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Neuroscience Jan 2019Astrocytes are emerging as important players in synaptic function, and, consequently, on brain function and animal behavior. According to the Tripartite Synapse concept,... (Review)
Review
Astrocytes are emerging as important players in synaptic function, and, consequently, on brain function and animal behavior. According to the Tripartite Synapse concept, astrocytes are integral elements involved in synaptic function. They establish bidirectional communication with neurons, whereby they respond to synaptically released neurotransmitters and, in turn, release gliotransmitters that influence neuronal and synaptic activity. Accumulating evidence is revealing that the mechanisms and functional consequences of astrocyte-neuron signaling are more complex than originally thought. Furthermore, astrocyte-neuron signaling is not based on broad, unspecific interaction; rather, it is a synapse-, cell- and circuit-specific phenomenon that presents a high degree of complexity. This diversity and complexity of astrocyte-synapse interactions greatly enhance the degrees of freedom of the neural circuits and the consequent computational power of the neural systems.
Topics: Animals; Astrocytes; Cell Communication; Humans; Neuronal Plasticity; Neurons; Organ Specificity; Synaptic Transmission
PubMed: 30458223
DOI: 10.1016/j.neuroscience.2018.11.010 -
Molecular Psychiatry Jan 2022The prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among... (Review)
Review
The prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among glutamatergic principal neurons and GABAergic interneurons, as well as its long-range connections with other brain regions, have been functionally linked to specific behaviors, ranging from working memory to reward seeking. The efficacy of synaptic signaling in the PFC network is profundedly influenced by monoaminergic inputs via the activation of dopamine, adrenergic, or serotonin receptors. Stress hormones and neuropeptides also exert complex effects on the synaptic structure and function of PFC neurons. Dysregulation of PFC synaptic transmission is strongly linked to social deficits, affective disturbance, and memory loss in brain disorders, including autism, schizophrenia, depression, and Alzheimer's disease. Critical neural circuits, biological pathways, and molecular players that go awry in these mental illnesses have been revealed by integrated electrophysiological, optogenetic, biochemical, and transcriptomic studies of PFC. Novel epigenetic mechanism-based strategies are proposed as potential avenues of therapeutic intervention for PFC-involved diseases. This review provides an overview of PFC network organization and synaptic modulation, as well as the mechanisms linking PFC dysfunction to the pathophysiology of neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Insights from the preclinical studies offer the potential for discovering new medical treatments for human patients with these brain disorders.
Topics: Humans; Interneurons; Memory, Short-Term; Neurons; Prefrontal Cortex; Synaptic Transmission
PubMed: 33875802
DOI: 10.1038/s41380-021-01092-3 -
Cell Feb 2023Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear....
Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.
Topics: Mice; Animals; CA1 Region, Hippocampal; Hippocampus; Neuronal Plasticity; Learning; Neurons; Synaptic Transmission; Mammals
PubMed: 36669484
DOI: 10.1016/j.cell.2022.12.035 -
Neuron May 2017AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority... (Review)
Review
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition. Furthermore, AMPAR assembly, trafficking, and functional heterogeneity depends on a large repertoire of auxiliary subunits-a feature that is particularly striking for this type of iGluR. Here, we discuss how the subunit structure, stoichiometry, and auxiliary subunits generate a heterogeneous plethora of receptors, each tailored to fulfill a vital role in fast synaptic signaling and plasticity.
Topics: Animals; Glutamic Acid; Humans; Neuronal Plasticity; Protein Isoforms; Protein Processing, Post-Translational; Protein Subunits; Protein Transport; RNA Processing, Post-Transcriptional; Receptors, AMPA; Synaptic Transmission
PubMed: 28521126
DOI: 10.1016/j.neuron.2017.04.009 -
Nature Reviews. Neuroscience May 2019Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to... (Review)
Review
Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.
