g/kg khat, 4 g/kg ethanol, combined khat and ethanol (4 g/kg each), a normal saline control, and an untreated group. Treatments were administered orally for 28 continuous days; brains were then harvested, sectioned, and routine hematoxylin–eosin staining was done. Following photomicrography, ImageJ® software captured data regarding neuron number and size. Results No differences occurred in counts of both granular and pyramidal projection neurons in the motor cortex and all four subfields of the hippocampal formation. Khat dose-dependently increased pyramidal neuron size in the motor cortex and the CA3 region, but had different effects on granular neuron size in the dentate gyrus and the motor cortex. Mean pyramidal neuron size for the ethanol-only treatment was larger than that for the 2 g/kg khat group, and the saline control group, in CA3 and in the motor cortex. Concomitant khat and ethanol increased granular neuron size in the motor cortex, compared to the 2 g/kg khat group, the 4 g/kg khat group, and the 4 g/kg ethanol group. In the CA3 region, the 4 g/kg ethanol group showed a larger mean pyramidal neuron size than the combined khat and ethanol group. Conclusion These results suggest that concomitant khat and ethanol exposure changes granular and pyramidal projection neuron sizes differentially in the motor cortex and hippocampus, compared to the effects of chronic exposure to these two drugs separately. PMID:27785113

  3. Chronic intermittent hypoxia depresses afferent neurotransmission in NTS neurons by a reduction in the number of active synapses.

    PubMed

    Almado, Carlos Eduardo L; Machado, Benedito H; Leão, Ricardo M

    2012-11-21

    Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr(2+)) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

  4. Pyramid Lake Renewable Energy Project

    SciTech Connect

    John Jackson

    2008-03-14

    The Pyramid Lake Paiute Tribe is a federally recognized Tribe residing on the Pyramid Lake Reservation in western Nevada. The funding for this project was used to identify blind geothermal systems disconnected from geothermal sacred sites and develop a Tribal energy corporation for evaluating potential economic development for profit.

  5. PYRAMID LAKE RENEWEABLE ENERGY PLAN

    SciTech Connect

    HIGH DESERT GEOCULTURE, LLC

    2009-06-06

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

  6. Pyramid Power for Collaborative Planning.

    ERIC Educational Resources Information Center

    Schumm, Jeanne Shay; And Others

    1997-01-01

    Describes the Planning Pyramid, a framework to help regular and special education teachers cover required curriculum while modifying learning requirements to meet individual differences. The pyramid's base represents "what all students will learn," the middle portion "what most students will learn," and the top portion "what some students will…

  7. Adult-like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons.

    PubMed

    Python, François; Stocker, Reinhard F

    2002-04-15

    We provide a detailed analysis of the larval head chemosensory system of Drosophila melanogaster, based on confocal microscopy of cell-specific reporter gene expression in P[GAL4] enhancer trap lines. In particular, we describe the neuronal composition of three external and three pharyngeal chemosensory organs, the nerve tracts chosen by their afferents, and their central target regions. With a total of 21 olfactory and 80 gustatory neurons, the sensory level is numerically much simpler than that of the adult. Moreover, its design is different than in the adult, showing an association between smell and taste sensilla. In contrast, the first-order relay of the olfactory afferents, the larval antennal lobe (LAL), exhibits adult-like features both in terms of structure and cell number. It shows a division into approximately 30 subunits, reminiscent of glomeruli in the adult antennal lobe. Taken together, the design of the larval chemosensory system is a "hybrid," with larval-specific features in the periphery and central characteristics in common with the adult. The largely reduced numbers of afferents and the similar architecture of the LAL and the adult antennal lobe, render the larval chemosensory system of Drosophila a valuable model system, both for studying smell and taste and for examining the development of its adult organization.

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

    PubMed

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

    2014-07-16

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

  9. Identification of inputs to olivocochlear neurons using transneuronal labeling with pseudorabies virus (PRV).

    PubMed

    Brown, M Christian; Mukerji, Sudeep; Drottar, Marie; Windsor, Alanna M; Lee, Daniel J

    2013-10-01

    Olivocochlear (OC) neurons respond to sound and provide descending input that controls processing in the cochlea. The identities of neurons in the pathways providing inputs to OC neurons are incompletely understood. To explore these pathways, the retrograde transneuronal tracer pseudorabies virus (Bartha strain, expressing green fluorescent protein) was used to label OC neurons and their inputs in guinea pigs. Labeling of OC neurons began 1 day after injection into the cochlea. On day 2 (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a correlation between the numbers of these transneuronally labeled neurons and the number of labeled medial (M) OC neurons, suggesting that the spread of labeling proceeds mainly via synapses on MOC neurons. In the cochlear nucleus, the transneuronally labeled neurons were multipolar cells including the subtype known as planar cells. In the central nucleus of the inferior colliculus, transneuronally labeled neurons were of two principal types: neurons with disc-shaped dendritic fields and neurons with dendrites in a stellate pattern. Transneuronal labeling was also observed in pyramidal cells in the auditory cortex and in centers not typically associated with the auditory pathway such as the pontine reticular formation, subcoerulean nucleus, and the pontine dorsal raphe. These data provide information on the identity of neurons providing input to OC neurons, which are located in auditory as well as non-auditory centers.

  10. Neuronal beacon.

    PubMed

    Black, B; Mondal, A; Kim, Y; Mohanty, S K

    2013-07-01

    The controlled navigation of the axonal growth cone of a neuron toward the dendrite of its synaptic partner neuron is the fundamental process in forming neuronal circuitry. While a number of technologies have been pursued for axonal guidance over the past decades, they are either invasive or not controllable with high spatial and temporal resolution and are often limited by low guidance efficacy. Here, we report a neuronal beacon based on light for highly efficient and controlled guidance of cortical primary neurons.

  11. Sexual dimorphism in neuronal number of the posterodorsal medial amygdala is independent of circulating androgens and regional volume in adult rats.

    PubMed

    Morris, John A; Jordan, Cynthia L; Breedlove, S Marc

    2008-02-10

    The posterodorsal medial amygdala (MePD) in rodents integrates olfactory and pheromonal information, which, coupled with the appropriate hormonal signals, may facilitate or repress reproductive behavior in adulthood. MePD volume and neuronal soma size are greater in male rats than in females, and these sexual dimorphisms are maintained by adult circulating hormone levels. Castration of adult males causes these measures to shrink to the size seen in females 4 weeks later, whereas testosterone treatment of adult females for 4 weeks enlarges these measures to the size of males. We used stereological methods to count the number of cells in the MePD and found that, in addition to the sex difference in regional volume and soma size, males also have more MePD neurons than do females, yet these numbers are unaffected by the presence or absence of androgen in adults of either sex. Males also have more glial cells than do females, but, in contrast to the effects on neuronal number, the number of glial cells is affected by androgen in the right MePD of both sexes and, therefore, may contribute to regional volume changes in adulthood in that hemisphere. Thus, regional volume, neuronal size, and glial numbers vary in the MePD of adult rats in response to circulating androgens, but neuronal number does not. These results suggest that the sex difference in neuronal number in the rat MePD may be "organized" by androgens prior to adulthood, whereas regional volume, neuronal size, and glial numbers can be altered by androgens in adulthood. PMID:18076082

  12. Afadin Regulates Puncta Adherentia Junction Formation and Presynaptic Differentiation in Hippocampal Neurons

    PubMed Central

    Toyoshima, Daisaku; Mandai, Kenji; Maruo, Tomohiko; Supriyanto, Irwan; Togashi, Hideru; Inoue, Takahito; Mori, Masahiro; Takai, Yoshimi

    2014-01-01

    The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation. PMID:24587018

  13. Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia).

    PubMed

    Coppola, Vincent J; Kanyok, Nate; Schreiber, Austin J; Flaim, Mary E; Bingman, Verner P

    2016-05-01

    The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered.

  14. Experimental Investigation of Composite Pressure Vessel Performance and Joint Stiffness for Pyramid and Inverted Pyramid Joints

    NASA Technical Reports Server (NTRS)

    Verhage, Joseph M.; Bower, Mark V.; Gilbert, Paul A. (Technical Monitor)

    2001-01-01

    The focus of this study is on the suitability in the application of classical laminate theory analysis tools for filament wound pressure vessels with adhesive laminated joints in particular: pressure vessel wall performance, joint stiffness and failure prediction. Two 18-inch diameter 12-ply filament wound pressure vessels were fabricated. One vessel was fabricated with a 24-ply pyramid laminated adhesive double strap butt joint. The second vessel was fabricated with the same number of plies in an inverted pyramid joint. Results from hydrostatic tests are presented. Experimental results were used as input to the computer programs GENLAM and Laminate, and the output compared to test. By using the axial stress resultant, the classical laminate theory results show a correlation within 1% to the experimental results in predicting the pressure vessel wall pressure performance. The prediction of joint stiffness for the two adhesive joints in the axial direction is within 1% of the experimental results. The calculated hoop direction joint stress resultant is 25% less than the measured resultant for both joint configurations. A correction factor is derived and used in the joint analysis. The correction factor is derived from the hoop stress resultant from the tank wall performance investigation. The vessel with the pyramid joint is determined to have failed in the joint area at a hydrostatic pressure 33% value below predicted failure. The vessel with the inverted pyramid joint failed in the wall acreage at a hydrostatic pressure within 10% of the actual failure pressure.

  15. An orthogonal oriented quadrature hexagonal image pyramid

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.; Ahumada, Albert J., Jr.

    1987-01-01

    An image pyramid has been developed with basis functions that are orthogonal, self-similar, and localized in space, spatial frequency, orientation, and phase. The pyramid operates on a hexagonal sample lattice. The set of seven basis functions consist of three even high-pass kernels, three odd high-pass kernels, and one low-pass kernel. The three even kernels are identified when rotated by 60 or 120 deg, and likewise for the odd. The seven basis functions occupy a point and a hexagon of six nearest neighbors on a hexagonal sample lattice. At the lowest level of the pyramid, the input lattice is the image sample lattice. At each higher level, the input lattice is provided by the low-pass coefficients computed at the previous level. At each level, the output is subsampled in such a way as to yield a new hexagonal lattice with a spacing sq rt 7 larger than the previous level, so that the number of coefficients is reduced by a factor of 7 at each level. The relationship between this image code and the processing architecture of the primate visual cortex is discussed.

  16. Total number and size distribution of motor neurons in the spinal cord of normal and EMC-virus infected mice — a stereological study

    PubMed Central

    WEBER, UNO J.; BOCK, TROELS; BUSCHARD, KARSTEN; PAKKENBERG, BENTE

    1997-01-01

    The encephalomyocarditis virus of the diabetogenic M-strain (EMC-M) is known to cause diabetes in mice. The EMC-M virus has also been shown to cause paresis in some of the infected animals. The clinical features include an acute ascending predominantly motor paralysis, developing within days. This resembles acute idiopathic polyneuritis. The alpha motor neurons would be a possible target for the virus, so two parameters, the total number and the size distribution of motor neurons, were therefore selected for further investigation in 6 mice with neurological involvement and compared with 6 control mice. The optical fractionator method was applied for estimating the total number of motor neurons and the 3D size distribution was estimated using the rotator method in a vertical design. No difference was found in the total number of motor neurons and the size distributions were similar in the 2 groups. This design can be used as a model for the estimation of the total number of motor neurons and their size distribution in other experimental animal models. PMID:9418991

  17. Effects of age and insulin-like growth factor-1 on neuron and synapse numbers in area CA3 of hippocampus.

    PubMed

    Poe, B H; Linville, C; Riddle, D R; Sonntag, W E; Brunso-Bechtold, J K

    2001-01-01

    Age-related effects associated with the hippocampus include declines in numbers of neurons and synapses in the dentate gyrus and area CA1, and decreased cognitive ability as assessed with the Morris water maze. The present study quantified both neuron and synapse number in the same tissue block of area CA3 of the hippocampus. No investigations of both density of neurons and synapses together in area CA3 of hippocampus have been performed previously, despite its importance as the terminal field of dentate gyrus mossy fibers, the second synapse in the trisynaptic circuit in the hippocampus. Numerical density of neurons and synapses were assessed in 4-, 18-, and 29-month-old rats receiving infusions of saline into the lateral ventricle and in 29-month-old rats receiving infusions of insulin-like growth factor-1 (IGF-1). Numerical density of neurons of the stratum pyramidale of CA3 of hippocampus remained constant across the life span as did the numerical density of synapses in stratum lucidum of area CA3. Despite the reported role of IGF-1 in synaptogenesis and improvements in behavior with age, ventricular infusion of this growth factor did not affect the numerical density of neurons or synapses in 29-month-old rats when compared to saline-infused old rats. Further, reported effects of IGF-1 on adult neurogenesis in the dentate gyrus are not reflected in an IGF-1-related increase in synapse density in this region.

  18. Cell Number and Neuropil Alterations in Subregions of the Anterior Hippocampus in a Female Monkey Model of Depression

    PubMed Central

    Willard, Stephanie L.; Riddle, David R.; Forbes, M. Elizabeth; Shively, Carol A.

    2013-01-01

    Background The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. More women are clinically depressed than men, yet the depressed female brain is little studied. We reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown. The present study represents the first systematic morphological investigation of the entire hippocampus in depressed female primates. Methods Cellular determinants of hippocampal size were examined in subregions of anterior and posterior hippocampus in antidepressant-naive, adult female monkeys characterized for behavioral depression and matched on variables that influence hippocampal size (n=8 depressed, 8 nondepressed). Unbiased stereology was used to estimate neuronal and glial numbers, neuronal soma size, and regional and layer volumes. Results Neuropil and cell layer volumes were reduced in cornu ammonis (CA)1 and dentate gyrus (DG) of the anterior but not the posterior hippocampus of depressed compared to nondepressed monkeys. Glial numbers were 30% lower in anterior CA1 and DG of depressed monkeys, with no differences observed in the posterior hippocampus. Granule neuron number tended towards a reduction in anterior DG; pyramidal neuron number was unchanged in any region. Size of pyramidal neurons and glial densities tended to be reduced throughout the whole hippocampus of depressed monkeys, whereas neuronal densities were unchanged. Conclusions The reduced size of the anterior hippocampus in depressed females appears to arise from alterations in numbers of glia and extent of neuropil, but not numbers of neurons, in CA1 and DG. PMID:23607969

  19. Organization and number of orexinergic neurons in the hypothalamus of two species of Cetartiodactyla: A comparison of giraffe (Giraffa camelopardalis) and harbour porpoise (Phocoena phocoena)

    PubMed Central

    Dell, Leigh-Anne; Patzke, Nina; Bhagwandin, Adhil; Bux, Faiza; Fuxe, Kjell; Barber, Grace; Siegel, Jerome M.; Manger, Paul R.

    2012-01-01

    The present study describes the organization of the orexinergic (hypocretinergic) neurons in the hypothalamus of the giraffe and harbour porpoise – two members of the mammalian Order Cetartiodactyla which is comprised of the even-toed ungulates and the cetaceans as they share a monophyletic ancestry. Diencephalons from two sub-adult male giraffes and two adult male harbour porpoises were coronally sectioned and immunohistochemically stained for orexin-A. The staining revealed that the orexinergic neurons could be readily divided into two distinct neuronal types based on somal volume, area and length, these being the parvocellular and magnocellular orexin-A immunopositive (OxA+) groups. The magnocellular group could be further subdivided, on topological grounds, into three distinct clusters – a main cluster in the perifornical and lateral hypothalamus, a cluster associated with the zona incerta and a cluster associated with the optic tract. The parvocellular neurons were found in the medial hypothalamus, but could not be subdivided, rather they form a topologically amorphous cluster. The parvocellular cluster appears to be unique to the Cetartiodactyla as these neurons have not been described in other mammals to date, while the magnocellular nuclei appear to be homologous to similar nuclei described in other mammals. The overall size of both the parvocellular and magnocellular neurons (based on somal volume, area and length) were larger in the giraffe than the harbour porpoise, but the harbour porpoise had a higher number of both parvocellular and magnocellular orexinergic neurons than the giraffe despite both having a similar brain mass. The higher number of both parvocellular and magnocellular orexinergic neurons in the harbour porpoise may relate to the unusual sleep mechanisms in the cetaceans. PMID:22683547

  20. Organization and number of orexinergic neurons in the hypothalamus of two species of Cetartiodactyla: a comparison of giraffe (Giraffa camelopardalis) and harbour porpoise (Phocoena phocoena).

