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Another rodent model, using rats, was used to determine to what extent cortical 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. Medium spiny neurons (MSNs) and fast spiking interneurons exhibited increased activity during tics. All of the MSNs were only active during the tics. All of the FSIs were active during tics but a minority followed this increase in activity by a decrease. Four different patterns were seen in globus pallidus neurons. 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. The effects of cortical input were studied by using short bursts of high-frequency stimulus pulses 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 both incoming excitatory cortical input and the time since the previous tic occurred. These results support the idea that the corticostriatal network is fundamentally associated with tic occurrence.  Adult mice were used to examine the role of GABA in tic generation. The GABA-A antagonist picrotoxin was injected into areas throughout the cortex and striatum \citep{25597650}. Infusions into the central and dorsolateral striatum produced tic-like movements of the front paw, hind paw or head. Infusions into the dorsomedial striatum did not have a significant behavioral effect. Infusion into the ventral striatum produced increased locomotor activation in addition to sterotypical sniffing and wall licking without tic-like movements. Infusions into the sensorimotor cortex produced tic-like movements in addition to increased behavioral activation involving cage exploration, 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 glutamatergic activity in tic generation. Infusion of a GABA-A agonist into the sensorimotor cortex prior to picrotoxin infusion in the dorsolateral striatum also resulted in significant tic suppression. EEG recordings allowed experimenters to rule out seizures. seizures as a cause of the tic-like movements.  The authors summarize these results as providing evidence that the generation of tic-like movements are related to cortico-striatal interactions, with a key role for glutatmateric afferents, rather than to autonomous striatal activity. The brain circuits underlying tics were studied using a genetically engineered mouse model of TS+OCD ("Ticcy" D1CT-7 transgenic mice) \citep{26453289}. In these mice a small region of dopaminoceptive D1-receptor-containing somatosensory cortical and limbic neurons is chronically potentiated, which results in cortical and amygdalar glutamatergic excitation of striatothalamic, striatopallidal and nigrostriatal subcircuits. Tics were decreased by the use of drugs that acted at different points in this "hyperglutamergic cortico-striato-thalamo-cortical circuit." Excitatory forebrain serotonin and norepinephrine activity was blocked by ritanserin (a serotonin 2a/2c antagonist) and prazosin (an \( \alpha_{1} \) adrenergic antagonist) respectively. In contrast, downstream striatothalamic neurons' glutamate-triggered GABA output and downstream nigrostriatal neurons' glutamate-triggered co-modulatory dopamine output were blocked by moxonidine (an imidazoline receptor subtype 1 agonist) and bromocriptine (a dopamine agonist) respectively. All four of these drugs decreased tic frequency and were considered to be "circuit-breakers" for the hyperglutamatergic cortico/amygdalo-striato-thalamo-cortical circuit, providing evidence for an important role of glutamate in generating the abnormal movements in this model.