Synaptic Activity in Chronically Injured, Epileptogenic Sensory-Motor Neocortex

2002 ◽  
Vol 88 (1) ◽  
pp. 2-12 ◽  
Author(s):  
Huifang Li ◽  
David A. Prince
Keyword(s):  
Patch Clamp ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Average Frequency ◽  
Synaptic Activity ◽  
Cortical Hyperexcitability ◽  
Significant Difference ◽  
Sensory Motor ◽  
Layer V

We recorded spontaneous and evoked synaptic currents in pyramidal neurons of layer V in chronically injured, epileptogenic neocortex to assess changes in the efficacy of excitatory and inhibitory neurotransmission that might promote cortical hyperexcitability. Partial sensory-motor neocortical isolations with intact blood supply (“undercuts”) were made in 20 rats on postnatal day 21–25 and examined 2–6 wk later in standard brain slice preparations using whole cell patch-clamp techniques. Age-matched, uninjured naive rats ( n = 20) were used as controls. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (s- and mEPSCs; s- and mIPSCs) were recorded using patch-clamp techniques. The average frequency of s- and mEPSCs was significantly higher, while that of s- and mIPSCs was significantly lower in neurons of undercuts versus controls. The increased frequency of excitatory events was due to an increase in both s- and mEPSC frequency, suggesting an increased number of excitatory contacts and/or increased release probability at excitatory terminals. No significant difference was observed in 10–90% rise time of these events. The input-output slopes of fast, short-latency, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor-mediated components of evoked EPSCs were steeper in undercuts than in controls. The peak amplitude of the AMPA/KA component of EPSCs evoked by supra-threshold stimuli was significantly greater in the partially isolated neocortex. In contrast, the N-methyl-d-aspartate receptor-mediated component of evoked EPSCs was not significantly different in neurons of injured versus control cortex, suggesting that the increased AMPA/KA component was due to postsynaptic alterations. Results support the conclusion that layer V pyramidal neurons receive increased AMPA/KA receptor-mediated excitatory synaptic drive and decreased GABAA receptor-mediated inhibition in this chronically injured, epileptogenic cortex. This shift in the balance of excitatory and inhibitory synaptic activation of layer V pyramidal cells toward excitation might be maladaptive and play a critical role in epileptogenesis.

Dendritic changes of the pyramidal neurons in layer V of sensory-motor cortex of the rat brain during the postresuscitation period

Resuscitation ◽  
1997 ◽  
Vol 35 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Victor A Akulinin ◽  
Sergey S Stepanov ◽  
Valeriy V Semchenko ◽  
Pavel V Belichenko
Keyword(s):  
Motor Cortex ◽  
Rat Brain ◽  
Pyramidal Neurons ◽  
Postresuscitation Period ◽  
Sensory Motor ◽  
Layer V

scholarly journals Two Populations of Layer V Pyramidal Cells of the Mouse Neocortex: Development and Sensitivity to Anesthetics

2005 ◽  
Vol 94 (5) ◽  
pp. 3357-3367 ◽  
Author(s):  
Elodie Christophe ◽  
Nathalie Doerflinger ◽  
Daniel J. Lavery ◽  
Zoltán Molnár ◽  
Serge Charpak ◽  
...  
Keyword(s):  
Action Potential ◽  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Subcortical Structures ◽  
Contralateral Cortex ◽  
Layer V ◽  
Intrinsic Membrane Properties ◽  
Two Populations

Previous studies have shown that layer V pyramidal neurons projecting either to subcortical structures or the contralateral cortex undergo different morphological and electrophysiological patterns of development during the first three postnatal weeks. To isolate the determinants of this differential maturation, we analyzed the gene expression and intrinsic membrane properties of layer V pyramidal neurons projecting either to the superior colliculus (SC cells) or the contralateral cortex (CC cells) by combining whole cell recordings and single-cell RT-PCR in acute slices prepared from postnatal day (P) 5–7 or P21–30 old mice. Among the 24 genes tested, the calcium channel subunits α1B and α1C, the protease Nexin 1, and the calcium-binding protein calbindin were differentially expressed in adult SC and CC cells and the potassium channel subunit Kv4.3 was expressed preferentially in CC cells at both stages of development. Intrinsic membrane properties, including input resistance, amplitude of the hyperpolarization-activated current, and action potential threshold, differed quantitatively between the two populations as early as from the first postnatal week and persisted throughout adulthood. However, the two cell types had similar regular action potential firing behaviors at all developmental stages. Surprisingly, when we increased the duration of anesthesia with ketamine–xylazine or pentobarbital before decapitation, a proportion of mature SC cells, but not CC cells, fired bursts of action potentials. Together these results indicate that the two populations of layer V pyramidal neurons already start to differ during the first postnatal week and exhibit different firing capabilities after anesthesia.

