Abstract
The cerebellum is most renowned for its role in sensorimotor control and coordination, but a growing number of anatomical and physiological studies are demonstrating its deep involvement in cognitive and emotional functions. Recently, the development and refinement of optogenetic techniques boosted research in the cerebellar field and, impressively, revolutionized the methodological approach and endowed the investigations with entirely new capabilities. This translated into a significant improvement in the data acquired for sensorimotor tests, allowing one to correlate single-cell activity with motor behavior to the extent of determining the role of single neuronal types and single connection pathways in controlling precise aspects of movement kinematics. These levels of specificity in correlating neuronal activity to behavior could not be achieved in the past, when electrical and pharmacological stimulations were the only available experimental tools. The application of optogenetics to the investigation of the cerebellar role in higher-order and cognitive functions, which involves a high degree of connectivity with multiple brain areas, has been even more significant. It is possible that, in this field, optogenetics has changed the game, and the number of investigations using optogenetics to study the cerebellar role in non-sensorimotor functions in awake animals is growing. The main issues addressed by these studies are the cerebellar role in epilepsy (through connections to the hippocampus and the temporal lobe), schizophrenia and cognition, working memory for decision making, and social behavior. It is also worth noting that optogenetics opened a new perspective for cerebellar neurostimulation in patients (e.g., for epilepsy treatment and stroke rehabilitation), promising unprecedented specificity in the targeted pathways that could be either activated or inhibited.
Highlights
The first reports on cerebellar structure and the first hypothesis on function pointed out its high degree of connectivity with the rest of the brain and the possible relationship with higher-order functions [1]
Since the nineteenth century, with the work of Flourens, the cerebellum has been investigated for its role in motor functions, while the role of its extensive connectivity to other brain areas was overlooked
Concerning the section about the role of cerebellum in the sensorimotor system, the focus will be on the unprecedented level of detail that optogenetics allow to achieve in terms of specific neuronal types or pathways involved in precise aspects of movement
Summary
The first reports on cerebellar structure and the first hypothesis on function pointed out its high degree of connectivity with the rest of the brain and the possible relationship with higher-order functions [1]. Optogenetics proved to be a game-changing tool that neuroscience needed in order to achieve stimulation specificity, in vitro and in vivo, that was not foreseeable only twenty years ago This technical revolution affected cerebellar research too, allowing huge steps in understanding the cerebellar contribution to both motor and non-motor functions. The non-sensorimotor section will summarize the main findings of the last decade, where the use of optogenetics allowed us to tackle the role of cerebellum in functions and behaviors usually associated with other brain areas. This optogenetic revolution in cerebellar investigations might be key in achieving cerebellar stimulation (or inhibition) as a clinical treatment for a broad spectrum of disorders. We will provide a focused and critical summary of recent advances in cerebellar optogenetics and its applications to study neuronal circuits in physiological or pathological conditions, highlighting the advantages of photostimulation techniques, as well as emerging questions and future perspectives
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