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Neuroscience Research Mar 2020An important yet very challenging goal of neuroscience is to understand how brain activity drives cognition and behavior. Many useful tools have been developed to study... (Review)
Review
An important yet very challenging goal of neuroscience is to understand how brain activity drives cognition and behavior. Many useful tools have been developed to study neurons and synapses, the fundamental units of brain activity. Here, we review recently developed methods to visualize and manipulate active neurons and synapses, providing useful and compelling information about functional neuronal circuitry.
Topics: Animals; Brain; Genetic Engineering; Humans; Neurons; Synapses
PubMed: 31899202
DOI: 10.1016/j.neures.2019.12.020 -
Neuron Oct 2013The constant dynamic movement of synapses and their components has emerged in the last decades as a key feature of synaptic transmission and its plasticity.... (Review)
Review
The constant dynamic movement of synapses and their components has emerged in the last decades as a key feature of synaptic transmission and its plasticity. Intramolecular protein movements drive conformation changes important to transduce transmitter binding into signaling. Constant cytoskeletal rearrangements power synapse shape movements. Vesicular trafficking at the pre- and postsynapse underlies transmitter release and receptor traffic between the cell surface and intracellular compartments, respectively. Receptor movement in the plane of the plasma membrane by thermally powered Brownian diffusion movement and reversible trapping by receptor-scaffold interactions has emerged as the main mechanism to dynamically organize the synaptic membrane in nanoscale domains. We will discuss here the different conceptual and methodological advances that have led to a rethinking of the synapse as an organelle whose function is tightly linked to its dynamic organization.
Topics: Animals; Models, Neurological; Neurons; Nonlinear Dynamics; Synapses
PubMed: 24183020
DOI: 10.1016/j.neuron.2013.10.013 -
Current Opinion in Neurobiology Aug 2022Our daily experiences and learnings are stored in the form of memories. These experiences trigger synaptic plasticity and persistent structural and functional changes in... (Review)
Review
Our daily experiences and learnings are stored in the form of memories. These experiences trigger synaptic plasticity and persistent structural and functional changes in neuronal synapses. Recently, cellular studies of memory storage and engrams have emerged over the last decade. Engram cells reflect interconnected neurons via modified synapses. However, we were unable to observe the structural changes arising from synaptic plasticity in the past, because it was not possible to distinguish the synapses between engram cells. To overcome this barrier, dual-eGRASP (enhanced green fluorescent protein reconstitution across synaptic partners) technology can label specific synapses among multiple synaptic ensembles. Selective labeling of engram synapses elucidated their role by observing the structural changes in synapses according to the memory state. Dual-eGRASP extends cellular level engram studies to introduce the era of synaptic level studies. Here, we review this concept and possible applications of the dual-eGRASP, including recent studies that provided visual evidence of structural plasticity at the engram synapse.
Topics: Learning; Memory; Neuronal Plasticity; Neurons; Synapses
PubMed: 35598549
DOI: 10.1016/j.conb.2022.102552 -
Cellular and Molecular Life Sciences :... Aug 2006Proper brain connectivity and neuronal transmission rely on the accurate assembly of neurotransmitter receptors, cell adhesion molecules and several other scaffolding... (Review)
Review
Proper brain connectivity and neuronal transmission rely on the accurate assembly of neurotransmitter receptors, cell adhesion molecules and several other scaffolding and signaling proteins at synapses. Several new exciting findings point to an important role for the neuroligin family of adhesion molecules in synapse development and function. In this review, we summarize current knowledge of the structure of neuroligins and neurexins, their potential binding partners at the synapse. We also discuss their potential involvement in several aspects of synapse development, including induction, specificity and stabilization. The implication of neuroligins in cognitive disorders such as autism and mental retardation is also discussed.
Topics: Animals; Asperger Syndrome; Central Nervous System; Humans; Models, Biological; Nerve Tissue Proteins; Neural Cell Adhesion Molecules; Synapses
PubMed: 16794786
DOI: 10.1007/s00018-006-6061-3 -
Cells Oct 2022Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity... (Review)
Review
Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity and specialization across brain regions. Whether all astrocytes are poised to signal in a multitude of ways, or are instead tuned to surrounding synapses and how astroglial signaling is altered in psychiatric and cognitive disorders are fundamental questions for the field. In recent years, molecular and morphological characterization of astroglial types has broadened our ability to design studies to better analyze and manipulate specific functions of astroglia. Recent data emerging from these studies will be discussed in depth in this review. I also highlight remaining questions emerging from new techniques recently applied toward understanding the roles of astrocytes in synapse regulation in the adult brain.
Topics: Astrocytes; Brain; Signal Transduction; Synapses
PubMed: 36231097
DOI: 10.3390/cells11193135 -
Molecular Biology of the Cell Nov 2018Many brain disorders exhibit altered synapse formation in development or synapse loss with age. To understand the complexities of human synapse development and... (Review)
Review
Many brain disorders exhibit altered synapse formation in development or synapse loss with age. To understand the complexities of human synapse development and degeneration, scientists now engineer neurons and brain organoids from human-induced pluripotent stem cells (hIPSC). These hIPSC-derived brain models develop both excitatory and inhibitory synapses and functional synaptic activity. In this review, we address the ability of hIPSC-derived brain models to recapitulate synapse development and insights gained into the molecular mechanisms underlying synaptic alterations in neuronal disorders. We also discuss the potential for more accurate human brain models to advance our understanding of synapse development, degeneration, and therapeutic responses.