    PubMed

    Dell, Leigh-Anne; Patzke, Nina; Bhagwandin, Adhil; Bux, Faiza; Fuxe, Kjell; Barber, Grace; Siegel, Jerome M; Manger, Paul R

    2012-07-01

    The present study describes the organization of the orexinergic (hypocretinergic) neurons in the hypothalamus of the giraffe and harbour porpoise--two members of the mammalian Order Cetartiodactyla which is comprised of the even-toed ungulates and the cetaceans as they share a monophyletic ancestry. Diencephalons from two sub-adult male giraffes and two adult male harbour porpoises were coronally sectioned and immunohistochemically stained for orexin-A. The staining revealed that the orexinergic neurons could be readily divided into two distinct neuronal types based on somal volume, area and length, these being the parvocellular and magnocellular orexin-A immunopositive (OxA+) groups. The magnocellular group could be further subdivided, on topological grounds, into three distinct clusters--a main cluster in the perifornical and lateral hypothalamus, a cluster associated with the zona incerta and a cluster associated with the optic tract. The parvocellular neurons were found in the medial hypothalamus, but could not be subdivided, rather they form a topologically amorphous cluster. The parvocellular cluster appears to be unique to the Cetartiodactyla as these neurons have not been described in other mammals to date, while the magnocellular nuclei appear to be homologous to similar nuclei described in other mammals. The overall size of both the parvocellular and magnocellular neurons (based on somal volume, area and length) were larger in the giraffe than the harbour porpoise, but the harbour porpoise had a higher number of both parvocellular and magnocellular orexinergic neurons than the giraffe despite both having a similar brain mass. The higher number of both parvocellular and magnocellular orexinergic neurons in the harbour porpoise may relate to the unusual sleep mechanisms in the cetaceans.

  1. Organization and number of orexinergic neurons in the hypothalamus of two species of Cetartiodactyla: a comparison of giraffe (Giraffa camelopardalis) and harbour porpoise (Phocoena phocoena).

    PubMed

    Dell, Leigh-Anne; Patzke, Nina; Bhagwandin, Adhil; Bux, Faiza; Fuxe, Kjell; Barber, Grace; Siegel, Jerome M; Manger, Paul R

    2012-07-01

    The present study describes the organization of the orexinergic (hypocretinergic) neurons in the hypothalamus of the giraffe and harbour porpoise--two members of the mammalian Order Cetartiodactyla which is comprised of the even-toed ungulates and the cetaceans as they share a monophyletic ancestry. Diencephalons from two sub-adult male giraffes and two adult male harbour porpoises were coronally sectioned and immunohistochemically stained for orexin-A. The staining revealed that the orexinergic neurons could be readily divided into two distinct neuronal types based on somal volume, area and length, these being the parvocellular and magnocellular orexin-A immunopositive (OxA+) groups. The magnocellular group could be further subdivided, on topological grounds, into three distinct clusters--a main cluster in the perifornical and lateral hypothalamus, a cluster associated with the zona incerta and a cluster associated with the optic tract. The parvocellular neurons were found in the medial hypothalamus, but could not be subdivided, rather they form a topologically amorphous cluster. The parvocellular cluster appears to be unique to the Cetartiodactyla as these neurons have not been described in other mammals to date, while the magnocellular nuclei appear to be homologous to similar nuclei described in other mammals. The overall size of both the parvocellular and magnocellular neurons (based on somal volume, area and length) were larger in the giraffe than the harbour porpoise, but the harbour porpoise had a higher number of both parvocellular and magnocellular orexinergic neurons than the giraffe despite both having a similar brain mass. The higher number of both parvocellular and magnocellular orexinergic neurons in the harbour porpoise may relate to the unusual sleep mechanisms in the cetaceans. PMID:22683547

  2. Fractal analysis of Mesoamerican pyramids.

    PubMed

    Burkle-Elizondo, Gerardo; Valdez-Cepeda, Ricardo David

    2006-01-01

    A myth of ancient cultural roots was integrated into Mesoamerican cult, and the reference to architecture denoted a depth religious symbolism. The pyramids form a functional part of this cosmovision that is centered on sacralization. The space architecture works was an expression of the ideological necessities into their conception of harmony. The symbolism of the temple structures seems to reflect the mathematical order of the Universe. We contemplate two models of fractal analysis. The first one includes 16 pyramids. We studied a data set that was treated as a fractal profile to estimate the Df through variography (Dv). The estimated Fractal Dimension Dv = 1.383 +/- 0.211. In the second one we studied a data set to estimate the Dv of 19 pyramids and the estimated Fractal Dimension Dv = 1.229 +/- 0.165.

  3. Evidence for changes in numbers of synaptic inpcuts onto KNDy and GnRH neurones during the preovulatory LH surge in the ewe

    PubMed Central

    Merkley, Christina M.; Coolen, Lique M.; Goodman, Robert L.; Lehman, Michael N.

    2016-01-01

    Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto GnRH neurones. ARC kisspeptin cells that co-localize neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown to also co-express the glutamatergic marker, vGlut2, in mice. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the goal of this study was to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, the latter group sacrificed at the time of the luteinising (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to luteal phase; as these did not contain kisspeptin they do not arise from KNDy neurons. In contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in both the POA and mediobasal hypothalamus was also increased during the LH surge. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during the ovine oestrous cycle, changes which may contribute to the generation of the preovulatory GnRH/LH surge. PMID:25976424

  4. Distribution of pyramidal cells associated with perineuronal nets in the neocortex of rat.

    PubMed

    Alpár, Alán; Gärtner, Ulrich; Härtig, Wolfgang; Brückner, Gert

    2006-11-20

    Perineuronal nets are lattice-like accumulations of extracellular matrix components around the cell body and perisomatic portion of certain neurons. Whereas interneurons associated to this specific neuron-associated sheath have been elaborately classified, less effort has been undertaken to describe the occurrence of perineuronal nets around pyramidal neurons. Our aim was to give a detailed and comparative description of the occurrence of net-associated pyramidal cells throughout the rat neocortex as well as to systematically and comparatively analyze the relation of main projection types of principal neurons to the presence of perineuronal nets. The present study revealed that perineuronal nets stained with WFA were associated rather rarely to pyramidal cells compared to interneurons in layers II/III and V/VI of rat neocortex. However, their frequency was considerably different between various cortical areas with a maximum in visual cortex and with a minimum in secondary motor cortices. Further analysis revealed that neuron-associated matrix sheaths around principal cells were more common in the primary than in the secondary fields of corresponding areas and they were more numerous in infra-than in supragranular layers in most regions. Subfields of cortical areas also differed regarding the occurrence of net-associated principal cells, and the subtlety of cortical representation seemed to correlate with the frequency of perineuronal nets around pyramidal neurons in the primary somatosensory cortex. It appears that net-associated pyramidal cells do not have a projection pattern restricted to distinct target regions. Rather a functional heterogeneity of the pyramidal cell population contributing to specific intra-or subcortical projections is suggested.

  5. A Rebuttal of NTL Institute's Learning Pyramid

    ERIC Educational Resources Information Center

    Letrud, Kare

    2012-01-01

    This article discusses the learning pyramid corroborated by National Training Laboratories Institute. It present and compliment historical and methodological critique against the learning pyramid, and call upon NTL Institute ought to retract their model.

  6. Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type.

    PubMed

    Wise, Leslie M; Sadowski, Renee N; Kim, Taehyeon; Willing, Jari; Juraska, Janice M

    2016-03-01

    Bisphenol A (BPA), an endocrine disruptor used in a variety of consumer products, has been found to alter the number of neurons in multiple brain areas in rats following exposure in perinatal development. Both the number of neurons and glia also change in the medial prefrontal cortex (mPFC) during adolescence, and this process is known to be influenced by gonadal hormones which could be altered by BPA. In the current study, we examined Long-Evans male and female rats that were administered BPA (0, 4, 40, or 400μg/kg/day) during adolescent development (postnatal days 27-46). In adulthood (postnatal day 150), the number of neurons and glia in the mPFC were stereologically assessed in methylene blue/azure II stained sections. There were no changes in the number of neurons, but there was a significant dose by sex interaction in number of glia in the mPFC. Pairwise comparisons between controls and each dose showed a significant increase in the number of glia between 0 and 40μg/kg/day in females, and a significant decrease in the number of glia between 0 and 4μg/kg/day in males. In order to determine the type of glial cells that were changing in these groups in response to adolescent BPA administration, adjacent sections were labelled with S100β (astrocytes) and IBA-1 (microglia) in the mPFC of the groups that differed. The number of microglia was significantly higher in females exposed to 40μg/kg/day than controls and lower in males exposed to 4μg/kg/day than controls. There were no significant effects of adolescent exposure to BPA on the number of astrocytes in male or females. Thus, adolescent exposure to BPA produced long-term alterations in the number of microglia in the mPFC of rats, the functional implications of which need to be explored. PMID:26828634

  7. Integrating Early Childhood Mental Health Consultation with the Pyramid Model. Issue Brief

    ERIC Educational Resources Information Center

    Perry, Deborah F.; Kaufmann, Roxane K.

    2009-01-01

    A growing number of states and communities are implementing the Pyramid Model in early care and education settings, and in many of these places there are also early childhood mental health consultation (ECMHC) programs operating. This policy brief provides an overview of ECMHC, how it can support the implementation of the Pyramid Model and the…

  8. Postsynaptic Adenosine A2A Receptors Modulate Intrinsic Excitability of Pyramidal Cells in the Rat Basolateral Amygdala

    PubMed Central

    Rau, Andrew R.; Ariwodola, Olusegun J.

    2015-01-01

    Background: The basolateral amygdala plays a critical role in the etiology of anxiety disorders and addiction. Pyramidal neurons, the primary output cells of this region, display increased firing following exposure to stressors, and it is thought that this increase in excitability contributes to stress responsivity and the expression of anxiety-like behaviors. However, much remains unknown about the underlying mechanisms that regulate the intrinsic excitability of basolateral amygdala pyramidal neurons. Methods: Ex vivo gramicidin perforated patch recordings were conducted in current clamp mode where hyper- and depolarizing current steps were applied to basolateral amygdala pyramidal neurons to assess the effects of adenosine A2A receptor modulation on intrinsic excitability. Results: Activation of adenosine A2A receptors with the selective A2A receptor agonist CGS-21680 significantly increased the firing rate of basolateral amygdala pyramidal neurons in rat amygdala brain slices, likely via inhibition of the slow afterhyperpolarization potential. Both of these A2A receptor-mediated effects were blocked by preapplication of a selective A2A receptor antagonist (ZM-241385) or by intra-pipette infusion of a protein kinase A inhibitor, suggesting a postsynaptic locus of A2A receptors on basolateral amygdala pyramidal neurons. Interestingly, bath application of the A2A receptor antagonist alone significantly attenuated basolateral amygdala pyramidal cell firing, consistent with a role for tonic adenosine in the regulation of the intrinsic excitability of these neurons. Conclusions: Collectively, these data suggest that adenosine, via activation of A2A receptors, may directly facilitate basolateral amygdala pyramidal cell output, providing a possible balance for the recently described inhibitory effects of adenosine A1 receptor activation on glutamatergic excitation of basolateral amygdala pyramidal cells. PMID:25716780

  9. Gaze shift duration, independent of amplitude, influences the number of spikes in the burst for medium-lead burst neurons in pontine reticular formation

    PubMed Central

    Freedman, Edward G.

    2013-01-01

    Abstract Changes in the direction of the line of sight (gaze) allow successive sampling of the visual environment. Saccadic eye movements accomplish this goal when the head does not move. Medium-lead burst neurons (MLBs) in the paramedian pontine reticular formation (PPRF) discharge a high frequency burst of action potentials starting ~12 ms before the saccade begins. A subgroup of MLBs rostral of abducens nucleus monosynaptically excites oculomotor neurons. The number of spikes in the presaccadic burst is correlated with the amplitude of the horizontal component of the saccade, and the peak discharge rate is correlated with peak eye velocity. During head-unrestrained gaze shifts, a linear relationship between the number of action potentials in MLB bursts and gaze (but not eye) amplitude has been reported. The anatomical connection of MLBs to motor neurons and the similarity between the phasic motor neuron burst and MLB discharge have raised questions about the usefulness of counting spikes in MLBs to determine their role in eye-head coordination. We investigated this issue using a behavioral technique that permits a dissociation of eye movement amplitude and duration during constant vector gaze shifts. Surprisingly, during gaze shifts of constant amplitude and direction, we observe a nearly linear, positive correlation between saccade duration and spike number associated with a negative correlation between spike number and saccade amplitude. These data constrain models of the oculomotor controller and may further define the time-dependence of hypothesized neural integration in this system. PMID:21842410

  10. Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.

    PubMed

    Vanmarsenille, Lieselot; Giannandrea, Maila; Fieremans, Nathalie; Verbeeck, Jelle; Belet, Stefanie; Raynaud, Martine; Vogels, Annick; Männik, Katrin; Õunap, Katrin; Jacqueline, Vigneron; Briault, Sylvain; Van Esch, Hilde; D'Adamo, Patrizia; Froyen, Guy

    2014-03-01

    Copy number gains at Xq28 are a frequent cause of X-linked intellectual disability (XLID). Here, we report on a recurrent 0.5 Mb tandem copy number gain at distal Xq28 not including MECP2, in four male patients with nonsyndromic mild ID and behavioral problems. The genomic region is duplicated in two families and triplicated in a third reflected by more distinctive clinical features. The X-inactivation patterns in carrier females correspond well with their clinical symptoms. Our mapping data confirm that this recurrent gain is likely mediated by nonallelic homologous recombination between two directly oriented Int22h repeats. The affected region harbors eight genes of which RAB39B encoding a small GTPase, was the prime candidate since loss-of-function mutations had been linked to ID. RAB39B is expressed at stable levels in lymphocytes from control individuals, suggesting a tight regulation. mRNA levels in our patients were almost two-fold increased. Overexpression of Rab39b in mouse primary hippocampal neurons demonstrated a significant decrease in neuronal branching as well as in the number of synapses when compared with the control neurons. Taken together, we provide evidence that the increased dosage of RAB39B causes a disturbed neuronal development leading to cognitive impairment in patients with this recurrent copy number gain.

  11. Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative tauopathy.

    PubMed

    Crimins, Johanna L; Rocher, Anne B; Peters, Alan; Shultz, Penny; Lewis, Jada; Luebke, Jennifer I

    2011-11-01

    Cortical neuron death is prevalent by 9 months in rTg(tau(P301L))4510 tau mutant mice (TG) and surviving pyramidal cells exhibit dendritic regression and spine loss. We used whole-cell patch-clamp recordings to investigate the impact of these marked structural changes on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) of layer 3 pyramidal cells in frontal cortical slices from behaviorally characterized TG and non-transgenic (NT) mice at this age. Frontal lobe function of TG mice was intact following a short delay interval but impaired following a long delay interval in an object recognition test, and cortical atrophy and cell loss were pronounced. Surviving TG cells had significantly reduced dendritic diameters, total spine density, and mushroom spines, yet sEPSCs were increased and sIPSCs were unchanged in frequency. Thus, despite significant regressive structural changes, synaptic responses were not reduced in TG cells, indicating that homeostatic compensatory mechanisms occur during progressive tauopathy. Consistent with this idea, surviving TG cells were more intrinsically excitable than NT cells, and exhibited sprouting of filopodia and axonal boutons. Moreover, the neuropil in TG mice showed an increased density of asymmetric synapses, although their mean size was reduced. Taken together, these data indicate that during progressive tauopathy, cortical pyramidal cells compensate for loss of afferent input by increased excitability and establishment of new synapses. These compensatory homeostatic mechanisms may play an important role in slowing the progression of neuronal network dysfunction during neurodegenerative tauopathies.