Topics: Animals; Epilepsy; Humans; Neuroglia; Neurons; Synaptic Transmission
PubMed: 30792501
DOI: 10.1038/s41583-019-0126-4 -
Frontiers in Neural Circuits 2019
Topics: Animals; Humans; Neurotransmitter Agents; Synaptic Transmission
PubMed: 30971899
DOI: 10.3389/fncir.2019.00019 -
Molecular and Cellular Neurosciences Mar 2023The postsynaptic density (PSD) of excitatory synapses is built from a wide variety of scaffolding proteins, receptors, and signaling molecules that collectively... (Review)
Review
The postsynaptic density (PSD) of excitatory synapses is built from a wide variety of scaffolding proteins, receptors, and signaling molecules that collectively orchestrate synaptic transmission. Seminal work over the past decades has led to the identification and functional characterization of many PSD components. In contrast, we know far less about how these constituents are assembled within synapses, and how this organization contributes to synapse function. Notably, recent evidence from high-resolution microscopy studies and in silico models, highlights the importance of the precise subsynaptic structure of the PSD for controlling the strength of synaptic transmission. Even further, activity-driven changes in the distribution of glutamate receptors are acknowledged to contribute to long-term changes in synaptic efficacy. Thus, defining the mechanisms that drive structural changes within the PSD are important for a molecular understanding of synaptic transmission and plasticity. Here, we review the current literature on how the PSD is organized to mediate basal synaptic transmission and how synaptic activity alters the nanoscale organization of synapses to sustain changes in synaptic strength.
Topics: Synapses; Synaptic Transmission; Receptors, Glutamate; Post-Synaptic Density; Nanostructures; Neuronal Plasticity
PubMed: 36720293
DOI: 10.1016/j.mcn.2023.103819 -
Neural Plasticity 2015
Topics: Animals; Humans; Neuroglia; Neuronal Plasticity; Synaptic Transmission
PubMed: 26346673
DOI: 10.1155/2015/723891 -
Glia Jan 2023In the last decades, astrocytes have emerged as important regulatory cells actively involved in brain function by exchanging signaling with neurons. The endocannabinoid... (Review)
Review
In the last decades, astrocytes have emerged as important regulatory cells actively involved in brain function by exchanging signaling with neurons. The endocannabinoid (eCB) signaling is widely present in many brain areas, being crucially involved in multiple brain functions and animal behaviors. The present review presents and discusses current evidence demonstrating that astrocytes sense eCBs released during neuronal activity and subsequently release gliotransmitters that regulate synaptic transmission and plasticity. The eCB signaling to astrocytes and the synaptic regulation mediated by astrocytes activated by eCBs are complex phenomena that exhibit exquisite spatial and temporal properties, a wide variety of downstream signaling mechanisms, and a large diversity of functional synaptic outcomes. Studies investigating this topic have revealed novel regulatory processes of synaptic function, like the lateral regulation of synaptic transmission and the active involvement of astrocytes in the spike-timing dependent plasticity, originally thought to be exclusively mediated by the coincident activity of pre- and postsynaptic neurons, following Hebbian rules for associative learning. Finally, the critical influence of astrocyte-mediated eCB signaling on animal behavior is also discussed.
Topics: Animals; Endocannabinoids; Neuronal Plasticity; Synaptic Transmission; Signal Transduction; Astrocytes
PubMed: 36408881
DOI: 10.1002/glia.24256 -
Neuropharmacology Jun 2022NMDA receptors play vital roles in a broad array of essential brain functions, from synaptic transmission and plasticity to learning and memory. Historically, the... (Review)
Review
NMDA receptors play vital roles in a broad array of essential brain functions, from synaptic transmission and plasticity to learning and memory. Historically, the fundamental roles of NMDARs were attributed to their specialized properties of ion flux. More recently, it has become clear that NMDARs also signal in an ion flux-independent manner. Here, we review these non-ionotropic NMDAR signaling mechanisms that have been reported to contribute to a broad array of neuronal functions and dysfunctions including synaptic transmission and plasticity, cell death and survival, and synaptic alterations associated with neurological disorders.
Topics: Learning; Neuronal Plasticity; Neurons; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Synaptic Transmission
PubMed: 35278420
DOI: 10.1016/j.neuropharm.2022.109019