Spatio-temporal Molecular Mechanisms Regulating Synapse Function and Neural Circuit Dynamics

Synapses, derived from the Greek word for "connections," are the primary sites where neurons exchange information. There are 150 trillion synapses in the human brain, which are central to brain functions such as memory, learning, and emotion. Synapses are constantly forming, eliminating, and reorganizing throughout life. A synapse contains thousands of proteins with spatiotemporal expression patterns and dynamics that govern these synaptic events. To gain a better understanding of brain function, we are now able to quantitatively and comprehensively study synaptic molecules with recent advances in imaging and omics technologies. One of the key findings of these studies is that spatiotemporal molecular dysfunction is a hallmark of neurodegenerative and neuropsychiatric disorders in their early stages. Thus, a major focus of research has been to elucidate the spatiotemporal dynamics and function of synaptic molecules to determine their physiological and pathological functions in the brain.

The primary goal of this topic is to understand the spatiotemporal regulation and significance of synaptic molecules. In the 1950s, the synaptic structure was first clearly identified by electron microscopy as a fixed monochrome image. Over the next seven decades, neuroscientists developed transcriptomics and connectomics to explore genomic and neural circuit information in the brain. However, there is still a gap in our understanding of how neural gene expression and neural circuits relate to brain function because we lack knowledge of spatiotemporal protein information and its relationship to synaptic dynamics. It's time to address this issue. With recent developments in synaptic molecular imaging, modulation techniques, liquid-liquid phase separation, omics analysis and protein structure analysis, we have begun to gain insight into the spatiotemporal and functional dynamics of synaptic molecules that control brain circuit activity. This Research Topic aims to bring together Original Research and Review articles that address conceptual and technical advances in spatial and temporal molecular dynamics and function in the context of synaptic function and neural dysfunction.

This Research Topic will cover a wide range of in vitro and in vivo studies on the spatiotemporal functional dynamics of synaptic molecules. This topic will focus on conceptual and technological advances (imaging techniques such as live imaging, single molecule imaging, tissue clearing and gene editing based protein labeling; modulation techniques such as DREADD, optogenetics and protein or compound delivery; liquid-liquid phase separations in vitro and in cells; comprehensive and targeted omics analyses; structural analyses including cryo-EM). Another focus of this topic is molecular dynamics during neuronal morphogenesis, neuronal circuit activity and behavior. We also welcome both original and review articles that provide insight into the pathophysiology of neurodegenerative and neuropsychiatric disorders caused by defective spatiotemporal synaptic molecules, as well as novel treatments and therapeutic approaches. This topic will also cover the spatial and temporal regulation of non-synaptic proteins that control neural development and function.

Below is a list of subtopics of interest.

- Original Research and Review articles that address the spatial and temporal information, dynamics, and functional analysis of nano- and mesoscale synaptic proteins that control neuronal morphogenesis, neuronal circuit activity, and behavior.

- Original research and review articles on pathomechanisms and treatments of neurodegenerative and neuropsychiatric disorders caused by dysregulation of spatiotemporal molecular functions.

- Reviews of traditional and novel techniques for analyzing spatiotemporal regulation of synaptic proteins, such as single-molecule imaging, visualization, manipulation, omics, structural analysis, and liquid-liquid separation.