Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation.

Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.

Dopaminergic modulation of receptive fields in rat sensorimotor cortex.

Dopaminergic projections to primary sensorimotor cortex (SMC) have been described anatomically, but their functional role is unknown. The objective here was to characterize how dopamine modulates the somatosensory evoked potential (SEP) and its receptive field in SMC. SEPs were evoked by median and tibial nerve stimulation and recorded using thin-film multielectrode arrays implanted epidurally over the caudal sensorimotor cortex of rats. SEP amplitudes and receptive fields were measured before and after intracortical injection of a D1- (SCH 23390) or a D2-receptor antagonist (raclopride). Both increased maximum SEP amplitudes by 107.5% and 82.1%, respectively (p<0.01), while vehicle application had no effect (5.9% change). SEP latencies and receptive fields remained unchanged. Dopamine antagonists increase the excitability of sensorimotor cortex to afferent signals. Dopamine, therefore, expectedly reduces SMC excitability thereby improving sensory signal-to-noise ratio. Dopaminergic modulation may render SMC circuitry more effective in processing sensory information from different sources.

Thin-film epidural microelectrode arrays for somatosensory and motor cortex mapping in rat.

Assessments of somatosensory and motor cortical somatotopy in vivo can provide important information on sensorimotor physiology. Here, novel polyimide-based thin-film microelectrode arrays (72 contacts) implanted epidurally, were used for recording of somatosensory evoked potentials (SEPs) and somatosensory cortex somatotopic maps of the rat. The objective was to evaluate this method with respect to precision and reliability. SEPs and somatosensory maps were measured twice within one session and again after 8 days of rest. Additionally, motor cortex maps were acquired once to assess the spatial relationship between somatosensory and motor representations of fore- and hindlimb within one individual. Somatosensory maps were well reproduced within and between sessions. SEP amplitudes and latencies were highly reliable within one recording session (combined intraclass correlation 90.5%), but less so between sessions (21.0%). Somatosensory map geometry was stable within and between sessions. For the forelimb the somatosensory representation had a 30% overlap with the corresponding motor area. No significant overlap was found for the hindlimb. No evidence for cortical injury was found on histology (Nissl). Thin-film epidural electrode array technology enables a detailed assessment of sensorimotor cortex physiology in vivo and can be used in longitudinal designs enabling studies of learning and plasticity processes.