Friday, May 9, 2025
5/9/2025
Local and Long-Range Cortical Circuits Underlying Tactile Perception - PROJECT SUMMARY Perception can only fully be understood in the context of behavior. Stimulus feature binding, sensorimotor integration, and information routing are each an aspect of sensory processing that is dynamically engaged on a moment-to-moment basis depending on behavioral demands. Deficits in each of these aspects of perception are hallmarks of a range of neurological disorders. Sensory neocortex is important for all modes of perception but how it can support these computations and flexibly utilize them is not understood. Proposed theoretical models of perceptual processes have largely been derived from prior studies consisting of recordings from small populations of neurons. These studies have historically lacked information regarding molecular identity of recorded neurons and their local and long-range connectivity. Consequently, existing models largely fail to consider how neurons are organized into circuits, either localized to one brain area or spanning multiple connected areas, to carry out these computations. Incorporating molecular and anatomical information would allow theoretical models to be validated and refined into circuit implementations that are both more biologically realistic and could inform other cortex-dependent cognitive functions. In this project, we focus on the mouse whisker system as a model to understand how sensorimotor areas support tactile perception. We have established whisker-based tasks in the mouse for investigating different aspects of sensory processing. We will deploy a range of tools that we have developed that combines multi-area two-photon microscopy, fine-scale and long-range neuroanatomy, spatial transcriptomics, and neural perturbation to assay sensorimotor circuits during goal-directed behavior. We will apply these tools to determine the role that local and long-range cortical dynamics play in the processing of sensory information. We will focus on: 1) obtaining a fine-scale wiring diagram in primary somatosensory cortex (S1) that supports stimulus feature binding into conjunctive representations. 2) identifying cell-type-specific circuit motifs in S1 that can differentiate and integrate sensory and motor information. 3) identifying the neural dynamics and anatomical connections that support information flow between cortical areas during goal-directed behavior. Through these circuit-level dissections, our goal is to test and evaluate existing computational models of cortical function that will help to explain both perception and behavior.
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