Our sense of touch is essential for our ability to perform fine manual tasks and for affective behaviors, and disruptions in tactile sensitivity can profoundly affect quality of life. Low-threshold mechanoreceptor (LTMR) neurons detect non-painful tactile stimuli in the periphery and transmit this information to the central nervous system (CNS). Our lab has produced genetic tools that enable visualization and functional manipulation of the major LTMR subtypes in the mouse, revealing that primary LTMR afferents transmit highly organized information about the nature and position of the touch stimulus they detect. However, the mechanisms that establish LTMR connectivity in the CNS to produce the functional organization of mechanosensory inputs remain unknown. In particular, the role of neural activity during LTMR morphogenesis, central targeting, and synaptogenesis has not been tested. The goal of my proposed research is to characterize the structural and functional development of LTMR neurons, and to test the role of activity in establishing organized patterns of LTMR connectivity in the CNS.
Aim 1 will use genetic tools to characterize the acquisition of LTMR morphologies and central targeting patterns, as well as synapse formation between LTMRs and their CNS targets.
In Aim 2 I will use electrophysiological recordings to monitor the maturation of functional response properties in LTMRs, and will generate genetic tools to investigate the role of neural activity during LTMR central targeting and synaptogenesis. Together, my proposed research will define how the circuits that process tactile stimuli are established to allow for the exquisite spatial and functional organization of somatosensory representations in the CNS. Understanding how touch circuits are assembled during development will guide research efforts aimed at promoting the regeneration of sensory axons following nerve damage in conditions of injury or disease, as well as the design of effective neural prosthetics to restore sensory function.

Public Health Relevance

Our sense of touch is essential for life, as it contributes to social behaviors and to actions that require fine motor control, and is mediated by sensory neurons that receive input from the skin and transmit this information to the central nervous system (CNS). In my proposed research, I will characterize the structural and functional development of genetically identified neurons that respond to non-painful touch stimuli in mice, and determine the role of neural activity during their targeting and synapse formation in the CNS. Understanding how mechanosensory circuits are assembled during development will inform efforts to promote the regeneration of sensory axons in conditions of injury or disease, as well as the creation of effective neural prosthetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS106807-01
Application #
9541255
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Gnadt, James W
Project Start
2018-04-01
Project End
2021-06-30
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
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