Synaptic activity in chronically injured, epileptogenic sensory-motor neocortex.
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, alpha-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 GABA(A) 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.
Li
Huifang
H
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Prince
David A
DA
D000818:Animals; D002908:Chronic Disease; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D009044:Motor Cortex / Q000503:physiopathology*; D019579:Neocortex / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*