Cerebellar mechanisms for governing goal-directed and social behaviours

Projektinformationen

CEREBELLARCODE

ID Finanzhilfevereinbarung: 101033438

DOI

10.3030/101033438

Das Projekt endete am 7 Dezember 2022

EK-Unterschriftsdatum 24 Februar 2021

Startdatum 1 März 2021

Enddatum 28 Februar 2023

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 224 933,76

EU-Beitrag

€ 224 933,76

Koordiniert durch

UNIVERSITY COLLEGE LONDON
United Kingdom

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

Berichtszeitraum: 2021-03-01 bis 2023-02-28

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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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