Abstract
We recently demonstrated that the collaterals of substantia nigra (SN) projection neurons can implement divisive feedback inhibition, or gain control (Brown et al., 2014). While in vivo recordings were consistent with divisive feedback inhibition, a causal test was lacking. A gain control model of the nigral microcircuit implies behavioral effects of disrupting intranigral inhibition that are distinct from previous functional models. To test the model predictions experimentally, we develop a chemogenetic approach that can selectively suppress synaptic release within the substantial nigra without affecting the propagation of activity to extranigral targets. We observe behavioral consequences of suppressing intranigral inhibition that are uniquely consistent with a gain control model. Our data further suggest that if endogenous metabotropic signaling can modulate intranigral synapses, this would provide a circuit mechanism for an exploitation/exploration trade-off in which the timing and variability of goal-directed movements are controlled independently of changes in action.
