David D. Ginty, PhD
Department of Neurobiology
Howard Hughes Medical Institute
Harvard Medical School
(January 21, 2015)
The Functional Organization of Neurons That Underlie the Sense of Touch
A gentle touch to the arm, the feeling of a hand on the shoulder — how do we recognize these sensations? Dr. Ginty’s work focuses on a type of sensor, the low-threshold mechanoreceptors, and their role in the detection of touch. Using a mouse model, Dr. Ginty has determined that these mechanoreceptors are directly connected, in an organized fashion, to the spinal cord. Dr. Ginty’s research is currently examining the hypothesis that different subtypes of mechanoreceptors are part of a network of spinal cord neurons and interneurons that project processed touch information directly to the brain.
The somatosensory system endows us with a remarkable capacity for object recognition, texture discrimination, sensory-motor feedback, and social exchange. Innocuous touch of the skin is detected by a large group of physiologically distinct low-threshold mechanoreceptors (LTMRs) whose cell bodies are located in dorsal root ganglia and cranial ganglia.
In this lecture, I describe our recent advances in genetic labeling of LTMR subtypes and our findings regarding the function, development and organization of LTMRs circuits that underlie the sense of touch. My colleagues and I have generated a mouse LTMR molecular-genetic toolbox that enables interrogation of the physiology, morphology, function, and development of each LTMR subtype. Using these genetic tools and anatomical and physiological approaches, we have defined developmental, morphological and functional properties of LTMRs. We found that neurons that form circumferential endings associated with hair follicles respond to gentle stroking of the skin. We also observed hat LTMR subtypes whose peripheral projections innervate the same small region of skin exhibit central projections that terminate within narrow, three-dimensional columns of the spinal cord dorsal horn. These spinal cord LTMR columns represent units of functional organization that receive and process LTMR subtype activity ensembles emanating from the skin.
We posit that spinal cord interneurons directly receive and process LTMR activities, whereas spinal cord projection neurons carry processed touch information from spinal cord LTMR columns to the brain. To test these ideas and to gain insight into touch information processing in the spinal cord, we recently generated an array of spinal cord dorsal horn neuron subtype-specific molecular genetic tools that enable functional characterization of spinal cord dorsal horn neuronal populations. Mouse lines that enable analysis of 11 distinct spinal cord interneuron subtypes are being used to elucidate the development, physiological properties, morphologies, synaptic connectivity patterns, and functions of spinal cord interneuron subtypes. Thus, at least 11 distinct neuronal types in the spinal cord dorsal horn receive and process LTMR inputs. The mechanisms of development of LTMR subtypes, and the functional organization of LTMR circuits within the spinal cord dorsal horn that underlie the perception of touch are the focus of current research.