Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior

Abstract

SummaryThe immense behavioral repertoire of animals necessitates mechanisms that select and suppress 15 specific actions depending on current goals. The prefrontal cortex (PFC) has been suggested to orchestrate these processes by biasing activity in its target structures, but how its vastly converging inputs and diverging outputs are coordinated to control goal-oriented actions remains unclear. Here we use a bilateral task in which mice select between symmetric but opposing actions to show that distinct outputs from a subdivision of the PFC, the anterior cingulate cortex (ACC), promote 20 correct and suppress incorrect actions. Surprisingly, ACC outputs to the superior colliculus principally inhibit incorrect actions. Optogenetic analyses and a projection-based activity model make the unexpected prediction that feedback from the ACC to the visual cortex promotes correct actions, which we confirm. Our results show that anatomically non-overlapping but functionally complementary PFC outputs bidirectionally control actions, and suggest a candidate organizing 25 principle for PFC circuits.

Neural mechanisms of sensorimotor transformation and action selection

“…Recent studies have also identified the contribution of specific ACC outputs to visual behavior. Distinct subpopulations of ACC projection neurons target either the visual cortex or the superior colliculus (Huda et al ., ). Anatomical analysis using virus‐mediated disynaptic tracing revealed that these two subpopulations receive inputs from overlapping but distinct set of presynaptic areas, suggesting anatomical and functional specialization of these two output circuits (Zhang et al ., ).…”

“…In agreement, we recently showed that these outputs exert context‐dependent modulation over visually guided action selection. We trained head‐fixed mice on a two‐choice visual detection task and used projection‐specific optogenetics to probe the contribution of ACC outputs to visual cortex and superior colliculus to behavior (Huda et al ., ). We found that top‐down outputs from the ACC to the visual cortex are necessary for selection of correct actions.…”

“…We found that top‐down outputs from the ACC to the visual cortex are necessary for selection of correct actions. Surprisingly, outputs to the superior colliculus are crucially involved in preventing erroneous responses (Huda et al ., ). Whether circuits centered around ACC outputs to the visual cortex and superior colliculus differentially contribute to visual attention is not yet clear, but our findings provide the first evidence that these outputs coordinate distinct aspects of visuomotor behavior.…”

“…This area has been variously called anterior cingulate cortex (ACC), M2, and A24b by different groups (Koike et al ., ; Zhang et al ., ; Leinweber et al ., ); we refer to it here with the generic term ACC in keeping with the nomenclature used by common mouse brain atlases (Paxinos & Franklin, ). Importantly, the ACC receives inputs from both primary and higher visual cortex (Huda et al ., , ; Fillinger et al ., ), exhibits visual responses at network and single‐neuron levels (Huda et al ., ; Murakami et al ., ), and sends top‐down projections to the visual cortex and the superior colliculus (Zhang et al ., , ; Leinweber et al ., ; Fillinger et al ., ; Huda et al ., ). Studies employing causal manipulations using chemogenetics and optogenetics show that ACC activity guides optimal performance on visual detection tasks that require sustained attention in freely moving mice (Koike et al ., ; White et al ., ).…”

Brain‐wide mapping of inputs to the mouse lateral posterior (LP/Pulvinar) thalamus–anterior cingulate cortex network

“…Furthermore, while the fronto‐parietal networks typical of primates are less prominent in rodents, the rodent ACC and secondary motor areas (MOs) have been associated with comparable sensorimotor functions. Notably, a region of the rodent ACC/MOs has been described as rodent “frontal orienting field” (FOF), in putative homology to the primate FEF, given the ACC/MOs area's extensive connectivity with the SC and the visual areas (Zingg et al., 2014, but see Preuss & Wise, 2021), as well as its functional involvement in controlling eye movements (Sato et al., 2019) and other orienting actions (Ebbesen et al., 2018; Huda et al., 2020).…”