scholarly journals Balance of Inhibitory and Excitatory Synaptic Activity Is Altered in Fast-Spiking Interneurons in Experimental Cortical Dysplasia

2009 ◽  
Vol 102 (4) ◽  
pp. 2514-2525 ◽  
Author(s):  
Fu-Wen Zhou ◽  
Huan-Xin Chen ◽  
Steven N. Roper
Keyword(s):  
Intractable Epilepsy ◽  
Pyramidal Cells ◽  
Simultaneous Recording ◽  
Cortical Dysplasia ◽  
Normal Function ◽  
Synaptic Activity ◽  
Short Term ◽  
Postsynaptic Currents ◽  
Cortical Interneurons ◽  
Fast Spiking

Cortical dysplasia (CD) is a common cause of intractable epilepsy in children and adults. We have studied rats irradiated in utero as a model of CD to better understand mechanisms that underlie dysplasia-associated epilepsy. Prior studies have shown a reduction in the number of cortical interneurons and in the frequency of inhibitory postsynaptic currents (IPSCs) in pyramidal cells in this model. They have also shown a reduced frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the surviving cortical interneurons. However, the inhibitory synaptic contacts were not examined in that study. The current experiments were performed to assess inhibitory synaptic activity in fast-spiking (FS) interneurons in irradiated rats and controls and the balance of excitatory and inhibitory synaptic activity in these cells. Whole cell recordings were obtained from layer IV FS cells in controls and comparable FS cells in irradiated rats. The frequency of spontaneous and miniature IPSCs was reduced in dysplastic cortex, but the amplitude of these currents was unchanged. Stimulus-evoked IPSCs showed short-term depression in control and short-term facilitation in dysplastic cortex. Simultaneous recording of spontaneous EPSCs and IPSCs showed a shift in the ratio of excitation-to-inhibition in favor of inhibition in FS cells from dysplastic cortex. The same shift toward inhibition was seen when miniature EPSCs and IPSCs were examined. These results show that FS cells in dysplastic cortex have a relative lack of excitatory drive. This may result in an important class of inhibitory cells that are less able to perform their normal function especially in periods of increased excitatory activity.

Disparities in Short-Term Depression Among Prefrontal Cortex Synapses Sustain Persistent Activity in a Balanced Network

2019 ◽  
Vol 30 (1) ◽  
pp. 113-134 ◽  
Author(s):  
Jae Young Yoon ◽  
Hyoung Ro Lee ◽  
Won-Kyung Ho ◽  
Suk-Ho Lee
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Cells ◽  
Excitatory Synapses ◽  
Persistent Activity ◽  
Neural Basis ◽  
Short Term ◽  
Postsynaptic Currents ◽  
Different Types ◽  
Fast Spiking ◽  
Balanced Network

Abstract Persistent activity of cue-representing neurons in the prefrontal cortex (PFC) is regarded as a neural basis for working memory. The contribution of short-term synaptic plasticity (STP) at different types of synapses comprising the cortical network to persistent activity, however, remains unclear. Characterizing STP at synapses of the rat PFC layer 5 network, we found that PFC synapses exhibit distinct STP patterns according to presynaptic and postsynaptic identities. Excitatory postsynaptic currents (EPSCs) from corticopontine (Cpn) neurons were well sustained throughout continued activity, with stronger depression at synapses onto fast-spiking interneurons than those onto pyramidal cells. Inhibitory postsynaptic currents (IPSCs) were sustained at a weaker level compared with EPSC from Cpn synapses. Computational modeling of a balanced network incorporating empirically observed STP revealed that little depression at recurrent excitatory synapses, combined with stronger depression at other synapses, could provide the PFC with a unique synaptic mechanism for the generation and maintenance of persistent activity.

scholarly journals Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria

2014 ◽  
Vol 112 (7) ◽  
pp. 1703-1713 ◽  
Author(s):  
Xiaoming Jin ◽  
Kewen Jiang ◽  
David A. Prince
Keyword(s):  
Laser Scanning ◽  
Fluorescent Protein ◽  
Intractable Epilepsy ◽  
Pyramidal Cells ◽  
Mean Amplitude ◽  
Cortical Layer ◽  
Synaptic Connectivity ◽  
Postsynaptic Currents ◽  
Fast Spiking ◽  
Layer V

A variety of major developmental cortical malformations are closely associated with clinically intractable epilepsy. Pathophysiological aspects of one such disorder, human polymicrogyria, can be modeled by making neocortical freeze lesions (FL) in neonatal rodents, resulting in the formation of microgyri. Previous studies showed enhanced excitatory and inhibitory synaptic transmission and connectivity in cortical layer V pyramidal neurons in the paramicrogyral cortex. In young adult transgenic mice that express green fluorescent protein (GFP) specifically in parvalbumin positive fast-spiking (FS) interneurons, we used laser scanning photostimulation (LSPS) of caged glutamate to map excitatory and inhibitory synaptic connectivity onto FS interneurons in layer V of paramicrogyral cortex in control and FL groups. The proportion of uncaging sites from which excitatory postsynaptic currents (EPSCs) could be evoked (hotspot ratio) increased slightly but significantly in FS cells of the FL vs. control cortex, while the mean amplitude of LSPS-evoked EPSCs at hotspots did not change. In contrast, the hotspot ratio of inhibitory postsynaptic currents (IPSCs) was significantly decreased in FS neurons of the FL cortex. These alterations in synaptic inputs onto FS interneurons may result in an enhanced inhibitory output. We conclude that alterations in synaptic connectivity to cortical layer V FS interneurons do not contribute to hyperexcitability of the FL model. Instead, the enhanced inhibitory output from these neurons may partially offset an earlier demonstrated increase in synaptic excitation of pyramidal cells and thereby maintain a relative balance between excitation and inhibition in the affected cortical circuitry.