scholarly journals Prenatal Exposure to Ethanol Alters Synaptic Activity in Layer V/VI Pyramidal Neurons of the Somatosensory Cortex

2019 ◽  
Vol 30 (3) ◽  
pp. 1735-1751 ◽  
Author(s):  
Laurie C Delatour ◽  
Pamela W L Yeh ◽  
Hermes H Yeh
Keyword(s):  
Somatosensory Cortex ◽  
Prenatal Exposure ◽  
Pyramidal Neurons ◽  
Female Offspring ◽  
Ethanol Exposure ◽  
Synaptic Activity ◽  
Prenatal Ethanol Exposure ◽  
Patch Clamp Recording ◽  
Cortical Pyramidal Neurons ◽  
Layer V

Abstract Fetal alcohol spectrum disorder (FASD) encompasses a range of cognitive and behavioral deficits, with aberrances in the function of cerebral cortical pyramidal neurons implicated in its pathology. However, the mechanisms underlying these aberrances, including whether they persist well beyond ethanol exposure in utero, remain to be explored. We addressed these issues by employing a mouse model of FASD in which pregnant mice were exposed to binge-type ethanol from embryonic day 13.5 through 16.5. In both male and female offspring (postnatal day 28–32), whole-cell patch clamp recording of layer V/VI somatosensory cortex pyramidal neurons revealed increases in the frequency of excitatory and inhibitory postsynaptic currents. Furthermore, expressing channelrhodopsin in either GABAergic interneurons (Nkx2.1Cre-Ai32) or glutamatergic pyramidal neurons (Emx1IRES Cre-Ai32) revealed a shift in optically evoked paired-pulse ratio. These findings are consistent with an excitatory-inhibitory imbalance with prenatal ethanol exposure due to diminished inhibitory but enhanced excitatory synaptic strength. Prenatal ethanol exposure also altered the density and morphology of spines along the apical dendrites of pyramidal neurons. Thus, while both presynaptic and postsynaptic mechanisms are affected following prenatal exposure to ethanol, there is a prominent presynaptic component that contributes to altered inhibitory and excitatory synaptic transmission in the somatosensory cortex.

Impaired Cl− Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex

2005 ◽  
Vol 93 (4) ◽  
pp. 2117-2126 ◽  
Author(s):  
Xiaoming Jin ◽  
John R. Huguenard ◽  
David A. Prince
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Gabaergic Inhibition ◽  
Adult Rats ◽  
Positive Shift ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

In the mature brain, the K+/Cl− cotransporter KCC2 is important in maintaining low [Cl−]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl−]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl (∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. There was no significant difference in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and –71.8 ± 2.8 mV, respectively). However, when loaded with Cl− by applying muscimol puffs at 0.2 Hz for 60 s, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl− loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut, P < 0.01). The positive shift in ECl 3 s after the beginning of Cl− loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl−]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl−]i regulation. The results suggest an impairment in Cl− extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

scholarly journals Somadendritic Backpropagation of Action Potentials in Cortical Pyramidal Cells of the Awake Rat

1998 ◽  
Vol 79 (3) ◽  
pp. 1587-1591 ◽  
Author(s):  
György Buzsáki ◽  
Adam Kandel
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Current Source ◽  
Pyramidal Cells ◽  
Apical Dendrite ◽  
Individual Layer ◽  
Awake Rat ◽  
Density Analysis ◽  
Freely Behaving ◽  
Layer V

Buzsáki, György and Adam Kandel. Somadendritic backpropagation of action potentials in cortical pyramidal cells of the awake rat. J. Neurophysiol. 79: 1587–1591, 1998. The invasion of fast (Na+) spikes from the soma into dendrites was studied in single pyramidal cells of the sensorimotor cortex by simultaneous extracellular recordings of the somatic and dendritic action potentials in freely behaving rats. Field potentials and unit activity were monitored with multiple-site silicon probes along trajectories perpendicular to the cortical layers at spatial intervals of 100 μm. Dendritic action potentials of individual layer V pyramidal neurons could be recorded up to 400 μm from the cell body. Action potentials were initiated at the somatic recording site and traveled back to the apical dendrite at a velocity of 0.67 m/s. Current source density analysis of the action potential revealed time shifted dipoles, supporting the view of active spike propagation in dendrites. The presented method is suitable for exploring the conditions affecting the somadendritic propagation action of potentials in the behaving animal.

