Hippocampus Of Snap-25, And Alpha <sub>, 2 </ Sub> Receptor Role In Learning And Memory

Part I Hippocampal SNAP-25 is involved in memory consolidationAs a synaptosomal protein, SNAP-25 plays a key role in a number of neuronal functions including axonal growth, dendrite formation, and fusion of synaptic vesicles with membrane. It was also reported that following the induction of long-term potentiation (LTP) in the hippocampus, the expression of SNAP-25 increased. Using a learning/memory behavior screening, we identified SNAP-25 as one of the differentially expressed genes in the hippocampus upon behavioral training. Inhibition of SNAP-25 by intracerebroventricular antisense oligonucleotide caused a deficit in long-term, but not short-term, memory for step-down inhibitory avoidance. These results suggest a close relationship of altered SNAP-25 level with learning and/or memory consolidation. To test this, we locally infused the antisense oligonucleotides of SNAP-25 gene into the CAl or CA3 region in rats. We observed that, intra-CAl or CA3 infusion of the SNAP-25 antisense oligonucleotides impaired long-term contextual fear memory and spatial memory, and suppressed long-term potentiation (LTP) of synaptic transmission in the CAl or CA3 region. The inhibitory effect on LTP was not mediated by pre-synaptic mechanism because paired pulse facilitation (PPF) of synaptic transmission was not affected after administration of the antisense oligonucleotides. Together, the results suggest that hippocampal SNAP-25 is involved in memory consolidation.