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Altered Sensory Experience Exacerbates Stable Dendritic Spine and Synapse Loss in a Mouse Model of Huntington's Disease.

Murmu, Reena LU ; Li, Wen LU ; Szepesi, Zsuzsanna LU and Li, Jia-Yi LU (2015) In Journal of Neuroscience 35(1). p.287-298
Abstract
A key question in Huntington's disease (HD) is what underlies the early cognitive deficits that precede the motor symptoms and the characteristic neuronal death observed in HD. The mechanisms underlying cognitive symptoms in HD remain unknown. Postmortem HD brain and animal model studies demonstrate pathologies in dendritic spines and abnormal synaptic plasticity before motor symptoms and neurodegeneration. Experience-dependent synaptic plasticity caused by mechanisms such as LTP or novel sensory experience potentiates synaptic strength, enhances new dendritic spine formation and stabilization, and may contribute to normal cognitive processes, such as learning and memory. We have previously reported that under baseline conditions (without... (More)
A key question in Huntington's disease (HD) is what underlies the early cognitive deficits that precede the motor symptoms and the characteristic neuronal death observed in HD. The mechanisms underlying cognitive symptoms in HD remain unknown. Postmortem HD brain and animal model studies demonstrate pathologies in dendritic spines and abnormal synaptic plasticity before motor symptoms and neurodegeneration. Experience-dependent synaptic plasticity caused by mechanisms such as LTP or novel sensory experience potentiates synaptic strength, enhances new dendritic spine formation and stabilization, and may contribute to normal cognitive processes, such as learning and memory. We have previously reported that under baseline conditions (without any sensory manipulation) neuronal circuitry in HD (R6/2 mouse model) was highly unstable, which led to a progressive loss of persistent spines in these mice, and that mutant huntingtin was directly involved in the process. Here, we investigated whether pathological processes of HD interfere with the normal experience-dependent plasticity of dendritic spines in the R6/2 model. Six weeks of two-photon in vivo imaging before and after whisker trimming revealed that sensory deprivation exacerbates loss of persistent-type, stable spines in R6/2 mice compared with wild-type littermates. In addition, sensory deprivation leads to impaired transformation of newly generated spines into persistent spines in R6/2 mice. As a consequence, reduced synaptic density and decreased PSD-95 protein levels are evident in their barrel cortical neurons. These data suggest that mutant huntingtin is implicated in maladaptive synaptic plasticity, which could be one of the plausible mechanisms underlying early cognitive deficits in HD. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Neuroscience
volume
35
issue
1
pages
287 - 298
publisher
Society for Neuroscience
external identifiers
  • pmid:25568121
  • wos:000349407200024
  • scopus:84920508062
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0244-14.2015
language
English
LU publication?
yes
id
d820005a-a387-4433-b612-1ff09e7b439f (old id 5040959)
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http://www.ncbi.nlm.nih.gov/pubmed/25568121?dopt=Abstract
date added to LUP
2015-02-02 18:39:05
date last changed
2017-11-19 03:07:34
@article{d820005a-a387-4433-b612-1ff09e7b439f,
  abstract     = {A key question in Huntington's disease (HD) is what underlies the early cognitive deficits that precede the motor symptoms and the characteristic neuronal death observed in HD. The mechanisms underlying cognitive symptoms in HD remain unknown. Postmortem HD brain and animal model studies demonstrate pathologies in dendritic spines and abnormal synaptic plasticity before motor symptoms and neurodegeneration. Experience-dependent synaptic plasticity caused by mechanisms such as LTP or novel sensory experience potentiates synaptic strength, enhances new dendritic spine formation and stabilization, and may contribute to normal cognitive processes, such as learning and memory. We have previously reported that under baseline conditions (without any sensory manipulation) neuronal circuitry in HD (R6/2 mouse model) was highly unstable, which led to a progressive loss of persistent spines in these mice, and that mutant huntingtin was directly involved in the process. Here, we investigated whether pathological processes of HD interfere with the normal experience-dependent plasticity of dendritic spines in the R6/2 model. Six weeks of two-photon in vivo imaging before and after whisker trimming revealed that sensory deprivation exacerbates loss of persistent-type, stable spines in R6/2 mice compared with wild-type littermates. In addition, sensory deprivation leads to impaired transformation of newly generated spines into persistent spines in R6/2 mice. As a consequence, reduced synaptic density and decreased PSD-95 protein levels are evident in their barrel cortical neurons. These data suggest that mutant huntingtin is implicated in maladaptive synaptic plasticity, which could be one of the plausible mechanisms underlying early cognitive deficits in HD.},
  author       = {Murmu, Reena and Li, Wen and Szepesi, Zsuzsanna and Li, Jia-Yi},
  issn         = {1529-2401},
  language     = {eng},
  number       = {1},
  pages        = {287--298},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Altered Sensory Experience Exacerbates Stable Dendritic Spine and Synapse Loss in a Mouse Model of Huntington's Disease.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0244-14.2015},
  volume       = {35},
  year         = {2015},
}