  12. Distinct properties of two major excitatory inputs to hippocampal pyramidal cells: a computational study.

    PubMed

    Káli, Szabolcs; Freund, Tamás F

    2005-10-01

    The two main sources of excitatory input to CA1 pyramidal cells, the Schaffer collaterals (SC) and the perforant path (PP), target different regions of the dendritic tree. This spatial segregation may have important consequences for the way in which different inputs affect the activity of principal neurons. We constructed detailed biophysical models of CA1 pyramidal cells, incorporating a variety of active conductances, and investigated the ability of synapses located in different dendritic segments to elicit a somatic voltage response. Synaptic efficacy as seen by the soma was strongly dependent on the site of the synapse, with PP inputs being more severely attenuated than SC inputs. Variability within SC inputs, but not between SC inputs and PP inputs, could be eliminated by appropriate scaling of synaptic efficacy. The spatial and temporal summation of multiple synaptic inputs was also investigated. While summation of SC inputs was linear up to the somatic spike threshold, PP inputs summed in a strongly sublinear fashion, with the somatic response remaining subthreshold even following the simultaneous activation of a large number of synapses and during stimulation with high-frequency trains. Finally, the relative impact of different pathways on somatic activity could be effectively altered by modulating the kinetic properties of dendritic transient K+ channels, corresponding to the activation of ascending modulatory neurotransmitter systems. In this case, the efficacy of the PP was enhanced by the dendritic generation and limited spread of action potentials. Strong PP activation could also evoke dendritic Ca++ spikes, which often triggered a somatic burst. PMID:16262641

  13. Working range of stimulus flux transduction determines dendrite size and relative number of pheromone component receptor neurons in moths.

    PubMed

    Baker, T C; Domingue, M J; Myrick, A J

    2012-05-01

    We are proposing that the "relative" abundances of the differently tuned pheromone-component-responsive olfactory receptor neurons (ORNs) on insect antennae are not a result of natural selection working to maximize absolute sensitivity to individual pheromone components. Rather, relative abundances are a result of specifically tuned sensillum-plus-ORN units having been selected to accurately transduce and report to the antennal lobe the maximal ranges of molecular flux imparted by each pheromone component in every plume strand. To not reach saturating stimulus flux levels from the most concentrated plume strands of a pheromone blend, the dendritic surface area of the ORN type that is tuned to the most abundant component of a pheromone blend is increased in dendritic diameter in order to express a greater number of major pheromone component-specific odorant receptors. The increased ability of these enlarged dendrite, major component-tuned ORNs to accurately report very high flux of its component results in a larger working range of stimulus flux able to be accurately transduced by that type of ORN. However, the larger dendrite size and possibly other high-flux adjustments in titers of pheromone-binding proteins and degrading enzymes cause a decrease in absolute sensitivity to lower flux levels of the major component in lower concentration strands of the pheromone blend. In order to restore the ability of the whole-antenna major pheromone component-specific channel to accurately report to its glomerulus the abundance of the major component in lower concentration strands, the number of major component ORNs over the entire antenna is adjusted upward, creating a greater proportion of major component-tuned ORNs than those tuned to minor components. Pheromone blend balance reported by the whole-antennal major and minor component channels in low plume-flux strands is now restored, and the relative fluxes of the 2 components occurring in both low- and high-flux strands are

  14. Evaluation of the Cost-Effectiveness of Pyramidal, Modified Pyramidal and Monoscreen Traps for the Control of the Tsetse Fly, Glossina fuscipes fuscipes, in Uganda

    PubMed Central

    Abila, P.P.; Okello-Onen, J.; Okoth, J.O.; Matete, G.O.; Wamwiri, F.; Politzar, H.

    2007-01-01

    Several trap designs have been used for sampling and control of the tsetse fly, Glossina fuscipes fuscipes, Newstead (Diptera: Glossinidae) based on preferences of individual researchers and program managers with little understanding of the comparative efficiency and cost-effectiveness of trap designs. This study was carried out to evaluate the cost-effectiveness of four commonly used trap designs: monoscreen, modified pyramidal and pyramidal, relative to the standard biconical trap. The study was performed under high tsetse challenge on Buvuma Island, Lake Victoria, Uganda, using a 4 × 4 Latin square design replicated 3 times, so as to separate the trap positions and day effects from the treatment effect. A total of 12 trap positions were tested over 4 days. The monoscreen trap caught significantly higher numbers of G. f. fuscipes (P<0.05) followed by biconical, modified pyramidal and pyramidal traps. Analysis of variance showed that treatment factor was a highly significant source of variation in the data. The index of increase in trap catches relative biconical were O.60 (pyramidal), 0.68 (modified pyramidal) and 1.25 (monoscreen). The monoscreen trap was cheaper (US$ 2.61) and required less material to construct than pyramidal trap (US$ 3.48), biconical and the modified pyramidal traps (US$ 4.06 each). Based on the number of flies caught per meter of material, the monoscreen trap proved to be the most cost-effective (232 flies/m) followed by the biconical trap (185 flies/m). The modified pyramidal and the pyramidal traps caught 112 and 125 flies/m, respectively. PMID:20345292

  15. The number of Purkinje neurons and their topology in the cerebellar vermis of normal and reln haplodeficient mouse.

    PubMed

    Magliaro, Chiara; Cocito, Carolina; Bagatella, Stefano; Merighi, Adalberto; Ahluwalia, Arti; Lossi, Laura

    2016-09-01

    The Reeler heterozygous mice (reln(+/-)) are haplodeficient in the gene (reln) encoding for the reelin glycoprotein (RELN) and display reductions in brain/peripheral RELN similar to autistic or schizophrenic patients. Cytoarchitectonic alterations of the reln(+/-) brain may be subtle, and are difficult to demonstrate by current histological approaches. We analyzed the number and topological organization of the Purkinje neurons (PNs) in five vermal lobules - central (II-III), culmen (IV-V), tuber (VIIb), uvula (IX), and nodulus (X) - that process different types of afferent functional inputs in reln(+/+) and reln(+/-) adult mice (P60) of both sexes (n=24). Animals were crossed with L7GFP mice so that the GFP-tagged PNs could be directly identified in cryosections. Digital images from these sections were processed with different open source software for quantitative topological and statistical analyses. Diversity indices calculated were: maximum caliper, density, area of soma, dispersion along the XZ axis, and dispersion along the YZ axis. We demonstrate: i. reduction in density of PNs in reln(+/-) males (14.37%) and reln(+/-) females (17.73%) compared to reln(+/+) males; ii. that reln(+/-) males have larger PNs than other genotypes, and females (irrespective of the reln genetic background) have smaller PNs than reln(+/+) males; iii. PNs are more chaotically arranged along the YZ axis in reln(+/-) males than in reln(+/+) males and, except in central lobulus, reln(+/-) females. Therefore, image processing and statistics reveal previously unforeseen gender and genotype-related structural differences in cerebellum that may be clues for the definition of novel biomarkers in human psychiatric disorders. PMID:26996540

  16. The Periodic Pyramid

    ERIC Educational Resources Information Center

    Hennigan, Jennifer N.; Grubbs, W. Tandy

    2013-01-01

    The chemical elements present in the modern periodic table are arranged in terms of atomic numbers and chemical periodicity. Periodicity arises from quantum mechanical limitations on how many electrons can occupy various shells and subshells of an atom. The shell model of the atom predicts that a maximum of 2, 8, 18, and 32 electrons can occupy…

  17. Pyramidal-Reflector Solar Heater

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Motor-driven reflector compensates for seasonal changes in Sun's altitude. System has flat-plate absorbers mounted on north side of attic interior. Skylight window on south-facing roof admits Sunlight into attic, lined with mirrors that reflect light to absorbers. Reflectors are inner surfaces of a pyramid lying on its side with window at its base and absorber plates in a cross-sectional plane near its apex.

  18. Pyramidal inversion domain boundaries revisited

    SciTech Connect

    Remmele, T.; Albrecht, M.; Irmscher, K.; Fornari, R.; Strassburg, M.

    2011-10-03

    The structure of pyramidal inversion domain boundaries in GaN:Mg was investigated by aberration corrected transmission electron microscopy. The analysis shows the upper (0001) boundary to consist of a single Mg layer inserted between polarity inverted GaN layers in an abcab stacking. The Mg bound in these defects is at least one order of magnitude lower than the chemical Mg concentration. Temperature dependent Hall effect measurements show that up to 27% of the Mg acceptors is electrically compensated.

  19. Endothelial nitric oxide synthase localized to hippocampal pyramidal cells: implications for synaptic plasticity.

    PubMed Central

    Dinerman, J L; Dawson, T M; Schell, M J; Snowman, A; Snyder, S H

    1994-01-01

    Using antibodies that react selectively with peptide sequences unique to endothelial nitric oxide synthase (eNOS), we demonstrate localizations to neuronal populations in the brain. In some brain regions, such as the cerebellum and olfactory bulb, eNOS and neuronal NOS (nNOS) occur in the same cell populations, though in differing proportions. In the hippocampus, localizations of the two enzymes are strikingly different, with eNOS more concentrated in hippocampal pyramidal cells than in any other brain area, whereas nNOS is restricted to occasional interneurons. In many brain regions NADPH diaphorase staining reflects NOS catalytic activity. Hippocampal pyramidal cells do not stain for diaphorase with conventional paraformaldehyde fixation but stain robustly with glutaraldehyde fixatives, presumably reflecting eNOS catalytic activity. eNOS in hippocampal pyramidal cells may generate the NO that has been postulated as a retrograde messenger of long-term potentiation. Images PMID:7514300

  20. Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1

    PubMed Central

    2014-01-01

    Background Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehavioral phenotypes associated with chromosome 15q11-q13.1 duplication (Dup15q) syndrome. Methods We have generated induced pluripotent stem cell (iPSC) lines from five different individuals containing CNVs of 15q11-q13.1. The iPSC lines were differentiated into mature, functional neurons. Gene expression across the 15q11-q13.1 locus was compared among the five iPSC lines and corresponding iPSC-derived neurons using quantitative reverse transcription PCR (qRT-PCR). Genome-wide gene expression was compared between neurons derived from three iPSC lines using mRNA-Seq. Results Analysis of 15q11-q13.1 gene expression in neurons derived from Dup15q iPSCs reveals that gene copy number does not consistently predict expression levels in cells with interstitial duplications of 15q11-q13.1. mRNA-Seq experiments show that there is substantial overlap in the genes differentially expressed between 15q11-q13.1 deletion and duplication neurons, Finally, we demonstrate that UBE3A transcripts can be pharmacologically rescued to normal levels in iPSC-derived neurons with a 15q11-q13.1 duplication. Conclusions Chromatin structure may influence gene expression across the 15q11-q13.1 region in neurons. Genome-wide analyses suggest that common neuronal pathways may be disrupted in both the Angelman and Dup15q syndromes. These data demonstrate that our disease-specific stem cell models provide a new tool to decipher the underlying cellular and genetic disease mechanisms of ASD and may also offer a

  1. Distribution and change in number of gonadotropin-releasing hormone-1 neurons following activation of the photoneuroendocrine system in the chick, Gallus gallus.

    PubMed

    Kuenzel, Wayne J; Golden, Christopher D

    2006-09-01

    The photoneuroendocrine system (PNES) of chicks was activated by transferring birds to a long photoperiod and by giving them a diet supplemented with sulfamethazine (SMZ), a compound that augments the effect of long-day photostimulation. We wished to determine (1) the number of gonadotropin-releasing hormone-1 (GnRH-1) neurons in each identified nucleus (n.) in the subpallium and diencephalon and the major terminal fields (TFs) of GnRH-1 neurons, and (2) the effect of SMZ on the immunoreactive expression of GnRH-1 in perikarya. Four groups of birds were exposed to one of two light treatments, viz., light:dark (LD) cycles of LD20:4 or LD8:16, and given one of two rations, viz., control or one supplemented with SMZ (n=5/treatment). After 3 days, chicks were anesthetized, and their brains were prepared for immunocytochemistry with an antibody identifying GnRH-1 neurons. Seven areas or nuclei contained GnRH-1 neurons: paramedial septal n., preoptic periventricular n./periventricular hypothalamic n., bed n. of the pallial commissure (NCPa), parvocellular lateral and medial septal n., lateral septum near the ventral horn of the lateral ventricle, parvocellular lateral anterior thalamic n., and displaced thalamic neurons. Six TFs of GnRH neurons were found including the organum vasculosum of lamina terminalis (OVLT), preoptic recess (POR), hypothalamic recess (HR), lateral septum adjacent to the ventral horn of the lateral ventricle (SL-VLvh) associated with the choroid plexus, subseptal organ (SSO), and external zone of the median eminence. The extensive TFs for GnRH-1 neurons in the OVLT, POR/HR, SL-VLvh, and SSO suggested that a large amount of the peptide was secreted into the ventricular system. The NCPa responded to the photoperiod and SMZ treatments combined, with a significant increase in GnRH-1 cell number compared with birds fed control diets and exposed to a short-day photoperiod. More than 73% of GnRH-1 neurons resided in the septal region of the subpallium

  2. Reaction time, impulse speed, overall synaptic delay and number of synapses in tactile reaction neuronal circuits of normal subjects and thinner sniffers.

    PubMed

    Chentanez, T; Keatisuwan, W; Akaraphan, A; Chaunchaiyakul, R; Lechanavanich, C; Hiranrat, S; Chaiwatcharaporn, C; Glinsukon, T

    1988-01-01

    In control subjects, warned auditory reaction time (RT) for a given effector organ was less than the warned visual RT for the same organ. The RT of the circuits between eye or ear or sites of tactile stimulation (SOS) and the index fingers were significantly shorter than that between eye or ear or the same SOS and the right or left big toes. The greater the distance between the SOS and the brain the longer the RT of the response by a given effector organ. The overall signal speed (OASS) from the neck to the index finger was less than that from the neck to the big toe. The OASS from the neck to a given effector was less than that from the toe to the same effector. Sensory nerve impulse speed was slightly faster than motor nerve impulse speed. The overall synaptic delay and estimated number of synapses (ENOS) of simple tactile reaction neuronal circuits of normal subjects did not significantly vary with site of tactile stimulation or effector organ. The mean number of synapses of various tactile reaction neuronal circuits of normal subjects was estimated to be between 69 and 77, which is far greater than the number of synapses in the touch-tactile and motor pathways combined. The overall synaptic delay in the tactile reaction neuronal circuits between SOS and the left and right big toes were significantly lower in sniffers than in control subjects. This may be due to a decrease in either the average synaptic delay, the number of synapses, or both in the tactile reaction neuronal circuits between sites of stimulation and big toes (but not index fingers) in sniffers. PMID:3393601

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

    NASA Astrophysics Data System (ADS)

    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

  4. Genetically Encoded Green Fluorescent Ca2+ Indicators with Improved Detectability for Neuronal Ca2+ Signals

    PubMed Central

    Sadakari, Junko; Gengyo-Ando, Keiko; Kagawa-Nagamura, Yuko; Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Imaging the activities of individual neurons with genetically encoded Ca2+ indicators (GECIs) is a promising method for understanding neuronal network functions. Here, we report GECIs with improved neuronal Ca2+ signal detectability, termed G-CaMP6 and G-CaMP8. Compared to a series of existing G-CaMPs, G-CaMP6 showed fairly high sensitivity and rapid kinetics, both of which are suitable properties for detecting subtle and fast neuronal activities. G-CaMP8 showed a greater signal (Fmax/Fmin = 38) than G-CaMP6 and demonstrated kinetics similar to those of G-CaMP6. Both GECIs could detect individual spikes from pyramidal neurons of cultured hippocampal slices or acute cortical slices with 100% detection rates, demonstrating their superior performance to existing GECIs. Because G-CaMP6 showed a higher sensitivity and brighter baseline fluorescence than G-CaMP8 in a cellular environment, we applied G-CaMP6 for Ca2+ imaging of dendritic spines, the putative postsynaptic sites. By expressing a G-CaMP6-actin fusion protein for the spines in hippocampal CA3 pyramidal neurons and electrically stimulating the granule cells of the dentate gyrus, which innervate CA3 pyramidal neurons, we found that sub-threshold stimulation triggered small Ca2+ responses in a limited number of spines with a low response rate in active spines, whereas supra-threshold stimulation triggered large fluorescence responses in virtually all of the spines with a 100% activity rate. PMID:23240011

  5. Increased dendritic extent in hippocampal CA1 neurons from aged F344 rats.

    PubMed

    Pyapali, G K; Turner, D A

    1996-01-01

    Age-related dendritic alterations were evaluated in F344 rats following a water maze assessment of spatial memory. Based on the probe trial times, 39% of the aged animals were designated impaired. CA1 pyramidal neurons were labeled intracellularly with neurobiotin in brain slices prepared from these animals. Neurons (aged: n = 15; young: n = 11) were reconstructed using a microscope-based three-dimensional system. Increased dendritic length was observed in the aged neurons both for basal dendrites (aged = 4.54 mm and young = 3.33 mm) and the entire neurons (aged = 14.8 mm and young = 10.8 mm). However, dendritic length values did not correlate with the individual animal's probe trial time. Sholl analysis revealed a diffuse increase in dendritic branch intersections in the cells from aged rats, which on branch order analysis was noted to be due to an increased number of distal branches. Mean electrotonic distance to dendritic terminals, a functional assessment of synaptic efficacy, was longer in the aged neurons (aged = 0.67 lambda and young = 0.55 lambda). These results suggest a lengthening and increased complexity of CA1 pyramidal neurons with successful aging, which may represent either an intrinsic response to aging or a reactive partial denervation response to a loss of afferent inputs.

