Role of Monkey Cerebellar Nuclei in Skill for Sequential Movement(順序運動の記憶における小脳核の役割)

Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience—a process that may be facilitated by early electrical coupling between neuronal subsets—and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.

The emergence of functional microcircuits in visual cortex

Movement is the way by which we interact with the world. This often only becomes apparent in case of motor apparatus dysfunction such as in neurological conditions of movement disorders highlighting how seemingly effortless the nervous system performs movement generation. Moreover, many animal species are capable of moving in a stunningly vast array of ways which underscores the requirement for sophisticated degrees of control. Furthering insight into motor control therefore underlies a fascination for the complexity of the nervous system as well as a substantial medical interest. 

To understand the role of motor cortex, a high-level brain area, in the control of sensory guided movements, I first trained head-fixed mice to navigate a two-dimensional virtual reality environment with occasional perturbations of the expected visual feedback. During learning, I used activity manipulation by optogenetics to understand the involvement of motor cortex in active behavior. Additionally, using activity recording by two-photon calcium imaging in genetically defined projection cell types, I probed for neuronal activity patterns potentially mediating this behavior. 

I found that motor cortex is a critical brain area for execution of visually guided behavior which mediates the learning of the navigation task. Activity recordings yielded a myriad of neuronal responses correlating with the mouse behavior, often multiplexed within the same cell. Critically, activity patterns during spontaneously executed, expected behavior differed from those during reactive behavior induced by unexpected perturbations of the virtual environment. These differences in neuronal activation could underlie the behavioral effects observed during optogenetic activity manipulations. Finally, I observed cell type-specific, learning-related changes. Notably, presumed motor output mediating cells increased in activation as mice became more efficient at executing the task. 

I discuss these findings in the context of recent theories of brain function suggesting that the nervous system not only predicts the dynamics of the subject’s environment but also generates movement in reaction to future predicted body states.

Role of mouse motor cortex in the behavioral response to unpredictable visual feedback

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Role of mouse motor cortex in the behavioral response to unpredictable visual feedback