Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex

Xiaoming Jin, John R. Huguenard, David A. Prince

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Reduced synaptic inhibition is an important factor contributing to posttraumatic epileptogenesis. Axonal sprouting and enhanced excitatory synaptic connectivity onto rodent layer V pyramidal (Pyr) neurons occur in epileptogenic partially isolated (undercut) neocortex. To determine if enhanced excitation also affects inhibitory circuits, we used laser scanning photostimulation of caged glutamate and whole-cell recordings from GAD67-GFP-expressing mouse fast spiking (FS) interneurons and Pyr cells in control and undercut in vitro slices to map excitatory and inhibitory synaptic inputs. Results are 1) the region-normalized excitatory postsynaptic current (EPSC) amplitudes and proportion of uncaging sites from which EPSCs could be evoked (hotspot ratio) "increased" significantly in FS cells of undercut slices; 2) in contrast, these parameters were significantly "decreased" for inhibitory postsynaptic currents (IPSCs) in undercut FS cells; and 3) in rat layer V Pyr neurons, we found significant decreases in IPSCs in undercut versus control Pyr neurons. The decreases were mainly located in layers II and IV, suggesting a reduction in the efficacy of interlaminar synaptic inhibition. Results suggest that there is significant synaptic reorganization in this model of posttraumatic epilepsy, resulting in increased excitatory drive and reduced inhibitory input to FS interneurons that should enhance their inhibitory output and, in part, offset similar alterations in innervation of Pyr cells.

Original languageEnglish
Pages (from-to)1094-1104
Number of pages11
JournalCerebral Cortex
Volume21
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Pyramidal Cells
Neocortex
Rodentia
Inhibitory Postsynaptic Potentials
Interneurons
Excitatory Postsynaptic Potentials
Patch-Clamp Techniques
Glutamic Acid
Epilepsy
Lasers

Keywords

  • caged glutamate
  • electrophysiology
  • interneurons
  • posttraumatic epilepsy
  • synaptic transmission

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex. / Jin, Xiaoming; Huguenard, John R.; Prince, David A.

In: Cerebral Cortex, Vol. 21, No. 5, 05.2011, p. 1094-1104.

Research output: Contribution to journalArticle

Jin, Xiaoming ; Huguenard, John R. ; Prince, David A. / Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex. In: Cerebral Cortex. 2011 ; Vol. 21, No. 5. pp. 1094-1104.
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