Differential Involvement of Three Brain Regions during Mouse Skill Learning

Abstract

Human skill learning is marked by a gradual decrease in reaction time (RT) and errors as the skill is acquired. To better understand the influence of brain areas thought to be involved in skill learning, we trained mice to associate visual-spatial cues with specific motor behaviors for a water reward. Task acquisition occurred over weeks and performance approximated a power function as often found with human skill learning. Using optogenetics we suppressed the primary visual cortex (V1), anterior cingulate cortex (ACC), or dorsal hippocampus (dHC) on 20% of trials at different stages of learning. Intermittent suppression of the V1 greatly reduced task performance on suppressed trials across multiple stages but did not change the overall rate of learning. In accord with some recent models of skill learning, ACC suppression produced higher error rates on suppressed trials throughout learning the skill, with effects intensifying in the later stages. This would suggest that cognitive influences mediated by the anterior cingulate continue throughout learning. Suppression of the hippocampus only modestly affected performance, with largely similar effects seen across stages. These results indicate different degrees of V1, ACC, and dHC involvement in acquisition and performance of this visual-spatial task and that the structures operate in parallel, and not in series, across learning stages.

Interpreting the role of the striatum during multiple phases of motor learning

“…project to the striatum, especially the NAc 40 , and their activity has been shown to correlate with motor learning [138][139][140] . Similarly to the striatum, the limbic system is activated at various phases of motor learning and can influence the acquisition of motor skill via direct and indirect connections to the striatum (Figure 1) 4,138,141 .…”

Decision Making as a Learned Skill in Mice and Humans

“…In human skill learning, changes in performance and reaction time have been described as fitting a power function ( Fitts and Posner, 1967 ; Anderson, 1982 ). Similarly, we found that in mice trained in a 2-alternative forced choice (2-AFC) task, reaction time decreased and accuracy increased roughly as a power function relative to training time ( Weible et al, 2019 ). In our study, we utilized optogenetics to enable suppression of activity in excitatory neurons through activation of inhibitory parvalbumin-positive interneurons (PV-INs).…”

“…Suppression of ACC activity reduced accuracy across multiple stages of training. Suppression of dHC more selectively impacted performance late in training (adapted from Weible et al, 2019 ).…”

“…The posterior pathway linking the HC and the parietal lobe via entorhinal cortex represents the evolutionarily old pathway for navigation in rodents and serves as the source of spontaneous retrieval of unwanted thoughts regardless of content in humans. The rodent work summarized in this article is limited to the relatively simple incompatible reaction time task we used ( Weible et al, 2019 ). This limitation is reduced somewhat by the similar conclusion from more complex human studies involving categorization or the think no-think procedure.…”

Neurotransmitters, Cell Types, and Circuit Mechanisms of Motor Skill Learning and Clinical Applications

“…In the mouse cerebellum, the memory of oculomotor learning could be artificially implanted by optogenetic stimulation of the Purkinje cells or the climbing fibers (178). Optogenetic suppressions of different brain regions at different stages of skill training enable us to better understand when and how each region gets involved into learning: (1) primary visual cortex (V1) suppression could reduce accuracy across all training stages; (2) anterior cingulate cortex (ACC) suppression decreased accuracy during learning; and (3) hippocampus suppression affected learning more mildly (179). The combination of optogenetics, in vivo imaging, and pharmacological manipulations revealed that sensory experience transduced through the granule neuron pathway could orchestrate motor learning through remodeling chromatin architecture and neural circuit activity in the anterior dorsal cerebellar vermis of mouse brain (180).…”