We have demonstrated that acetylcholine (ACh) release, as measured by in vivo microdialysis, is increased in the temporal lobe of monkeys during performance of a visual recognition task and that a cholinergic antagonist, scopolamine, injected directly into a discrete region of this lobe, the perirhinal cortex, impairs performance on this task. This result not only supports the proposal that the cholinergic system is critical in memory formation, but also provides evidence that the perirhinal cortex is a crucial component in the neural circuitry underlying recognition memory. The mnemonic effects of ACh may be mediated through interactions with other neurochemicals, such as glutamate. We began testing this hypothesis by examining the effects of systemic administration of a glutamatergic NMDA channel blocker, MK-801, or a glycine site agonist that is a positive modulator of NMDA receptors, d-cycloserine, on monkeys' performance on the visual recognition task. We found that while MK-801 disrupts visual recognition memory, d-cycloserine produces an even greater improvement than do drugs that enhance available ACh, such as the cholinesterase inhibitor, physostigmine. In addition, d-cycloserine completely reversed the mnemonic deficits induced by blockage of glycine sites by HA-966 and significantly counteracted the impairing effects of both scopolamine and MK-801. By contrast, physostigmine reversed the impairment produced only by scopolamine, not by MK-801. We interpret these results to indicate that the critical event for visual recognition is the potentiation of activity mediated by the NMDA receptor. We also have begun to examine whether glutamate interacts with dopamine, a neurochemical which has been implicated in the cognitive process termed working memory. Our initial studies demonstrated that MPTP administration, which depletes striatal dopamine, produced deficits on spatial delayed response, a form of working memory, even when motor dysfunction was recovered 10 years following MPTP exposure. Replacing dopamine by injecting levodopa dose-dependently ameliorated this deficit.
| 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 |