  6. Electrical stimulation of embryonic neurons for 1 hour improves axon regeneration and the number of reinnervated muscles that function.

    PubMed

    Liu, Yang; Grumbles, Robert M; Thomas, Christine K

    2013-07-01

    Motoneuron death after spinal cord injury or disease results in muscle denervation, atrophy, and paralysis. We have previously transplanted embryonic ventral spinal cord cells into the peripheral nerve to reinnervate denervated muscles and to reduce muscle atrophy, but reinnervation was incomplete. Here, our aim was to determine whether brief electrical stimulation of embryonic neurons in the peripheralnerve changes motoneuron survival, axon regeneration, and muscle reinnervation and function because neural depolarization is crucial for embryonic neuron survival and may promote activity-dependent axon growth. At 1 week after denervation by sciatic nerve section, embryonic day 14 to 15 cells were purified for motoneurons, injected into the tibial nerve of adult Fischer rats, and stimulated immediatelyfor up to 1 hour. More myelinated axons were present in tibial nerves 10 weeks after transplantation when transplants had been stimulated acutely at 1 Hz for 1 hour. More muscles were reinnervated if the stimulation treatment lasted for 1 hour. Reinnervation reduced muscle atrophy, with or without the stimulation treatment. These data suggest that brief stimulation of embryonic neurons promotes axon growth, which has a long-term impact on muscle reinnervation and function. Muscle reinnervation is important because it may enable the use of functional electrical stimulation to restore limb movements. PMID:23771218

  7. Cocaine-conditioned place preference is predicted by previous anxiety-like behavior and is related to an increased number of neurons in the basolateral amygdala.

    PubMed

    Ladrón de Guevara-Miranda, David; Pavón, Francisco J; Serrano, Antonia; Rivera, Patricia; Estivill-Torrús, Guillermo; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J; Castilla-Ortega, Estela

    2016-02-01

    The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap. PMID:26523857

  8. Cocaine-conditioned place preference is predicted by previous anxiety-like behavior and is related to an increased number of neurons in the basolateral amygdala.

    PubMed

    Ladrón de Guevara-Miranda, David; Pavón, Francisco J; Serrano, Antonia; Rivera, Patricia; Estivill-Torrús, Guillermo; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J; Castilla-Ortega, Estela

    2016-02-01

    The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap.

  9. Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females

    PubMed Central

    Sadowski, Renee N.; Wise, Leslie M.; Park, Pul Y.; Schantz, Susan L.; Juraska, Janice M.

    2014-01-01

    Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400 μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1-9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC were parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400 μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400 μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders. PMID:25193849

  10. Curcumin and sertraline prevent the reduction of the number of neurons and glial cells and the volume of rats' medial prefrontal cortex induced by stress.

    PubMed

    Noorafshan, Ali; Abdollahifar, Mohammad-Amin; Asadi-Golshan, Reza; Rashidian-Rashidabadi, Ali; Karbalay-Doust, Saied

    2014-01-01

    Chronic stress induces morphological changes in the neurons of several brain regions, including medial prefrontal cortex (mPFC). This region is involved in variety of behavioral tasks, including learning and memory. Our previous work showed that stress impaired function. The present work extends the earlier work to study mPFC in stressed and non-stressed rats with or without sertraline or curcumin treatments using stereological methods. Sertraline is a selective serotonin reuptake inhibitor and curcumin is the main ingredient of turmeric with neuroprotective effects. In this study, 42 male rats were randomly assigned to seven groups: stress + distilled water, stress + olive oil, stress + curcumin (100 mg/kg/day), stress + sertraline (10 mg/kg/day), curcumin, sertraline, and control groups. After 56 days, the right mPFC was removed. The volume of mPFC and its subdivisions and the total number of neurons and glia were estimated. The results showed ~8%, ~8%, and 24% decrease in the volume of the mPFC and its prelimbic and infralimbic subdivisions, respectively. However, the anterior cingulated cortex remained unchanged. Also, the total number of the neurons and glial cells was significantly reduced (11% and 5%, respectively) in stress (+distilled water or olive oil) group in comparison to the non-stressed rats (P<0.01). However, no significant reduction was observed in the volume of the mPFC and its subdivisions as well as the total number of the neurons and glial cells in stress + sertraline and stress + curcumin groups in comparison to the non-treated stressed rats (P<0.01). The result indicated that treatment of rats with curcumin and sertraline could prevent the stress-induced changes in mPFC. PMID:24718043

  11. The pyramids of Greece: Ancient meridian observatories?

    NASA Astrophysics Data System (ADS)

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

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

  12. Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex.

    PubMed

    van Brederode, J F; Foehring, R C; Spain, W J

    2000-01-01

    We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the morphological and electrophysiological properties of atypically oriented pyramidal cells located at the layer 1/2 border of the juvenile rat neocortex. Orientation of the apical dendrite varied from oblique (>20 degrees from vertical) to truly horizontal (90 degrees from vertical). The length of the apical dendrite ranged from 150 to 400 microm. The total horizontal domain of the dendritic tree (including basal dendrites) of the longest horizontal pyramids exceeded 500 microm, but we also found short horizontal cells with horizontal dendritic domains of less than 300 microm. In addition, atypically oriented pyramids had long horizontal axon collaterals in layer 1/2. Electrophysiologically, atypically oriented pyramidal cells had intrinsic membrane properties similar to regularly oriented pyramids that have been described in the superficial layers at this age in the rat. Cells that fired repetitively were all regular spiking. In addition, we identified a subgroup of neurons (20%) in this sample, which were unable to fire more than a few spikes at the beginning of the current pulse. We suggest that the unique orientation and size of their dendritic trees and the length and arrangement of their local axons collaterals make atypically oriented pyramids in layer 2 ideally suited to perform horizontal integration of synaptic inputs in the neocortex.

  13. Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

    The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of

  14. Ultrastructural characteristics of human adult and infant cerebral cortical neurons.

    PubMed Central

    Ong, W Y; Garey, L J

    1991-01-01

    Biopsy specimens of human cerebral cortex from three adults and two infants were studied by correlating their light microscopic features in semithin sections with their ultrastructural characteristics. There was good tissue preservation, due to a minimum delay between obtaining the specimens and fixation. Pyramidal cells had a prominent apical dendrite, fine heterochromatin clumps in the nucleus and generally small numbers of cytoplasmic organelles, except for numerous free ribosomes in some of the large pyramids of Layers III to VI. Non-pyramidal cells lacked an apical dendrite and were further classified, on size and ultrastructure, into small, medium and large types. Large numbers of asymmetrical and symmetrical synapses were present in the neuropil but very few axosomatic synapses were found in the human cerebral cortex compared with subhuman primates and other mammals. Some symmetrical synapses were characterised by the presence of wide pre- and postsynaptic densities. The same general features of the adult cortex were also encountered in the infant, with certain exceptions. Many of the infant neurons had less densely packed heterochromatin, but greater numbers of free ribosomes, compared with the adult, and lipofuscin was absent. There was a total absence of myelinated fibres from the infant cortex; more large diameter dendrites were present than in the adult and axosomatic synapses were commoner. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:2050578

  15. HERC 1 Ubiquitin Ligase Mutation Affects Neocortical, CA3 Hippocampal and Spinal Cord Projection Neurons: An Ultrastructural Study

    PubMed Central

    Ruiz, Rocío; Pérez-Villegas, Eva María; Bachiller, Sara; Rosa, José Luis; Armengol, José Angel

    2016-01-01

    The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity. PMID:27147983

  16. HERC 1 Ubiquitin Ligase Mutation Affects Neocortical, CA3 Hippocampal and Spinal Cord Projection Neurons: An Ultrastructural Study.

    PubMed

    Ruiz, Rocío; Pérez-Villegas, Eva María; Bachiller, Sara; Rosa, José Luis; Armengol, José Angel

    2016-01-01

    The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity. PMID:27147983

  17. Active browsing using similarity pyramids

    NASA Astrophysics Data System (ADS)

    Chen, Jau-Yuen; Bouman, Charles A.; Dalton, John C.

    1998-12-01

    In this paper, we describe a new approach to managing large image databases, which we call active browsing. Active browsing integrates relevance feedback into the browsing environment, so that users can modify the database's organization to suit the desired task. Our method is based on a similarity pyramid data structure, which hierarchically organizes the database, so that it can be efficiently browsed. At coarse levels, the similarity pyramid allows users to view the database as large clusters of similar images. Alternatively, users can 'zoom into' finer levels to view individual images. We discuss relevance feedback for the browsing process, and argue that it is fundamentally different from relevance feedback for more traditional search-by-query tasks. We propose two fundamental operations for active browsing: pruning and reorganization. Both of these operations depend on a user-defined relevance set, which represents the image or set of images desired by the user. We present statistical methods for accurately pruning the database, and we propose a new 'worm hole' distance metric for reorganizing the database, so that members of the relevance set are grouped together.

  18. Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors.

    PubMed

    Meyer, Danielle L; Davies, Daniel R; Barr, Jeffrey L; Manzerra, Pasquale; Forster, Gina L

    2012-06-01

    Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9 days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.

  19. Phase precession and phase-locking of hippocampal pyramidal cells.

    PubMed

    Bose, A; Recce, M

    2001-01-01

    We propose that the activity patterns of CA3 hippocampal pyramidal cells in freely running rats can be described as a temporal phenomenon, where the timing of bursts is modulated by the animal's running speed. With this hypothesis, we explain why pyramidal cells fire in specific spatial locations, and how place cells phase-precess with respect to the EEG theta rhythm for rats running on linear tracks. We are also able to explain why wheel cells phase-lock with respect to the theta rhythm for rats running in a wheel. Using biophysically minimal models of neurons, we show how the same network of neurons displays these activity patterns. The different rhythms are the result of inhibition being used in different ways by the system. The inhibition is produced by anatomically and physiologically diverse types of interneurons, whose role in controlling the firing patterns of hippocampal cells we analyze. Each firing pattern is characterized by a different set of functional relationships between network elements. Our analysis suggests a way to understand these functional relationships and transitions between them.

  20. Development and validation of a food pyramid for Swiss athletes.

    PubMed

    Mettler, Samuel; Mannhart, Christof; Colombani, Paolo C

    2009-10-01

    Food-guide pyramids help translate nutrient goals into a visual representation of suggested food intake on a population level. No such guidance system has ever been specifically designed for athletes. Therefore, the authors developed a Food Pyramid for Swiss Athletes that illustrates the number of servings per food group needed in relation to the training volume of an athlete. As a first step, an average energy expenditure of 0.1 kcal . kg(-1) . min(-1) for exercise was defined, which then was translated into servings of different food groups per hour of exercise per day. Variable serving sizes were defined for athletes' different body-mass categories. The pyramid was validated by designing 168 daily meal plans according to the recommendations of the pyramid for male and female athletes of different body-mass categories and training volumes of up to 4 hr/d. The energy intake of the meal plans met the calculated reference energy requirement by 97% +/- 9%. The carbohydrate and protein intakes were linearly graded from 4.6 +/- 0.6-8.5 +/- 0.8 g . kg(-1) . d(-1) and 1.6 +/- 0.2-1.9 +/- 0.2 g . kg(-1) . d(-1), respectively, for training volumes of 1-4 hr of exercise per day. The average micronutrient intake depended particularly on the dietary energy intake level but was well above the dietary reference intake values for most micronutrients. No tolerable upper intake level was exceeded for any micronutrient. Therefore, this Food Pyramid for Swiss Athletes may be used as a new tool in sports nutrition education (e.g., teaching and counseling). PMID:19910652

  1. Development and validation of a food pyramid for Swiss athletes.

    PubMed

    Mettler, Samuel; Mannhart, Christof; Colombani, Paolo C

    2009-10-01

    Food-guide pyramids help translate nutrient goals into a visual representation of suggested food intake on a population level. No such guidance system has ever been specifically designed for athletes. Therefore, the authors developed a Food Pyramid for Swiss Athletes that illustrates the number of servings per food group needed in relation to the training volume of an athlete. As a first step, an average energy expenditure of 0.1 kcal . kg(-1) . min(-1) for exercise was defined, which then was translated into servings of different food groups per hour of exercise per day. Variable serving sizes were defined for athletes' different body-mass categories. The pyramid was validated by designing 168 daily meal plans according to the recommendations of the pyramid for male and female athletes of different body-mass categories and training volumes of up to 4 hr/d. The energy intake of the meal plans met the calculated reference energy requirement by 97% +/- 9%. The carbohydrate and protein intakes were linearly graded from 4.6 +/- 0.6-8.5 +/- 0.8 g . kg(-1) . d(-1) and 1.6 +/- 0.2-1.9 +/- 0.2 g . kg(-1) . d(-1), respectively, for training volumes of 1-4 hr of exercise per day. The average micronutrient intake depended particularly on the dietary energy intake level but was well above the dietary reference intake values for most micronutrients. No tolerable upper intake level was exceeded for any micronutrient. Therefore, this Food Pyramid for Swiss Athletes may be used as a new tool in sports nutrition education (e.g., teaching and counseling).

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

    PubMed

    Wang, Hong; Gondré-Lewis, Marjorie C

    2013-01-01

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

  3. Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors.

    PubMed

    Hermann, Andreas; Kim, Jeong Beom; Srimasorn, Sumitra; Zaehres, Holm; Reinhardt, Peter; Schöler, Hans R; Storch, Alexander

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC1F-NSC) or two (OCT4, KLF4; hiPSC2F-NSC) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB) or four reprogramming factors (hiPSC4F-FIB). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC1F-NSC and hiPSC2F-NSC was as efficient as iPSC3F-FIB or iPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.

  4. Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease.

    PubMed

    Lim, Andrew S P; Ellison, Brian A; Wang, Joshua L; Yu, Lei; Schneider, Julie A; Buchman, Aron S; Bennett, David A; Saper, Clifford B

    2014-10-01

    Fragmented sleep is a common and troubling symptom in ageing and Alzheimer's disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer's disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer's disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer's disease had fewer galaninergic intermediate nucleus neurons than those without (estimate -2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was <1 year (estimate -0.0013, standard error = 0.0005, P = 0.023). This association did not differ between individuals with and without Alzheimer's disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin

  5. Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons.

    PubMed

    Sobieraj, Jeffery C; Kim, Airee; Fannon, McKenzie J; Mandyam, Chitra D

    2016-01-01

    Exercise (physical activity) has been proposed as a treatment for drug addiction. In rodents, voluntary wheel running reduces cocaine and nicotine seeking during extinction, and reinstatement of cocaine seeking triggered by drug-cues. The purpose of this study was to examine the effects of chronic wheel running during withdrawal and protracted abstinence on extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats, and to determine a potential neurobiological correlate underlying the effects. Rats were given extended access to methamphetamine (0.05 mg/kg, 6 h/day) for 22 sessions. Rats were withdrawn and were given access to running wheels (wheel runners) or no wheels (sedentary) for 3 weeks after which they experienced extinction and reinstatement of methamphetamine seeking. Extended access to methamphetamine self-administration produced escalation in methamphetamine intake. Methamphetamine experience reduced running output, and conversely, access to wheel running during withdrawal reduced responding during extinction and, context- and cue-induced reinstatement of methamphetamine seeking. Immunohistochemical analysis of brain tissue demonstrated that wheel running during withdrawal did not regulate markers of methamphetamine neurotoxicity (neurogenesis, neuronal nitric oxide synthase, vesicular monoamine transporter-2) and cellular activation (c-Fos) in brain regions involved in relapse to drug seeking. However, reduced methamphetamine seeking was associated with running-induced reduction (and normalization) of the number of tyrosine hydroxylase immunoreactive neurons in the periaqueductal gray (PAG). The present study provides evidence that dopamine neurons of the PAG region show adaptive biochemical changes during methamphetamine seeking in methamphetamine dependent rats and wheel running abolishes these effects. Given that the PAG dopamine neurons project onto the structures of the extended amygdala, the present findings also

  6. The evolutionary transition to sideways-walking gaits in brachyurans was accompanied by a reduction in the number of motor neurons innervating proximal leg musculature.

