Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 20, Issue 6, Pages 1593-1603Publisher
WILEY
DOI: 10.1111/j.1460-9568.2004.03600.x
Keywords
antisense oligonucleotides; hippocampus; long-term potentiation; memory; rat; SNAP-25
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Funding
- NIDA NIH HHS [DA09444, DA11891, DA1347] Funding Source: Medline
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As a synaptosomal protein, SNAP-25 plays a role in a number of neuronal functions including axonal growth, dendrite formation, fusion of synaptic vesicles with membrane and the expression of long-term potentiation (LTP) in the hippocampus. Using a learning/memory behavior screening, we identified SNAP-25 as one of the differentially expressed genes in the hippocampus upon behavioral training. The inhibition of SNAP-25 with intracerebroventricular antisense oligonucleotide caused a deficit in long- but not short-term memory for step-down inhibitory avoidance. Intra-CA1 infusion of the SNAP-25 antisense oligonucleotide impaired long-term contextual fear memory and spatial memory and interfered with the LTP of synaptic transmission in the CA1 region. The inhibitory effect on LTP was not mediated by a pre-synaptic mechanism because paired pulse facilitation of synaptic transmission was not affected after administration of the antisense oligonucleotide. Together, the results suggest that SNAP-25 in the CA1 region is involved in memory consolidation.
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