The sense of touch enables everyday human behaviors, including feeding, navigation and social interaction. The goal of this research is to define the peripheral mechanisms that encode touch in mammals. This project focuses on Merkel cell-neurite complexes, which are gentle-touch receptors found in body sites specialized for fine touch. Mechanosensitive Merkel cells form synaptic-like contacts with fast-conducting afferents of dorsal root ganglia. Merkel cells are proposed to activate sensory afferents by neurotransmitter release at conventional chemical synapses, however, the molecular mechanisms of neurotransmission remain unknown. This application?s central hypothesis is that Merkel cells employ SNARE-dependent vesicular release of monoaminergic neurotransmitters to activate firing in sensory afferents. The hypothesis will be tested using a combination of live-cell imaging, transgenic mouse models, ex vivo electrophysiology, pharmacology, and sensory behavioral tests.
Aim 1 will test if Merkel cells employ SNARE-mediated vesicle release of neurotransmitter.
Aim 2 will determine whether Merkel cells employ monoaminergic neurotransmission to excite firing in tactile afferents.
Aim 3 will elucidate if monoaminergic neurotransmission is required for gentle-touch evoked behaviors. The proposed studies will define the molecular mechanisms of synaptic transmission and post-synaptic receptor pathways at the Merkel cell-neurite complex. This knowledge will our understanding of the fundamental principles that govern tactile function and encoding in the healthy nervous system.

Public Health Relevance

The sense of touch is fundamental to our daily life. Indeed, touch is required for the complex circuitry that enables us to interact with the outside world, such as the sensory feedback that guides fine motor skills, especially during the acquisition of new motor behaviors. However, despite the importance of touch, the biological mechanisms that govern this sense remain incompletely understood. This proposal aims to elucidate fundamental molecular mechanisms through which touch stimuli are transmitted to the nervous system, in order to reveal how the healthy nervous system registers tactile features of our daily environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS105449-02
Application #
9604995
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gnadt, James W
Project Start
2017-12-01
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Physiology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032