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Annual Review of Neuroscience Jul 2020Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational... (Review)
Review
Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional capabilities and limitations. Although standard, correlation-based, Hebbian synaptic plasticity has been the primary focus of neuroscientists for decades, it is inherently limited. Three-factor plasticity rules supplement Hebbian forms with neuromodulation and eligibility traces, while true supervised types go even further by adding objectives and instructive signals. Finally, a recently discovered hippocampal form of synaptic plasticity combines the above elements, while leaving behind the primary Hebbian requirement. We suggest that the effort to determine the neural basis of adaptive behavior could benefit from renewed experimental and theoretical investigation of more powerful directed types of synaptic plasticity.
Topics: Animals; Humans; Learning; Memory; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 32075520
DOI: 10.1146/annurev-neuro-090919-022842 -
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 -
Neuroscience Letters Jan 2019Astrocytes, the neural homeostatic cells, play a key role in the information processing in the central nervous system. They express multiple receptors which respond to a...
Astrocytes, the neural homeostatic cells, play a key role in the information processing in the central nervous system. They express multiple receptors which respond to a number of chemical messengers and get excited as evidenced by an increase in second messengers in short and delayed time domains. Astrocytes secrete numerous neuroactive agents and mount various homeostatic responses. These signal integrating functions are key factors of neuropathology (better termed astroneuropathology): they provide for neuroprotection through both homeostatic support and astroglial reactivity; failure in astroglial defensive or supporting capabilities facilitates evolution of neurological disorders.
Topics: Animals; Astrocytes; Homeostasis; Humans; Nervous System Diseases; Neurons; Synaptic Transmission
PubMed: 30031035
DOI: 10.1016/j.neulet.2018.07.026 -
Frontiers in Neural Circuits 2019
Topics: Animals; Humans; Neurotransmitter Agents; Synaptic Transmission
PubMed: 30971899
DOI: 10.3389/fncir.2019.00019 -
The New England Journal of Medicine Jul 2015
Topics: Biomedical Research; Humans; Neurotransmitter Agents; Placebo Effect; Placebos; Synaptic Transmission
PubMed: 26132938
DOI: 10.1056/NEJMp1504023 -
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 -
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 -
Current Opinion in Neurobiology Aug 2017Throughout history, epilepsy affects about 1-2% of the population worldwide. Epilepsy can be caused by traumatic brain injury, exposure to certain toxins and drugs, and... (Review)
Review
Throughout history, epilepsy affects about 1-2% of the population worldwide. Epilepsy can be caused by traumatic brain injury, exposure to certain toxins and drugs, and mutations of genes that often encode synaptic proteins. In addition to conventional linkage and association studies, the recent trio exome sequencing in epilepsy and proteomic analysis in autoimmune synaptopathies have accelerated identification of novel epilepsy-related proteins, most of which play critical roles in synaptic transmission. Furthermore, super-resolution microscopy analysis has revealed subsynaptic nanoscale distribution of presynaptic and postsynaptic proteins and suggests a precise trans-synaptic alignment of neurotransmitter release to receptors. Such identification and characterization of epilepsy-related synaptic proteins have been promoting the development of anti-epileptic drugs and the understanding of mechanisms of synaptic transmission.
Topics: Epilepsy; Humans; Nerve Tissue Proteins; Proteomics; Synaptic Transmission
PubMed: 28219682
DOI: 10.1016/j.conb.2017.02.001