Orienting oneself in space requires a single, stable sense of head direction. This sense relies on the head-direction cell system (HD cells), a neuronal network distributed across several brain structures whose neurons fire selectively according to the orientation of the animal's head in the horizontal plane. A remarkable property of this system is the constant temporal coordination among HD cells: their correlation structure is maintained regardless of the animal's behavior, its state of vigilance, or the available sensory inputs, thereby ensuring a single, persistent directional signal. The mechanisms underlying this temporal organization, however, remained unknown, as did the question of whether it self-organizes or depends on inputs external to the HD system.
To investigate the role of the cerebellum in this organization, the authors simultaneously recorded the single-unit activity of HD cells in two distinct structures, the anterodorsal nucleus of the thalamus and the retrosplenial cortex, in freely moving adult mice using tetrodes. Two transgenic mouse models specifically targeting the plasticity of cerebellar Purkinje cells were compared with their controls: one deficient in protein kinase C (PKC)-dependent long-term depression (L7-PKCI line), the other deficient in protein phosphatase 2B (PP2B)-dependent potentiation (L7-PP2B line). Recordings were carried out under controlled sensory conditions, notably in the presence or absence of external visual cues (light and dark conditions).
The results reveal the existence of two distinct HD networks within the retrosplenial cortex and the thalamus, whose temporal coordination into a single directional signal requires cerebellar computation. Pairs of HD cells indeed lose their temporal coordination, specifically upon the removal of external sensory inputs. Moreover, the two cerebellar mechanisms play dissociable roles: PP2B-dependent processes facilitate the anchoring of the HD signal to external cues, whereas PKC-dependent processes are necessary for signal stability based on self-motion cues. Thus, L7-PKCI mice exhibit unstable HD cells in darkness, whereas L7-PP2B mice show reduced stability and poor control by external cues under light conditions.
The authors rule out the hypothesis of a bias in the angular velocity signal, as the firing properties of the cells encoding this velocity remained unchanged, and attribute the observed alterations to a defect in cerebellum-dependent multisensory integration. Ultimately, this work suggests the existence of multiple direction signals in the mouse brain, whose temporal coordination and spatial stability are orchestrated by the cerebellum, which thereby contributes to preserving a single, stable sense of direction.