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Neuroscience. 2013 Oct 10;250:60-9. doi: 10.1016/j.neuroscience.2013.06.048. Epub 2013 Jul 2.

Persistent changes of corticostriatal plasticity in dt(sz) mutant hamsters after age-dependent remission of dystonia.

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1
Oscar-Langendorff-Institute of Physiology, University Medicine Rostock, 18057 Rostock, Germany.

Abstract

Abnormal plasticity in the cortico-basal ganglia-thalamocortical loop has been suggested to represent a key factor in the pathophysiology of dystonia. In a model of primary paroxysmal dystonia, the dt(sz) mutant hamster, previous experiments have shown a strongly increased long-term potentiation (LTP) in comparison to non-dystonic control hamsters. These basal changes, i.e. in the absence of dystonia, were found in young animals at an age of 5 weeks, when the age-dependent dystonia in dt(sz) mutant reaches highest severity. In the present study we examined in corticostriatal slices (1) whether the increases in synaptic plasticity can be modulated by stressful stimuli which induce dystonic episodes in young mutant hamsters, and (2) whether increases of LTP persist after spontaneous remission of dystonia in animals older than 10 weeks. The present data show that in slices of young mutant hamsters the extent of LTP was not influenced by the presence of dystonia: In comparison to age-matched control hamsters, LTP was increased in mutant hamsters independent of preceding stressful stimulation. After remission of dystonia, i.e., in older dt(sz) mutant hamsters >10 weeks, only LTP could be elicited, while in preparations from age-matched control hamsters, either LTP or long-term depression developed, depending on previous behavioral challenge. We conclude that in mature brain, corticostriatal connections have the potential for changes in metaplasticity, while in dt(sz) mutant hamsters this metaplasticity is persistently infringed even though stress-inducible dystonic symptoms are lost.

KEYWORDS:

ACSF; ANOVA; GP; LTD; LTP; MSN; N-methyl-d-aspartate; NMDA; PPF; PPR; analysis of variance; artificial cerebrospinal fluid; development; dystonia; fEPSPs; field excitatory postsynaptic potentials; globus pallidus; long-term potentiation; long-term-depression; medium-sized spiny neurons; paired pulse ratio; paired-pulse facilitation; synaptic plasticity

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