The patterns and synaptic properties of horizontal intracortical connections in the rat motor cortex

1993 ◽  
Vol 70 (4) ◽  
pp. 1553-1569 ◽  
Author(s):  
V. A. Aroniadou ◽  
A. Keller
Keyword(s):  
Motor Cortex ◽  
Deep Layer ◽  
Pyramidal Cells ◽  
Middle Layer ◽  
Synaptic Activity ◽  
Adult Rats ◽  
Retrograde Labeling ◽  
Connectivity Patterns ◽  
Layer V ◽  
Dendritic Fields

1. The laminar distribution of synaptic activity in the primary motor cortex, elicited by stimulation of intracortical, horizontal afferents, was studied in young (12-17 days old) and adult rats using the in vitro brain slice preparation. Connectivity patterns were deduced from current-source density (CSD) analyses of field potential depth profiles and were confirmed by anatomic data of retrograde cell labeling after focal injections of a fluorescent tracer. 2. According to the CSD distributions, horizontal axons in layer II/III provide strong monosynaptic input to dendrites of layer II and III pyramidal cells in a distant column, and weaker monosynaptic input to layer V and VI cells by synapsing on dendritic fields at the border of layer III and V and in deep layer V. When these pathways are activated, layer II/III cells may relay excitatory activity to upper and deep layer V, as well as to other cells in layer II/III of the same column. Axons arising from layer V provide monosynaptic input to pyramidal cells in all layers of neighboring columns, by synapsing in two dendritic fields: one in the superficial layers and the other in middle layer V. Activation of these pathways may generate a disynaptic intracolumnar input from layer II/III cells to middle layer V, as well as to other cells in layer II/III. Similar patterns of synaptic activity were elicited by stimulation from 0.45 to 2 mm distal to the recorded column. There were no apparent differences between young and adult rats in the connectivity patterns revealed by the CSD analyses. 3. Tracer injections in layer III resulted in retrograde labeling of cells in layers II/III and V, at distances > 2 mm from the injection site, whereas injections in layer V resulted in retrograde labeling of cells at long distances in layer V and to a lesser extent in layer II/III. These findings indicate that neurons in layer V project, via horizontal axon collaterals, for long distances within layers III and V, whereas the horizontal axon collaterals of layer III cells are restricted, for the most part, to the superficial layers. 4. Suppression of inhibitory activity by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI) did not alter the pattern of the CSD distributions. All synaptic currents present in the control medium were enhanced by application of BMI, although the effect was more pronounced on the polysynaptic components.(ABSTRACT TRUNCATED AT 400 WORDS)

Astrocyte expression of D2-like dopamine receptors in the prefrontal cortex

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Mihovil Mladinov ◽  
Davor Mayer ◽  
Luka Brčić ◽  
Elizabeth Wolstencroft ◽  
Nguyen Man ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dopamine Receptors ◽  
Glial Cells ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Tissue Samples ◽  
Strong Expression ◽  
Layer V ◽  
The Right ◽  
Protoplasmic Astrocytes

AbstractThe dopaminergic system is of crucial importance for understanding human behavior and the pathogenesis of many psychiatric and neurological conditions. The majority of studies addressing the localization of dopamine receptors (DR) examined the expression of DR in neurons, while its expression, precise anatomical localization and possible function in glial cells have been largely neglected. Here we examined the expression of D2-like family of DR in neuronal and glial cells in the normal human brain using immunocytochemistry and immunofluorescence. Tissue samples from the right orbitomedial (Brodmann’s areas 11/12), dorsolateral (areas 9/46) and dorsal medial (area 9) prefrontal cortex were taken during autopsy from six subjects with no history of neurological or psychiatric disorders, formalin-fixed, and embedded in paraffin. The sections were stained using novel anti-DRD2, anti-DRD3, and anti-DRD4 monoclonal antibodies. Adjacent sections were labeled with an anti-GFAP (astroglial marker) and an anti-CD68 antibody (macrophage/microglial marker). The pyramidal and non-pyramidal cells of all three regions analyzed had strong expression of DRD2 and DRD4, whereas DRD3 were very weakly expressed. DRD2 were more strongly expressed in layer III compared to layer V pyramidal neurons. In contrast, DRD4 receptors had a stronger expression in layer V neurons. The most conspicuous finding was the strong expression of DRD2, but not DRD3 or DRD4, receptors in the white matter fibrous astrocytes and in layer I protoplasmic astrocytes. Weak DRD2-immunoreactivity was also observed in protoplasmic astrocytes in layers III and V. These results suggest that DR-expressing astrocytes directly participate in dopaminergic transmission of the human prefrontal cortex.

