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Trends in Neurosciences Mar 2016Action potentials invading the presynaptic terminal trigger discharge of docked synaptic vesicles (SVs) by opening voltage-dependent calcium channels (CaVs) and... (Review)
Review
Action potentials invading the presynaptic terminal trigger discharge of docked synaptic vesicles (SVs) by opening voltage-dependent calcium channels (CaVs) and admitting calcium ions (Ca(2+)), which diffuse to, and activate, SV sensors. At most synapses, SV sensors and CaVs are sufficiently close that release is gated by individual CaV Ca(2+) nanodomains centered on the channel mouth. Other synapses gate SV release with extensive Ca(2+) microdomains summed from many, more distant CaVs. We review the experimental preparations, theories, and methods that provided principles of release nanophysiology and highlight expansion of the field into synaptic diversity and modifications of release gating for specific synaptic demands. Specializations in domain gating may adapt the terminal for roles in development, transmission of rapid impulse frequencies, and modulation of synaptic strength.
Topics: Animals; Neurotransmitter Agents; Synapses; Synaptic Transmission
PubMed: 26896416
DOI: 10.1016/j.tins.2016.01.005 -
Scientific Reports Oct 2020Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical...
Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy-the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.
Topics: Animals; Chiroptera; Gene Expression; Hippocampus; Learning; Memory; Mice; Neural Pathways; Neuronal Plasticity; Shrews; Species Specificity; Synaptic Transmission; Synaptotagmins
PubMed: 33024184
DOI: 10.1038/s41598-020-73547-6 -
Neuroscience Nov 2019Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as... (Review)
Review
Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as major players in regulating presynaptic neurotransmitter release, accumulative evidence over recent years has identified several SNARE proteins implicated in important postsynaptic processes such as neurotransmitter receptor trafficking and synaptic plasticity. Here we analyze the emerging data revealing this novel functional dimension for SNAREs with a focus on the molecular specialization of vesicular recycling and fusion in dendrites compared to those at axon terminals and its impact in synaptic transmission and plasticity.
Topics: Animals; Humans; Neuronal Plasticity; Neurons; SNARE Proteins; Synaptic Transmission
PubMed: 30458218
DOI: 10.1016/j.neuroscience.2018.11.012 -
Neuroscience May 2016Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity... (Review)
Review
Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes.
Topics: Animals; Astrocytes; Humans; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 25862587
DOI: 10.1016/j.neuroscience.2015.04.001 -
Current Biology : CB May 2020Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The... (Review)
Review
Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.
Topics: Animals; Biological Evolution; Neurons; Synapses; Synaptic Transmission
PubMed: 32428501
DOI: 10.1016/j.cub.2020.04.008 -
Frontiers in Neural Circuits 2019The neocortex is densely innervated by basal forebrain (BF) cholinergic neurons. Long-range axons of cholinergic neurons regulate higher-order cognitive function and... (Review)
Review
The neocortex is densely innervated by basal forebrain (BF) cholinergic neurons. Long-range axons of cholinergic neurons regulate higher-order cognitive function and dysfunction in the neocortex by releasing acetylcholine (ACh). ACh release dynamically reconfigures neocortical microcircuitry through differential spatiotemporal actions on cell-types and their synaptic connections. At the cellular level, ACh release controls neuronal excitability and firing rate, by hyperpolarizing or depolarizing target neurons. At the synaptic level, ACh impacts transmission dynamics not only by altering the presynaptic probability of release, but also the magnitude of the postsynaptic response. Despite the crucial role of ACh release in physiology and pathophysiology, a comprehensive understanding of the way it regulates the activity of diverse neocortical cell-types and synaptic connections has remained elusive. This review aims to summarize the state-of-the-art anatomical and physiological data to develop a functional map of the cellular, synaptic and microcircuit effects of ACh in the neocortex of rodents and non-human primates, and to serve as a quantitative reference for those intending to build data-driven computational models on the role of ACh in governing brain states.