    PubMed

    Vidal-Gadea, Andrés G; Belanger, Jim H

    2013-11-01

    The forwards-walking portly crab, Libinia emarginata is an ancient brachyuran. Its phylogenetic position and behavioral repertoire make it an excellent candidate to reveal the adaptations, which were required for brachyuran crabs to complete their transition to sideways-walking from their forwards-walking ancestors. Previously we showed that in common with other forwards-walking (but distantly related) crustaceans, L. emarginata relies more heavily on its more numerous proximal musculature to propel itself forward than its sideways-walking closer relatives. We investigated if the proximal musculature of L. emarginata is innervated by a greater number of motor neurons than that of sideways-walking brachyurans. We found the distal musculature of spider crabs is innervated by a highly conserved number of motor neurons. However, innervation of its proximal musculature is more numerous than in closely-related (sideways-walking) species, resembling in number and morphology those described for forwards-walking crustaceans. We propose that transition from forward- to sideways-walking in crustaceans involved a decreased role for the proximal leg in favor of the more distal merus-carpus joint.

  7. Sulfite leads to neuron loss in the hippocampus of both normal and SOX-deficient rats.

    PubMed

    Kocamaz, Erdogan; Adiguzel, Esat; Er, Buket; Gundogdu, Gulşah; Kucukatay, Vural

    2012-08-01

    Sulfites are compounds commonly used as preservatives in foods, beverages and pharmaceuticals. Sulfite is also endogenously generated during the metabolism of sulfur-containing amino acids and drugs. It has been shown that sulfite is a highly toxic molecule. Many studies have examined the effects of sulfite toxicity, but the effect of ingested sulfite on the number of neurons in the hippocampus has not yet been reported. The present study was undertaken to investigate the effect of ingested sulfite on pyramidal neurons by counting cells in CA1 and CA3-2 subdivisions of the rat hippocampus. For this purpose, rats were assigned to one of four groups (6 rats per group): control (C), sulfite (S), deficient (D) and deficient+sulfite (DS). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding 200ppm tungsten (W) to their drinking water. Sulfite (70mg/kg) was also administered to the animals via their drinking water. At the end of the experimental period, the rats were sacrificed by exsanguination under anesthesia, and their brains and livers quickly removed. The livers were used for a SOX activity assay, and the brains were used for neuronal counts in a known fraction of the CA1 and CA3-2 subdivisions of the left hippocampus using the optical fractionator method, which is a stereological method. The results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA3-2) in the S, D and DS groups compared with the control group. It is concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA3-2 subdivisions in both normal and SOX deficient rat hippocampus. This finding provides supporting evidence that sulfite is a neurotoxic molecule.

  8. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    PubMed

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-01

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity.

  9. Chronically reinforced, operant olfactory conditioning increases the number of newborn GABAergic olfactory periglomerular neurons in the adult rat.

    PubMed

    Tapia-Rodríguez, Miguel; Esquivelzeta-Rabell, José F; Gutiérrez-Ospina, Gabriel

    2012-12-01

    The mammalian brain preserves the ability to replace olfactory periglomerular cells (PGC) throughout life. Even though we have detailed a great deal the mechanisms underlying stem and amplifying cells maintenance and proliferation, as well as those modulating migration and differentiation, our knowledge on PGC phenotypic plasticity is at best fragmented and controversial. Here we explored whether chronically reinforced olfactory conditioning influences the phenotype of newborn PGC. Accordingly, olfactory conditioned rats showed increased numbers of GAD 65/67 positive PGC. Because such phenotypic change was not accompanied neither by increments in the total number of PGC, or periglomerular cell nuclei labeled with bromodeoxyuridine, nor by reductions in the number of tyrosine hydroxylase (TH), calbindin (CB) or calretinin (CR) immunoreactive PGC, we speculate that increments in the number of GABAergic PGC occur at the expense of other PGC phenotypes. In any event, these results support that adult newborn PGC phenotype may be subjected to phenotypic plasticity influenced by sensory stimulation.

  10. Control of cortical neuronal migration by glutamate and GABA

    PubMed Central

    Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

  11. Control of cortical neuronal migration by glutamate and GABA.

    PubMed

    Luhmann, Heiko J; Fukuda, A; Kilb, W

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca(2+) transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis.

  12. Extracorporeal shockwave application to the distal femur of rabbits diminishes the number of neurons immunoreactive for substance P in dorsal root ganglia L5.

    PubMed

    Hausdorf, Jörg; Lemmens, Marijke A M; Kaplan, Suleyman; Marangoz, Cafer; Milz, Stefan; Odaci, Ersan; Korr, Hubert; Schmitz, Christoph; Maier, Markus

    2008-05-01

    Application of extracorporeal shockwaves to the musculoskeletal system can induce long-term analgesia in the treatment of chronic painful diseases such as calcifying tendonitis of the shoulder, tennis elbow and chronic plantar fasciitis. However, the molecular and cellular mechanisms underlying this phenomenon are largely unknown. Recently it was shown that application of extracorporeal shockwaves to the distal femur of rabbits can lead to reduced concentration of substance P in the shockwaves' focal zone. In the present study we investigated the impact of extracorporeal shockwaves on the production of substance P within dorsal root ganglia in vivo. High-energy shockwaves were applied to the ventral side of the right distal femur of rabbits. After six weeks, the dorsal root ganglia L5 to L7 were investigated with high-precision design-based stereology. The application of extracorporeal shockwaves caused a statistically significant decrease in the mean number of neurons immunoreactive for substance P within the dorsal root ganglion L5 of the treated side compared with the untreated side, without affecting the total number of neurons within this dorsal root ganglion. No effect was observed in the dorsal root ganglia L6 and L7, respectively. These data might further contribute to our understanding of the molecular and cellular mechanisms in the induction of long-term analgesia by extracorporeal shockwave application to the musculoskeletal system.

  13. Maskless inverted pyramid texturization of silicon.

    PubMed

    Wang, Yan; Yang, Lixia; Liu, Yaoping; Mei, Zengxia; Chen, Wei; Li, Junqiang; Liang, Huili; Kuznetsov, Andrej; Xiaolong, Du

    2015-06-02

    We discovered a technical solution of such outstanding importance that it can trigger new approaches in silicon wet etching processing and, in particular, photovoltaic cell manufacturing. The so called inverted pyramid arrays, outperforming conventional pyramid textures and black silicon because of their superior light-trapping and structure characteristics, can currently only be achieved using more complex techniques involving lithography, laser processing, etc. Importantly, our data demonstrate a feasibility of inverted pyramidal texturization of silicon by maskless Cu-nanoparticles assisted etching in Cu(NO3)2 / HF / H2O2 / H2O solutions and as such may have significant impacts on communities of fellow researchers and industrialists.

  14. Optical Properties of Nested Pyramidal Nanoshells.

    PubMed

    Lin, Julia Y; Hasan, Warefta; Yang, Jiun-Chan; Odom, Teri W

    2010-01-01

    This paper describes the fabrication and characterization of nested Au pyramidal nanoshells. These particles exhibited two plasmon resonances at visible and near-infrared wavelengths that could be manipulated depending on the size of the gap between inner and outer pyramidal shells. We found that larger gaps (30 nm) exhibited much larger Raman scattering responses compared to smaller gaps (5 nm) in the nested pyramidal shells. The SERS-activity of these anisotropic particles can be optimized by adjusting the distances between the inner and outer Au shells. PMID:20431688

  15. Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus.

    PubMed

    Iwano, Tomohiko; Masuda, Aki; Kiyonari, Hiroshi; Enomoto, Hideki; Matsuzaki, Fumio

    2012-08-01

    The brain is composed of diverse types of neurons that fulfill distinct roles in neuronal circuits, as manifested by the hippocampus, where pyramidal neurons and granule cells constitute functionally distinct domains: cornu ammonis (CA) and dentate gyrus (DG), respectively. Little is known about how these two types of neuron differentiate during hippocampal development, although a set of transcription factors that is expressed in progenitor cells is known to be required for the survival of granule cells. Here, we demonstrate in mice that Prox1, a transcription factor constitutively expressed in the granule cell lineage, postmitotically functions to specify DG granule cell identity. Postmitotic elimination of Prox1 caused immature DG neurons to lose the granule cell identity and in turn terminally differentiate into the pyramidal cell type manifesting CA3 neuronal identity. By contrast, Prox1 overexpression caused opposing effects on presumptive hippocampal pyramidal cells. These results indicate that the immature DG cell has the potential to become a granule cell or a pyramidal cell, and Prox1 defines the granule cell identity. This bi-potency is lost in mature DG cells, although Prox1 is still required for correct gene expression in DG granule cells. Thus, our data indicate that Prox1 acts as a postmitotic cell fate determinant for DG granule cells over the CA3 pyramidal cell fate and is crucial for maintenance of the granule cell identity throughout the life.

  16. Corticospinal mirror neurons.

    PubMed

    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.

  17. Hippocampal sclerosis in the parkinsonism-dementia complex of Guam: quantitative examination of neurons, neurofibrillary tangles, and TDP-43 immunoreactivity in CA1.

    PubMed

    Oyanagi, Kiyomitsu; Yamazaki, Mineo; Hashimoto, Tomoyo; Asakawa, Mika; Wakabayashi, Koichi; Takahashi, Hitoshi

    2015-06-01

    The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs. PMID:25783521

  18. Hippocampal sclerosis in the parkinsonism-dementia complex of Guam: quantitative examination of neurons, neurofibrillary tangles, and TDP-43 immunoreactivity in CA1.

    PubMed

    Oyanagi, Kiyomitsu; Yamazaki, Mineo; Hashimoto, Tomoyo; Asakawa, Mika; Wakabayashi, Koichi; Takahashi, Hitoshi

    2015-06-01

    The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs.

  19. Antireflective properties of pyramidally textured surfaces.

    PubMed

    Deinega, Alexei; Valuev, Ilya; Potapkin, Boris; Lozovik, Yurii

    2010-01-15

    Antireflective properties of pyramidally textured surfaces at normal light incidence are studied by the finite-difference time-domain (FDTD) method. Optimal parameters for the period of the texture and the pyramid height are found. The asymptotic behavior of the reflection coefficient with an increasing height-to-base size ratio for the pyramids is also estimated for two limiting approximations: the effective medium theory (EMT) and geometric optics. For calculations in the geometric optics limit the ray tracing method was applied. The FDTD results for these limits are in agreement with the EMT and with the ray tracing calculations. It was found that the key factor influencing the optimal scatterer size is the character of the substrate tiling by the pyramid bases. PMID:20081936

  20. Distribution of SMI-32-immunoreactive neurons in the central auditory system of the rat.

    PubMed

    Ouda, Ladislav; Druga, Rastislav; Syka, Josef

    2012-01-01

    SMI-32 antibody recognizes a non-phosphorylated epitope of neurofilament proteins, which are thought to be necessary for the maintenance of large neurons with highly myelinated processes. We investigated the distribution and quantity of SMI-32-immunoreactive(-ir) neurons in individual parts of the rat auditory system. SMI-32-ir neurons were present in all auditory structures; however, in most regions they constituted only a minority of all neurons (10-30%). In the cochlear nuclei, a higher occurrence of SMI-32-ir neurons was found in the ventral cochlear nucleus. Within the superior olivary complex, SMI-32-ir cells were particularly abundant in the medial nucleus of the trapezoid body (MNTB), the only auditory region where SMI-32-ir neurons constituted an absolute majority of all neurons. In the inferior colliculus, a region with the highest total number of neurons among the rat auditory subcortical structures, the percentage of SMI-32-ir cells was, in contrast to the MNTB, very low. In the medial geniculate body, SMI-32-ir neurons were prevalent in the ventral division. At the cortical level, SMI-32-ir neurons were found mainly in layers III, V and VI. Within the auditory cortex, it was possible to distinguish the Te1, Te2 and Te3 areas on the basis of the variable numerical density and volumes of SMI-32-ir neurons, especially when the pyramidal cells of layer V were taken into account. SMI-32-ir neurons apparently form a representative subpopulation of neurons in all parts of the rat central auditory system and may belong to both the inhibitory and excitatory systems, depending on the particular brain region.

  1. Work, gravitational energy and the Great Pyramid

    NASA Astrophysics Data System (ADS)

    Tort, A. C.

    2015-09-01

    According to the Greek historian Herodotus, it took a task force of 100 000 men and 20 years to build up the Great Pyramid of Gizeh or Khufu’s Pyramid. In this work we discuss an analytical solution obtained in the framework of basic Newtonian mechanics that allows us to check Herodotus’s statement. Numerical estimates are compared to more detailed calculations. An estimation of the dietary energy intake necessary to accomplish the task is also discussed.

  2. Pyramidal micromirrors for microsystems and atom chips

    NASA Astrophysics Data System (ADS)

    Trupke, M.; Ramirez-Martinez, F.; Curtis, E. A.; Ashmore, J. P.; Eriksson, S.; Hinds, E. A.; Moktadir, Z.; Gollasch, C.; Kraft, M.; Vijaya Prakash, G.; Baumberg, J. J.

    2006-02-01

    Concave pyramids are created in the (100) surface of a silicon wafer by anisotropic etching in potassium hydroxide. High quality micromirrors are then formed by sputtering gold onto the smooth silicon (111) faces of the pyramids. These mirrors show great promise as high quality optical devices suitable for integration into micro-optoelectromechanical systems and atom chips. We have shown that structures of this shape can be used to laser-cool and hold atoms in a magneto-optical trap.

  3. Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

    PubMed Central

    Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

    2013-01-01

    Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non

  4. Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease

    PubMed Central

    Vittori, Angelica; Breda, Carlo; Repici, Mariaelena; Orth, Michael; Roos, Raymund A.C.; Outeiro, Tiago F.; Giorgini, Flaviano; Hollox, Edward J.

    2014-01-01

    Huntington's disease (HD) is a devastating neurodegenerative disorder which is inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT) protein. Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients. The length of the CAG repeat is inversely correlated with age of onset (AO) in HD patients, while environmental and genetic factors can further modulate this parameter. Here, we explored whether the recently described copy-number variation (CNV) of the gene SLC2A3—which encodes the neuronal glucose transporter GLUT3—could modulate AO in HD. Strikingly, we found that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals, and that this correlated with increased levels of GLUT3 in HD patient cells. To our knowledge this is the first time that CNV of a candidate gene has been found to modulate HD pathogenesis. Furthermore, we found that increasing dosage of Glut1—the Drosophila melanogaster homologue of this glucose transporter—ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration and life expectancy. As alterations in glucose metabolism have been implicated in HD pathogenesis, this study may have important therapeutic relevance for HD. PMID:24452335

  5. Fabrication of Single-Photon Sources by Use of Pyramidal Quantum-Dot Microcavities

    NASA Astrophysics Data System (ADS)

    Rülke, Daniel; Reinheimer, C.; Schaadt, D. M.; Kalt, H.; Hetterich, M.

    In recent years the interest in single-photon emitters for quantum-optical applications is strongly increasing. For this purpose, we have investigated In(Ga)As quantum-dots (QDs) embedded in reversed pyramidal GaAs microcavities (Fig. 52.1a). Even though it has been shown recently, that such cavities can act as high-Q optical resonators [1], our focus has been on the directional radiation of the QD emission due to reflection at the facets of the reversed pyramids. With QDs embedded close to the vertex of the four facets and a base angle adaptable between 35° and 55° the pyramids can be perceived as a kind of retroreflector. Since the QD layer is inserted near the tip of the predicted reversed pyramid during molecular-beam epitaxial (MBE) growth, the average number of QDs inside the cavity can be reduced to one, depending on the size of the pyramid and density of QDs. The pyramidal cavities are shaped after MBE growth by a wet-chemical etching process with a solution of H3PO4, H2O2 and H2O [2, 3].

