European Commission logo
English English
CORDIS - EU research results
CORDIS

The neuroscience of tickling: cerebellar mechanisms and sensory prediction

Periodic Reporting for period 2 - NeuroTick (The neuroscience of tickling: cerebellar mechanisms and sensory prediction)

Reporting period: 2021-09-01 to 2022-08-31

The cerebellum (‘the little brain’, a region in the back of the brain containing more than half of all brain cells) plays an important role in the coordination of movement as well as cognitive functions. In humans, damage to the cerebellum around birth is associated with a higher risk of developing autism spectrum disorder. However, how exactly the cerebellum coordinates cognitive functions is still unclear.

The first aim of this project was to get a better understanding of the neuronal mechanisms by which the cerebellum plays a role in cognition. Our work will have important implications for both our understanding of cerebellar control of neocortical brain regions during sensory and cognitive processing, as well as for our understanding of autism spectrum disorder.

The second aim of this project was to develop a tool to improve analysis of recordings from the cerebellar cortex, and provide this tool open-access to the cerebellar community. Currently, high-density silicon probes are commonly used to record brain activity. The advantage of these probes is that hundreds of cells can be recorded simultaneously. However, the downside is that it is currently not possible to determine the exact cell type these cells belong to. For this project, we aimed to address that issue by providing automatic cell-type classification in the cerebellar cortex.

Third, we had a less conventional and more creative approach to study the brain. We aimed to address the question of how humans are able to recognize kin, and how preserved kin-recognition is in the most severe criminals of our society. Our assumption was that many mental faculties will be disrupted in offenders of cannibalistic homicides. Knowing whether kin recognition is disrupted or preserved, as in other cannibalistic animal species, helps us to understand how important and evolutionary preserved kin recognition is for humans.

Going forward, ultimately we aim to combine cerebellar mechanisms of cognition and social behaviour such as kin-recognition by studying tickling in rats. The cerebellum is the reason you cannot tickle yourself: it already predicts your movements, removing the element of surprise which is essential for tickling. Play-fight behaviour such as tickling is naturalistic behaviour in rats. By combining all three previous aims, we can better understand the neuronal mechanisms by which the cerebellum controls cognitive and social behaviours.
Aim 1: Cerebellar contribution to cognition and autism
We trained mice to perform a complex working memory decision-making task. Using mice allowed us to manipulate activity in specific brain regions as well as perform detailed high-quality recordings of brain activity which are not feasible in humans, thus getting a better insight into the exact neuronal mechanisms during specific behaviours. Suprisingly, when we specifically perturbed neuronal activity in the cerebellum during this cognitive task, either by using a cerebellum-specific mouse model of autism spectrum disorder or by using optogenetic activation of the cerebellum, we found enhanced function. While most animal models of disease lead to impairments, we discovered improved learning of the evidence accumulation decision task and altered activity in forebrain areas. We propose that the cerebellum regulates sensory reactivity at a brainwide level to regulate task persistence and learning. The results from this aim have now been published as a pre-print (Oostland et al., BioRxiv, 2021), and presented in a short video format which was prepared for the Society for Neuroscience 2021 meeting which is now available online (https://scholar.princeton.edu/sites/default/files/oostland_sfn_2021_withcc.mp4). In addition, we published a book chapter about the contributions of the cerebellum in decision-making (Deverett & Oostland, 2023).

Aim 2: Automated cell-type classification in the cerebellum
This part of the project turned into an international collaboration, as multiple labs across the world had individual efforts with unique approaches to reach the same goal: developing an automated cell type identification from Neuropixels recordings from the cerebellar cortex. Thus, we teamed up into the C4 collective: the Cerebellum Cell type Classification Collaboration (C4). The specific contribution of this fellowship to C4 was the development of a ground-truth dataset with characteristics from five different cell types acquired using Neuropixels recordings in mice. To acquire this ground-truth dataset, we further developed the optotagging method and performed numerous recordings. Together, C4 presented four linked posters at the Society for Neuroscience (SfN) annual meeting in 2022. We are now developing this project into one manuscript from all labs combined. This combined approach will yield the best result for an open-source classifier to be used by the whole cerebellum community, not limited to specifics of one individual lab, but useable across a wide range of methods, approaches, and species.

Aim 3: Kin-avoidance in cannibalistic homicides
The results from this aim have now been published in a peer-reviewed paper (Oostland & Brecht, Frontiers in Psychology, 2020) and more information for the general public about this topic as well as the full data set is now available on www.cannibalismresearch.org for anyone to browse. To investigate whether kin recognition is still in place in offenders of cannibalistic homicides, we generated a unique data set of information about 121 cannibals with approximately 631 victims, operating worldwide since 1900. We found that cannibalistic homicides are a distinct category of homicides with a unique pattern of murder methods, offenders, and victims, and only rarely ate kin. The preserved kin-recognition and kin-protection in offenders of cannibalistic homicides is not unlike the behaviour of cannibalistic fish or tadpoles, and points to anti-kin-ingestion mechanisms evolved from kin-selection many hundred millions of years ago.
Aim 1: Cerebellar contribution to cognition and autism
Here, we used a unique combination of in vivo electrophysiology in awake behaving animals, genetic manipulations, optogenetic manipulations, and computational latent-state analysis of behaviour to gain new insights in how the activity in the cerebellum can lead to enhanced functions and improved learning, including in a cerebellum-specific mouse model of ASD. This recasts ASD not so much as a disorder but as a variation that, in particular niches, can be adaptive.

Aim 2: Automated cell-type classification in the cerebellum
We further developed and improved the optotagging method, which can also be useful for researchers in other fields and applicable to other brain areas. We will continue the development of the automated cell-type classificatier and make it freely available for other researchers to use. Once widely implemented, this will improve and accelerate many research projects and contribute to advanced understanding of the cerebellum.

Aim 3: Kin-avoidance in cannibalistic homicides
This project had a very unique approach to studying kin recognition. By making the dataset about the cannibalistic homicides freely available on the public website www.cannibalismresearch.org with all data easy to use and browse for the general public, anyone interested in true crime can use this dataset to advance our understanding of the behaviour of offenders of cannibalistic homicides.
Islands of enhanced functions in a cerebellum-specific mouse model of autism spectrum disorder (ASD)