RT Journal Article
SR Electronic
T1 Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 090209
DO 10.1101/090209
A1 Jennifer Brown
A1 Kathleen A. Martin
A1 Joshua T. Dudman
YR 2016
UL http://biorxiv.org/content/early/2016/11/28/090209.abstract
AB 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.