NMDA receptor membrane expression during long-term memory consolidation in the central nervous system of the crab Neohelice granulata.

ANGELES SALLES; YANIL HEPP; MARTIN CARBO TANO; MARIA EUGENIA PEDREIRA; RAMIRO FREUDENTHAL

Montevideo

Congreso; XII congress international society for neuroethology; 2016

international society for neuroethology

The molecular foundations by which memory is stored are still being unravelled. Alterations in the strength of synaptic connections between neurons are the key to the formation of a memory trace. These alterations may be in part driven by the molecular composition of synaptic membranes. NMDAR-dependent changes in strength of glutamatergic synapses are thought to underlie some forms of learning and memory both in vertebrates and invertebrates. The changes might be due to a differential expression of the NMDAR subunits or to a dynamic cellular trafficking that shifts during the formation of a memory. This trafficking does not only include NMDARs movement between synaptic and extra-synaptic localizations but also the cycling between intracellular compartments and the plasma membrane, a process called surface expression. In this study we aimed to analyse the changes in surface expression of the NMDAR during the consolidation of contextual learning in the crab Neohelice granulata. Our results show that the surface expression of the NR1 subunit of the receptor changes after training without affecting its general expression. Firstly, immediately after training, the surface expression of the NMDAR NR1 subunit is downregulated. Later, 3 hours after training, this surface expression is upregulated, returning to naïve and control levels 24 hours after training. The changes observed in NMDAR surface expression are restricted to the central brain, a structure involved in learning and memory processes, and are not seen in the thoracic ganglion. To further study the activation pathways that underlie these changes in surface expression of the NMDAR NR1 subunit we used the competitive antagonist of GABA A receptors, bicuculline, indirectly inducing the activation of the glutamatergic pathway. Interestingly, an increment in surface expression of the NR1 subunit was found in the central brain of the crab 3 hours after administration of the drug. This increment was similar to the observed at the same time point after training. A cocktail of MK-801 and CNQX aimed at inhibiting basal NMDA and AMPA activation was injected at same time point and no change was detected when the surface expression was evaluated. These results suggest that the changes observed in NR1 in the brain could be part of an event of metaplasticity that first, during the downregulation, is helping in the stability of the trace and later at 3 hours post training changes the threshold of synapse activation.