The Globus Pallidus Pars Interna in Goal-Oriented and Routine Behaviors: Resolving a Long-Standing Paradox

International audienceBackground: There is an apparent contradiction between experimental data showing that the basal ganglia are involved in goal-oriented and routine behaviors and clinical observations. Lesion or disruption by deep brain stimulation of the globus pallidus interna has been used for various therapeutic purposes ranging from the improvement of dystonia to the treatment of Tourette's syndrome. None of these approaches has reported any severe impairment in goal-oriented or automatic movement. Method: To solve this conundrum, we trained 2 monkeys to perform a variant of a 2-armed bandit-task (with different reward contingencies). In the latter we alternated blocks of trials with choices between familiar rewarded targets that elicit routine behavior and blocks with novel pairs of targets that require an intentional learning process. Results: Bilateral inactivation of the globus pallidus interna, by injection of muscimol, prevents animals from learning new contingencies while performance remains intact, although slower for the familiar stimuli. We replicate in silico these data by adding lateral competition and Hebbian learning in the cortical layer of the theoretical model of the cortex–basal ganglia loop that provided the framework of our experimental approach. Conclusion: The basal ganglia play a critical role in the deliberative process that underlies learning but are not necessary for the expression of routine movements. Our approach predicts that after pallidotomy or during stimulation, patients should have difficulty with complex decision-making processes or learning new goal-oriented behaviors. V C 2016 Movement Disorder Societ

In vivo electrophysiological validation of DREADD‐based modulation of pallidal neurons in the non‐human primate

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Easy rider: monkeys learn to drive a wheelchair to navigate through a complex maze.

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations

Maze and task description.

<p>The maze consists in a 3×3rooms. The rooms are not segregated by a physical door and only the room where the monkey is currently in is illuminated. The starting position for the monkey (represented by the graphic of a monkey in a wheelchair) and the reward position (represented by the drop of water) remain the same throughout a block of trials, but are modified for each block. The monkey must learn to navigate a specific path to reach the reward. After they reach the criterion (3 or 10 corrects trials in short or long training blocks respectively) animals enter a probe phase. (A; C; E; G) Acquisition phases for specific probe types, (B) Type 1 probe test (triple dissociation|, (D) Type 2 probe test (cue versus place), (F) Type 3 probe test (place versus direction), (H) Type 4 probe test (direction versus cue).</p

Adapted powered wheelchair.

<p>(A) The monkey sits in an electric powered wheelchair that is controlled by a joystick under the right hand, (B) the monkey learned to follow a route from room to room by choosing the one door in each room with one symbol illuminated.</p

Monkeys' learning comparison.

<p>Monkeys performances (p values of the trials and errors to reach the two criteria) and their evolution (early versus late) were compared by using a One Way Repeated Measures ANOVA test.</p

Learning rate improved with training.

<p>Early training comprised the first 10(A–B and C–D respectively) there was a significant decrease in the number of trials to reach the criterion and of the number of errors. (* p<0.05 for pooled monkeys' performances).</p

Monkeys' choices comparison.

<p>Choices distribution had been compared between monkeys (p value).</p

Probe Tests results: Comparisons of strategies used in probe tests in the 4 different tasks.

<p>(A) Type 1, triple dissociation, (B) Type 2, place versus direction probe; (C) Type 3, place versus cue and (D) Type 4, cue versus direction (*p<0.05).</p

Easy Rider: Monkeys Learn to Drive a Wheelchair to Navigate through a Complex Maze

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