Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain

Abstract

Physical exercise promotes motor skill learning in normal individuals and those with neurological disorders but its mechanism of action is unclear. We find that one week of voluntary wheel running enhances the acquisition of motor skills in normal adult mice. One week of running also induces switching from ACh to GABA expression in neurons in the caudal pedunculopontine nucleus (cPPN). Consistent with regulation of motor skills, we show that the switching neurons make projections to the substantia nigra (SN), ventral tegmental area (VTA) and ventrolateral-ventromedial nuclei of the thalamus (VL-VM). Use of viral vectors to override transmitter switching blocks the beneficial effect of running on motor skill learning. We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders.

Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice

“…The observation of the relatively late differentiation of Ia-PNs led us to investigate whether the identity of Ia-PN subtypes remains versatile in adult life following changes in sensorimotor activity. To test this, we used motor skill learning that has been intensely studied in the realm of neuroplasticity 34 – 36 . More specifically, we assessed the composition of Ia-PN subtypes in DRG of wild-type mice with access to free-wheel running for 4 weeks, which is known to induce experience-dependent plasticity in the central nervous system 36 – 38 .…”

“…To test this, we used motor skill learning that has been intensely studied in the realm of neuroplasticity 34 – 36 . More specifically, we assessed the composition of Ia-PN subtypes in DRG of wild-type mice with access to free-wheel running for 4 weeks, which is known to induce experience-dependent plasticity in the central nervous system 36 – 38 . During the entire training period, running (Run) and sedentary (Sed) mice were single housed in enhanced environment: large rat cage, wooden sticks, nest and free access to a running wheel (Fig.…”

Examination of cortically projecting cholinergic neurons following exercise and environmental intervention in a rodent model of fetal alcohol spectrum disorders

“…Indeed, ChAT + neurons in the peripheral and central nervous systems may become GABAergic or glutamatergic. It is suggested that cholinergic phenotypic plasticity is necessary for fine-tuning of movement and procedural learning across the lifespan as well as transitioning between physiological states like the "fight-or-flight" response and rest (Li & Spitzer, 2020;Spitzer, 2017). It is possible that AE during the brain growth spurt leads to a neurotransmitter switch, altering the phenotype of neurons in NBM in adulthood.…”

“…Interestingly, our results suggest that cholinergic neurons in NBM are resistant to phenotypic change resulting from either behavioral intervention tested in adolescence-adulthood. Specific cholinergic nuclei are more amenable to phenotypic alteration in adolescenceadulthood than others, namely those in the midbrain, brainstem, and septum (Hall & Savage, 2016;Li & Spitzer, 2020;Spitzer, 2017). Phenotypic plasticity of cholinergic neurons in NBM is under explored.…”

Independent respiratory and locomotor rhythms in running mice

“…Bar-graphs to the right are distribution histograms of the phases of inspiratory bursts and the same reference limb for all n events from 7 animals. a paradigm known to enhance locomotor skills (Chen et al, 2019;Li and Spitzer, 2020). Animals were then implanted with EMG electrodes and challenged to treadmill running at the 3 speeds on a level or inclined treadmill as well as to the air puff driven gallop as performed above.…”