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### Animal models  Rodent and monkey tic models have been developed in an attempt to study the mechanisms involved in tic generation more directly and a number of studies were published in 2015 using mice. In a rodent model removing about half of the cholinergic interneurons in the dorsolateral striatum produced increased fragmented grooming behavior in response to a repeated unpredictable acoustic startle stimuli and increased repetitive sniffing in response to D-amphetamine challenge \citep{25561540}. Ablation in the dorsomedial striatum did not produce similar deficits. None of the experimental conditions produced a change in prepulse inhibition. Another rodent model was used to determine to what extent cortical input and striatal input affected the temporal and spatial properties of motor tics \citep{26674861}. Biccuculline injections into the anterior striatal motor region produced focal tics in the forelimb area. The medium spiny neurons (MSNs) and the fast spiking interneurons exhibited increased activity during tics. Almost all of the MSNs were only active during the tics while a minority of the FSIs exhibited a decrease in activity. About half of the globus pallidus neurons demonstrated increased activity during the tic while the rest showed only inhibition or a combination of inhibition and excitation. Short bursts of high-frequency stimulus pulses were applied at random intervals to the region of the primary motor cortex representing the forelimb. Stimulation was provided before and after the bicuculline injections. The results suggested that the precise timing of tic occurrence was related to the summation of incoming excitatory cortical input and the time since the previous tic. These results supported the idea that the corticostrial corticostriatal  network is fundamentally associated with tic occurrence. The GABA-A antagonist picrotoxin was injected into targets throughout corticostriatal regions in adult mice \citep{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.