Cheryl Richards edited Pathophysiology.md  about 8 years ago

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The GABA-A antagonist picrotoxin was injected into targets throughout corticostriatal regions in adult mice \cite{25597650}. Infusions into the central and dorsolateral striatum produced intermittent non-rhythmic stereotyped lifting of the front or hind paw or head jerks. Infusions into the dorsomedial striatum did not have a significant behavioral effect. Infusion into the ventral striaum produced locomotor activation with sterotypical sniffing and wall licking. Infusions into the sensorimotor cortex produced similar movements in addition to exploration of the cage. sniffing and occasional licking. When an NMDA receptor antagonist was infused into the dorsolateral striatum prior to infusing picrotoxin into the same location, tic frequency decreased significantly thus demonstrating the role of glutamateric activity in tic generation. Infusion of a GABA-A antagonist into the sensorimotor cortex 10 minutes before picrotoxin infusion into the dorsolateral striatum also resulted in significant tic suppression.EEG recordings allowed experimenters to determine whether the infusions were causing seizures or not. The interpretation of these results was that the tic-like movements were generated from enhanced striatal responsivity to afferent glutamatergic synaptic input rather than to autonomous striatal activity.   The brain circuits underlying tics were studied using the first genetically engineered mouse model of TS+OCD ("Ticcy" D1CT-7) transgenic mice \cite{26453289}. This In these mice a small region of dopaminoceptive D1+ somatosensory cortical and limbic neurons is chronically potentiated which results in cortical and amygdalar glutamatergic excitation of striatothalamic, striatopallidal and nigrostriatal subcircuits. Four different drugs were used with Ticcy mice to clarify the role of glutamate in tic generation.  ### Neuroimaging and electrophysiology studies