  6. Modified MyPyramid for Older Adults.

    PubMed

    Lichtenstein, Alice H; Rasmussen, Helen; Yu, Winifred W; Epstein, Susanna R; Russell, Robert M

    2008-01-01

    In 1999 we proposed a Modified Food Guide Pyramid for adults aged 70+ y. It has been extensively used in a variety of settings and formats to highlight the unique dietary challenges of older adults. We now propose a Modified MyPyramid for Older Adults in a format consistent with the MyPyramid graphic. It is not intended to substitute for MyPyramid, which is a multifunctional Internet-based program allowing for the calculation of individualized food-based dietary guidance and providing supplemental information on food choices and preparation. Pedagogic issues related to computer availability, Web access, and Internet literacy of older adults suggests a graphic version of MyPyramid is needed. Emphasized are whole grains and variety within the grains group; variety and nutrient density, with specific emphasis on different forms particularly suited to older adults' needs (e.g. frozen) in the vegetables and fruits groups; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group. Underlying themes stress nutrient- and fiber-rich foods within each group and food sources of nutrients rather than supplements. Fluid and physical activity icons serve as the foundation of MyPyramid for Older Adults. A flag to maintain an awareness of the potential need to consider supplemental forms of calcium, and vitamins D and B-12 is placed at the top of the pyramid. Discussed are newer concerns about potential overnutrition in the current food landscape available to older adults. PMID:18156396

  7. Modified MyPyramid for Older Adults.

    PubMed

    Lichtenstein, Alice H; Rasmussen, Helen; Yu, Winifred W; Epstein, Susanna R; Russell, Robert M

    2008-01-01

    In 1999 we proposed a Modified Food Guide Pyramid for adults aged 70+ y. It has been extensively used in a variety of settings and formats to highlight the unique dietary challenges of older adults. We now propose a Modified MyPyramid for Older Adults in a format consistent with the MyPyramid graphic. It is not intended to substitute for MyPyramid, which is a multifunctional Internet-based program allowing for the calculation of individualized food-based dietary guidance and providing supplemental information on food choices and preparation. Pedagogic issues related to computer availability, Web access, and Internet literacy of older adults suggests a graphic version of MyPyramid is needed. Emphasized are whole grains and variety within the grains group; variety and nutrient density, with specific emphasis on different forms particularly suited to older adults' needs (e.g. frozen) in the vegetables and fruits groups; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group. Underlying themes stress nutrient- and fiber-rich foods within each group and food sources of nutrients rather than supplements. Fluid and physical activity icons serve as the foundation of MyPyramid for Older Adults. A flag to maintain an awareness of the potential need to consider supplemental forms of calcium, and vitamins D and B-12 is placed at the top of the pyramid. Discussed are newer concerns about potential overnutrition in the current food landscape available to older adults.

  8. Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

    PubMed

    Ash, Jessica A; Velazquez, Ramon; Kelley, Christy M; Powers, Brian E; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

    2014-10-01

    Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large.

  9. Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

    PubMed

    Ash, Jessica A; Velazquez, Ramon; Kelley, Christy M; Powers, Brian E; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

    2014-10-01

    Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. PMID:24932939

  10. Cortical neuronal cytoskeletal changes associated with FIV infection

    NASA Technical Reports Server (NTRS)

    Jacobson, S.; Henriksen, S. J.; Prospero-Garcia, O.; Phillips, T. R.; Elder, J. H.; Young, W. G.; Bloom, F. E.; Fox, H. S.

    1997-01-01

    HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

  11. Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex.

    PubMed Central

    Thomson, A M; West, D C; Hahn, J; Deuchars, J

    1996-01-01

    1. Using dual intracellular recordings in slices of adult rat neocortex, twenty-four IPSPs activated by single presynaptic interneurones were studied in simultaneously recorded pyramidal cells. Fast spiking interneurones inhibited one in four or five of their close pyramidal neighbours. No reciprocal connections were observed. After recordings neurones were filled with biocytin. 2. Interneurones that elicited IPSPs were classified as classical fast spiking (n = 10), as non-classical fast spiking (n = 3, including one burst-firing interneurone), as unclassified, or slow interneurones (n = 8), or as regular spiking interneurones (n = 3), i.e. interneurones whose electrophysiological characteristics were indistinguishable from those of pyramidal cells. 3. All of the seven classical fast spiking cells anatomically fully recovered had aspiny, beaded dendrites. Their partially myelinated axons ramified extensively, varying widely in shape and extent, but randomly selected labelled axon terminals typically innervated somata and large calibre dendrites on electron microscopic examination. One 'autapse' was demonstrated. One presumptive regular spiking interneurone axon made four somatic and five dendritic connections with unlabelled targets. 4. Full anatomical reconstructions of labelled classical fast spiking interneurones and their postsynaptic pyramids (n = 5) demonstrated one to five boutons per connection. The two recorded IPSPs that were fully reconstructed morphologically (3 and 5 terminals) were, however, amongst the smallest recorded (< 0.4 mV). Some connections may therefore involve larger numbers of contacts. 5. Single axon IPSPs were between 0.2 and 3.5 mV in average amplitude at -55 to -60 mV. Extrapolated reversal potentials were between -70 and -82 mV. IPSP time course correlated with the type of presynaptic interneurone, but not with IPSP latency, amplitude, reversal potential, or sensitivity to current injected at the soma. 6. Classical fast spiking

  12. Neurons in the White Matter of the Adult Human Neocortex

    PubMed Central

    Suárez-Solá, M. Luisa; González-Delgado, Francisco J.; Pueyo-Morlans, Mercedes; Medina-Bolívar, O. Carolina; Hernández-Acosta, N. Carolina; González-Gómez, Miriam; Meyer, Gundela

    2009-01-01

    The white matter (WM) of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system. PMID:19543540

  13. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

    PubMed Central

    Bressel, Olaf Christian; Khan, Mona

    2015-01-01

    ABSTRACT Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene‐targeted strains of the OR‐IRES‐marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, “count every cell” strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain‐specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17‐fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene‐targeted strains. J. Comp. Neurol. 524:199–209, 2016. © 2015 Wiley Periodicals, Inc. PMID:26100963

  14. Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number.

    PubMed

    Kwon, Hyung-Bae; Kozorovitskiy, Yevgenia; Oh, Won-Jong; Peixoto, Rui T; Akhtar, Nazia; Saulnier, Jessica L; Gu, Chenghua; Sabatini, Bernardo L

    2012-12-01

    Members of the neuroligin family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, the function of neuroligins in vivo in the regulation of synapse formation and synapse number has been difficult to establish. We found that neuroligin-1 (NL1), which is located at excitatory postsynaptic densities, regulates activity-dependent synaptogenesis and mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number was not sensitive to absolute NL1 levels but instead depended on transcellular differences in the relative amounts of NL1. These effects were independent of the cell-autonomous regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data indicate that transcellular competitive processes govern synapse formation and number in developing cortex and that NL1 has a central function in these processes.

  15. The pyramid system for multiscale raster analysis

    USGS Publications Warehouse

    De Cola, L.; Montagne, N.

    1993-01-01

    Geographical research requires the management and analysis of spatial data at multiple scales. As part of the U.S. Geological Survey's global change research program a software system has been developed that reads raster data (such as an image or digital elevation model) and produces a pyramid of aggregated lattices as well as various measurements of spatial complexity. For a given raster dataset the system uses the pyramid to report: (1) mean, (2) variance, (3) a spatial autocorrelation parameter based on multiscale analysis of variance, and (4) a monofractal scaling parameter based on the analysis of isoline lengths. The system is applied to 1-km digital elevation model (DEM) data for a 256-km2 region of central California, as well as to 64 partitions of the region. PYRAMID, which offers robust descriptions of data complexity, also is used to describe the behavior of topographic aspect with scale. ?? 1993.

  16. Maskless inverted pyramid texturization of silicon

    PubMed Central

    Wang, Yan; Yang, Lixia; Liu, Yaoping; Mei, Zengxia; Chen, Wei; Li, Junqiang; Liang, Huili; Kuznetsov, Andrej; Xiaolong, Du

    2015-01-01

    We discovered a technical solution of such outstanding importance that it can trigger new approaches in silicon wet etching processing and, in particular, photovoltaic cell manufacturing. The so called inverted pyramid arrays, outperforming conventional pyramid textures and black silicon because of their superior light-trapping and structure characteristics, can currently only be achieved using more complex techniques involving lithography, laser processing, etc. Importantly, our data demonstrate a feasibility of inverted pyramidal texturization of silicon by maskless Cu-nanoparticles assisted etching in Cu(NO3)2 / HF / H2O2 / H2O solutions and as such may have significant impacts on communities of fellow researchers and industrialists. PMID:26035520

  17. Maskless inverted pyramid texturization of silicon.

    PubMed

    Wang, Yan; Yang, Lixia; Liu, Yaoping; Mei, Zengxia; Chen, Wei; Li, Junqiang; Liang, Huili; Kuznetsov, Andrej; Xiaolong, Du

    2015-01-01

    We discovered a technical solution of such outstanding importance that it can trigger new approaches in silicon wet etching processing and, in particular, photovoltaic cell manufacturing. The so called inverted pyramid arrays, outperforming conventional pyramid textures and black silicon because of their superior light-trapping and structure characteristics, can currently only be achieved using more complex techniques involving lithography, laser processing, etc. Importantly, our data demonstrate a feasibility of inverted pyramidal texturization of silicon by maskless Cu-nanoparticles assisted etching in Cu(NO3)2 / HF / H2O2 / H2O solutions and as such may have significant impacts on communities of fellow researchers and industrialists. PMID:26035520

  18. Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons.

    PubMed

    Sato, Haruka; Fukutani, Yuma; Yamamoto, Yuji; Tatara, Eiichi; Takemoto, Makoto; Shimamura, Kenji; Yamamoto, Nobuhiko

    2012-10-31

    The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner. PMID:23115177

  19. Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons.

    PubMed

    Sato, Haruka; Fukutani, Yuma; Yamamoto, Yuji; Tatara, Eiichi; Takemoto, Makoto; Shimamura, Kenji; Yamamoto, Nobuhiko

    2012-10-31

    The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.

  20. Imaging Golgi Outposts in Fixed and Living Neurons.

    PubMed

    Bisbal, Mariano; Quassollo, Gonzalo; Caceres, Alfredo

    2016-01-01

    Here we describe the use of confocal microscopy in combination with antibodies specific to Golgi proteins to visualize dendritic Golgi outposts (GOPs) in cultured hippocampal pyramidal neurons. We also describe the use of spinning disk confocal microscopy, in combination with ectopically expressed glycosyltransferases fused to GFP variants, to visualize GOPs in living neurons. PMID:27631999

  1. Neuronal damage in hippocampal subregions induced by various durations of transient cerebral ischemia in gerbils using Fluoro-Jade B histofluorescence.

    PubMed

    Yu, Dong-Kun; Yoo, Ki-Yeon; Shin, Bich Na; Kim, In Hye; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon; Cho, Yong-Jun; Kang, Il-Jun; Kim, Young-Myeong; Won, Moo-Ho

    2012-02-01

    Although there are many studies on ischemic brain damage in the gerbil, which is a good model of transient cerebral ischemia, studies on neuronal damage according to the duration of ischemia-reperfusion (I-R) time are limited. We carried out neuronal damage in the gerbil hippocampus after various durations of I-R (5, 10, 15 and 20 min) using Fluoro-Jade B (F-J B, a maker for neuronal degeneration) histofluorescence as well as cresyl violet (CV) staining. The changes of CV positive ((+)) neurons were well detected in the hippocampal CA1 region, not in the other regions. F-J B histofluorescence staining showed apparent neuronal damage in all the hippocampal subregions. In the CA1, most of the pyramidal neurons of the stratum pyramidale (SP) were stained with F-J B (about 100/mm(2) in a section), and F-J B(+) neurons in the other ischemia-groups were not changed. In the CA2, a few F-J B(+) neurons were detected in the SP of the 5 min ischemia-group, and F-J B(+) neurons were gradually increased with the longer time of ischemia: in the 20 min ischemia-group, the mean number of F-J B(+) neurons was about 85/mm(2) in a section. In the CA3, some F-J B(+) neurons were observed only in the SP of the 20 min ischemia-group. In the dentate gyrus, some F-J B positive neurons were detected only in the polymorphic layer (PL) of the 5 min ischemia-group, and the number of F-J B(+) neurons were gradually increased with the longer ischemic time. Our findings indicate that F-J B histofluorescence showed a very high quality of neuronal damage in all the hippocampal subregions.

  2. Coexistence of glutamatergic spine synapses and shaft synapses in substantia nigra dopamine neurons

    PubMed Central

    Jang, Miae; Bum Um, Ki; Jang, Jinyoung; Jin Kim, Hyun; Cho, Hana; Chung, Sungkwon; Kyu Park, Myoung

    2015-01-01

    Dopamine neurons of the substantia nigra have long been believed to have multiple aspiny dendrites which receive many glutamatergic synaptic inputs from several regions of the brain. But, here, using high-resolution two-photon confocal microscopy in the mouse brain slices, we found a substantial number of common dendritic spines in the nigral dopamine neurons including thin, mushroom, and stubby types of spines. However, the number of dendritic spines of the dopamine neurons was approximately five times lower than that of CA1 pyramidal neurons. Immunostaining and morphological analysis revealed that glutamatergic shaft synapses were present two times more than spine synapses. Using local two-photon glutamate uncaging techniques, we confirmed that shaft synapses and spine synapses had both AMPA and NMDA receptors, but the AMPA/NMDA current ratios differed. The evoked postsynaptic potentials of spine synapses showed lower amplitudes but longer half-widths than those of shaft synapses. Therefore, we provide the first evidence that the midbrain dopamine neurons have two morphologically and functionally distinct types of glutamatergic synapses, spine synapses and shaft synapses, on the same dendrite. This peculiar organization could be a new basis for unraveling many physiological and pathological functions of the midbrain dopamine neurons. PMID:26435058

  3. Plasmin potentiates synaptic N-methyl-D-aspartate receptor function in hippocampal neurons through activation of protease-activated receptor-1.

    PubMed

    Mannaioni, Guido; Orr, Anna G; Hamill, Cecily E; Yuan, Hongjie; Pedone, Katherine H; McCoy, Kelly L; Berlinguer Palmini, Rolando; Junge, Candice E; Lee, C Justin; Yepes, Manuel; Hepler, John R; Traynelis, Stephen F

    2008-07-18

    Protease-activated receptor-1 (PAR1) is activated by a number of serine proteases, including plasmin. Both PAR1 and plasminogen, the precursor of plasmin, are expressed in the central nervous system. In this study we examined the effects of plasmin in astrocyte and neuronal cultures as well as in hippocampal slices. We find that plasmin evokes an increase in both phosphoinositide hydrolysis (EC(50) 64 nm) and Fura-2/AM fluorescence (195 +/- 6.7% above base line, EC(50) 65 nm) in cortical cultured murine astrocytes. Plasmin also activates extracellular signal-regulated kinase (ERK1/2) within cultured astrocytes. The plasmin-induced rise in intracellular Ca(2+) concentration ([Ca(2+)](i)) and the increase in phospho-ERK1/2 levels were diminished in PAR1(-/-) astrocytes and were blocked by 1 microm BMS-200261, a selective PAR1 antagonist. However, plasmin had no detectable effect on ERK1/2 or [Ca(2+)](i) signaling in primary cultured hippocampal neurons or in CA1 pyramidal cells in hippocampal slices. Plasmin (100-200 nm) application potentiated the N-methyl-D-aspartate (NMDA) receptor-dependent component of miniature excitatory postsynaptic currents recorded from CA1 pyramidal neurons but had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate- or gamma-aminobutyric acid receptor-mediated synaptic currents. Plasmin also increased NMDA-induced whole cell receptor currents recorded from CA1 pyramidal cells (2.5 +/- 0.3-fold potentiation over control). This effect was blocked by BMS-200261 (1 microm; 1.02 +/- 0.09-fold potentiation over control). These data suggest that plasmin may serve as an endogenous PAR1 activator that can increase [Ca(2+)](i) in astrocytes and potentiate NMDA receptor synaptic currents in CA1 pyramidal neurons.

  4. Toddler Teachers' Use of "Teaching Pyramid" Practices

    ERIC Educational Resources Information Center

    Branson, Diane; Demchak, MaryAnn

    2011-01-01

    Effective strategies to promote social-emotional development and prevent occurrence of challenging behaviors in young children is critical. The "Teaching Pyramid", a framework for supporting social-emotional development and preventing and addressing challenging behaviors, was developed for preschool children. This mixed methods study investigated…

  5. Ancient Pyramids Help Students Learn Math Concepts

    ERIC Educational Resources Information Center

    Smith, Courtney D.; Stump, Amanda M.; Lazaros, Edward J.

