Human Molecular Genetics, Vol 8, 839-846, Copyright © 1999 by Oxford University Press
MT Usdin, PF Shelbourne, RM Myers and DV Madison
Cognitive impairment is an early symptom of Huntington's disease (HD). Mice
engineered to carry the HD mutation in the endogenous huntingtin gene
showed a significant reduction in long-term potentiation (LTP), a measure
of synaptic plasticity often thought to be involved in memory. However, LTP
could be induced in mutant slices by an 'enhanced' tetanic stimulus,
implying that the LTP-producing mechanism is intact in mutant mice, but
that their synapses are less able to reach the threshold for LTP induction.
Mutant mice showed less post-tetanic potentiation than wild-type animals,
and also showed decreased paired pulse facilitation, suggesting that
excitatory synapses in HD mutant mice are impaired in their ability to
sustain transmission during repetitive stimulation. We show that mutants,
while normal in their ability to transmit at low frequencies, released
significantly less glutamate during higher frequency synaptic activation.
Thus, a reduced ability of Huntington synapses to respond to repetitive
synaptic demand of even moderate frequency could result not only in a
functional impairment of LTP induction, but could also serve as a substrate
for the cognitive symptoms that comprise the early-stage pathology of HD.
ARTICLES
Impaired synaptic plasticity in mice carrying the Huntington's disease mutation
Department of Genetics, B111 Beckman Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
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|
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