MicroConsol

The MicroConsol project investigates the role of microglia in sleep-dependent memory consolidation at the synaptic level. Learning and memory involve the activation and strengthening of neuronal assemblies through Hebbian plasticity, with synaptic reorganization playing a key role in memory storage. Sleep, particularly through sharp-wave ripples and thalamocortical spindles, has been identified as a critical period for memory consolidation, facilitating the transfer and stabilization of information from the hippocampus to the cortex. While neuronal cell bodies and dendrites have been extensively studied in this context, little is known about the role of synapses in sleep-driven memory processes. Microglia, traditionally known as immune cells, are now recognized as active participants in synaptic remodeling. Preliminary evidence suggests that microglia interact with synapses in an activity-dependent manner, particularly during sleep spindles, potentially influencing memory consolidation. The primary objective of MicroConsol is to elucidate how microglial dynamics contribute to synaptic changes that underlie memory storage in S1. To achieve this, the project focuses on three major research aims: (1) determining whether dendritic spines activated during learning are selectively reactivated during sleep spindles; (2) examining the specificity of microglial contacts with reactivated spines and their functional impact on synaptic remodeling; and (3) identifying the role of Cx3cr1 signaling in microglia-mediated memory consolidation and the causal link of spindles with morphodynamic changes. The project employs a combination of behavioral tasks, two-photon microscopy, in vivo imaging, and electrophysiological recordings in mice. A whisker-dependent sensory association task is used to study learning-induced synaptic changes, followed by imaging during subsequent sleep periods to track microglial interactions. To assess the role of the Cx3cr1 pathway, Cx3Cr1 invalidation will be applied to disrupt microglia-synapse signaling and evaluate its effects on memory retention. Additionally, optogenetic manipulations of thalamic circuits will be used to investigate the link between spindle activity and microglial morphodynamics. Expected outcomes include a deeper understanding of how synaptic reactivation during spindles contributes to memory consolidation, the identification of microglia as key regulators of this process, and the elucidation of molecular pathways involved in microglia-synapse communication. This research has the potential to redefine the role of non-neuronal cells in cognition and provide insights into neurodevelopmental and neurodegenerative disorders where microglial function is impaired. MicroConsol integrates open science practices. Ethical considerations, including adherence to the 6R principles (Replacement, Reduction, Refinement, Robustness, Registration, and Reporting), are central to the project. The interdisciplinary collaboration between neuroscience, imaging, and computational analysis ensures a comprehensive approach to addressing fundamental questions in memory research. By unveiling the cellular mechanisms linking sleep and memory, MicroConsol aims to provide novel insights into brain plasticity and cognitive function, with implications for therapeutic strategies targeting memory disorders associated to sleep.