scholarly journals Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

2020 ◽  
Author(s):  
Cristiana Vagnoni ◽  
Liad J. Baruchin ◽  
Filippo Ghezzi ◽  
Sara Ratti ◽  
Zoltán Molnár ◽  
...  
Keyword(s):  
Long Range ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Cortical Circuits ◽  
Motor Processing ◽  
Efferent Connections ◽  
Sensory Motor ◽  
Sensory Evoked ◽  
Inside Out

ABSTRACTDevelopment of the cortical circuits for sensory-motor processing require the coordinated integration of both columnar and long-range synaptic connections. To understand how this occurs at the level of individual neurons we have explored the timeline over which vasoactive intestinal peptide (VIP)-expressing interneurons integrate into mouse somatosensory cortex. We find a distinction in emergent long-range anterior-motor and columnar glutamatergic inputs onto layer (L)2 and L3 VIP+ interneurons respectively. In parallel, VIP+ interneurons form efferent connections onto both pyramidal cells and interneurons in the immediate column in an inside-out manner. Cell-autonomous deletion of the fate-determinant transcription factor, Prox1, spares long-range anterior-motor inputs onto VIP+ interneurons, but leads to deficits in local connectivity. This imbalance in the somatosensory circuit results in altered spontaneous and sensory-evoked cortical activity in vivo. This identifies a critical role for VIP+ interneurons, and more broadly interneuron heterogeneity, in formative circuits of neocortex.

Increased Pyramidal Excitability and NMDA Conductance Can Explain Posttraumatic Epileptogenesis Without Disinhibition: A Model

1999 ◽  
Vol 82 (4) ◽  
pp. 1748-1758 ◽  
Author(s):  
Paul C. Bush ◽  
David A. Prince ◽  
Kenneth D. Miller
Keyword(s):  
Experimental Data ◽  
Pyramidal Neurons ◽  
Rapid Development ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Excitatory Postsynaptic Potential ◽  
Physiological Basis ◽  
Postsynaptic Potential ◽  
Layer V ◽  
Epileptiform Events

Partially isolated cortical islands prepared in vivo become epileptogenic within weeks of the injury. In this model of chronic epileptogenesis, recordings from cortical slices cut through the injured area and maintained in vitro often show evoked, long- and variable-latency multiphasic epileptiform field potentials that also can occur spontaneously. These events are initiated in layer V and are synchronous with polyphasic long-duration excitatory and inhibitory potentials (currents) in neurons that may last several hundred milliseconds. Stimuli that are significantly above threshold for triggering these epileptiform events evoke only a single large excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). We investigated the physiological basis of these events using simulations of a layer V network consisting of 500 compartmental model neurons, including 400 principal (excitatory) and 100 inhibitory cells. Epileptiform events occurred in response to a stimulus when sufficient N-methyl-d-aspartate (NMDA) conductance was activated by feedback excitatory activity among pyramidal cells. In control simulations, this activity was prevented by the rapid development of IPSPs. One manipulation that could give rise to epileptogenesis was an increase in the threshold of inhibitory interneurons. However, previous experimental data from layer V pyramidal neurons of these chronic epileptogenic lesions indicate: upregulation, rather than downregulation, of inhibition; alterations in the intrinsic properties of pyramidal cells that would tend to make them more excitable; and sprouting of their intracortical axons and increased numbers of presumed synaptic contacts, which would increase recurrent EPSPs from one cell onto another. Consistent with this, we found that increasing the excitability of pyramidal cells and the strength of NMDA conductances, in the face of either unaltered or increased inhibition, resulted in generation of epileptiform activity that had characteristics similar to those of the experimental data. Thus epileptogenesis such as occurs after chronic cortical injury can result from alterations of intrinsic membrane properties of pyramidal neurons together with enhanced NMDA synaptic conductances.

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