Cholinergic modulation of interhemispheric inhibition in the mouse motor cortex

Abstract

Interhemispheric inhibition (IHI) of the homotopic motor cortex is believed to be effective for accurate unilateral motor function. However, the cellular mechanisms underlying IHI during unilateral motor behavior remain unclear. Furthermore, the impact of the neuromodulator acetylcholine (ACh) on IHI and the associated cellular mechanisms are not well understood. To address this knowledge gap, we conducted recordings of neuronal activity from the bilateral motor cortex of mice during the paw-reaching task. Subsequently, we analyzed interhemispheric spike correlation at the cell-pair level, classifying putative cell types to explore the underlying cellular circuitry mechanisms of IHI. We found a cell-type pair-specific enhancement of the interhemispheric spike correlation when the mice were engaged in the reaching task. We also found that the interhemispheric spike correlation was modulated by pharmacological ACh manipulation. The local field responses to contralateral excitation differed along the cortical depths, and muscarinic receptor antagonism enhanced the inhibitory component of the field response in deep layers. The muscarinic subtype M2 receptor is predominantly expressed in deep cortical neurons, including GABAergic interneurons. These results suggest that GABAergic interneurons expressing muscarinic receptors in deep layers mediate the neuromodulation of IHI in the homotopic motor cortex.

Younger adult brain utilizes interhemispheric strategy of recruiting ipsilateral dorsal premotor cortex for complex finger movement, but not aging brain

“…For example, when the brain or the spinal cord is injured, the brain often recruits normally-underused cortical sensorimotor areas (dorsal premotor cortex [PMd], primary motor cortex [M1], primary somatosensory cortex [S1], and superior parietal cortex of Area 2) during ipsilateral hand/finger movements (Grefkes & Fink, 2020; Hoy et al, 2004; Jang et al, 2004; Lotze et al, 2006; Ward et al, 2008). Recently, animal studies have suggested that such recruitment of ipsilateral sensorimotor cortices is mediated by disinhibition of interhemispheric inhibition between the left and right motor cortices (Yamaguchi et al, 2023) by acetylcholine modulating GABAergic interneurons (Handa et al, 2024). In stroke patients, jamming transcranial magnetic stimulation (TMS) to the ipsilateral sensorimotor cortices disrupts finger movement, especially the TMS to the PMd disrupts the movement more than when it is applied to the M1 and the superior parietal lobule (Lotze et al, 2006).…”

Theoretical proposal for restoration of hand motor function utilizing plasticity of motor-cortical interhemispheric interaction

“…In other words, this bilateral mode is the first step toward restoring motor function (Grefkes and Fink, 2020). Recent animal studies have suggested that this bilaterally active mode is caused by disinhibition of interhemispheric inhibition between the left and right motor cortices (Yamaguchi et al, 2023) by acetylcholine modulating GABAergic interneurons (Handa et al, 2024).…”