Functional Connectome Analysis of the Striatum with Optogenetics.

Neural circuit function is determined not only by anatomical connections but also by the strength and nature of the connections, that is functional or physiological connectivity. To elucidate functional connectivity, selective stimulation of presynaptic terminals of an identified neuronal population is crucial. However, in the central nervous system, intermingled input fibers make selective electrical stimulation impossible. With optogenetics, this becomes possible, and enables the comprehensive study of functional synaptic connections between an identified population of neurons and defined postsynaptic targets to determine the functional connectome. By stimulating convergent synaptic inputs impinging on individual postsynaptic neurons, low frequency and small amplitude synaptic connections can be detected. Further, the optogenetic approach enables the measurement of cotransmission and its relative strength. Recently, optogenetic methods have been more widely used to study synaptic connectivity and revealed novel synaptic connections and revised connectivity of known projections. In this chapter, I focus on functional synaptic connectivity in the striatum, the main input structure of the basal ganglia, involved in the motivated behavior, cognition, and motor control, and its disruption in a range of neuropsychiatric disorders.