Stress impacts sensory variability through cortical sensory activity motifs

Alexander Mcgirr,James D Boyd,Timothy H Murphy,Paul D Metzak,Allen W Chan,Jeffrey Ledue

doi:10.1038/s41398-020-0713-1

Abstract

Medically unexplained symptoms in depression are common. These individual-specific complaints are often considered an ‘idiom of distress’, yet animal studies suggest that cortical sensory representations are flexible and influenced by spontaneous cortical activity. We hypothesized that stress would reveal activity dynamics in somatosensory cortex resulting in greater sensory-evoked response variability. Using millisecond resolution in vivo voltage sensitive dye (VSD) imaging in mouse neocortex, we characterized spontaneous regional depolarizations within limb and barrel regions of somatosensory cortex, or spontaneous sensory motifs, and their influence on sensory variability. Stress revealed an idiosyncratic increase in spontaneous sensory motifs that is normalized by selective serotonin reuptake inhibitor treatment. Spontaneous motif frequency is associated with increased variability in sensory-evoked responses, and we optogenetically demonstrate that regional depolarization in somatosensory cortex increases sensory-evoked variability for seconds. This reveals a putative circuit level target for changes in sensory processing and for unexplained physical complaints in stress-related psychopathology.

Highlights

Depressive disorders are associated with somatic symptoms for which medical causes cannot be identified[1]
When spontaneous regionally synchronized depolarizations occur in sensory cortex, the magnitude of sensory-evoked responses are decreased compared to the same sensory stimulus delivered while the region is hyperpolarized with minimal membrane potential variance[5,7]
Due to weak cross-talk between iGluSnFR and ChrimsonR (Fig. S5), we elicited and quantified sensory responses in the hemisphere contralateral to the ChrimsonR driven activity (Fig. 5d) as we have previously shown that unilateral optical stimulation evokes bilateral voltage sensitive dye (VSD) motifs[32]

Summary

Introduction

Depressive disorders are associated with somatic symptoms for which medical causes cannot be identified[1]. Even brief stresses result in new onset somatic symptoms[2]. These symptoms are idiosyncratic and fluctuant over time, both in terms of anatomical location and quality[3]. Imaging and electrophysiology in model species suggests that cortical sensory representations are flexible, as identical stimuli do not reproducibly elicit the same responses[5,6,7,8]. In part, this is related to a bidirectional relationship between spontaneous activity in cortex and sensory stimuli. Trial-to-trial variability is increased when sensory stimuli are delivered surrounding a depolarized state, whereas they are more reliable during a hyperpolarized state[9]

Objectives

Methods

Results

Conclusion