Biology subjects

del Castillo-Berges, D.

Publications and source records attributed to del Castillo-Berges, D..

2 recordsLinked to original sources

bioRxiv2026

NREM Oscillations Mediate Synaptic Proteome Remodelling to Support Synapse Stabilisation

Synapses are known to remodel their proteome during sleep. However, the exact mechanisms driving this remodelling and its impact on synaptic function or cognition are not well understood. We combine 24-hour EEG recordings with time-resolved synaptic proteomics in a model of SYNGAP1-Related Disorders to reveal a mechanism by which slow-waves and spindles, two NREM sleep oscillations, mediate the remodelling of the synaptic proteome. Moreover, we uncover that this remodelling promotes synaptic stabilization, which could support sleep-dependent memory consolidation. In contrast, the increase of slow-waves and decrease of spindles found in Syngap1+/- mice would activate molecular pathways involved in synaptic weakening instead of stabilization. This is consistent with the proposed roles of slow-waves and spindles in synaptic downscaling and potentiation, respectively. Here, we provide evidence on how NREM oscillations regulate the synaptic proteome and reveal a pathological mechanism that could be of relevance to all neurodevelopmental disorders coursing with sleep disturbances.

neuroscience↗

bioRxiv2024

Synaptic proteome diversity is primarily driven by gene regulation of glutamate receptors and their regulatory proteins

Synapses formed by equivalent pairs of pre- and postsynaptic neurons have similar electrophysiological characteristics, belonging to the same type. However, these are generally confined to microscopic brain regions, precluding their proteomic analysis. This fact has greatly limited our ability to investigate the molecular basis of synaptic physiology. We introduce a procedure to characterise the synaptic proteome of microscopic brain regions and explore the molecular diversity among the synapses forming the trisynaptic circuit in the hippocampus. While we observe a remarkable proteomic diversity among these synapses, we also report that proteins involved in the regulation of the function of glutamate receptors are differentially expressed in all of them. Moreover, neuron-specific gene expression programs would contribute to their regulation. Here, we introduce a combined proteomics and transcriptomics analysis uncovering a previously unrecognised neuron-specific control of synaptic proteome diversity, directed towards the regulation of glutamate receptors and their regulatory proteins.

neuroscience↗