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Frontiers in Neural Circuits 2016"Neuronal assemblies" are defined here as coalitions within the brain of millions of neurons extending in space up to 1-2 mm, and lasting for hundreds of milliseconds:... (Review)
Review
"Neuronal assemblies" are defined here as coalitions within the brain of millions of neurons extending in space up to 1-2 mm, and lasting for hundreds of milliseconds: as such they could potentially link bottom-up, micro-scale with top-down, macro-scale events. The perspective first compares the features versus of this underappreciated "meso-scale" level of brain processing, secondly considers the various diverse functions in which assemblies may play a pivotal part, and thirdly analyses whether the surprisingly spatially extensive and prolonged temporal properties of assemblies can be described exclusively in terms of classic synaptic transmission or whether additional, different types of signaling systems are likely to operate. Based on our own voltage-sensitive dye imaging (VSDI) data acquired we show how restriction to only one signaling process, i.e., synaptic transmission, is unlikely to be adequate for modeling the full profile of assemblies. Based on observations from VSDI with its protracted spatio-temporal scales, we suggest that two other, distinct processes are likely to play a significant role in assembly dynamics: "volume" transmission (the passive diffusion of diverse bioactive transmitters, hormones, and modulators), as well as electrotonic spread via gap junctions. We hypothesize that a combination of all three processes has the greatest potential for deriving a realistic model of assemblies and hence elucidating the various complex brain functions that they may mediate.
Topics: Animals; Gap Junctions; Nerve Net; Neurons; Synaptic Transmission
PubMed: 28119576
DOI: 10.3389/fncir.2016.00114 -
Biochimica Et Biophysica Acta.... Nov 2022Adequate homeostasis of lipid, protein and carbohydrate metabolism is essential for cells to perform highly specific tasks in our organism, and the brain, with its... (Review)
Review
Adequate homeostasis of lipid, protein and carbohydrate metabolism is essential for cells to perform highly specific tasks in our organism, and the brain, with its uniquely high energetic requirements, posesses singular characteristics. Some of these are related to its extraordinary dotation of synapses, the specialized subcelluar structures where signal transmission between neurons occurs in the central nervous system. The post-synaptic compartment of excitatory synapses, the dendritic spine, harbors key molecules involved in neurotransmission tightly packed within a minute volume of a few femtoliters. The spine is further compartmentalized into nanodomains that facilitate the execution of temporo-spatially separate functions in the synapse. Lipids play important roles in this structural and functional compartmentalization and in mechanisms that impact on synaptic transmission. This review analyzes the structural and dynamic processes involving lipids at the synapse, highlighting the importance of their homeostatic balance for the physiology of this complex and highly specialized structure, and underscoring the pathologies associated with disbalances of lipid metabolism, particularly in the perinatal and late adulthood periods of life. Although small variations of the lipid profile in the brain take place throughout the adult lifespan, the pathophysiological consequences are clinically manifested mostly during late adulthood. Disturbances in lipid homeostasis in the perinatal period leads to alterations during nervous system development, while in late adulthood they favor the occurrence of neurodegenerative diseases.
Topics: Lipidomics; Lipids; Neurons; Synapses; Synaptic Transmission
PubMed: 35964712
DOI: 10.1016/j.bbamem.2022.184033 -
Developmental Neurobiology May 2017Electrical synapses are finding increasing representation and importance in our understanding of signaling in the nervous system. In contrast to chemical synapses, at... (Review)
Review
Electrical synapses are finding increasing representation and importance in our understanding of signaling in the nervous system. In contrast to chemical synapses, at which molecules are evolutionary conserved, vertebrate and invertebrate electrical synapses represent molecularly different structures that share a common communicating strategy that allows them to serve very similar functions. A better understanding of differences and commonalities regarding the structure, function and regulation of vertebrate and invertebrate electrical synapses will lead to a better understanding of the properties and functional diversity of this modality of synaptic communication. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 517-521, 2017.
Topics: Animals; Electrical Synapses; Synaptic Transmission
PubMed: 28188695
DOI: 10.1002/dneu.22488 -
Medical Science Monitor : International... Jan 2023Alzheimer disease (AD) is a chronic and heterogeneous neurodegenerative disorder characterized by complex pathological processes involving neuroinflammation,... (Review)
Review
Alzheimer disease (AD) is a chronic and heterogeneous neurodegenerative disorder characterized by complex pathological processes involving neuroinflammation, neurodegeneration, and synaptic dysfunction. Understanding the exact neurobiological mechanisms underlying AD pathology may help to provide a biomarker for early diagnosis or at least for assessment of vulnerability to dementia development. Neural plasticity is defined as a capability of the brain to respond to alterations including aging, injury, or learning, with a crucial role of synaptic elements. Long-term potentiation (LTP) and long-term depression (LTD) are important in regulating synaptic connections between neural cells in functional plasticity. Synaptic loss and impairment of the brain's plasticity in AD leads to cognitive impairment, and one of important roles of synaptic biomarkers is monitoring synaptic dysfunction, response to treatment, and predicting future development of AD. Synaptic biomarkers are undoubtedly very promising in developing novel approach to AD treatment and control, especially in the era of aging of societies, which is one of the most common risk factor of AD. Implementing a widespread measurement of synaptic biomarkers of AD will probably be crucial in early diagnosis of AD, early therapeutic intervention, monitoring progression of the disease, or response to treatment. One of the most important challenges is finding a biomarker whose blood concentration correlates with its level in the central nervous system (CNS). This review aims to present the current status of biomarkers of activity-dependent plasticity and persistent enhancement of synaptic transmission in Alzheimer disease.
