Cerebellum, navigation and memory (CeZaMe)

We aim at understanding the neural bases of navigation and spatial memory. The principal objective of our work is to provide a comprehensive characterization of how the cerebellum participates to spatial cognition.

This contribution presumably operates, at different levels, including the computation of sensory-motor signals and a functional influence on forebrain areas supporting memory and executive functions (e.g. hippocampus and/or associative cortices).

Our research is divided in two complementary axes that we address using a translational approach both in mice obtained by conditional mutagenesis and in humans:

  • 1) Understand the dynamics of the brain navigation network by measuring functional activity of the cerebellum and the forebrain areas during navigation.
  • 2) Develop behavioral markers to evaluate spatial cognition under pathological state (i.e. Alzheimer disease, Autism Spectrum Disorders), both in patients and mice models.

The technical strength of our project lies in the combination of multi-scale experimental techniques: in vivo electrophysiology (spikes activity and local field potential), optogenetic control of neuronal activity, brain imaging and multi-parametric analysis of complex navigation behavior, using innovative tests in real-world and virtual reality environments. 

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The CeZame lab studies the neural bases of memory from a spatial cognition perspective.

As we navigate into the world, our brain forms a neural representation of space, travelled distances and followed directions. This neural representation is stable enough to allow efficient navigation in a known environment and flexible enough to be updated when exploring a new place. Yet, we ignore what mechanisms subtend such properties.

Our group already demonstrated the influence of the cerebellum in shaping goal-directed navigation and the hippocampal spatial activity. We posit that the cerebellum acts as a gate filtering sensory signals to stabilize or update our neural representation of space during navigation. To this end, we take a translational multi-scale approach: using brain imaging in humans and electrophysiology recordings in mice, we assess the activity of cerebro-cerebellar networks during real or virtual navigation tasks.

This work contributes to better understand how alterations in sensori-motor processing may impact cognitive functions. This question is of particular interest for cognitive disorders associated with sensory integration on the one hand or spatial representation deficits on the other hand (resp. Autism, Alzheimer).

Highlights

Cerebellum and space coding. The cerebellum is classically associated with motor control and motor learning, and its role in navigation has long been considered as a post-hoc monitoring of the motor output. In that context, our primary results revealing that intact cerebellar plasticity was crucial for accurate hippocampal place-cell activity (Rochefort et al., 2011) and optimal self-localization (Burguiere et al., 2005) were a major breakthrough. Those results are now reinforced and expanded across species by our recent results reporting an interaction between the hippocampus and the cerebellum Crus I during sequence-based navigation in humans (Igloi et al., 2015).

Development of new behavioral biomarkers. Laure Rondi-Reig created the Starmaze task (Rondi-Reig et al., 2006). This test has been used for differential diagnosis of Alzheimer patients (Bellassen et al., 2012) and characterization of spatial and temporal memory brain networks (Igloi et al., 2010; 2015). Associated Navigation Analysis Tools (NAT and NAT-h) have been developed by the CeZaMe team (Jarlier et al., 2010) to automatically extract individual and/or pathology-specific behavioral biomarker of cognitive functions (softwares protected by the “Agence de protection des Programme” (APP) n° IDDN.FR.001340015.000.S.P.2015.000.20700 - SATT Lutech).

Future directions

To specify the function of the cerebellum in navigation, the CeZame team seeks to elucidate its role in different processes that underlie spatial cognition such as sensory integration, error prediction and the construction of the spatial representation. Our project relies on a multi-scale approach, ranging from the disruption of gene expression and optogenetics control of neuronal activity to the study of the networks dynamics. For this purpose, we develop behavioral tools which can evaluate spatial cognition performances in both real and virtual environments, in parallel for humans and mice. We characterize the dynamics of the brain networks involved in these tasks by measuring simultaneously the activity of the cerebellum and regions of the forebrain, using fMRI in humans and in vivo electrophysiological recording in mice obtained by conditional mutagenesis. We aim at linking physiological activity of the cerebellum alone or in interaction with the hippocampus to specific behavioral epochs.

This integrative and translational approach allows us to provide new tools to analyze spatial representation deficits in various pathologies (Alzheimer's disease, autism) and, in the longer term, should help to design innovative behavioural biomarkers for neurological and/or psychiatric disorders.

Collaborations

Local network

  • The team is part of the Laboratory of excellence BioPsy (director: JA Girault). L. Rondi-Reig is member of the steering committee of the Labex. 
  • The team is part of Neuroscience School of Paris (ENP-director: P. Gaspar) which aims at strengthening the synergy, competitiveness and visibility of the Île-de-France laboratories in Neuroscience

National collaboration

  • Collège de Fance
  • ENS-Biology Department (Paris)
  • Institut des Systèmes intelligents et Robotiques (ISIR) (Paris)
  • Pasteur Institute
  • Université Aix-Marseille (Marseille)

International collaboration

  • CI De Zeeuw: Erasmus University (Netherland)
  • F. Battaglia: SILS Center (Netherland)
  • N. Burgess: UCL (London)