Scanned optogenetic control of mammalian somatosensory input to map input-specific behavioral outputs.

Ara Schorscher-Petcu,Liam E Browne,Flóra Takács

doi:10.7554/elife.62026

Abstract

Somatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and higher-order processes related to pain and touch. However, somatosensory inputs are challenging to control in awake mammals due to the diversity and nature of contact stimuli. Application of cutaneous stimuli is currently limited to relatively imprecise methods as well as subjective behavioral measures. The strategy we present here overcomes these difficulties, achieving 'remote touch' with spatiotemporally precise and dynamic optogenetic stimulation by projecting light to a small defined area of skin. We mapped behavioral responses in freely behaving mice with specific nociceptor and low-threshold mechanoreceptor inputs. In nociceptors, sparse recruitment of single-action potentials shapes rapid protective pain-related behaviors, including coordinated head orientation and body repositioning that depend on the initial body pose. In contrast, activation of low-threshold mechanoreceptors elicited slow-onset behaviors and more subtle whole-body behaviors. The strategy can be used to define specific behavioral repertoires, examine the timing and nature of reflexes, and dissect sensory, motor, cognitive, and motivational processes guiding behavior.

Highlights

The survival of an organism depends on its ability to detect and respond appropriately to its environment
The design of the optical strategy had eight criteria: (1) that somatosensory stimuli are delivered non-invasively without touching or approaching the mice; (2) localization of stimuli are spatially precise and accurate (
We have shown that the analysis can be customized to incorporate computational tools that facilitate quantification and reveal insights into complex behavioral responses

Summary

Introduction

The survival of an organism depends on its ability to detect and respond appropriately to its environment. Cutaneous stimuli are used to study a wide range of neurobiological mechanisms since neurons densely innervating skin function to provide diverse information as the body interfaces with its immediate environment. Olfactory and auditory stimuli, somatosensory inputs are challenging to deliver in awake unrestrained mammals This is due to the nature of stimuli that require contact and the diversity of stimulus features encoded by afferents that innervate skin. Recent advances in machine vision and markerless pose estimation have enabled the dissection of animal behavioral sequences (Mathis et al, 2018; Pereira et al, 2019; Wiltschko et al, 2015) These have not been adapted to study behavioral outputs relating to specific cutaneous inputs. We dissect discrete behavioral components of local paw responses, head orienting and body repositioning behaviors, and determine how these specific behavioral components relate to precise somatosensory inputs

Design of the optical approach

Discussion

Materials and methods