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Abstract The function of neuronal circuits, and its perturbation by psychoactive molecules or disease-associated genetic variants, is governed by the interplay between synapse activity and synaptic protein localization and synthesis across a heterogeneous synapse population. Here, we combine in situ measurement of synaptic multiprotein compositions and activation states, synapse activity in calcium traces or glutamate spiking, and local translation of specific genes, across the same individual synapses. We demonstrate how this high-dimensional data enables identification of interdependencies in the multiprotein-activity network, and causal dissection of complex synaptic phenotypes in disease-relevant chemical and genetic NMDAR loss of function that translatein vivo. We show how this method generalizes to other subcellular systems by deriving mitochondrial protein networks, and, using support vector machines, its value in overcoming animal variability in phenotyping. Integrating multiple synapse information modalities enables deep structure-function characterization of synapse populations and their responses to genetic and chemical perturbations. 

Abstract BackgroundThe coronavirus disease 2019 (COVID-19) pandemic may have disproportionally impacted vulnerable groups such as people who inject drugs (PWID) through reduced health care services as well as social changes from pandemic mitigation measures. Understanding how the COVID-19 pandemic and associated mitigation strategies subsequently changed the trajectory of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission is critical to estimating disease burdens, identifying outbreak risk, and developing informed intervention strategies. MethodsUsing behavioral data from the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based cohort of PWID in Baltimore, United States, and an individual-based network model, we explored the impacts of service disruptions combined with changes in social networks and injecting behaviors of PWID on HCV and HIV transmission. ResultsAnalyses of ALIVE data showed that during the pandemic, there was an acceleration in injection cessation trajectories overall, but those who continued injecting increased the frequency of injection; at the same time, individual drug-use networks became smaller and the probability of injecting with others decreased. Simulation results demonstrated that HCV and HIV prevalence increased from service disruptions alone, but these effects were mitigated when including observed behavior changes in addition. ConclusionsModel results combined with rich individual behavioral data indicated that pandemic-induced behavioral changes of PWID that lasted longer than service disruptions could have offset the increasing disease burden caused by disrupted service access during the pandemic.