Distinct patterns of activity in individual cortical neurons and local networks in primary somatosensory cortex of mice evoked by square-wave mechanical limb stimulation.

Mischa V Bandet,Bin Dong,Ian R Winship,Gennady S Cymbalyuk

doi:10.1371/journal.pone.0236684

Mischa V Bandet, Bin Dong + Show 2 more

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https://doi.org/10.1371/journal.pone.0236684

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Abstract

Artificial forms of mechanical limb stimulation are used within multiple fields of study to determine the level of cortical excitability and to map the trajectory of neuronal recovery from cortical damage or disease. Square-wave mechanical or electrical stimuli are often used in these studies, but a characterization of sensory-evoked response properties to square-waves with distinct fundamental frequencies but overlapping harmonics has not been performed. To distinguish between somatic stimuli, the primary somatosensory cortex must be able to represent distinct stimuli with unique patterns of activity, even if they have overlapping features. Thus, mechanical square-wave stimulation was used in conjunction with regional and cellular imaging to examine regional and cellular response properties evoked by different frequencies of stimulation. Flavoprotein autofluorescence imaging was used to map the somatosensory cortex of anaesthetized C57BL/6 mice, and in vivo two-photon Ca2+ imaging was used to define patterns of neuronal activation during mechanical square-wave stimulation of the contralateral forelimb or hindlimb at various frequencies (3, 10, 100, 200, and 300 Hz). The data revealed that neurons within the limb associated somatosensory cortex responding to various frequencies of square-wave stimuli exhibit stimulus-specific patterns of activity. Subsets of neurons were found to have sensory-evoked activity that is either primarily responsive to single stimulus frequencies or broadly responsive to multiple frequencies of limb stimulation. High frequency stimuli were shown to elicit more population activity, with a greater percentage of the population responding and greater percentage of cells with high amplitude responses. Stimulus-evoked cell-cell correlations within these neuronal networks varied as a function of frequency of stimulation, such that each stimulus elicited a distinct pattern that was more consistent across multiple trials of the same stimulus compared to trials at different frequencies of stimulation. The variation in cortical response to different square-wave stimuli can thus be represented by the population pattern of supra-threshold Ca2+ transients, the magnitude and temporal properties of the evoked activity, and the structure of the stimulus-evoked correlation between neurons.

Highlights

Investigations of how the somatosensory cortex responds to artificial forms of stimulation, and to what extent patterns of regional and cellular activity can distinguish between distinct stimuli with overlapping characteristics, is important in interpreting studies that use such stimuli to elicit cortical responses in the healthy brain, or as a measure of cortical excitability and plasticity during disease or after injury [1,2,3,4,5]
While square-wave and sinusoidal patterns of mechanical limb stimulation have been used in studies after cortical injury, and those studies identified deficits in the amplitude and fidelity of evoked activity after damage to the somatosensory cortex, a more detailed investigation across multiple frequencies and intensities of stimulation has not been performed with mechanical square-wave stimuli
The present study investigated the sensory-evoked Ca2+ response in the primary somatosensory cortex of mice to different frequencies and durations of mechanical squarewave limb stimulation using piezoelectric bending actuators

Summary

Introduction

Investigations of how the somatosensory cortex responds to artificial forms of stimulation, and to what extent patterns of regional and cellular activity can distinguish between distinct stimuli with overlapping characteristics, is important in interpreting studies that use such stimuli to elicit cortical responses in the healthy brain, or as a measure of cortical excitability and plasticity during disease or after injury [1,2,3,4,5]. Artificial stimuli used for rodent research that may be thought of as relatively simple in comparison to naturalistic stimuli or movements, such as limb oscillation through a single axis of motion, still likely result in the generation of complex multimodal sensory information in the periphery These multimodal signals may arise from activation of mechanoreceptors at the stimulator attachment site, the propagation of vibration at the fundamental and harmonic frequencies to distal Pacinian corpuscles closely associated with joints and bones [23], the activation of proprioceptive receptors within the muscles and joints, and to a large potential array of signals arising due to deflections of hair follicle associated mechanoreceptors (for review, see [24]). Particular subsets of cutaneous and proprioceptive mechanoreceptors have long been known in non-human primates to be tuned to characteristics such as stimulus intensity, frequency and receptive field location [7,8,25,26,27,28], the harmonics resulting from square-wave oscillation of the entire forelimb or hindlimb of mice would likely elicit highly mixed activity in mechanoreceptor populations, with weighted preference to mechanoreceptor populations most sensitive to the particular frequencies and biomechanics of the stimulus

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