motor learning; dopamine; reward; recovery; rehabilitation
Schubring-Giese Maximilian, Leemburg Susan, Luft Andreas Rüdiger, Hosp Jonas Aurel (2016), Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats., in PloS one
, 11(6), 0157859-0157859.
Hertler B, Buitrago M M, Luft A R, Hosp J A (2016), Temporal course of gene expression during motor memory formation in primary motor cortex of rats., in Neurobiology of learning and memory
, 136, 105-115.
Schubring-Giese M, Luft A R, Hosp J A (2016), The effect of surgery and intracerebral injections on motor skill learning in rats: results from a database analysis., in Behavioural brain research
, 313, 310-4.
Gloor C, Luft AR, Hosp JA (2015), Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning, in Neurobiol Learn Mem
, 125, 189-194.
Lambercy O, M Schubring-Giese, B Vigaru, R Gassert, A R Luft, J A Hosp (2014), Sub-processes of motor learning revealed by a robotic manipulandum for rodents., in Behavioural brain research
, 278C, 569-576.
Hosp J A, Mann S, Wegenast-Braun B M, Calhoun M E, Luft A R (2013), Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning., in Neuroscience
, 250, 557-64.
Rioult-Pedotti Mengia, Pekanovic Anna, Osei Atiemo Clement, Marshall C, Luft Andreas R, Dopamine promotes motor cortex plasticity and motor skill learning via PLC activation., in PLOS One
Hosp Jonas, Nolan Helen E, Luft Andreas R, Topography and collateralization of dopaminergic projections to primary motor cortex in rats., in Exp Brain Res
Motor skill learning is a unique ability of the brain because it leads to an enormously stable and permanent form of memory. The mechanisms of motor skill learning are likely similar to those of motor recovery, namely the plasticity of central motor networks. Therefore skill learning paradigms can serve as a model to study the foundations of brain recovery. We previously identified a dopaminergic projection from ventral tegmental area (VTA) to primary motor cortex (M1) that enables skill learning and motor cortical synaptic plasticity in the form of long term potentiation (LTP) in the rat. Potentially this pathway can be used therapeutically to boost M1 plasticity and thereby movement recovery after brain injury. Before any informed clinical translation is feasible, a thorough understanding of the functional role of the VTA-to-M1 projection is imperative. The objective of the current proposal is to elucidate this functional role. We investigate two possibilities: The VTA-to-M1 projections relays similar reward signals like the ones VTA sends to nucleus accumbens and prefrontal cortex. However, these signals are dependent on reward expectancy which applies to associative learning but is difficult to translate to processes like the gradual acquisition of a motor skill. Alternatively, the projections encodes something else, which could either be a distinct behavioral event, e.g. a completion of the movement sequence, leading to a phasic VTA burst, or it could be a continuous factor that augments learning by increasing tonic dopaminergic discharge of VTA-to-M1 neurons. In Aims 1 and 2, we will investigate whether tonic or phasic VTA firing leads to DA (DA) release in M1 and which mode of release supports LTP in layer II/III - a form of synaptic plasticity involved in motor skill learning. In Aim 3, if phasic DA release is more effective, we will search for the behavioral event during motor skill training that triggers DA release in M1. Alternatively, if the tonic VTA firing mode prevails, we will seek factors that are able to modulate this drive: motivation, reward, sleep, stress and/or exercise leading to neurotrophic factor expression.The knowledge obtained with the proposed experiments will shed light on basic and so far unexplored mechanisms of motor skill learning. If the findings also hold in models of recovery in future experiments, they may lay the ground for a novel therapeutic approach that uses DA augmentation to boost training-related recovery after brain injury, e.g. by delivering appropriate feedback, by deep-brain stimulation of VTA or application of dopaminergic agents. Considering that empirical data provides preliminary evidence that dopaminergic modulation is effective in rehabilitation , such a therapy is conceivable but requires a thorough understanding of the physiology to fully exploit its potential.