SIMULATING VERTICAL AND HORIZONTAL INHIBITION WITH SHORT-TERM DYNAMICS IN A MULTI-COLUMN MULTI-LAYER MODEL OF NEOCORTEX

2014 ◽  
Vol 24 (05) ◽  
pp. 1440002 ◽  
Author(s):  
BEATA STRACK ◽  
KIMBERLE M. JACOBS ◽  
KRZYSZTOF J. CIOS
Keyword(s):  
Epileptiform Activity ◽  
Inhibitory Neuron ◽  
Normal Function ◽  
Spiking Neurons ◽  
Layer Model ◽  
Neuronal Connectivity ◽  
Short Term ◽  
Short Term Plasticity ◽  
Low Threshold ◽  
Fast Spiking

The paper introduces a multi-layer multi-column model of the cortex that uses four different neuron types and short-term plasticity dynamics. It was designed with details of neuronal connectivity available in the literature and meets these conditions: (1) biologically accurate laminar and columnar flows of activity, (2) normal function of low-threshold spiking and fast spiking neurons, and (3) ability to generate different stages of epileptiform activity. With these characteristics the model allows for modeling lesioned or malformed cortex, i.e. examine properties of developmentally malformed cortex in which the balance between inhibitory neuron subtypes is disturbed.

Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria

2005 ◽  
Vol 93 (2) ◽  
pp. 687-696 ◽  
Author(s):  
K. M. Jacobs ◽  
D. A. Prince
Keyword(s):  
Rat Model ◽  
Pyramidal Neurons ◽  
Intractable Epilepsy ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
Cell Group ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Layer V

Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human 4-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole cell excitatory postsynaptic currents and GABAA receptor-mediated inhibitory currents (EPSCs and IPSCs) from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked IPSCs was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m)IPSCs, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamate receptor antagonist application resulted in a significantly greater reduction in spontaneous IPSC frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature EPSCs was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

scholarly journals Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yoshiyuki Kubota ◽  
Satoru Kondo ◽  
Masaki Nomura ◽  
Sayuri Hatada ◽  
Noboru Yamaguchi ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Physiological Data ◽  
Functional Differences ◽  
Cortical Interneurons ◽  
Fast Spiking ◽  
Functionally Diverse ◽  
Cell Inhibition ◽  
Cell Somata ◽  
Global Inhibition

Inhibitory interneurons target precise membrane regions on pyramidal cells, but differences in their functional effects on somata, dendrites and spines remain unclear. We analyzed inhibitory synaptic events induced by cortical, fast-spiking (FS) basket cells which innervate dendritic shafts and spines as well as pyramidal cell somata. Serial electron micrograph (EMg) reconstructions showed that somatic synapses were larger than dendritic contacts. Simulations with precise anatomical and physiological data reveal functional differences between different innervation styles. FS cell soma-targeting synapses initiate a strong, global inhibition, those on shafts inhibit more restricted dendritic zones, while synapses on spines may mediate a strictly local veto. Thus, FS cell synapses of different sizes and sites provide functionally diverse forms of pyramidal cell inhibition.

scholarly journals Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nishant Singh ◽  
Thomas Bartol ◽  
Herbert Levine ◽  
Terrence Sejnowski ◽  
Suhita Nadkarni
Keyword(s):  
Endoplasmic Reticulum ◽  
Normal Function ◽  
Synaptic Activity ◽  
Calcium Signal ◽  
Short Term ◽  
Short Term Plasticity ◽  
Hippocampal Synapses ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
History Of

AbstractShort-term plasticity preserves a brief history of synaptic activity that is communicated to the postsynaptic neuron. This is primarily regulated by a calcium signal initiated by voltage dependent calcium channels in the presynaptic terminal. Imaging studies of CA3-CA1 synapses reveal the presence of another source of calcium, the endoplasmic reticulum (ER) in all presynaptic terminals. However, the precise role of the ER in modifying STP remains unexplored. We performed in-silico experiments in synaptic geometries based on reconstructions of the rat CA3-CA1 synapses to investigate the contribution of ER. Our model predicts that presynaptic ER is critical in generating the observed short-term plasticity profile of CA3-CA1 synapses and allows synapses with low release probability to operate more reliably. Blocking the ER lowers facilitation in a manner similar to what has been previously characterized in animal models of Alzheimer’s disease and underscores the important role played by presynaptic stores in normal function.

scholarly journals Author response: Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons

2015 ◽  
Author(s):  
Yoshiyuki Kubota ◽  
Satoru Kondo ◽  
Masaki Nomura ◽  
Sayuri Hatada ◽  
Noboru Yamaguchi ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Author Response ◽  
Cortical Interneurons ◽  
Fast Spiking

Dopaminergic Modulation of Short-Term Synaptic Plasticity in Fast-Spiking Interneurons of Primate Dorsolateral Prefrontal Cortex

2005 ◽  
Vol 94 (6) ◽  
pp. 4168-4177 ◽  
Author(s):  
G. Gonzalez-Burgos ◽  
S. Kroener ◽  
J. K. Seamans ◽  
D. A. Lewis ◽  
G. Barrionuevo
Keyword(s):  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Receptor Activation ◽  
Spike Timing ◽  
D1 Receptor ◽  
Synaptic Activity ◽  
Excitatory Postsynaptic Potential ◽  
Short Term ◽  
Dorsolateral Prefrontal ◽  
Fast Spiking

Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 μM) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 μM) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 μM), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-d-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.

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