CE37 - Neurosciences intégratives et cognitives

Multi-modular Basis of Motor Adaptation and Learning – MultiMod

Multi-Modular Basis of Motor Adaptation and Learning

The cerebellum is a major brain structure with extensive output pathways both descending to motor effectors and ascending to the forebrain. One of its striking features is the organization in multiple specialized modules. Recently, the cerebellum has started to be recognized as a useful target for therapeutic transcranial stimulation. Yet, such empirical procedures are limited by the current lack of knowledge on how the cerebellar functional modules are recruited and coordinate their activity.

Cerebellum and motor learning

Our hypothesis is that the adaptation to a novel sensorimotor situation (skill learning or following a peripheral trauma) involves the coordinated recruitment of multiple cerebellar modules.<br />To demonstrate this, we will 1) characterize the role of cerebellar modules in adapting locomotion and in learning a locomotor skill using chemogenetics and accelerated rotarod, 2) localize these modules and study their connectivity in vitro and in vivo, 3) visualize and manipulate the coupling between modules in vivo during behavior using a highly innovative closed-loop optical fiberscope.

Our project covers multiple scales, from synaptic mapping, closed-loop mesoscale imaging and stimulation in behaving animal, multi-synaptic pathways manipulation and high resolution behavioral analysis. In this project we also developed (partner 3) an unique fiberscope able to read/write the activity on wide, mesoscale, fields that we will use for study of cerebello-forebrain circuits in motor learning.

Our project take a resolute approach to identify the different functional cerebellar modules involved, map their synaptic connectivity pattern in the cerebellar cortex and their changes following adaptation and learning, and manipulate the activity of these modules using a photonics approach allowing us to identify the regions of interest in vivo based on their activity, and performed spatially structured stimulation limited to these regions. To our knowledge, there is no case of such combination of approach to study the locomotion, and it should provide very novel insight into cerebellar contribution of function and learning.
The data obtained so far show complementary roles of cerebello-striatal and cerebello-cortical pathways in the consolidation and maintenance of motor learning, the former affecting the consolidation phase of learning and the latter the maintenance phase.

We study the cerebellum-forebrain circuits in motor learning.

Preprint :

Dual contributions of cerebellar-thalamic networks to learning and offline consolidation of a complex motor task
Andres P Varani, Romain W Sala, Caroline Mailhes-Hamon, Jimena L Frontera, Clément Léna, Daniela Popa
bioRxiv 2020.08.27.270330; doi: doi.org/10.1101/2020.08.27.270330

Cerebellar connectivity maps embody individual adaptive behavior
Ludovic Spaeth, Jyotika Bahuguna, Theo Gagneux, Kevin Dorgans, Izumi Sugihara, Bernard Poulain, Demian Battaglia, Philippe Isope
bioRxiv 2021.02.24.432563; doi: doi.org/10.1101/2021.02.24.432563

The cerebellum is a major brain structure with extensive output pathways both descending to motor effectors and ascending to the forebrain. One of its striking features is the organization in multiple specialized modules. Recently, the cerebellum has started to be recognized as a useful target for therapeutic transcranial stimulation. Yet, such empirical procedures are limited by the current lack of knowledge on how the cerebellar functional modules are recruited and coordinate their activity. Our hypothesis is that the adaptation to a novel sensorimotor situation (skill learning or following a peripheral trauma) involves the coordinated recruitment of multiple cerebellar modules. To demonstrate this, we will 1) characterize the role of cerebellar modules in adapting locomotion and in learning a locomotor skill using chemogenetics and accelerated rotarod, 2) localize these modules and study their connectivity in vitro and in vivo, 3) visualize and manipulate the coupling between modules in vivo during behavior using a highly innovative closed-loop optical fiberscope.

Project coordination

Daniela Popa (Institut de biologie de l'Ecole Normale Supérieure)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INCI Institut des Neurosciences Cellulaires et Intégratives (UPR 3212)
IBENS Institut de biologie de l'Ecole Normale Supérieure
IBENS Institut de biologie de l'Ecole Normale Supérieure

Help of the ANR 582,178 euros
Beginning and duration of the scientific project: September 2019 - 48 Months

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