Cerebellar mechanisms for governing goal-directed and social behaviours

Project Information

CEREBELLARCODE

Grant agreement ID: 101033438

DOI

10.3030/101033438

Project terminated on 7 December 2022

EC signature date 24 February 2021

Start date 1 March 2021

End date 28 February 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 224 933,76

EU contribution

€ 224 933,76

Coordinated by

UNIVERSITY COLLEGE LONDON
United Kingdom

Periodic Reporting for period 1 - CEREBELLARCODE (Cerebellar mechanisms for governing goal-directed and social behaviours)

Reporting period: 2021-03-01 to 2023-02-28

Summary of the context and overall objectives of the project

Understanding how neural circuits drive behavior is a fundamental goal of neuroscience. The cerebellar cortex is an ideal brain region for investigating this problem due to its so-called simple structure: a three-layer structure and canonical connectivity motif between a relatively small number of cell types. While traditionally considered crucial for motor learning and performance, emerging evidence suggests that the cerebellum also plays a key role in higher-order processing, particularly in reward processing and social interaction. In humans, cerebellar dysfunction has been associated with both motor deficits and autism spectrum disorder (ASD), characterized by impaired social behavior and reward processing.

The main objective of this project was to identify activity-based "fingerprints" of different cerebellar cell types to establish a causal relationship between cell types and their roles in both motor and non-motor functional domains. The project had four specific aims: (1) to develop a classifier for identifying cerebellar cell types based on their neural firing patterns, (2) to reveal the role of different cerebellar cell types in goal-directed behavior, (3) to investigate the role of different cerebellar cell types in social behavior, and (4) to compare the engagement of cerebellar circuits in animal models of ASD and wildtype mice during social behavior. By achieving these aims, the project aimed to contribute to a better understanding of the cerebellum's role in various behaviors, including social behavior and ASD.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The main objective of this project was to reveal the role of different cerebellar cell types in social interaction and reward processing. To achieve this, we used chronic Neuropixels recording in freely moving mice during self-initiated exploration of social or novel stimuli (three-chamber task), with the aim of generating a library of cerebellar cells and identifying their cell type by their neural signatures.

We recorded neural activity from Crus 1 of the cerebellum during different behavioral states, including random foraging in an open field, exploration of social and non-social novel stimuli, and free social interaction in an open field, in order to investigate the role of cerebellar neurons in social preference.

As part of aims 2-3, we recorded neural activity from the same neurons during a three-chamber test over three days to evaluate how different cerebellar neurons underlie social preference. However, due to around half of the mice not showing the expected social preference reported in the literature, we also recorded neural activity during free social interaction in an open field with two mice allowed to freely interact for 30 minutes. The behavior was recorded and classified into different features such as close interaction, sniffing, chasing, and nonsocial behaviors like grooming, walking, and running. We identified a small number of cells whose activity was correlated with specific behavioral features.
To address aim 4, we used ASD model mice. We performed the same tasks (three-chamber task and free social interaction task) but were unable to identify any significant differences in neural activity recorded from Crus 1 or in behavioral performance.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The study utilized chronic Neuropixels recording in a free-moving animal to generate a library of cerebellar cells recorded from Crus 1 during social interaction. The researchers were able to track the activity of the same units across days and evaluate their role in different aspects of behavior. However, the main limitation was the low number of recorded cells, as chronic recordings in the cerebellum yield a low number of neurons that decreases over time. Despite identifying a small number of cells whose activity was correlated with specific behavioral features, the low number of collected neurons prevented them from revealing a causal relationship between neural activity and behavior. Additionally, the researchers used ASD model mice in the same experimental setup but could not identify any significant differences in neural activity recorded from Crus 1 or in behavioral performance.

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