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Role of dopaminergic projections from VTA to primary motor cortex for motor skill learning: explicit versus implicit rewards

English title Role of dopaminergic projections from VTA to primary motor cortex for motor skill learning: explicit versus implicit rewards
Applicant Luft Andreas
Number 135471
Funding scheme Project funding (Div. I-III)
Research institution Neurologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.06.2011 - 31.12.2014
Approved amount 375'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Neurology, Psychiatry

Keywords (5)

motor learning; dopamine; reward; recovery; rehabilitation

Lay Summary (German)

Lead
Lay summary
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Motorisches Lernen ist eine zentrale Fähigkeit des Gehirns, die Anpassungen von Bewegungen an die Umwelt ermöglicht. Lernvorgänge spielen auch bei der Erholung von Bewegungen nach Hirnverletzungen eine Rolle. Im Tiermodell haben wir eine Verbindung zwischen einem Hirnareal, das für motorisches Lernen wichtig ist (der motorischen Hirnrinde) und einer Region, die Belohnungsreize kodiert, gefunden. Diese Verbindung ist für motorisches Lernen essentiell, denn sie erlaubt Veränderungen der Synapsenstärke in der motorischen Hirnrinde, somit das Abspeichern von neuen Bewegungen. Im aktuellen Projekt wollen wir untersuchen, welche Belohnungsreize diesen Prozess unterstützen und wie wir motorisches Lernen durch gezielte Stimulation dieser Zellen verbessern können. Wir verwenden dazu ein Tiermodell für motorisches Lernen, in dem Ratten mit einer Pfote ein kleines Nahrungskügelchen greifen müssen. Mittels elektrophysiologischen Mess- und Stimulationsverfahren wollen wir untersuchen, wann die „Belohnungsneurone“ feuern und wie man sie beeinflussen kann.

Die gewonnenen Erkenntnisse könnten Grundlage für die Entwicklung neuartiger Therapien für die Rehabilitationsbehandlung nach Hirnverletzungen sein.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.
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.
Temporal course of gene expression during motor memory formation in primary motor cortex of rats.
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.
The effect of surgery and intracerebral injections on motor skill learning in rats: results from a database analysis.
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.
Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning
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.
Sub-processes of motor learning revealed by a robotic manipulandum for rodents.
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.
Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.
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.
Dopamine promotes motor cortex plasticity and motor skill learning via PLC activation.
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, 1.
Topography and collateralization of dopaminergic projections to primary motor cortex in rats.
Hosp Jonas, Nolan Helen E, Luft Andreas R, Topography and collateralization of dopaminergic projections to primary motor cortex in rats., in Exp Brain Res, 1-11.

Collaboration

Group / person Country
Types of collaboration
Johns Hopkins Universität, Baltimore United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Society for Neuroscience, annual meeting 2012 Poster Functional characterization of VTA input to primary motor cortex in the rat 13.10.2012 New Orleans, USA, United States of America Leemburg Susan; Luft Andreas;


Self-organised

Title Date Place
Neurorehabilitation and plasticity 07.06.2012 Zurich, Switzerland

Knowledge transfer events



Self-organised

Title Date Place
Schlaganfallrehabiliation, Forum USZ 19.10.2016 UniversitätsSpital Zürich, Switzerland
Schlaganfallrehabilitation, Stroke Day 30.10.2015 UniversitätsSpital Zürich, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Zurich Brain Fair German-speaking Switzerland 2012

Abstract

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 [1], such a therapy is conceivable but requires a thorough understanding of the physiology to fully exploit its potential.
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