    2010-01-01

    This article presents an activity that allows students to use mathematics and critical-thinking skills to emulate processes used by the ancient Egyptians to prepare the site for the Pyramids of Giza. To accomplish this, they use three different methods. First, they create a square using only simple technological tools that were available to the…

  6. Vegetarian food guide pyramid: a conceptual framework.

    PubMed

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

    1999-09-01

    The purpose of this article and the accompanying vegetarian food guide pyramid graphic is to provide the conceptual framework for the development of a new and unique food guide. Food guides for vegetarians have tended to be adaptations of guides developed for the general nonvegetarian population instead of being designed to emphasize the healthy components of vegetarian dietary patterns. A subcommittee of the organizers of the Third International Congress on Vegetarian Nutrition began a process that led to the development of a pyramid-shaped graphic illustration and a supporting document, both of which were introduced at the congress. The 5 major plant-based food groups (whole grains, legumes, vegetables, fruit, nuts, and seeds) form the trapezoid-shaped lower portion of the pyramid. Optional food groups, which may be avoided by some vegetarians (vegetable oils, dairy, eggs, and sweets), form the smaller, separate, triangle-shaped top portion of the pyramid. The supporting document discusses the concepts that affect vegetarian food guidance and the rationale for selecting the food groups. It is hoped that this framework will provide the impetus for further research and discussion and will lead to the development of a guide that is nutritionally adequate, is conducive to good health, and can be adopted by vegetarians of diverse eating practices. PMID:10479240

  7. Pyramid Servings Database (PSDB) for NHANES III

    Cancer.gov

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

  8. The Vegetable Group. The Food Guide Pyramid.

    ERIC Educational Resources Information Center

    Frost, Helen

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

  9. Vegetarian food guide pyramid: a conceptual framework.

    PubMed

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

    1999-09-01

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

  10. The Dairy Group. The Food Guide Pyramid.

    ERIC Educational Resources Information Center

    Frost, Helen

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

  11. The Fruit Group. The Food Guide Pyramid.

    ERIC Educational Resources Information Center

    Frost, Helen

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

  12. The Grain Group. The Food Guide Pyramid.

    ERIC Educational Resources Information Center

    Frost, Helen

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

  13. Eating Right. The Food Guide Pyramid.

    ERIC Educational Resources Information Center

    Frost, Helen

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

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

    ERIC Educational Resources Information Center

    Easley, Edgar M.; Wigglesworth, David C.

    1979-01-01

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

  15. Food Pyramids and Bio-Accumulation.

    ERIC Educational Resources Information Center

    Baker, Valerie

    1998-01-01

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

  16. Ovarian hormones influence corticotropin releasing factor receptor colocalization with delta opioid receptors in CA1 pyramidal cell dendrites

    PubMed Central

    Williams, Tanya J.; Akama, Keith T.; Knudsen, Margarete G.; McEwen, Bruce S.; Milner, Teresa A.

    2011-01-01

    Stress interacts with addictive processes to increase drug use, drug seeking, and relapse. The hippocampal formation (HF) is an important site at which stress circuits and endogenous opioid systems intersect and likely plays a critical role in the interaction between stress and drug addiction. Our prior studies demonstrate that the stress-related neuropeptide corticotropin-releasing factor (CRF) and the delta-opioid receptor (DOR) colocalize in interneuron populations in the hilus of the dentate gyrus and stratum oriens of CA1 and CA3. While independent ultrastructural studies of DORs and CRF receptors suggest that each receptor is found in CA1 pyramidal cell dendrites and dendritic spines, whether DORs and CRF receptors colocalize in CA1 neuronal profiles has not been investigated. Here, hippocampal sections of adult male and proestrus female Sprague-Dawley rats were processed for dual label pre-embedding immunoelectron microscopy using well-characterized antisera directed against the DOR for immunoperoxidase and against the CRF receptor for immunogold. DOR-immunoreactivity (-ir) was found presynaptically in axons and axon terminals as well as postsynaptically in somata, dendrites and dendritic spines in stratum radiatum of CA1. In contrast, CRF receptor-ir was predominantly found postsynaptically in CA1 somata, dendrites, and dendritic spines. CRF receptor-ir frequently was observed in DOR-labeled dendritic profiles and primarily was found in the cytoplasm rather than at or near the plasma membrane. Quantitative analysis of CRF receptor-ir colocalization with DOR-ir in pyramidal cell dendrites revealed that proestrus females and males show comparable levels of CRF receptor-ir per dendrite and similar cytoplasmic density of CRF receptor-ir. In contrast, proestrus females display an increased number of dual-labeled dendritic profiles and increased membrane density of CRF receptor-ir in comparison to males. We further examined the functional consequences of CRF

  17. Widespread changes in neurotransmitter expression and number of enteric neurons and interstitial cells of Cajal in lethal spotted mice: an explanation for persisting dysmotility after operation for Hirschsprung's disease?

    PubMed

    Sandgren, Katarina; Larsson, Lars T; Ekblad, Eva

    2002-05-01

    Gastrointestinal motor dysfunction persists in a large number of children subjected to surgical treatment for Hirschsprung's disease, indicating abnormalities in the remaining intestine. The aim of the study was to detect possible alterations in frequency and topographic distribution of enteric neurons and interstitial cells of Cajal in an experimental model (the lethal spotted mouse displaying a short rectal aganglionosis) for Hirschsprung's disease. Specimens from the intestinal tract from homozygous (aganglionic) and heterozygous (healthy littermates) were examined using histochemistry, in situ hybridization, and immunohistochemistry. In ileum and colon, ie, regions proximal to the aganglionosis, changes in the expression of neuropeptides and neuronal nitric oxide synthase and in the number of enteric neurons and interstitial cells of Cajal could be detected in homozygous versus heterozygous mice. The described changes are suggested to contribute to the dysmotility remaining after surgical resection of the aganglionic segment in Hirschsprung's disease.

  18. Teacher Acquisition of Functional Analysis Methods Using Pyramidal Training

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Thibeault, Matthew D.

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  1. LANDSAT-BASED WATER QUALITY MONITORING OF PYRAMID LAKE

    EPA Science Inventory

    Pyramid Lake Paiute Tribe (PLPT) in cooperation with federal, state and local entities has been able to increase stream flow, establish water quality standards and improve fish habitat in the Truckee River, a primary source of water for pyramid Lake. In the past, pyramid Lake wat...

  2. A novel short-term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells

    PubMed Central

    Sánchez-Aguilera, A; Sánchez-Alonso, J L; Vicente-Torres, M A; Colino, A

    2014-01-01

    Changes in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short-term plasticity of membrane excitability, which develops early after the eye-opening period in rats (P16–19 days) but not before that developmental stage (P9–12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca2+ entering through T-type Ca2+ channels. This increase in Ca2+ subsequently activated the Ca2+ sensor K+ channel interacting protein 3, which led to the increase of an A-type K+ current. These results suggest that Ca2+ modulation of somatic A-current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes. PMID:24756640

  3. Pyramidal fractal dimension for high resolution images.

    PubMed

    Mayrhofer-Reinhartshuber, Michael; Ahammer, Helmut

    2016-07-01

    Fractal analysis (FA) should be able to yield reliable and fast results for high-resolution digital images to be applicable in fields that require immediate outcomes. Triggered by an efficient implementation of FA for binary images, we present three new approaches for fractal dimension (D) estimation of images that utilize image pyramids, namely, the pyramid triangular prism, the pyramid gradient, and the pyramid differences method (PTPM, PGM, PDM). We evaluated the performance of the three new and five standard techniques when applied to images with sizes up to 8192 × 8192 pixels. By using artificial fractal images created by three different generator models as ground truth, we determined the scale ranges with minimum deviations between estimation and theory. All pyramidal methods (PM) resulted in reasonable D values for images of all generator models. Especially, for images with sizes ≥1024×1024 pixels, the PMs are superior to the investigated standard approaches in terms of accuracy and computation time. A measure for the possibility to differentiate images with different intrinsic D values did show not only that the PMs are well suited for all investigated image sizes, and preferable to standard methods especially for larger images, but also that results of standard D estimation techniques are strongly influenced by the image size. Fastest results were obtained with the PDM and PGM, followed by the PTPM. In terms of absolute D values best performing standard methods were magnitudes slower than the PMs. Concluding, the new PMs yield high quality results in short computation times and are therefore eligible methods for fast FA of high-resolution images.

  4. Pyramidal fractal dimension for high resolution images

    NASA Astrophysics Data System (ADS)

    Mayrhofer-Reinhartshuber, Michael; Ahammer, Helmut

    2016-07-01

    Fractal analysis (FA) should be able to yield reliable and fast results for high-resolution digital images to be applicable in fields that require immediate outcomes. Triggered by an efficient implementation of FA for binary images, we present three new approaches for fractal dimension (D) estimation of images that utilize image pyramids, namely, the pyramid triangular prism, the pyramid gradient, and the pyramid differences method (PTPM, PGM, PDM). We evaluated the performance of the three new and five standard techniques when applied to images with sizes up to 8192 × 8192 pixels. By using artificial fractal images created by three different generator models as ground truth, we determined the scale ranges with minimum deviations between estimation and theory. All pyramidal methods (PM) resulted in reasonable D values for images of all generator models. Especially, for images with sizes ≥1024 ×1024 pixels, the PMs are superior to the investigated standard approaches in terms of accuracy and computation time. A measure for the possibility to differentiate images with different intrinsic D values did show not only that the PMs are well suited for all investigated image sizes, and preferable to standard methods especially for larger images, but also that results of standard D estimation techniques are strongly influenced by the image size. Fastest results were obtained with the PDM and PGM, followed by the PTPM. In terms of absolute D values best performing standard methods were magnitudes slower than the PMs. Concluding, the new PMs yield high quality results in short computation times and are therefore eligible methods for fast FA of high-resolution images.

  5. Pyramidal fractal dimension for high resolution images.

    PubMed

    Mayrhofer-Reinhartshuber, Michael; Ahammer, Helmut

    2016-07-01

    Fractal analysis (FA) should be able to yield reliable and fast results for high-resolution digital images to be applicable in fields that require immediate outcomes. Triggered by an efficient implementation of FA for binary images, we present three new approaches for fractal dimension (D) estimation of images that utilize image pyramids, namely, the pyramid triangular prism, the pyramid gradient, and the pyramid differences method (PTPM, PGM, PDM). We evaluated the performance of the three new and five standard techniques when applied to images with sizes up to 8192 × 8192 pixels. By using artificial fractal images created by three different generator models as ground truth, we determined the scale ranges with minimum deviations between estimation and theory. All pyramidal methods (PM) resulted in reasonable D values for images of all generator models. Especially, for images with sizes ≥1024×1024 pixels, the PMs are superior to the investigated standard approaches in terms of accuracy and computation time. A measure for the possibility to differentiate images with different intrinsic D values did show not only that the PMs are well suited for all investigated image sizes, and preferable to standard methods especially for larger images, but also that results of standard D estimation techniques are strongly influenced by the image size. Fastest results were obtained with the PDM and PGM, followed by the PTPM. In terms of absolute D values best performing standard methods were magnitudes slower than the PMs. Concluding, the new PMs yield high quality results in short computation times and are therefore eligible methods for fast FA of high-resolution images. PMID:27475069

  6. Sparse Gamma Rhythms Arising through Clustering in Adapting Neuronal Networks

    PubMed Central

    Kilpatrick, Zachary P.; Ermentrout, Bard

    2011-01-01

    Gamma rhythms (30–100 Hz) are an extensively studied synchronous brain state responsible for a number of sensory, memory, and motor processes. Experimental evidence suggests that fast-spiking interneurons are responsible for carrying the high frequency components of the rhythm, while regular-spiking pyramidal neurons fire sparsely. We propose that a combination of spike frequency adaptation and global inhibition may be responsible for this behavior. Excitatory neurons form several clusters that fire every few cycles of the fast oscillation. This is first shown in a detailed biophysical network model and then analyzed thoroughly in an idealized model. We exploit the fact that the timescale of adaptation is much slower than that of the other variables. Singular perturbation theory is used to derive an approximate periodic solution for a single spiking unit. This is then used to predict the relationship between the number of clusters arising spontaneously in the network as it relates to the adaptation time constant. We compare this to a complementary analysis that employs a weak coupling assumption to predict the first Fourier mode to destabilize from the incoherent state of an associated phase model as the external noise is reduced. Both approaches predict the same scaling of cluster number with respect to the adaptation time constant, which is corroborated in numerical simulations of the full system. Thus, we develop several testable predictions regarding the formation and characteristics of gamma rhythms with sparsely firing excitatory neurons. PMID:22125486

  7. Melatonin promotes distal dendritic ramifications in layer II/III cortical pyramidal cells of rats exposed to toluene vapors.

    PubMed

    Pascual, Rodrigo; Bustamante, Carlos

    2010-10-01

    We have previously shown that toluene inhalation produces significant impairments in the basilar dendritic outgrowth of pyramidal cortical cells. This neurotoxic effect was markedly inhibited by melatonin administration at a dose of 5mg kg(-1). The present study was designed to determine whether toluene and melatonin equally affect all basilar dendritic segments or if a differential response exists between the segments. Twenty-eight male mice were weaned at postnatal day 21 (P21) and randomly assigned to either the control (C; n=10,) or toluene (T; n=18) group. Between P22-P32, male rats were placed into a glass chamber and exposed to either toluene vapors (5-000-6000 ppm) or clean air for 10 min a day. When toluene exposure ended (P32), animals were further assigned to the following experimental groups: (a) control/saline (C/S; n=10), (b) toluene/saline (T/S; n=10), or (c) toluene/melatonin 5mg kg(-1) (T/M; n=8). Melatonin or vehicle solutions were administered daily between P32 and P38. Forty-eight hours after the final toluene exposure, the animals were sacrificed, and the pyramidal cortical cells were stained using the Golgi-Cox-Sholl procedure. The number of basilar dendritic branches/order was counted using the centrifugal ordering method. The results indicate that (i) toluene inhalation significantly impairs both proximal and distal basilar dendritic ramifications (in the parietal and frontal/occipital cortices, respectively) and (ii) melatonin both protects neurons from toluene neurotoxicity in all cortical areas studied and increases the complexity of the dendritic tree above control values.

  8. Pyramid projection - validation of a new method of skin defect measurement.

    PubMed

    Růzicka, J; Nový, P; Vávra, F; Bolek, L; Benes, J

    2007-01-01

    This paper presents a new method for the determination of the volume, surface area and depth of skin defects. The method is based on the description of a spatial defect using a pyramid (made, for example, from injection needles), which is placed over the defect. The projection of the pyramid on to the defect is photographed using a digital camera and subsequently compared with the projection of the same pyramid on to a sheet of grid paper. The defect is mathematically reconstructed on a computer, and an optimal body shape describing the defect is found, using a number of simplifications and assumptions. The method was then validated using a plaster mold of a real foot with 19 defects simulating real wounds. These plaster wounds were molded using alginate hydrocolloid, and the volume, surface area and depth were measured and compared with the results of the pyramid projection by means of regression analysis.This method correlates in all variables with correlation coefficients higher than 0.9. It can be concluded that the projection pyramid method correlates well with the reference mold method and can be used with good results for a whole range of variables.

  9. Protracted postnatal development of inhibitory synaptic transmission in rat hippocampal area CA1 neurons.

    PubMed

    Cohen, A S; Lin, D D; Coulter, D A

    2000-11-01

    -channel conductance of subsynaptic GABA(A)Rs but rather to an increase in the number of open channels responding to a single GABA quantum, further supporting the hypothesis that synaptic receptors may not be saturated during synaptic function in adolescent neurons. These data demonstrate that inhibitory synaptic transmission undergoes a markedly protracted postnatal maturation in rat CA1 pyramidal neurons. In the first two postnatal weeks, mIPSCs are large in amplitude, are slow, and occur infrequently. By the third postnatal week, mIPSCs have matured kinetically but retain distinct responses to modulatory drugs, possibly reflecting continued immaturity in synaptic structure and function persisting through adolescence.

