How sensory and motor signals are integrated in the brain to produce perception of object location remains poorly understood. Primary somatosensory cortex (S1) is a candidate site for sensorimotor integration that underlies object localization. Mouse S1 is a powerful system in which to uncover general principles and specific circuit implementations of sensorimotor integration that shape perception of object location. Revealing these will provide fundamental knowledge of healthy cortex function from which processing disruptions from stroke, spinal injury, and other neurological disorders may be more fully understood. The long-term goal of this work is to understand cellular and circuit mechanisms underlying tactile perception. This proposal focuses on how S1 integrates sensory and motor signals during active touch behaviors. Head-fixed mice can determine the angular position of objects by active exploration with a single whisker. Sophisticated neural processing underlies this simple behavior, which makes it an excellent model system for dissecting circuit mechanisms of somatosensory integration. Several competing models exist for how the brain solves this task. They differ in the type, origin, and integration location of sensorimotor signals used. Distinguishing between these models is critical for understanding the role internal motor signals in cortical circuits play in construction of tactile perception. Prior studies failed to do so because of limitations in task design and quantification of behavioral variation. This proposal overcomes these limitations with innovative approaches that include an improved localization task, high-speed sensorimotor tracking, cell type- specific electrophysiology, calcium imaging, sophisticated decoding models, and closed-loop optogenetics. The overall objective of this proposal is to distinguish between sensorimotor integration models by quantifying behavior, identifying candidate codes for object location in S1, how these are constructed, and their influence on perception. Our central hypothesis is that object location is encoded by the set of excitatory neurons activated by touch in L5B of S1, and that object location tuning in L5B cells requires both thalamic input and motion-subtracted touch signals from L4 of S1. We further hypothesize that M1 input amplifies L5B activity without affecting object location tuning. This hypothesis is supported by our preliminary data including cell-type and layer-specific recordings in S1 and optogenetic circuit manipulation during object localization. The hypothesis will be tested by pursuing three Specific Aims. 1) Identify candidate codes for object location in S1 neurons. 2) Identify the origin of signals contributing to object location tuning in S1 neurons. 3) Test object localization models with closed-loop optogenetic manipulation of S1 circuits. The contribution of the proposed research will be significant because it will generate detailed knowledge about the neural dynamics in S1 that underlie touch perception, uncover general principles of sensorimotor integration and specific cortical circuit implementations of that integration during behavior, and package it all into a publically accessible resource.

Public Health Relevance

The proposed research is relevant to public health because it will produce fundamental knowledge of how patterns of neural activity in cortex generate tactile perception in a mouse model system. This is relevant to NIH?s mission because this knowledge is needed to understand sensorimotor processing disorders, which could reduce the impact of disabilities in millions of Americans living with stroke, spinal injury, and other neurological impairments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS102808-01A1
Application #
9470837
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
2017-11-15
Project End
2022-10-31
Budget Start
2017-11-15
Budget End
2018-10-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Southern California
Department
Biology
Type
Graduate Schools
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90033