Circuit mechanisms underlying cortical communications

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

To understand the principles of long-range connectivity in cortical communication, our efforts have focused on the following three projects during FY21. Functional connectivity of diverse long-range inputs to sensory cortex is aimed at achieving a mechanistic understanding of the functional connectivity of feedback / top-down projections to the primary sensory cortex. We have systematically examined the synaptic strength from different brain areas to diverse neuronal types in the primary somatosensory cortex (S1) and determined how the primary sensory cortex uses input-area-dependent, preferential recruitment of specific types of GABAergic interneurons to parse information from diverse feedback projections. Based on this framework, we investigate how cortical feedback projections to S1 are altered in a transgenic mouse line in which one of the neurodevelopmental (NDD) high risk genes is mutated in different types of GABAergic interneurons (INs). The second project, the structural organization of cortical subnetworks, is aimed at understanding the principles that govern the functional heterogeneity of principal neurons in sensory cortex. Neuronal activity in the superficial layer of the primary sensory cortex is highly heterogenous in relation to various aspects of the animal's behavior. We asked whether functionally heterogeneous subnetworks are constrained by specific long-range and local presynaptic ensembles. This study provides the circuit-based mechanism for the organization of cortical subnetworks. Using single cell-initiated, monosynaptic rabies virus tracing combined with calcium imaging, we found that behavior state-encoding (spontaneous movement) neurons show characteristic long-range and local presynaptic networks. Our results reveal connectivity rules that support functional heterogeneity of cortical principal cells. In the third project, we investigate the role of higher-order thalamic nucleus in sensory perception. Somatosensation is an active process. Active sensation is a form of goal-directed behavior and is thus inherently related to brain and behavioral states of the animal, such as intention, attention, and motivation. Despite that action and sensation are tightly integrated contingent on the animals goal during active sensation, the neuronal substrates and circuits that mediate such interaction remain poorly understood. Anatomical studies suggest that whisker-dependent sensorimotor integration takes place in multiple closed loops in the brain. Posteriomedial thalamic nucleus (POm), a higher-order thalamic nucleus, is one of the key nodes in these closed loop circuits. The mechanisms by which the POm neurons process information from multiple input sources and shape activity in downstream targets during active sensation is largely unknown. In the third project, we aim to achieve a comprehensive understanding of the neuronal circuits of the POm and its role in active sensation during natural and realistic behavioral condition. To this end, we have developed a self-initiated, two-alternative forced choice task in freely moving mice. Using this simple yet robust whisker-dependent sensory perception task, we characterize how diverse afferent inputs to POm differentially engage POm neurons in the context of motivation and active sensation. We test the hypothesis that cortical top-down, feedback inputs convey context-dependent information to POm during active sensation and thus modulate POm activity.