Synapses are specialized, multicellular junctions responsible for signal transmission and information processing in the nervous systems. The structure and molecular organization of synapses vary widely among neural circuits, cell types, and even across locations on the same cell, ultimately governing cognition and behavior. Deciphering the unique molecular architecture of functionally diverse brain synapses will be essential for determining the fundamental mechanisms of synaptic transmission and plasticity. Further insights in synapse molecular organization and dynamics across the lifespan will be required not just to understand physiological function but to decipher how synaptic dysfunction could lead to performance abnormalities, disrupting neuronal ensemble function, and eventually leading to disease.
Astounding progress of the past decades powered by molecular techniques has identified a rich synaptic proteome, revealed the first glimpses of an intricate nanometer-scale organization of key proteins, assessed roles of single proteins through knockdown, and mutagenesis, and made targeted comparisons between synapse types. Each of these advances has opened critical new questions now starting to be addressed with novel techniques to measure and control synaptic structure and advance our understanding of synaptic structure-function relationships.
New imaging modalities are elucidating synapse organization at the protein level. For instance, super-resolution light microscopy and multiplexed imaging techniques are poised to unravel the nanoscale molecular organization of distinct synapse types, and the molecular processes underlying trafficking events in neurotransmission. Application of high-resolution EM tomography combined with novel labeling techniques and molecular manipulation is allowing an unparalleled description of the molecular elements at the postsynaptic density and in presynaptic terminals. The integration of multi-scale imaging approaches with increasingly refined and quantitative synaptomic data, may provide powerful insights to synaptic molecular architecture.
At the same time, novel techniques to control and manipulate synaptic molecular organization have revolutionized our ability to test longstanding mechanistic hypotheses in vitro and in vivo. Optical control of protein interactions and subcellular targeting, experimental control of protein degradation, and single-cell gene editing offer powerful new tools and unprecedented precision of experimental design. And now penetrating many fields, artificial intelligence (AI) and deep learning are being leveraged for unbiased data analysis and to extract unanticipated meaning from vast and growing scales of data.
This Research Topic’s goal is to collect articles showing how we can harness new tools to measure and control the nanoscale molecular architecture at the synapse, advancing our characterization of the dynamic molecular mechanisms underlying synaptic function and plasticity.
To this aim, we welcome authors to focus on:
• Advances in super-resolution light microscopy, array tomography, expansion microscopy, multiprotein imaging, and variants of electron microscopy.
• Evidence supporting the development of novel high-resolution imaging techniques as well as the application of new experimental approaches to dissect synaptic molecular architecture with unprecedented resolution.
• Development and application of optical and molecular tools that permit an ever more precise control of synaptic molecular complexes.
• New computational tools for ever-greater analytic power, including experimental tools and deep learning, applied to synapse structure and function.
Further perspectives on the benefits and limitations of the use of new techniques will be helpful with an eye towards the future.
Synapses are specialized, multicellular junctions responsible for signal transmission and information processing in the nervous systems. The structure and molecular organization of synapses vary widely among neural circuits, cell types, and even across locations on the same cell, ultimately governing cognition and behavior. Deciphering the unique molecular architecture of functionally diverse brain synapses will be essential for determining the fundamental mechanisms of synaptic transmission and plasticity. Further insights in synapse molecular organization and dynamics across the lifespan will be required not just to understand physiological function but to decipher how synaptic dysfunction could lead to performance abnormalities, disrupting neuronal ensemble function, and eventually leading to disease.
Astounding progress of the past decades powered by molecular techniques has identified a rich synaptic proteome, revealed the first glimpses of an intricate nanometer-scale organization of key proteins, assessed roles of single proteins through knockdown, and mutagenesis, and made targeted comparisons between synapse types. Each of these advances has opened critical new questions now starting to be addressed with novel techniques to measure and control synaptic structure and advance our understanding of synaptic structure-function relationships.
New imaging modalities are elucidating synapse organization at the protein level. For instance, super-resolution light microscopy and multiplexed imaging techniques are poised to unravel the nanoscale molecular organization of distinct synapse types, and the molecular processes underlying trafficking events in neurotransmission. Application of high-resolution EM tomography combined with novel labeling techniques and molecular manipulation is allowing an unparalleled description of the molecular elements at the postsynaptic density and in presynaptic terminals. The integration of multi-scale imaging approaches with increasingly refined and quantitative synaptomic data, may provide powerful insights to synaptic molecular architecture.
At the same time, novel techniques to control and manipulate synaptic molecular organization have revolutionized our ability to test longstanding mechanistic hypotheses in vitro and in vivo. Optical control of protein interactions and subcellular targeting, experimental control of protein degradation, and single-cell gene editing offer powerful new tools and unprecedented precision of experimental design. And now penetrating many fields, artificial intelligence (AI) and deep learning are being leveraged for unbiased data analysis and to extract unanticipated meaning from vast and growing scales of data.
This Research Topic’s goal is to collect articles showing how we can harness new tools to measure and control the nanoscale molecular architecture at the synapse, advancing our characterization of the dynamic molecular mechanisms underlying synaptic function and plasticity.
To this aim, we welcome authors to focus on:
• Advances in super-resolution light microscopy, array tomography, expansion microscopy, multiprotein imaging, and variants of electron microscopy.
• Evidence supporting the development of novel high-resolution imaging techniques as well as the application of new experimental approaches to dissect synaptic molecular architecture with unprecedented resolution.
• Development and application of optical and molecular tools that permit an ever more precise control of synaptic molecular complexes.
• New computational tools for ever-greater analytic power, including experimental tools and deep learning, applied to synapse structure and function.
Further perspectives on the benefits and limitations of the use of new techniques will be helpful with an eye towards the future.