Profiling the transcallosal response of rat motor cortex evoked by contralateral optogenetic stimulation of glutamatergic cortical neurons

Abstract

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1-M1 interactions in rats. In male rats, we optogenetically stimulated glutamatergic neurons in right M1 and recorded the transcallosally evoked potential with chronically implanted electrodes in contralateral left M1 during dexmedetomidine anesthesia. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. Median N1 latencies remained stable, once stimulation elicited a reliable N1 peak and did not display a systematic shortening with increasing stimulation intensity or duration. Optogenetically stimulated glutamatergic neurons in M1 can reliably evoke a transcallosal response in anesthetized rats and can be used to characterize the relationship between "stimulation dose" and "response magnitude" (i.e., the gain function) of transcallosal M1-to-M1 glutamatergic connections. Detailed knowledge of the stimulus-response relationship is needed to optimize the efficacy of optogenetic stimulation. Since transcallosal M1-M1 interactions can also be probed non-invasively with transcranial magnetic stimulation in humans, our optogenetic stimulation approach bears translational potential for studying how unilateral M1 stimulation can induce interhemispheric plasticity.

Dose-response relationship between the variables of unilateral optogenetic stimulation and transcallosal evoked responses in rat motor cortex

“…We also wish to thank Søren Ellegaard for helping with the electrophysiological setup and Kristoffer H. Madsen for valuable suggestions and inputs with regards to statistics. An earlier version of this manuscript have previously appeared online in a preprint on BioRxiv (Skoven et al, 2021) and part of the data has been presented at a poster session by CSS at the Society for Neuroscience (SfN) -Neuroscience Meeting 2019 (Chicago, IL, United States). The conference abstract was submitted with the following title: "Transcallosal functional connectivity between motor cortices in rats probed with unilateral optogenetic stimulation of glutamatergic neurons" by the same authors.…”

Exploring white matter dynamics and morphology through interactive numerical phantoms: The White Matter Generator

“…Moreover, there is a relation between the morphology and function of the individual neurons. Morphological factors that affect the axonal conduction velocity include the axon diameter [6] [7], the myelin sheath thickness [8], and the length and spacing of nodes of Ranvier [9]. Quantifying the morphology of axons and brain white matter in general is thus of great interest for enhancing our understanding of various brain processes, and can provide a potential biomarker of disease.…”