Abstracts

RATIONALE: We assessed short-term synaptic plasticity in layer V pyramidal cells to test the hypothesis that hyperexcitability which develops after chronic injury is in part due to plastic changes in the efficacy of excitatory neurotransmission. The balance of spontaneous synaptic activity shifts towards excitation in chronically injured, epileptogenic neocortex (Li & Prince, 1999). METHODS: To further assess synaptic strength, we obtained whole cell patch recordings from layer V pyramidal neurons in somatosensory cortex brain slices taken from P36-43 rats that had a partially isolated cortical island prepared 2+ wks earlier. AMPA receptor-mediated EPSCs were evoked in APV and bicuculline with trains of 10 contant frequency stimuli. RESULTS: At 67 Hz stimulation, pyramidal neurons in partially isolated cortex had a greater synaptic depression (Paired-pulse ratio [amplitude of 2nd EPSC/1st EPSC]: 0.90 b 0.09 (n=12) in control vs. 0.62 b 0.05 (n=10), in undercut, p<0.02). The decay time constant of EPSC amplitudes ( w was faster in undercut ( : 26 b 4 ms [n=9]) than in control (44 b 6 ms [n=8], p<0.04) at 67 Hz. In contrast, no significant difference in synaptic depression and was observed with 10 Hz stimulation. Increasing extracellular calcium concentration ([Ca++]o)from 2 to 4 mM increased synaptic depression, while low [Ca++]o decreased it. To examine possible postsynaptic alterations in glutamate receptor subunit GluR2 that might have contributed to the observed changes in synaptic strength after cortical injury, we tested the I-V relationship of AMPA receptor-mediated EPSCs. Both control and undercut neurons had a linear I-V relationship and spermine, a biogenic polyamine that blocks AMPA receptors lacking GluR2, had no effect on the EPSCs recorded from neurons in isolated or control cortex. CONCLUSIONS: Our findings suggest a presynaptic locus of change in the frequency dependent modulation of short-term excitatory synaptic plasticity in chronically injured cortex. Supported by NIH grant NS12151 and the Morris and Pimley Research Funds.