Mouse substantia nigra responses to optogenetic stimulation of projections from striatum and globus pallidus

As a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior.  SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways' inhibitory actions.  Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways.  We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing.  Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.

Methods
This data was collected in the lab of Aryn Gittis at Carnegie Mellon University.  There is data from slice recordings and data from in vivo recordings, both in mice.  The slice data were collected with a MultiClamp 700B amplifier (Molecular Devices) and ITC-18 analog-to-digital board (HEKA) using Igor Pro software (Wavemetrics, RRID:SCR\_000325) and custom acquisition routines (Recording Artist; Richard C. Gerkin, Phoenix). Data were collected at 10 kHz and digitized at 40 kHz.