Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Avoidance Learning / drug effects
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Avoidance Learning / physiology
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Behavior, Animal
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Blotting, Northern / methods
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Blotting, Western / methods
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Cells, Cultured
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Conditioning, Classical / drug effects
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Conditioning, Classical / physiology
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Electric Stimulation / methods
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Fear
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Gene Expression Regulation / physiology
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Hippocampus / cytology
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Hippocampus / metabolism*
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In Situ Hybridization / methods
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Inhibition, Psychological
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Long-Term Potentiation / radiation effects
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Male
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Maze Learning / drug effects
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Membrane Proteins / physiology*
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Memory / drug effects
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Memory / physiology*
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Nerve Tissue Proteins / physiology*
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Oligonucleotides, Antisense / pharmacology
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Reaction Time / drug effects
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Reaction Time / physiology
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Spatial Behavior / physiology
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Synaptosomal-Associated Protein 25
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Time Factors
Substances
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Membrane Proteins
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Nerve Tissue Proteins
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Oligonucleotides, Antisense
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RNA, Messenger
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Snap25 protein, rat
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Synaptosomal-Associated Protein 25