The pathophysiology of the
tics that define
Gilles de la Tourette syndrome (TS) is not well understood. Local disinhibition within the striatum has been hypothesized to play a pathogenic role. In support of this, experimental disinhibition by local antagonism of
GABA-A receptors within the striatum produces
tic-like phenomenology in monkey and rat. We replicated this effect in mice via local
picrotoxin infusion into the dorsal striatum. Infusion of
picrotoxin into sensorimotor cortex produced similar movements, accompanied by signs of behavioral activation; higher-dose
picrotoxin in the cortex produced
seizures. Striatal inhibition with local
muscimol completely abolished
tic-like movements after either striatal or cortical
picrotoxin, confirming their dependence on the striatal circuitry; in contrast, cortical
muscimol attenuated but did not abolish movements produced by striatal
picrotoxin. Striatal
glutamate blockade eliminated
tic-like movements after striatal
picrotoxin, indicating that glutamatergic afferents are critical for their generation. These studies replicate and extend previous work in monkey and rat, providing additional validation for the local disinhibition model of
tic generation. Our results reveal a key role for corticostriatal glutamatergic afferents in the generation of
tic-like movements in this model.