Defining touch receptors and their central pathways controlling touch and pain

Touch perception begins with activation of peripheral low-threshold mechanoreceptors (LTMRs) subtypes, and LTMR activity ensembles are propagated to the central nervous system (CNS) where they are integrated. Understanding the unique response properties and functions of LTMR subtypes and how ensembles of LTMR activities are processed in the CNS are major goals of somatosensory research. In the first part of my thesis, I genetically identified a major mammalian LTMR subtype that is sensitive to gentle stroking of the skin and I defined the peripheral morphological structures that specify their unique mechanical receptivity. In a survey of mammalian skin, I found a preponderance of neurofilament-heavy chain+ circumferential endings associated with hair follicles, prompting the development of a genetic strategy to interrogate these neurons. Targeted in vivo recordings revealed them to be Aβ Field-LTMRs, identified 50 years ago but largely elusive thereafter. Remarkably, while Aβ Field-LTMRs are highly sensitive to gentle stroking of the skin, they are unresponsive to hair deflection, and they encode skin indentation in the noxious range across large, spotty receptive fields. Individual Aβ Field-LTMRs form up to 180 circumferential endings, making them the most anatomically expansive LTMR identified to date and suggesting their sensitivity to skin stroking arises through integration across many low-sensitivity circumferential endings. In the second part of my thesis, I have examined the anatomy and function of LTMRs and their spinal cord ascending pathways. I found that spinal cord projection neurons (PSDCs) that innervate the dorsal column nuclei via the dorsal column are critical for the development of mechanical allodynia in mouse models of neuropathic pain. This finding defines a novel ascending pathway for mechanical allodynia and challenges the traditional view in the field that the anterolateral tract carries all ascending pain information