GHRELIN INCREASES MEMORY CONSOLIDATION THROUGH HIPPOCAMPAL MECHANISMS DEPENDENT OF GLUTAMATE RELEASE AND NR2B SUBUNITS OF THE NMDA RECEPTOR.

MARISA GHERSI,; LAURA GABACH; BUTTELER FLORENCIA; VILCAES A; CARPIO; SCHIÖTH HB; MARIELA F. PEREZ; DE BARIOGLIO SR

Huerta Grande

Congreso; XXIX CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS (SAN); 2014

SAN

Ghrelin (Ghr) is a 28 amino acid peptide, which is synthesized both peripherally and centrally. It is known that Ghr participates in the modulation of several processes related to energy homeostasis, gastrointestinal functions, anxiety-like behavior and growth hormone releasing activity. This peptide is an endogenous agonist for the growth hormone secretagogue receptor (GHS-R). In the central nervous system, GHS-Rs are mainly expressed in the hypothalamus, and mediate the orexigenic effects. However, they are also expressed in extra-hypothalamic structures such as the hippocampus (hp), a brain structure involved in learning and memory processes. Previously, we have shown that Ghr administration in rats, either intracerebroventricularly or directly into brain areas such as the hp, amygdala or dorsal raphe nucleus enhances memory consolidation in the step-down test, in a dose-dependent manner. We have also demonstrated that hippocampal administration decreases the threshold to induce long term potentiation (LTP). The main events during memory consolidation coincide with the signaling pathways activated during the LTP induction in hippocampal CA1 and dentate gyrus. They are initiated by glutamate release and activation of NMDA and AMPA glutamate receptors. In the CA1 activation of NMDA receptors (NMDAR) seems to be necessary for memory formation. Functional NMDAR complexes are composed by NR1 and different NR2 subunits. Both NR2A and NR2B subunits play important roles in LTP and associative learning, and a critical requirement of NR2B subunit has been suggested for LTP induction. In addition, Ifenprodil, an NR2B-specific antagonist, completely blocks ?in vitro? LTP in hippocampal slices.