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Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome.

Publication ,  Journal Article
Hayrapetyan, V; Castro, S; Sukharnikova, T; Yu, C; Cao, X; Jiang, Y-H; Yin, HH
Published in: The European journal of neuroscience
March 2014

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation and impaired speech. Because patients with this disorder often exhibit motor tremor and stereotypical behaviors, which are associated with basal ganglia pathology, we hypothesized that AS is accompanied by abnormal functioning of the striatum, the input nucleus of the basal ganglia. Using mutant mice with maternal deficiency of AS E6-AP ubiquitin protein ligase Ube3a (Ube3a(m-/p+) ), we assessed the effects of Ube3a deficiency on instrumental conditioning, a striatum-dependent task. We used whole-cell patch-clamp recording to measure glutamatergic transmission in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Ube3a(m-/p+) mice were severely impaired in initial acquisition of lever pressing. Whereas the lever pressing of wild-type controls was reduced by outcome devaluation and instrumental contingency reversal, the performance of Ube3a(m-/p+) mice were more habitual, impervious to changes in outcome value and action-outcome contingency. In the DMS, but not the DLS, Ube3a(m-/p+) mice showed reduced amplitude and frequency of miniature excitatory postsynaptic currents. These results show for the first time a selective deficit in instrumental conditioning in the Ube3a deficient mouse model, and suggest a specific impairment in glutmatergic transmission in the associative corticostriatal circuit in AS.

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Published In

The European journal of neuroscience

DOI

EISSN

1460-9568

ISSN

0953-816X

Publication Date

March 2014

Volume

39

Issue

6

Start / End Page

1018 / 1025

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Synapses
  • Organ Specificity
  • Neurons
  • Neurology & Neurosurgery
  • Miniature Postsynaptic Potentials
  • Mice, Inbred C57BL
  • Mice
  • Glutamic Acid
  • Gene Deletion
 

Citation

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Hayrapetyan, V., Castro, S., Sukharnikova, T., Yu, C., Cao, X., Jiang, Y.-H., & Yin, H. H. (2014). Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome. The European Journal of Neuroscience, 39(6), 1018–1025. https://doi.org/10.1111/ejn.12442
Hayrapetyan, Volodya, Stephen Castro, Tatyana Sukharnikova, Chunxiu Yu, Xinyu Cao, Yong-Hui Jiang, and Henry H. Yin. “Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome.The European Journal of Neuroscience 39, no. 6 (March 2014): 1018–25. https://doi.org/10.1111/ejn.12442.
Hayrapetyan V, Castro S, Sukharnikova T, Yu C, Cao X, Jiang Y-H, et al. Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome. The European journal of neuroscience. 2014 Mar;39(6):1018–25.
Hayrapetyan, Volodya, et al. “Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome.The European Journal of Neuroscience, vol. 39, no. 6, Mar. 2014, pp. 1018–25. Epmc, doi:10.1111/ejn.12442.
Hayrapetyan V, Castro S, Sukharnikova T, Yu C, Cao X, Jiang Y-H, Yin HH. Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome. The European journal of neuroscience. 2014 Mar;39(6):1018–1025.
Journal cover image

Published In

The European journal of neuroscience

DOI

EISSN

1460-9568

ISSN

0953-816X

Publication Date

March 2014

Volume

39

Issue

6

Start / End Page

1018 / 1025

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Synapses
  • Organ Specificity
  • Neurons
  • Neurology & Neurosurgery
  • Miniature Postsynaptic Potentials
  • Mice, Inbred C57BL
  • Mice
  • Glutamic Acid
  • Gene Deletion