Topics: Humans; Alzheimer Disease; Synaptic Transmission; Neuronal Plasticity; Long-Term Potentiation; Biomarkers
PubMed: 36600577
DOI: 10.12659/MSM.938826 -
Preface: Cholinergic mechanisms: This is the Preface for the special issue "Cholinergic Mechanisms".Journal of Neurochemistry Sep 2021This special issue of the Journal of Neurochemistry, entitled "Cholinergic Mechanisms," presents 15 reviews and two original papers, which have been selected to cover...
This special issue of the Journal of Neurochemistry, entitled "Cholinergic Mechanisms," presents 15 reviews and two original papers, which have been selected to cover the broad spectrum of topics and disciplines presented at the XVIth International Symposium on Cholinergic Mechanisms (ISCM-XVI), ranging from the molecular and the cellular to the clinical and the cognitive mechanisms of cholinergic transmission. The authors discuss recent developments in the field, for instance, the association of cholinergic transmission with a number of important neurological and neuromuscular diseases in the central and peripheral nervous systems.
Topics: Acetylcholine; Animals; Brain; Cholinergic Agents; Cholinergic Neurons; Humans; Peripheral Nervous System; Synaptic Transmission
PubMed: 34458988
DOI: 10.1111/jnc.15480 -
International Journal of Molecular... Aug 2022NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of...
NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions.
Topics: Animals; Central Nervous System; Excitatory Postsynaptic Potentials; Mice; Peptides; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission
PubMed: 36012124
DOI: 10.3390/ijms23168867 -
Nature Reviews. Neuroscience Apr 2014Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one... (Review)
Review
Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function.
Topics: Animals; Brain; Electrical Synapses; Humans; Neurons; Synaptic Transmission
PubMed: 24619342
DOI: 10.1038/nrn3708 -
Cell Reports Nov 2019The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are...
The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresses inhibitory postsynaptic synaptic currents (IPSCs) and GABA-induced currents in lamina II somatostatin-expressing neurons in mouse spinal cord slices. IL-17 mainly expresses in spinal cord astrocytes, and its receptor IL-17R is detected in somatostatin-expressing neurons. Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity. Overexpression of IL-17 in spinal astrocytes is sufficient to induce mechanical allodynia in naive animals. In dorsal root ganglia, IL-17R expression in nociceptive sensory neurons is sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate neuron-glial interactions and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy.
Topics: Animals; Astrocytes; Excitatory Postsynaptic Potentials; Humans; Interleukin-17; Neuralgia; Neuroglia; Neurons; Peripheral Nervous System Diseases; Somatostatin; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 31747607
DOI: 10.1016/j.celrep.2019.10.085 -
Molecular Brain Aug 2013During development both Hebbian and homeostatic mechanisms regulate synaptic efficacy, usually working in opposite directions in response to neuronal activity....
BACKGROUND
During development both Hebbian and homeostatic mechanisms regulate synaptic efficacy, usually working in opposite directions in response to neuronal activity. Homeostatic plasticity has often been investigated by assaying changes in spontaneous synaptic transmission resulting from chronic circuit inactivation. However, effects of inactivation on evoked transmission have been less frequently reported. Importantly, contributions from the effects of circuit inactivation and reactivation on synaptic efficacy have not been individuated.
RESULTS
Here we show for developing hippocampal neurons in primary culture that chronic inactivation with TTX results in increased mean amplitude of miniature synaptic currents (mEPSCs), but not evoked synaptic currents (eEPSCs). However, changes in quantal properties of transmission, partially reflected in mEPSCs, accurately predicted higher-order statistical properties of eEPSCs. The classical prediction of homeostasis--increased strength of evoked transmission--was realized after explicit circuit reactivation, in the form of cells' pairwise connection probability. In contrast, distributions of eEPSC amplitudes for control and inactivated-then-reactivated groups matched throughout.
CONCLUSIONS
Homeostatic up-regulation of evoked synaptic transmission in developing hippocampal neurons in primary culture requires both the inactivation and reactivation stages, leading to a net increase in functional circuit connectivity.
Topics: Action Potentials; Animals; Evoked Potentials; Excitatory Postsynaptic Potentials; Homeostasis; Miniature Postsynaptic Potentials; Nerve Net; Rats; Synaptic Transmission
PubMed: 23965342
DOI: 10.1186/1756-6606-6-38 -
Scientific Reports Aug 2022Infrared (IR) neuromodulation (INM) has been demonstrated as a novel modulation modality of neuronal excitability. However, the effects of pulsed IR light on synaptic...
Infrared (IR) neuromodulation (INM) has been demonstrated as a novel modulation modality of neuronal excitability. However, the effects of pulsed IR light on synaptic transmission have not been investigated systematically. In this report, the IR light (2 μm) is used to directly modulate evoked synaptic transmission at the crayfish opener neuromuscular junction. The extracellularly recorded terminal action potentials (tAPs) and evoked excitatory postsynaptic currents (EPSCs) modulated by localized IR light illumination (500 ms, 3-13 mW) aimed at the synapses are analyzed. The impact of a single IR light pulse on the presynaptic Ca influx is monitored with Ca indicators. The EPSC amplitude is enhanced, and its rising phase is accelerated under relatively low IR light power levels and localized temperature rises. Increasing the IR light power reversibly suppresses and eventually blocks the EPSCs. Meanwhile, the synaptic delay, tAP amplitude, and presynaptic Ca influx decrease monotonously with higher IR light power. It is demonstrated for the first time that IR light illumination has bidirectional effects on evoked synaptic transmission. These results highlight the efficacy and flexibility of using pulsed IR light to directly control synaptic transmission and advance our understanding of INM of neural networks.
Topics: Action Potentials; Excitatory Postsynaptic Potentials; Neuromuscular Junction; Synapses; Synaptic Transmission
PubMed: 35987765
DOI: 10.1038/s41598-022-18139-2