Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex.
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.
Jin
Xiaoming
X
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Huguenard
John R
JR
Prince
David A
DA
D000818:Animals; D001925:Brain Damage, Chronic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D019579:Neocortex / Q000473:pathology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D009924:Organ Culture Techniques; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*