Spatial integration of thermotactile stimuli in the thalamocortical circuit and behavior

Max Delbrueck Centrum For Molecular Med, Berlin-Buch

Investigators

Abstract

Human perceptual studies quantifying spatial acuity in response to tactile and thermal stimuli have revealed fundamental differences in the discrimination capabilities of these two somatosensory modalities. Without a simultaneous tactile stimulus, the spatial acuity of thermal stimuli is extremely poor leading to gross misjudgments of stimulus location on the skin surface. However, studies of the spatial receptive fields of thermoreceptors have estimated the spatial extent to be only a few millimeters. This suggests that the spatial integration properties observed in perceptual studies must be occurring more centrally in the nervous system. Yet how these thermal inputs are processed and how this spatial integration compares to tactile stimuli remains largely unknown. Here, using a combination of behavior, electrophysiology and optical techniques in the hind paw system of mice, I aim to address the spatial integration properties of tactile and thermal stimuli to uncover neural mechanisms of somatosensory perception. I hypothesize that the tactile acuity of the mouse hind paw will be significantly better than the thermal acuity and that this will be reflected in both the spatial discrimination performance of the animal and the spatial receptive fields in the thalamocortical circuit. Spatial acuity of the mouse will be quantified using a head-fixed, paw-tethered behavioral paradigm (Aim 1). To investigate the link between neural activity and sensory perception, thalamic and cortical activity will be measured in mice performing this high spatial-resolution behavioral task (Aim 2). Finally, spatial perception of the mouse will be manipulated using a combination of optogenetic interventions (Aim 3). While there has been evidence of the differences in perception of these two somatosensory modalities for over 100 years, we have not yet been able to link the behavior to the neurophysiological underpinnings. Gaining fundamental knowledge of how thermotactile stimuli are integrated would provide a critical framework to interpret both natural patterns of neural activity as well as aberrant patterns present in clinical conditions. While this proposal is asking basic science questions, results from this work could have multiple clinical applications in the future including improved somatosensory prosthetics, thalamic pain relief, or peripheral deafferentation.