Biology subjects

Sala, R. W.

Publications and source records attributed to Sala, R. W..

4 recordsLinked to original sources

bioRxiv2025

Offline cerebello-cortico-striatal dynamics predict motor strategy exploration and retention in skill learning

Learning a motor skill requires exploring multiple possible solutions to find and retain an optimal strategy1-3. The exploration and consolidation of the motor strategy are usually considered to be segregated respectively between task practice and rest periods4-7. Here we show that two types of offline reactivations of neuronal representations of locomotor strategies in a brain-wide motor circuit are associated with exploration and retention. During short rests between trials, replays of these brainwide representations predict subsequent shifts in strategies indicating that distributed offline processes participate in strategy exploration. Shifts in strategy are consolidated, and their retention follows population reactivation in cerebellar sleep spindles and stabilization of cerebello-cerebral functional connectivity patterns, consistent with the role of spindles in brain plasticity. Overall, motor strategy optimization and consolidation are supported by two intertwined but distinct types of offline distributed reactivation events involving interregional interactions.

neuroscience↗

bioRxiv2024

Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice.

Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum primarily via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.

neuroscience↗

bioRxiv2022

Microglial TNFα controls GABAAR plasticity, slow waves and memory consolidation during sleep

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNF. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNF and P2RX7. We further show that microglia-specific depletion of TNF alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves and support memory consolidation.

neuroscience↗

bioRxiv2020

Bidirectional control of fear memories by the cerebellum through the ventrolateral periaqueductal grey

Fear conditioning is a form of associative learning that is known to involve brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memory, indicating a role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. In addition, we found that a FN - thalamic parafascicular nucleus pathway, which may relay cerebellar influence to the amygdala, is involved in anxiety and fear expression but not in fear memory. Our results reveal the contributions to the emotional system of the cerebellum, which exerts a potent control on the strength of the fear memory through excitatory FN-vlPAG projections.

neuroscience↗