Hippocampal NMDA receptor subunits involvement in memory

SNITCOFSKY M; BAEZ MV; COLETTIS N; CERCATO MC; AGUIRRE AI; CHELI VT; KORNISIUK E; JERUSALINSKY DA

Cancún

Congreso; I Congreso de la Federación de Asociaciones Latinoamericanas y del Caribe de Neurociencias (FALAN); 2012

Federación de Asociaciones Latinoamericanas y del Caribe de Neurociencias (FALAN).

NMDA (N-methyl-D-aspartate) receptors (R) of the dorsal hippocampus are required to consolidate inhibitory avoidance (IA) memory in rats and their inhibition with the channel blocker MK-801 immediately after IA training, gives rise to amnesia .This retrograde amnesia was prevented by previous exposure to an open field (OF) -two sessions of 3 minutes each, 24 hours apart- that led to habituation of exploration. Most of the hippocampal NMDAR subtypes contains GluN2A or GluN2B subunits. Inhibition of GluN2B-containing NMDAR by the selective antagonist ifenprodil enabled long-term memory (LTM) formation of IA with a subthreshold (0.3 mA) training, and caused facilitation when the training was just overtreshold (0.5mA), suggesting that hippocampal GluN2B containing receptors negatively modulate this memory Intrahippocampal injection of ifenprodil also facilitated memory formation of the hippocampus-dependent object location task. It was previously shown that a 5 min OF session led to STM as well as LTM formation. Although OF habituation was impaired by intrahippocampal MK801, ifenprodil did not alter this memory, suggesting that it does not depend on GluN2B containing receptors. Hippocampal protein extracts obtained 70 min after rat exposure to a 5 min OF session were analyzed by Westernblot for the NMDAR subunits. While GluN2A significantly increased, GluN2B appeared to remain unchanged, showing similar results to those obtained in other related models (i.e. LTP induction in hippocampal slices, Aguirre et al, IBRO 2011, Baez et al, 2012). These results corroborate that, although NMDAR in the dorsal hippocampus are required during IA consolidation, receptor subtypes containing GluN2B seem to inhibit memory consolidation of this tasks. Meanwhile, GluN2A increased when memory consolidation is still going on, as happens during LTP establishment, suggesting that they might be directly involved in synaptic plasticity underlying this process.