ABLATION OF FAST-SPIKING INTERNEURONS IN THE DORSAL STRIATUM, RECAPITULATING ABNORMALITIES SEEN POST-MORTEM IN TOURETTE SYNDROME, PRODUCES ANXIETY AND ELEVATED GROOMING

作者：Xu M; Li L; Pittenger C^*

来源：Neuroscience, 2016, 324: 321-329.

DOI：10.1016/j.neuroscience.2016.02.074

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

Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Postmortem 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 similar to 40%, paralleling the deficit found postmortem. 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.

• 出版日期2016-6-2