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Journal of Neuroscience, Vol 16, 2034-2043, Copyright © 1996 by Society for Neuroscience
NMDA-dependent modulation of CA1 local circuit inhibition
HC Grunze, DG Rainnie, ME Hasselmo, E Barkai, EF Hearn, RW McCarley and RW Greene
Department of Psychiatry, Harvard University, Cambridge, Massachusetts 02138, USA.
Whole-cell and extracellular recording techniques were used to examine
local circuit inhibition in the CA1 region of the rat hippocampus in vitro.
Activation, primarily of the recurrent inhibitory circuit by alvear
stimulation, elicited an IPSP in pyramidal neurons that was dependent, in
part, on NMDA receptor activation. Application of a tetanizing stimulus to
the alveus evoked long-term potentiation (LTP) of the intracellularly
recorded recurrent IPSPs. This LTP also was NMDA- dependent and was more
sensitive to blockade by the NMDA antagonists 2- amino-5-phosphonovalerate
(APV) and N-acetyl-aspartyl-glutamate, than the excitatory LTP produced by
Schaffer collateral stimulation. With regard to APV, the sensitivity of
inhibitory LTP was an order of magnitude greater. A biophysical simulation
of hippocampal CA1 circuitry was used in a model of learned pattern
recognition that included LTP in both excitatory and inhibitory recurrent
circuits. In this model, selective blockade of inhibitory LTP produced
aberrant spread of lateral excitation, resulting in confusion of normally
distinguishable patterns of neuronal activity. Consideration is given to
the possibility that selective 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.
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