Work by early anatomists identified long-range projections from somatosensory cortex that descend to the spinal cord dorsal horn, and these projections have been hypothesized to exert top-down control over somatosensory circuits. However, assessing the function of the somatosensory corticospinal neurons has proved intractable due to a lack of tools necessary for dissection of spinal cord neural circuits. I propose to use modern molecular genetic tools in conjunction with electrophysiological and behavioral analyses to assess the role of descending corticospinal inputs to the spinal cord dorsal horn. Leveraging anatomical findings using molecular genetic and viral tracing techniques, I will assess how activation of somatosensory corticospinal neurons influences dorsal horn processing of tactile information. To gain insights into the components of corticospinal-recipient circuits, I will silence individual interneuron subtypes within the dorsal horn and ask which subtypes are critical for cortical modulation of afferent input. In behaving animals, I will manipulate the activity of somatosensory corticospinal neurons to ask how these neurons contribute to tactile perception. Together, this work will reveal fundamental roles of descending corticospinal circuitry in the control of tactile information processing, and thus their influence in perception of an animal's tactile environment. Because normal tactile sensation is often disrupted in injury or disease, a better understanding of top-down control may contribute to therapies for mechanical allodynia after peripheral nerve injury, as well as for mechanosensory gating deficits exhibited in schizophrenia and some autism spectrum disorders (ASD).

Public Health Relevance

The sense of touch is integral to human experience, and pathologies that lead to impaired or hypersensitive touch can be debilitating. The goal of this proposal is to determine how somatosensory cortex influences the processing of gentle touch information in the spinal cord, and to map the spinal cord circuits that enable top- down control. Ultimately, better understanding of cortical influence in touch perception may inform efforts to treat tactile hypersensitivity often observed in chronic pain states, schizophrenia, or autism spectrum disorders (ASD).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS101843-01A1
Application #
9456975
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gnadt, James W
Project Start
2017-12-01
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115