Transcriptomic encoding of sensorimotor transformation in the midbrain

Sensorimotor transformation, a process that converts sensory stimuli into motor actions, is critical for the brain to initiate behaviors. Although the circuitry involved in sensorimotor transformation has been well delineated, the molecular logic behind this process remains poorly understood. Here, we performed high-throughput and circuit-specific single-cell transcriptomic analyses of neurons in the superior colliculus (SC), a midbrain structure implicated in early sensorimotor transformation. We found that SC neurons in distinct laminae express discrete marker genes. Of particular interest, Cbln2 and Pitx2 are key markers that define glutamatergic projection neurons in the optic nerve (Op) and intermediate gray (InG) layers, respectively. The Cbln2+ neurons responded to visual stimuli mimicking cruising predators, while the Pitx2+ neurons encoded prey-derived vibrissal tactile cues. By forming distinct input and output connections with other brain areas, these neuronal subtypes independently mediate behaviors of predator avoidance and prey capture. Our results reveal that, in the midbrain, sensorimotor transformation for different behaviors may be performed by separate circuit modules that are molecularly defined by distinct transcriptomic codes.

Transcriptomic encoding of sensorimotor transformation in the midbrain

ABSTRACTSensorimotor transformation, a process that converts sensory stimuli into motor actions, is critical for the brain to initiate behaviors. Although the circuitry involved in sensorimotor transformation has been well delineated, the molecular logic behind this process remains poorly understood. Here, we performed high-throughput and circuit-specific single-cell transcriptomic analyses of neurons in the superior colliculus (SC), a midbrain structure implicated in early sensorimotor transformation. We found that SC neurons in distinct laminae express discrete marker genes. Of particular interest, Cbln2 and Pitx2 are key markers that define glutamatergic projection neurons in the optic nerve (Op) and intermediate gray (InG) layers, respectively. The Cbln2+ neurons responded to visual stimuli mimicking cruising predators, while the Pitx2+ neurons encoded prey-derived vibrissal tactile cues. By forming distinct input and output connections with other brain areas, these neuronal subtypes independently mediate behaviors of predator avoidance and prey capture. Our results reveal that, in the midbrain, sensorimotor transformation for different behaviors may be performed by separate circuit modules that are molecularly defined by distinct transcriptomic codes.

Dynamic neuronal activation of a distributed cortico-basal ganglia-thalamus loop in learning a delayed sensorimotor task

The cortico-basal ganglia-thalamus (CBT) loop is important for behavior. However, the activity and learning-related modulation within the loop in behavior remain unclear. To tackle this problem, we trained mice to perform a delayed sensorimotor-transformation task and recorded single-unit activity during learning simultaneously from four regions in a CBT loop: prelimbic area (PrL), posterior premotor cortex (pM2), dorsomedial caudate/putamen (dmCP), and mediodorsal thalamus (MD). Sensory and decision related information were encoded by the neurons within the loop, with weak interaction among neurons of different coding ability. The functional interaction among regions within the loop was dynamically routed in the loop during different behavioral phases and contributed to explain decision-related neuronal activity. The neurons of PrL and dmCP exhibited learning-related reorganization in neuronal activity and more persistent coding of sensory and decision-related information. Thus, both sensory- and decision-related information are processed in a functionally interacted CBT loop that is modulated by learning.

Reflections on the differential organization of mirror neuron systems for hand and mouth and their role in the evolution of communication in primates

It is now generally accepted that the motor system is not purely dedicated to the control of behavior, but also has cognitive functions. Mirror neurons have provided a new perspective on how sensory information regarding others’ actions and gestures is coupled with the internal cortical motor representation of them. This coupling allows an individual to enrich his interpretation of the social world through the activation of his own motor representations. Such mechanisms have been highly preserved in evolution as they are present in humans, apes and monkeys. Recent neuroanatomical data showed that there are two different connectivity patterns in mirror neuron networks in the macaque: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and the new data show that it is connected with limbic structures. The mouth mirror sector seems to be wired not only for ingestive behaviors but also for orofacial communicative gestures and vocalizations. Notably, the hand and mouth mirror networks partially overlap, suggesting the importance of hand-mouth synergies not only for sensorimotor transformation, but also for communicative purposes in order to better convey and control social signals.

Task-dependent representations of stimulus and choice in mouse parietal cortex

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. To distinguish these possibilities, we trained mice of either sex to perform a visual discrimination task and imaged the activity of PPC populations during both engaged behavior and passive viewing. Unlike neurons in primary visual cortex (V1), which responded robustly to stimuli in both conditions, most neurons in PPC responded exclusively during task engagement. However, PPC responses were heterogeneous, with a smaller subset of neurons exhibiting stimulus-driven, contrast-dependent responses in both conditions. Neurons in PPC also exhibit stronger modulation by noise correlations relative to V1, as illustrated by a generalized linear model that takes into account both task variables and between-neuron correlations. To test whether PPC responses primarily encoded the stimulus or the learned sensorimotor contingency, we imaged the same neurons before and after re-training mice on a reversed task contingency. Unlike V1 neurons, most PPC neurons exhibited a dramatic shift in selectivity after re-training and reflected the new sensorimotor contingency, while a smaller subset of neurons preserved their stimulus selectivity. Mouse PPC is therefore strongly task-dependent, contains heterogeneous populations sensitive to stimulus and choice, and may play an important role in the flexible transformation of sensory inputs into motor commands.Significance StatementPerceptual decision making involves both processing of sensory information and mapping that information onto appropriate motor commands via learned sensorimotor associations. While visual cortex (V1) is known to be critical for sensory processing, it is unclear what circuits are involved in the process of sensorimotor transformation. While the mouse posterior parietal cortex (PPC) has been implicated in visual decisions, its specific role has been controversial. By imaging population activity while manipulating task engagement and sensorimotor contingencies, we demonstrate that PPC, unlike V1, is highly task-dependent, heterogeneous, and sensitive to the learned task demands. Our results suggest that PPC is more than a visual area, and may instead be involved in the flexible mapping of visual information onto appropriate motor actions.