Cerebellar control of a unitary head direction sense.

The head-direction (HD) system, a key neural circuit for navigation, consists of several anatomical structures containing neurons selective to the animal's head direction. HD cells exhibit ubiquitous temporal coordination across brain regions, independently of the animal's behavioral state or sensory inputs. Such temporal coordination mediates a single, stable, and persistent HD signal, which is essential for intact orientation. However, the mechanistic processes behind the temporal organization of HD cells are unknown. By manipulating the cerebellum, we identify pairs of HD cells recorded from two brain structures (anterodorsal thalamus and retrosplenial cortex) that lose their temporal coordination, specifically during the removal of the external sensory inputs. Further, we identify distinct cerebellar mechanisms that participate in the spatial stability of the HD signal depending on sensory signals. We show that while cerebellar protein phosphatase 2B-dependent mechanisms facilitate the anchoring of the HD signal on the external cues, the cerebellar protein kinase C-dependent mechanisms are required for the stability of the HD signal by self-motion cues. These results indicate that the cerebellum contributes to the preservation of a single and stable sense of direction.

A Liaison Brought to Light: Cerebellum-Hippocampus, Partners for Spatial Cognition.

This review focuses on the functional and anatomical links between the cerebellum and the hippocampus and the role of their interplay in goal-directed navigation and spatial cognition. We will describe the interactions between the cerebellum and the hippocampus at different scales: a macroscopic scale revealing the joint activations of these two structures at the level of neuronal circuits, a mesoscopic scale highlighting the synchronization of neuronal oscillations, and finally a cellular scale where we will describe the activity of hippocampal neuronal assemblies following a targeted manipulation of the cerebellar system. We will take advantage of this framework to summarize the different anatomical pathways that may sustain this multiscale interaction. We will finally consider the possible influence of the cerebellum on pathologies traditionally associated with hippocampal dysfunction.

The cerebellum promotes sequential foraging strategies and contributes to the directional modulation of hippocampal place cells.

The cerebellum contributes to goal-directed navigation abilities and place coding in the hippocampus. Here we investigated its contribution to foraging strategies. We recorded hippocampal neurons in mice with impaired PKC-dependent cerebellar functions (L7-PKCI) and in their littermate controls while they performed a task where they were rewarded for visiting a subset of hidden locations. We found that L7-PKCI and control mice developed different foraging strategies: while control mice repeated spatial sequences to maximize their rewards, L7-PKCI mice persisted to use a random foraging strategy. Sequential foraging was associated with more place cells exhibiting theta-phase precession and theta rate modulation. Recording in the dark showed that PKC-dependent cerebellar functions controlled how self-motion cues contribute to the selectivity of place cells to both position and direction. Thus, the cerebellum contributes to the development of optimal sequential paths during foraging, possibly by controlling how self-motion and theta signals contribute to place cell coding.

Novelty-Induced Phase-Locked Firing to Slow Gamma Oscillations in the Hippocampus: Requirement of Synaptic Plasticity.

Temporally precise neuronal firing phase-locked to gamma oscillations is thought to mediate the dynamic interaction of neuronal populations, which is essential for information processing underlying higher-order functions such as learning and memory. However, the cellular mechanisms determining phase locking remain unclear. By devising a virus-mediated approach to perform multi-tetrode recording from genetically manipulated neurons, we demonstrated that synaptic plasticity dependent on the GluR1 subunit of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor mediates two dynamic changes in neuronal firing in the hippocampal CA1 area during novel experiences: the establishment of phase-locked firing to slow gamma oscillations and the rapid formation of the spatial firing pattern of place cells. The results suggest a series of events potentially underlying the acquisition of new spatial information: slow gamma oscillations, originating from the CA3 area, induce the two GluR1-dependent changes of CA1 neuronal firing, which in turn determine information flow in the hippocampal-entorhinal system.