  10. Upper and Lower I/O Bounds for Pebbling r-Pyramids

    NASA Astrophysics Data System (ADS)

    Ranjan, Desh; Savage, John; Zubair, Mohammad

    Modern computers have several levels of memory hierarchy. To obtain good performance on these processors it is necessary to design algorithms that minimize I/O traffic to slower memories in the hierarchy. In this paper, we present I/O efficient algorithms to pebble r-pyramids and derive lower bounds on the number of I/O steps to do so. The r-pyramid graph models financial applications which are of practical interest and where minimizing memory traffic can have a significant impact on cost saving.

  11. Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs.

    PubMed

    Hashiguchi, Akihiro; Higuchi, Yujiro; Nomura, Miwa; Nakamura, Tomonori; Arata, Hitoshi; Yuan, Junhui; Yoshimura, Akiko; Okamoto, Yuji; Matsuura, Eiji; Takashima, Hiroshi

    2014-12-01

    To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light-chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype. PMID:25583183

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

    PubMed

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

    1997-06-27

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

  13. The pyramidal cell in cognition: a comparative study in human and monkey.

    PubMed

    Elston, G N; Benavides-Piccione, R; DeFelipe, J

    2001-09-01

    Here we present evidence that the pyramidal cell phenotype varies markedly in the cortex of different anthropoid species. Regional and species differences in the size of, number of bifurcations in, and spine density of the basal dendritic arbors cannot be explained by brain size. Instead, pyramidal cell morphology appears to accord with the specialized cortical function these cells perform. Cells in the prefrontal cortex of humans are more branched and more spinous than those in the temporal and occipital lobes. Moreover, cells in the prefrontal cortex of humans are more branched and more spinous than those in the prefrontal cortex of macaque and marmoset monkeys. These results suggest that highly spinous, compartmentalized, pyramidal cells (and the circuits they form) are required to perform complex cortical functions such as comprehension, perception, and planning.

  14. Short latency activation of pyramidal tract cells by Group I afferent volleys in the cat

    PubMed Central

    Swett, John E.; Bourassa, Charles M.

    1967-01-01

    1. The contralateral bulbar pyramids were explored with low impedance micro-electrodes in cats anaesthetized with chloralose to reveal the effect of Group I afferent volleys (deep radial nerve of the forelimb) on pyramidal tract (Pt) cells. 2. Low rate (0·5/sec) stimulation of Group I afferents produced small responses (5-30 μV) in the bulbar pyramid which could be detected only with response averaging methods. The responses appeared with an initial latency of 7·0-11·2 msec and reached peak amplitude in 15·7 msec (mean latency). The pyramidal tract origin of the potential was demonstrated by its depression at stimulus rates above 1-2 sec and its disappearance at rates above 4/sec. 3. Recordings of neurones in the Group I cortical projection zone of the posterior sigmoid gyrus revealed that several types of cells, including Pt cells, were activated by Group I afferent volleys. 4. Pt cells responding to Group I afferent volleys frequently received convergent actions from low threshold cutaneous nerve volleys. 5. Averaged response recordings from electrodes positioned in the medial portions of the lateral funiculus of the spinal cord at the level of C2, revealed a response to Group I afferent volleys as early as 7·4 msec which possessed the same characteristics as the relayed response to Group I in the bulbar pyramids. Some Pt cells, activated by Group I volleys orthodromically, could also be antidromically activated by stimulation of the recording site in C2. 6. It was concluded that group I afferent volleys can influence, after short latencies, Pt and non-Pt cells and that some of these Pt cells gave rise to axons incorporated in the corticospinal tract. PMID:16992239

  15. Both increases in immature dentate neuron number and decreases of immobility time in the forced swim test occurred in parallel after environmental enrichment of mice.

    PubMed

    Llorens-Martín, M V; Rueda, N; Martínez-Cué, C; Torres-Alemán, I; Flórez, J; Trejo, J L

    2007-07-13

    A direct relation between the rate of adult hippocampal neurogenesis in mice and the immobility time in a forced swim test after living in an enriched environment has been suggested previously. In the present work, young adult mice living in an enriched environment for 2 months developed considerably more immature differentiating neurons (doublecortin-positive, DCX(+)) than control, non-enriched animals. Furthermore, we found that the more DCX(+) cells they possessed, the lower the immobility time they scored in the forced swim test. This DCX(+) subpopulation is composed of mostly differentiating dentate neurons independently of the birthdates of every individual cell. However, variations found in this subpopulation were not the result of a general effect on the survival of any newborn neuron in the granule cell layer, as 5-bromo-2-deoxyuridine (BrdU)-labeled cells born during a narrow time window included in the longer lifetime period of DCX(+) cells, were not significantly modified after enrichment. In contrast, the survival of the mature population of neurons in the granule cell layer of the dentate gyrus in enriched animals increased, although this did not influence their performance in the Porsolt test, nor did it influence the dentate gyrus volume or granule neuronal nuclei size. These results indicate that the population of immature, differentiating neurons in the adult hippocampus is one factor directly related to the protective effect of an enriched environment against a highly stressful event.

  16. A pyramid-based approach to visual exploration of a large volume of vehicle trajectory data

    NASA Astrophysics Data System (ADS)

    Sun, Jing; Li, Xiang

    2012-12-01

    Advances in positioning and wireless communicating technologies make it possible to collect large volumes of trajectory data of moving vehicles in a fast and convenient fashion. These data can be applied to traffic studies. Behind this application, a methodological issue that still requires particular attention is the way these data should be spatially visualized. Trajectory data physically consists of a large number of positioning points. With the dramatic increase of data volume, it becomes a challenge to display and explore these data. Existing commercial software often employs vector-based indexing structures to facilitate the display of a large volume of points, but their performance downgrades quickly when the number of points is very large, for example, tens of millions. In this paper, a pyramid-based approach is proposed. A pyramid method initially is invented to facilitate the display of raster images through the tradeoff between storage space and display time. A pyramid is a set of images at different levels with different resolutions. In this paper, we convert vector-based point data into raster data, and build a gridbased indexing structure in a 2D plane. Then, an image pyramid is built. Moreover, at the same level of a pyramid, image is segmented into mosaics with respect to the requirements of data storage and management. Algorithms or procedures on grid-based indexing structure, image pyramid, image segmentation, and visualization operations are given in this paper. A case study with taxi trajectory data in Shanghai is conducted. Results demonstrate that the proposed method outperforms the existing commercial software.

  17. Principal component and cluster analysis of layer V pyramidal cells in visual and non-visual cortical areas projecting to the primary visual cortex of the mouse.

    PubMed

    Laramée, M E; Rockland, K S; Prince, S; Bronchti, G; Boire, D

    2013-03-01

    The long-distance corticocortical connections between visual and nonvisual sensory areas that arise from pyramidal neurons located within layer V can be considered as a subpopulation of feedback connections. The purpose of the present study is to determine if layer V pyramidal neurons from visual and nonvisual sensory cortical areas that project onto the visual cortex (V1) constitute a homogeneous population of cells. Additionally, we ask whether dendritic arborization relates to the target, the sensory modality, the hierarchical level, or laterality of the source cortical area. Complete 3D reconstructions of dendritic arbors of retrogradely labeled layer V pyramidal neurons were performed for neurons of the primary auditory (A1) and somatosensory (S1) cortices and from the lateral (V2L) and medial (V2M) parts of the secondary visual cortices of both hemispheres. The morphological parameters extracted from these reconstructions were subjected to principal component analysis (PCA) and cluster analysis. The PCA showed that neurons are distributed within a continuous range of morphologies and do not form discrete groups. Nevertheless, the cluster analysis defines neuronal groups that share similar features. Each cortical area includes neurons belonging to several clusters. We suggest that layer V feedback connections within a single cortical area comprise several cell types. PMID:22426333

  18. Synapse-to-neuron ratio is inversely related to neuronal density in mature neuronal cultures.

    PubMed

    Cullen, D Kacy; Gilroy, Meghan E; Irons, Hillary R; Laplaca, Michelle C

    2010-11-01

    Synapse formation is a fundamental process in neurons that occurs throughout development, maturity, and aging. Although these stages contain disparate and fluctuating numbers of mature neurons, tactics employed by neuronal networks to modulate synapse number as a function of neuronal density are not well understood. The goal of this study was to utilize an in vitro model to assess the influence of cell density and neuronal maturity on synapse number and distribution. Specifically, cerebral cortical neurons were plated in planar culture at densities ranging from 10 to 5000 neurons/mm², and synapse number and distribution were evaluated via immunocytochemistry over 21 days in vitro (DIV). High-resolution confocal microscopy revealed an elaborate three-dimensional distribution of neurites and synapses across the heights of high-density neuronal networks by 21 DIV, which were up to 18 μm thick, demonstrating the complex degree of spatial interactions even in planar high-density cultures. At 7 DIV, the mean number of synapses per neuron was less than 5, and this did not vary as a function of neuronal density. However, by 21 DIV, the number of synapses per neuron had jumped 30- to 80-fold, and the synapse-to-neuron ratio was greatest at lower neuronal densities (< 500 neurons/mm²; mean approximately 400 synapses/neuron) compared to mid and higher neuronal densities (500-4500 neurons/mm²; mean of approximately 150 synapses/neuron) (p<0.05). These results suggest a relationship between neuronal density and synapse number that may have implications in the neurobiology of developing neuronal networks as well as processes of cell death and regeneration.

  19. Compression asphyxia from a human pyramid.

    PubMed

    Tumram, Nilesh Keshav; Ambade, Vipul Namdeorao; Biyabani, Naushad

    2015-12-01

    In compression asphyxia, respiration is stopped by external forces on the body. It is usually due to an external force compressing the trunk such as a heavy weight on the chest or abdomen and is associated with internal injuries. In present case, the victim was trapped and crushed under the falling persons from a human pyramid formation for a "Dahi Handi" festival. There was neither any severe blunt force injury nor any significant pathological natural disease contributing to the cause of death. The victim was unable to remove himself from the situation because his cognitive responses and coordination were impaired due to alcohol intake. The victim died from asphyxia due to compression of his chest and abdomen. Compression asphyxia resulting from the collapse of a human pyramid and the dynamics of its impact force in these circumstances is very rare and is not reported previously to the best of our knowledge.

  20. The tufas of Pyramid Lake, Nevada

    USGS Publications Warehouse

    Benson, Larry V.

    2004-01-01

    Pyramid Lake is the site of some of the Earth's most spectacular tufa deposits. The Tufas are composed of calcium carbonate (CaCO3). The large tufa mounds, reef- and sheet-like tufas formed within Pyramid Lake, between 26,000 and 13,000 years (yr) ago, when the lake was part of pluvial Lake Lahontan. The mounds are composed of large interlocking spheres that contain multiple generations of a crystalline (thinolite) variety of tufa. Over time many of the mounds have fallen apart, exposing an internal network of tubes. The tubular structures are thought to have been created when springs discharged from the bottom of Pyramid Lake, supplying calcium that combined with carbonate dissolved in lake water to form the mounds. The reef- and sheet-like deposits contain pillow and pendant forms made up of a branching variety of tufa that often grades into dense layers or nodules. Dense layers of tufa also coat cobbles and boulders that were deposited in near-shore shallow-water areas. The thickest tufa deposits formed at lake-bottom sites of ground-water discharge and at overflow elevations1 where the lake was held at near-constant levels for long periods of time.

  1. Preserving the Pyramid of STI Using Buckets

    NASA Technical Reports Server (NTRS)

    Nelson, Michael L.; Maly, Kurt

    2004-01-01

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

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

    PubMed

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

    2012-03-01

    Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type-specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons. PMID:22246433

  3. Human cerebral cortex Cajal-Retzius neuron: development, structure and function. A Golgi study.

    PubMed

    Marín-Padilla, Miguel

    2015-01-01

    The development, morphology and possible functional activity of the Cajal-Retzius cell of the developing human cerebral cortex are explored herein. The C-RC, of extracortical origin, is the essential neuron of the neocortex first lamina. It receives inputs from afferent fibers that reach the first lamina early in development. Although the origin and function of these original afferent fibers remain unknown, their target is the first lamina sole neuron: the C-RC. This neuron orchestrates the arrival, size and stratification of all pyramidal neurons (of ependymal origin) of the neocortex gray matter. Its axonic terminals spread radially and horizontally throughout the entirety of the 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 neuronal' body 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 neocortex while their axonic collaterals will spread throughout its more recent ones and eventually will extend to great majority of the cortical surface. The neocortex first lamina evolution and composition and that of the C-RC are intertwined and mutually interdependent. It is not possible to understand the C-RC evolving morphology without understanding that of the first lamina. The first lamina composition and its structural and functional organizations obtained with different staining methods may be utterly different. These differences have added unnecessary confusion about its nature. The essential emptiness observed in hematoxylin and eosin preparations (most commonly used) contrast sharply with the concentration of dendrites (the cortex' largest) obtained using special (MAP-2) stain for dendrites. Only Golgi preparations

  4. Simultaneous visualization of cortical barrels and horseradish peroxidase-injected layer 5b vibrissa neurones in the rat.

    PubMed Central

    Ito, M

    1992-01-01

    1. Using diaminobenzidine (DAB) as a chromagen, horseradish peroxidase-injected neurones and cytochrome oxidase-stained barrels were visualized simultaneously in the rat vibrissa cortex. Neurones were initially tested during extracellular recording for responses to whisker deflections. This was followed by intracellular injection of the soma with horseradish peroxidase (HRP) and histological processing to visualize the HRP-stained neurone in an incubation solution which contained, in addition to DAB, cytochrome C for cytochrome oxidase (CO) reaction of the barrels. 2. Recording and intracellular staining were made in layer 5b under urethane anaesthesia. CO-stained barrels were observed in layer 4. Physiologically and morphologically characterized neurones were mostly large pyramidal neurones that responded to more than one whisker and displayed transient-type responses. 3. In tangential sections, the apical dendrite of the HRP-filled neurone was followed from the soma level upward as it ascended through the barrelfield in layer 4. The cross-section of the apical dendrite was found in the periphery of the CO-stained barrel. Using the apical dendrite as a guide, the basal dendritic field of the layer 5b pyramidal neurone was aligned on the pattern of layer 4 barrels. The soma was seen to project basal dendrites in all directions, involving one or two neighbouring barrels/columns. 4. In sixteen neurones examined in tangential sections, a complete spatial tuning map constructed by measuring sensitivity of the neurone to different whiskers could be compared to the basal dendritic field in relation to the pattern of overlying layer 4 barrels. The mean receptive field size in terms of the number of effective whiskers was 5.8 whereas the mean dendritic field size in terms of the number of barrels/columns involved was 2.2. In addition to the well-documented role of intracortical connectivity in elaboration of multi-whisker receptor fields in the cortical neurones, the role

  5. Sleep Fragmentation reduces Hippocampal CA1 Pyramidal Cell Excitability and Response to Adenosine

    PubMed Central

    Tartar, Jaime L.; McKenna, James T.; Ward, Christopher P.; McCarley, Robert W.; Strecker, Robert E.; Brown, Ritchie E.

    2009-01-01

    Sleep fragmentation (SF) impairs the restorative/cognitive benefits of sleep via as yet unidentified alterations in neural physiology. Previously, we found that hippocampal synaptic plasticity and spatial learning are impaired in a rat model of SF which utilizes a treadmill to awaken the animals every 2 min, mimicking the frequency of awakenings observed in human sleep apnea patients. Here, we investigated the cellular mechanisms responsible for these effects, using whole-cell patch-clamp recordings. 24h of SF decreased the excitability of hippocampal CA1 pyramidal neurons via decreased input resistance, without alterations in other intrinsic membrane or action potential properties (when compared to cage controls, or to exercise controls that experienced the same total amount of treadmill movement as SF rats). Contrary to our initial prediction, the hyperpolarizing response to bath applied adenosine (30 µM) was reduced in the CA1 neurons of SF treated rats. Our initial prediction was based on evidence that sleep loss upregulates cortical adenosine A1 receptors; however, the present findings are consistent with a very recent report that hippocampal A1 receptors are not elevated by sleep loss. Thus, increased adenosinergic inhibition is unlikely to be responsible for reduced hippocampal long-term potentiation in SF rats. Instead, the reduced excitability of CA1 pyramidal neurons observed here may contribute to the loss of hippocampal long-term potentiation and hippocampus-dependent cognitive impairments associated with sleep disruption. PMID:19914331

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