NMDA-DEPENDENT MODULATION OF CA1 LOCAL CIRCUIT INHIBITION

Whole-cell and extracellular recording techniques were used to examine local circuit inhibition in the CAI region of the rat hippocampus in vitro. Activation, primarily of the recurrent inhibitory circuit by al vear stimulation, elicited an IPSP in pyramidal neurons that was depen dent, in part, on NMDA receptor activation. Application of a tetanizin g stimulus to the alveus evoked long-term potentiation (LTP) of the in tracellularly recorded recurrent IPSPs. This LTP also was NMDA-depende nt and was more sensitive to blockade by the NMDA antagonists 2-amino- 5-phosphonovalerate (APV) and N-acetyl-aspartyl-glutamate, than the ex citatory LTP produced by Schaffer collateral stimulation, With regard to APV, the sensitivity of inhibitory LTP was an order of magnitude gr eater. A biophysical simulation of hippocampal CA1 circuitry was used in a model of learned pattern recognition that included LTP in both ex citatory and inhibitory recurrent circuits. In this model, selective b lockade of inhibitory LTP produced aberrant spread of lateral excitati on, resulting in confusion of normally distinguishable patterns of neu ronal activity. Consideration is given to the possibility that selecti ve disruption of NMDA-dependent modulation of local circuit inhibition may serve as a model for some aspects of dysfunction associated with NMDA-antagonist exposure and schizophrenia.