Action suppression reveals opponent parallel control via striatal circuits

BF Cruz, G Guiomar, S Soares, A Motiwala… - Nature, 2022 - nature.com
Nature, 2022nature.com
The direct and indirect pathways of the basal ganglia are classically thought to promote and
suppress action, respectively. However, the observed co-activation of striatal direct and
indirect medium spiny neurons (dMSNs and iMSNs, respectively) has challenged this view.
Here we study these circuits in mice performing an interval categorization task that requires
a series of self-initiated and cued actions and, critically, a sustained period of dynamic action
suppression. Although movement produced the co-activation of iMSNs and dMSNs in the …
Abstract
The direct and indirect pathways of the basal ganglia are classically thought to promote and suppress action, respectively. However, the observed co-activation of striatal direct and indirect medium spiny neurons (dMSNs and iMSNs, respectively) has challenged this view. Here we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and cued actions and, critically, a sustained period of dynamic action suppression. Although movement produced the co-activation of iMSNs and dMSNs in the sensorimotor, dorsolateral striatum (DLS), fibre photometry and photo-identified electrophysiological recordings revealed signatures of functional opponency between the two pathways during action suppression. Notably, optogenetic inhibition showed that DLS circuits were largely engaged to suppress—and not promote—action. Specifically, iMSNs on a given hemisphere were dynamically engaged to suppress tempting contralateral action. To understand how such regionally specific circuit function arose, we constructed a computational reinforcement learning model that reproduced key features of behaviour, neural activity and optogenetic inhibition. The model predicted that parallel striatal circuits outside the DLS learned the action-promoting functions, generating the temptation to act. Consistent with this, optogenetic inhibition experiments revealed that dMSNs in the associative, dorsomedial striatum, in contrast to those in the DLS, promote contralateral actions. These data highlight how opponent interactions between multiple circuit- and region-specific basal ganglia processes can lead to behavioural control, and establish a critical role for the sensorimotor indirect pathway in the proactive suppression of tempting actions.
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