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Neuroscience. 2016 Jun 2;324:321-9. doi: 10.1016/j.neuroscience.2016.02.074. Epub 2016 Mar 8.

Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming.

Author information

1
Department of Psychiatry, Yale University, New Haven, CT, United States.
2
Department of Psychiatry, Yale University, New Haven, CT, United States; Department of Psychology, Yale University, New Haven, CT, United States; Child Study Center, Yale University, New Haven, CT, United States; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States. Electronic address: Christopher.pittenger@yale.edu.

Abstract

Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast-spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. FSIs were reduced bilaterally by ∼40%, paralleling the deficit found post-mortem. This did not produce spontaneous stereotypies or tic-like movements, but there was increased stereotypic grooming after acute stress in two validated paradigms. Stereotypy after amphetamine, in contrast, was not elevated. FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders.

KEYWORDS:

Tourette syndrome; basal ganglia; fast-spiking interneurons; parvalbumin; tics

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