Topics: Brain; Cell Differentiation; Cells, Cultured; Humans; Induced Pluripotent Stem Cells; Models, Biological; Neurogenesis; Neurons; Organoids; Synapses
PubMed: 30475098
DOI: 10.1091/mbc.E18-04-0222 -
Annual Review of Neuroscience 2010Emerging evidence indicates that once established, synapses and dendrites can be maintained for long periods, if not for the organism's entire lifetime. In contrast to... (Review)
Review
Emerging evidence indicates that once established, synapses and dendrites can be maintained for long periods, if not for the organism's entire lifetime. In contrast to the wealth of knowledge regarding axon, dendrite, and synapse development, we understand comparatively little about the cellular and molecular mechanisms that enable long-term synapse and dendrite maintenance. Here, we review how the actin cytoskeleton and its regulators, adhesion receptors, and scaffolding proteins mediate synapse and dendrite maintenance. We examine how these mechanisms are reinforced by trophic signals passed between the pre- and postsynaptic compartments. We also discuss how synapse and dendrite maintenance mechanisms are compromised in psychiatric and neurodegenerative disorders.
Topics: Animals; Dendrites; Humans; Mental Disorders; Neurodegenerative Diseases; Synapses
PubMed: 20367247
DOI: 10.1146/annurev-neuro-060909-153204 -
Trends in Neurosciences Apr 2023Neuronal communication crucially relies on exocytosis of neurotransmitters from synaptic vesicles (SVs) which are clustered at synapses. To ensure reliable... (Review)
Review
Neuronal communication crucially relies on exocytosis of neurotransmitters from synaptic vesicles (SVs) which are clustered at synapses. To ensure reliable neurotransmitter release, synapses need to maintain an adequate pool of SVs at all times. Decades of research have established that SVs are clustered by synapsin 1, an abundant SV-associated phosphoprotein. The classical view postulates that SVs are crosslinked in a scaffold of protein-protein interactions between synapsins and their binding partners. Recent studies have shown that synapsins cluster SVs via liquid-liquid phase separation (LLPS), thus providing a new framework for the organization of the synapse. We discuss the evidence for phase separation of SVs, emphasizing emerging questions related to its regulation, specificity, and reversibility.
Topics: Humans; Synaptic Vesicles; Synapsins; Synapses; Synaptic Transmission; Biology
PubMed: 36725404
DOI: 10.1016/j.tins.2023.01.001 -
The EMBO Journal Sep 2018Parkinson's disease, the second most common neurodegenerative disorder, affects millions of people globally. There is no cure, and its prevalence will double by 2030. In... (Review)
Review
Parkinson's disease, the second most common neurodegenerative disorder, affects millions of people globally. There is no cure, and its prevalence will double by 2030. In recent years, numerous causative genes and risk factors for Parkinson's disease have been identified and more than half appear to function at the synapse. Subtle synaptic defects are thought to precede blunt neuronal death, but the mechanisms that are dysfunctional at synapses are only now being unraveled. Here, we review recent work and propose a model where different Parkinson proteins interact in a cell compartment-specific manner at the synapse where these proteins regulate endocytosis and autophagy. While this field is only recently emerging, the work suggests that the loss of synaptic homeostasis may contribute to neurodegeneration and is a key player in Parkinson's disease.
Topics: Autophagy; Endocytosis; Homeostasis; Humans; Parkinson Disease; Synapses
PubMed: 30065071
DOI: 10.15252/embj.201898960 -
Glia Jan 2013Microglia are the resident immune cells and phagocytes of our central nervous system (CNS). While most work has focused on the rapid and robust responses of microglia... (Review)
Review
Microglia are the resident immune cells and phagocytes of our central nervous system (CNS). While most work has focused on the rapid and robust responses of microglia during CNS disease and injury, emerging evidence suggests that these mysterious cells have important roles at CNS synapses in the healthy, intact CNS. Groundbreaking live imaging studies in the anesthetized, adult mouse demonstrated that microglia processes dynamically survey their environment and interact with other brain cells including neurons and astrocytes. More recent imaging studies have revealed that microglia dynamically interact with synapses where they appear to serve as "synaptic sensors," responding to changes in neural activity and neurotransmitter release. In the following review, we discuss the most recent work demonstrating that microglia play active roles at developing and mature synapses. We first discuss the important imaging studies that have led us to better understand the physical relationship between microglia and synapses in the healthy brain. Following this discussion, we review known molecular mechanisms and functional consequences of microglia-synapse interactions in the developing and mature CNS. Our current knowledge sheds new light on the critical functions of these mysterious cells in synapse development and function in the healthy CNS, but has also incited several new and interesting questions that remain to be explored. We discuss these open questions, and how the most recent findings in the healthy CNS may be related to pathologies associated with abnormal and/or loss of neural circuits.
Topics: Animals; Central Nervous System; Humans; Microglia; Neuronal Plasticity; Synapses
PubMed: 22829357
DOI: 10.1002/glia.22389