Synaptic messenger substances in memory processes

Nitric oxide (NO), carbon monoxide (CO), the platelet-activating factor (PAF) and arachidonic acid are released by stimulated neurons, enhance glutamate release at nerve terminals and have been proposed as synaptic messengers involved in plastic phenomena, such as the long-term potentiation of glutamatergic synapses. Long-term potentiation has been suggested to be a basic mechanism of memory processes. The microinjection of inhibitors of the synthesis of NO and CO or of antagonists of the receptors to PAF into brain structures known to be involved in memory (hippocampus, amygdala, entorhinal cortex), during its early phases, causes amnesia. This indicates that NO, CO and PAF modulate the early phases of memory, perhaps by modulating long-term potentiation. In addition, microinjections of a NO releaser or of a soluble form of PAF into the hippocampus produce memory enhancement.

Experiments suggesting a role for the platelet-activating factor in hippocampal and amygdala synapses in memory in rats

Platelet-activating factor (1-O-alky1-2-acetyl-sn-glycero-3-phosphocholine, PAF) is present in brain, is released from neurons in culture and, in hippocampal slices, enhances glutamate release and long-term potentiation (LTP) through an action on membrane receptors sensitive to the antagonist, BN 52021. This led to the proposal that PAF may be a retrograde messenger in the genesis of LTP. LTP has been, in turn, proposed as a mechanism of memory. Male Wistar rats were implanted bilaterally with cannulae aimed at the amygdala and the dorsal hippocampus. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5 mA footshock, and tested for retention 24 h later. BN 52021 (0.5 mug) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 min later. The findings support the idea that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala, and further suggest that PAF is involved in the development of this LTP.

Memory of inhibitory avoidance in the rat is regulated by glutamate metabotropic receptors and by calcium/calmodulin kinase II in the hippocampus

We studied the effect on memory of the bilateral intrahippocampal posttraining infusion of the glutamate metabotropic receptor (mGLUR) agonist, 1S,2R-aminocyclopentane dicarboxylate (ACPD), of the mGLUR antagonist, [RS]-alpha-methyl-4-carboxyphenyl glycine (MCPG), and of the inhibitor of calcium/calmodulin protein kinase II (CaM II), 1-[N,O-Bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine (KN62). Male Wistar rats were implanted with cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Immediately or 180 min after training they received an intrahippocampal infusion of saline (0.5 mul), KN62 (100 mumoles), ACPD (20 nmoles), MCPG (13 nmoles) or of ACPD plus MCPG in 0.5 mul of saline. When given immediately after training, KN62 and MCPG were amnestic and ACPD caused memory facilitation and antagonized the effect od MCPG. When given 180 min after training, the drugs had no effect on memory. The results indicate that the early phase of memory is regulated by mGLURs in the hippocampus and requires CaM II activity. The data support the suggestion that memory involves long-term potentiation in the hippocampus.