Evidence from our studies on the effects of systemic injections of pharmacological agents in behaving monkeys has led to the proposal that the formation of stimulus memories depends on interaction between the cholinergic and glutamatergic systems. More specifically, our evidence suggests that the critical event for storage of the trace or representation of a stimulus is the potentiation exerted by activation of the cholinergic muscarinic receptor on activity mediated by the glutamatergic NMDA receptor. To test this hypothesis, we have been examining the effects of microinjecting pharmacological agents directly into the perirhinal cortex, which is known from lesion studies to be the most critical area in the temporal lobe for stimulus recognition. Our results thus far have shown that, like systemic injections of a cholinergic muscarinic receptor antagonist (scopolamine), microinjecting this drug into perirhinal cortex impairs recognition memory. By contrast, recognition memory is unaffected by either systemic or perirhinal injections of dopaminergic receptor antagonists (e.g. haloperidol)). We have also demonstrated that, like systemic injections of an NMDA receptor antagonist (MK-801), perirhinal microinjections of such an antagonist (D-AP5) impairs recognition memory. Again by contrast, recognition memory is unaffected by perirhinal injections of a kainate/AMPA receptor antagonist (CNQX). These results provide preliminary support not only for the hypothesis regarding an interaction between muscarinic and NMDA receptor activation, but also for the notion that such interaction occurs within the neurons of the perirhinal cortex.
| Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer (2005) Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys. Proc Natl Acad Sci U S A 102:2158-61 |
