Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex

doi:10.1016/0163-1047(92)90982-A

Behavioral and Neural Biology

Volume 58, Issue 1, July 1992, Pages 76-80

https://doi.org/10.1016/0163-1047(92)90982-A Get rights and content

The blockers of glutamate receptors, aminophosphonovaleric acid (AP5) (5.0 μg) and ciano-nitro-quinoxalinedione (CNQX) (0.5 μg), were infused bilaterally into the amygdala, dorsal hippocampus, or entorhinal cortex of rats through indwelling cannulae 0, 90, 180, or 360 min after step-down inhibitory avoidance training. Animals were tested for retention 24 h after training. In the amygdala or hippocampus, AP5 was amnestic when given 0 min after training and CNQX was amnestic when given 0, 90, or 180 min after training. In the entorhinal cortex, AP5 was amnestic when given 90 or 180 min after training and CNQX had no effect. The results suggest that a phenomenon sensitive first to AP5 and then to CNQX in the amygdala and hippocampus, probably long-term potentiation (LTP), is crucial to post-training memory processing. LTP in these two structures could underlie their role in memory consolidation and could explain the late involvement of the entorhinal cortex in post-training memory processing.

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Research involving human participants indicates that memories of recently eaten meals limit how much is eaten during subsequent eating episodes; yet, the brain regions that mediate the inhibitory effects of ingestion-related memory on future intake are largely unknown. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memories of personal experiences, mediate the inhibitory effects of ingestion-related memory on future intake. Our research program aimed at testing this hypothesis has been influenced in large part by our mentor James McGaugh and his research on posttraining manipulations. In the present study, we used an activity-guided optogenetic approach to test the prediction that if dHC glutamatergic neurons limit future intake through a process that requires memory consolidation, then inhibition should increase subsequent intake when given soon after the end of a meal but delayed inhibition should have no effect. Viral vectors containing CaMKIIα-eArchT3.0-eYFP and fiber optic probes were placed in the dHC of male Sprague-Dawley rats. Compared to intake on a day when no inhibition was given, postmeal inhibition of dHC glutamatergic neurons given for 10 min after the end of a saccharin meal increased the likelihood that rats would consume a second meal 90 min later and significantly increased the amount of saccharin solution consumed during that next meal when the neurons were no longer inhibited. Importantly, delayed inhibition given 80 min after the end of the saccharin meal did not affect subsequent intake of saccharin. Given that saccharin has minimal postingestive gastric consequences, these effects are not likely due to the timing of interoceptive visceral cues generated by the meal. These data show that dHC glutamatergic neural activity is necessary during the early postprandial period for limiting future intake and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.
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¹: Work supported in part by Contract FAPERGS/FINEP No. 66.90.0528.00 to I.I. Drs. Jerusalinsky and Medina were visiting professors from the Laboratorio de Neurorreceptores, Instituto de Biologia Celular, Facultad de Medicina, Universidad de Buenos Aires, Argentina.

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Brief reportAmnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex

Pharmacology, Biochemistry and Behavior

Behavioral and Neural Biology

Neuroscience Letters

Neuroscience and Biobehavioral Reviews

Ontogenetic development of habit and memory formation in primates

Annals of the New York Academy of Sciences

Brief report
Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex