Synaptome maps change with circadian rhythms, the sleep-wake cycle and sleep deprivation
Item statusRestricted Access
Embargo end date27/06/2023
Understanding how circadian rhythms and vigilance states affect memory and synaptic plasticity is of major interest in biology. Their effects on the structural synaptic plasticity of the mouse brain have been investigated with low-resolution large-scale, or high-resolution small-scale approaches. The former methods are ineffectual in identifying local effects, while the latter have generated divergent findings, due to differences in brain regions surveyed, age of animals and experimental procedures implemented per publication. The impact of circadian and sleep-wake cycles (CR/SW) on the diverse excitatory synapse population of the brain remains elusive, requiring surveying with a systematic, brain-wide, high-resolution approach. By implementing the synaptome mapping technique (Cizeron et al., 2020; Zhu et al., 2018) we have been able to study the protein composition of individual excitatory synapses across the whole brain over a 24-hour period, and after 6 hours of Sleep Deprivation (SD). That was made possible with the brains of mice expressing fluorophore-tagged synaptic proteins important for memory and synaptic structure: Post-Synaptic density protein 95kDa (PSD95), Synapse-Associated protein 102kDa (SAP102) and Activity-regulated Cytoskeleton-Associated protein (Arc). Additionally, we analysed the changes in 3 excitatory synapse types and 37 subtypes as categorised by their PSD95 and SAP102 content (Cizeron et al., 2020; Zhu et al., 2018), as well as the changes in Arc distribution across neuronal compartments. Our results show that neither CR/SW, nor SD affect the excitatory synapse density in the brain, when PSD95 and SAP102 are used as markers. We found that SD induces stronger effects than CR/SW, especially in synapses of brain regions involved with memory, including the isocortex and hippocampus, where the size of PSD95 puncta is significantly reduced. Moreover, in the same areas we found decreased synaptic diversity following SD, as well as increased Long PSD95 Protein Lifetime (LPLs) and decreased Short PSD95 Protein Lifetime (SPLs) synapses, similarly to what has been described before in old mice (Bulovaite et al., 2021), which could be relevant to the detrimental effects of SD on memory. SAP102 was very minorly affected in the described conditions. Arc amount in synapses was found to be under circadian control, reaching max values in the active phase, while the number of synaptic terminals in which Arc is found and Arc distribution in those, was found to be under activity and/or sleep-wake control. Arc localisation in neuronal cell bodies, which maxed in the active and reached min in the resting phase in the Isocortex and Hippocampal neurons, was seen to be under circadian, sleep-wake and activity control, with the strength of influence of each of these variables depending on the brain region. Overall, this study found that the undisturbed sleep-wake cycle in sans stimulus conditions induces minor, region and subtype specific changes in synapses and their contents, while SD induces the synapses of “cognition areas” to shrink and be more homogeneous, as well as increases PSD95 lifetime.