Studies on cholinergic and noradrenergic projections and sensory inputs to the cingulate cortex in modulating sensory processing and sensorimotor transformation

Abstract

Neuromodulatory inputs from the basal forebrain (BF) and locus ceruleus (LC) are widespread in the mammalian cerebral cortex and are known to play important roles in attention and arousal, but little is known about the selectivity of their cortical projections. In the first study, we have identified anatomic and functional differences in the way BF cholinergic neurons and LC noradrenergic neurons project into primary sensory cortices using a dual retrobead tracing technique along with optogenetic stimulation. While BF projections are highly selective to individual sensory cortices, LC projections diverge into multiple sensory cortices. To our knowledge, this is the first definitive proof that BF and LC projections to primary sensory cortices show both anatomic and functional differences in selectivity for modulating cortical activity. In addition to subcortico-cortical projections, intra-cortical circuit networks are also important to mediate sensory-guided motor actions as well as efficient sensory processing. During the perceptual behaviors, robust activities are recruited from the sensory to frontal cortex, but exact neural mechanisms underlying precision in the motor decision based on relevant sensory cues remain unclear. Here, we manipulated and measured neural activities from the cingulate cortex (Cg) in head-fixed mouse performing a visual detection task. We found that inactivation of Cg disrupted the precise perceptual action with a failure of withholding impulsive action. We identified sensory and motor signals in Cg and found that two distinct neuronal populations in the Cg processing amplified sensory signals and ramped-down motor signals reliably encode trial-by-trial variations in timing of perceptual action. Furthermore, optogenetic activation of subset of sensory-responsive Cg cells was sufficient to release licking action. Our data demonstrate that the Cg is a key structure repressing impulsive action and transforming visual information to perceptual action via a ramp-to-threshold reduction in the neural signature of inhibitory control.