| First Author | Xu M | Year | 2016 |
| Journal | Neuroscience | Volume | 324 |
| Pages | 321-9 | PubMed ID | 26968763 |
| Mgi Jnum | J:235881 | Mgi Id | MGI:5803906 |
| Doi | 10.1016/j.neuroscience.2016.02.074 | Citation | Xu M, et al. (2016) Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming. Neuroscience 324:321-9 |
| abstractText | 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 approximately 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. |
