These new approaches, in combination with conventional physiology and behavioral analysis should advance our knowledge of the contribution of specific neuronal population to circuit function. For example, there is a growing appreciation that many “non-glutamatergic” neurons that release neuromodulators also co-release glutamate. Using optogentic tools, recent studies provided convincing evidence for this type of phenomenon in dopaminergic [64,65], serotonergic [66] and cholinergic neurons [67]. Striatal cholinergic interneurons express vesicular glutamate transporter 3 (vGluT3) [68], it is likely glutamate is co-released at interneuron terminals. However, it remains unclear under what circumstance glutamate is co-released and what the functional significance of this would be. Using a similar approach, recent studies suggest that cholinergic activation exerts strong di-synaptic inhibitory action onto striatal MSNs (possibly by co-release of glutamate and activation of nAChRs) [44]. This new finding adds a novel component to striatal microcircuits - feed-forward inhibition controlled by cholinergic interneurons. In the coming years, a molecular dissection of cholinergic function should be further propelled by optogentic tools. Application of these new approaches should allow us to gain a better understanding of cholinergic function in the cortico-thalamo-basal ganglia circuitry, potentially accelerating the development of new therapeutic strategies for psychomotor disorders.
