Hand preference switching with intra- and inter-hemispheric cholinergic modulation

Lateralization of motor skills such as hand preference is a common trait across various species, including humans and rodents. It's well known that humans can alter their dominant hand through training, a process often associated with psychological stress and the potential for developmental issues, including language impairments. Yet, the neural mechanisms underlying the hand switching remain largely obscure. Our research delves into this phenomenon in mice, revealing that they can also alter their hand preference via corrective training. We focused on the basal forebrain's cholinergic system, pivotal for motor function and known for its hemisphere-specific cholinergic projection. We hypothesize that cholinergic pathways within each hemisphere are crucial for the modulation of hand preference. We found that the unilateral depletion of cholinergic neurons in the basal forebrain with immunotoxin (Anti-Tac(Fv)-PE38; Okada et al., 2014; 2021) interrupted the switching of mice hand preference contralaterally. In a parallel approach, optogenetic suppression of cholinergic pathways in the primary motor cortex led to comparable results, indicating that the cholinergic activity is essential for the regulation of hand switching. In addition, unilateral activation of cholinergic neurons using the DREADD technique also obstructed the switching of hand preference ipsilaterally, indicating that the cholinergic control exerts modulatory influence on the contralateral hemisphere. These findings suggest that the competitive relationship between the cholinergic systems across hemispheres contribute to hand preference switching.