Source Paper
Dopamine in Motor Cortex Is Necessary for Skill Learning and Synaptic Plasticity
Katiuska Molina-Luna, Ana Pekanovic, Sebastian Röhrich, Benjamin Hertler, Maximilian Schubring-Giese et al.
PLoS ONE •
Source Paper
Katiuska Molina-Luna, Ana Pekanovic, Sebastian Röhrich, Benjamin Hertler, Maximilian Schubring-Giese et al.
PLoS ONE •
Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill.
Objective: To assess motor skill learning and forelimb reaching performance in rats through a trained reaching task involving door opening and food pellet retrieval
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Animals are food-restricted for 24 hours before first pre-training session. During pre-training, rats learn to open the motorized sliding door by nose-poking the light sensor in the rear wall. Door opening provides access to one food pellet located on a small horizontal board outside the cage.
Note: Food restriction occurs only before first pre-training session. During training, animals are kept slightly over initial weight by providing 50 mg/kg standard lab diet after each session. Water given ad libitum.
“Animals were food-restricted for 24 hr before the first pre-training session. Animals were first pre-trained for five days learning to open the motorized sliding door that covered the front window, by nose-poking the sensor in the rear”
During pre-training, pellets are retrieved by tongue from the horizontal board. Upon retrieval, the pellet is automatically replaced by the pellet dispenser.
Note: This establishes the association between door opening and food reward before requiring skilled reaching
“During pre-training pellets were retrieved by tongue. Upon retrieval the pellet was automatically replaced by a pellet dispenser”
Pre-training is followed by 6-15 days of motor skill training. The board is removed and the pellet is placed on a vertical post 1.5 cm away from the window, requiring forelimb retrieval. The first skill training session determines forelimb preference and consists of 50 door openings (trials).
Note: Forelimb preference determination is necessary before surgical instrumentation of the hemisphere contralateral to the preferred limb
“motor skill training that was initiated by removing the board and placing the pellet on a vertical post 1.5 cm away from the window. The first skill training session was to determine forelimb preference and consisted of 50 door openings”
After determining forelimb preference, the pedestal is shifted to one side of the window to allow reaching with the preferred limb only, contralateral to the hemisphere injected or instrumented for drug injection.
Note: This ensures reaching is performed with the preferred forelimb only
“the pedestal was shifted to one side of the window to allow reaching with the preferred limb only, contralateral to the hemisphere injected or instrumented for drug injection”
All subsequent training sessions after preference determination consist of 100 trials (door openings). Sessions are performed at the beginning of the dark phase. Each trial involves the rat performing a forelimb extension to target, pronation, paw opening, grasping motion, forelimb retention combined with supination to bring pellet to mouth.
Note: Sessions occur at beginning of dark phase. Daily sessions involve 115.8±5.7 forelimb movements (mean±SEM), automatically sensed by motion sensor
“All subsequent sessions consisted of 100 trials. Training sessions were performed at the beginning of the dark phase. Daily training sessions consisted of 100 trials (= door openings), involved 115.8±5.7 forelimb movements, mean±SEM, automatically sensed by a sensor between cage wall and pedestal) and lasted 24.8±0.5 min, mean±SEM”
Each reaching trial is scored as 'successful' (reach, grasp and retrieve) or 'unsuccessful' (pellet pushed off pedestal or dropped during retraction). Success rate is calculated as the ratio of successful trials to total trials per session (100).
Note: Rats mainly improve target reach and grasp elements during training
“Each reaching trial was scored as 'successful' (reach, grasp and retrieve) or 'unsuccessful' (pellet pushed off pedestal or dropped during retraction). The success rate was defined as the ratio of the number of successful trials and the total number of trials per session, i.e. 100”
The latency between pellet removal and subsequent door opening is used as an index of motivation.
“The latency between pellet removal and subsequent door opening was used as an index of motivation”
Adult male rats raised in animal facility, housed individually on 12/12-hr light/dark cycle (light on: 3am, off: 3pm)