Abstract
Dynamin 1-3 isoforms are known to be involved in endocytotic processes occurring during synaptic transmission. No data has directly linked dynamins yet with normal animal behavior. Here we show that dynamin pharmacologic inhibition markedly impairs hippocampal-dependent associative memory. Memory loss was associated with changes in synaptic function occurring during repetitive stimulation that is thought to be linked with memory induction. Synaptic fatigue was accentuated by dynamin inhibition. Moreover, dynamin inhibition markedly reduced long-term potentiation, post-tetanic potentiation, and neurotransmitter released during repetitive stimulation. Most importantly, the effect of dynamin inhibition onto memory and synaptic plasticity was due to a specific involvement of the dynamin 1 isoform, as demonstrated through a genetic approach with siRNA against this isoform to temporally block it. Taken together, these findings identify dynamin 1 as a key protein for modulation of memory and release evoked by repetitive activity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Dynamin I / antagonists & inhibitors
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Dynamin I / genetics
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Dynamin I / metabolism*
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Electric Stimulation
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology*
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Gene Expression
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Hippocampus / drug effects
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Hippocampus / physiology*
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Hydrazones / pharmacology
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Male
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Memory / drug effects
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Memory / physiology*
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Memory Disorders / chemically induced
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Memory Disorders / metabolism*
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Memory Disorders / physiopathology
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Mice
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Mice, Inbred C57BL
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Refractory Period, Electrophysiological / drug effects
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Refractory Period, Electrophysiological / physiology
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Synapses / drug effects
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Synapses / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Hydrazones
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N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
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RNA, Small Interfering
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Dynamin I