Cortical dopaminergic transmission and motor learning: Studies in a rodent motor learning model

Abstract

Motor learning is thought to play a crucial role for the adaptation of organisms to their environment. It has been shown in animal models as well as in humans, that the motor cortex is a key structure for movement learning. In this PhD thesis, electrophysiological and pharmacological approaches were used to investigate motor skill acquisition and motor memory consolidation in a rodent model from two different aspects: (1) learning effects in structural representation change and (2) mediation of skill acquisition by aminergic neurotransmission. In both studies a surface electrode array was used to stimulate motor cortex and produce maps of cortical representations of different body areas and specifically to identify forelimb clusters. In the first study, the change in forelimb representation was followed over time in animals that were subjected to a forelimb reach training paradighm and was compared to animals that exercised the arm, but did not acquire the reaching skill. In the first study, differences between activity (exercise) and learning-dependent motor map representations were demonstrated as modeled by muscle twitches in response to electrical stimulation. This study demonstrated that structural changes in the motor cortex mediate the acquisition of skills but not the storage of the motor memory. The second study was based on previous findings of our group that dopamine receptors are up-regulated during learning. Dopamine receptor antagonists were intracortically (i.c.) administered to rats that were trained in the reaching task and the effects of transient vs. permanent dopamine depletion were compared. Furthermore, animals that were permanently depleted of dopaminergic terminals in the motor cortex were administered dopamine i.c. by means of an osmotic pump. The learning capacity in these animals was recovered and reached levels comparable to those of controls. Overall, the thesis highlights the role of structural plasticity in motor cortex for skill acquisition and the importance of dopaminergic neurotransmission for the functional capacity of M1 neurons.

Motor learning is thought to play a crucial role for the adaptation of organisms to their environment. It has been shown in animal models as well as in humans, that the motor cortex is a key structure for movement learning. In this PhD thesis, electrophysiological and pharmacological approaches were used to investigate motor skill acquisition and motor memory consolidation in a rodent model from two different aspects: (1) learning effects in structural representation change and (2) mediation of skill acquisition by aminergic neurotransmission. In both studies a surface electrode array was used to stimulate motor cortex and produce maps of cortical representations of different body areas and specifically to identify forelimb clusters. In the first study, the change in forelimb representation was followed over time in animals that were subjected to a forelimb reach training paradighm and was compared to animals that exercised the arm, but did not acquire the reaching skill. In the first study, differences between activity (exercise) and learning-dependent motor map representations were demonstrated as modeled by muscle twitches in response to electrical stimulation. This study demonstrated that structural changes in the motor cortex mediate the acquisition of skills but not the storage of the motor memory. The second study was based on previous findings of our group that dopamine receptors are up-regulated during learning. Dopamine receptor antagonists were intracortically (i.c.) administered to rats that were trained in the reaching task and the effects of transient vs. permanent dopamine depletion were compared. Furthermore, animals that were permanently depleted of dopaminergic terminals in the motor cortex were administered dopamine i.c. by means of an osmotic pump. The learning capacity in these animals was recovered and reached levels comparable to those of controls. Overall, the thesis highlights the role of structural plasticity in motor cortex for skill acquisition and the importance of dopaminergic neurotransmission for the functional capacity of M1 neurons.