Topics: Acetylcholine; Animals; Computer Simulation; Models, Neurological; Neocortex; Synaptic Transmission
PubMed: 31031601
DOI: 10.3389/fncir.2019.00024 -
Wiley Interdisciplinary Reviews.... Sep 2017Synaptic transmission is dynamic, plastic, and highly regulated. Drosophila is an advantageous model system for genetic and molecular studies of presynaptic and... (Review)
Review
Synaptic transmission is dynamic, plastic, and highly regulated. Drosophila is an advantageous model system for genetic and molecular studies of presynaptic and postsynaptic mechanisms and plasticity. Electrical recordings of synaptic responses represent a wide-spread approach to study neuronal signaling and synaptic transmission. We discuss experimental techniques that allow monitoring synaptic transmission in Drosophila neuromuscular and central systems. Recordings of synaptic potentials or currents at the larval neuromuscular junction (NMJ) are most common and provide numerous technical advantages due to robustness of the preparation, large and identifiable muscles, and synaptic boutons which can be readily visualized. In particular, focal macropatch recordings combined with the analysis of neurosecretory quanta enable rigorous quantification of the magnitude and kinetics of transmitter release. Patch-clamp recordings of synaptic transmission from the embryonic NMJ enable overcoming the problem of lethality in mutant lines. Recordings from the adult NMJ proved instrumental in the studies of temperature-sensitive paralytic mutants. Genetic studies of behavioral learning in Drosophila compel an investigation of synaptic transmission in the central nervous system (CNS), including primary cultured neurons and an intact brain. Cholinergic and GABAergic synaptic transmission has been recorded from the Drosophila CNS both in vitro and in vivo. In vivo patch-clamp recordings of synaptic transmission from the neurons in the olfactory pathway is a very powerful approach, which has a potential to elucidate how synaptic transmission is associated with behavioral learning. WIREs Dev Biol 2017, 6:e277. doi: 10.1002/wdev.277 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Drosophila; Drosophila Proteins; Electrophysiology; Neuromuscular Junction; Neurons; Synaptic Transmission
PubMed: 28544556
DOI: 10.1002/wdev.277 -
Brain, Behavior, and Immunity Jan 2024Cytokines are potent immunomodulators exerting pleiotropic effects in the central nervous system (CNS). They influence neuronal functions and circuit activities with...
Cytokines are potent immunomodulators exerting pleiotropic effects in the central nervous system (CNS). They influence neuronal functions and circuit activities with effects on memory processes and behaviors. Here, we unravel a neuromodulatory activity of interleukin-15 (IL-15) in mouse brain. Acute exposure of hippocampal slices to IL-15 enhances gamma-aminobutyricacid (GABA) release and reduces glutamatergic currents, while chronic treatment with IL-15 increases the frequency of hippocampal miniature inhibitory synaptic transmission and impairs memory formation in the novel object recognition (NOR) test. Moreover, we describe that serotonin is involved in mediating the hippocampal effects of IL-15, because a selective 5-HTA receptor antagonist prevents the effects on inhibitory neurotransmission and ameliorates mice performance in the NOR test. These findings provide new insights into the modulatory activities of cytokines in the CNS, with implications on behavior.
Topics: Mice; Animals; Interleukin-15; Memory, Episodic; Hippocampus; Synaptic Transmission; Neurons
PubMed: 37992787
DOI: 10.1016/j.bbi.2023.11.015 -
Advances in Experimental Medicine and... 2016Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In... (Review)
Review
Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission.Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming.
Topics: Animals; Diet; Enteric Nervous System; Gastrointestinal Tract; Neurons; Synaptic Transmission
PubMed: 27379647
DOI: 10.1007/978-3-319-27592-5_19 -
The Journal of Neuroscience : the... Apr 2022The presynaptic action potential (AP) is required to drive calcium influx into nerve terminals, resulting in neurotransmitter release. Accordingly, the AP waveform is...
The presynaptic action potential (AP) is required to drive calcium influx into nerve terminals, resulting in neurotransmitter release. Accordingly, the AP waveform is crucial in determining the timing and strength of synaptic transmission. The calyx of Held nerve terminals of rats of either sex showed minimum changes in AP waveform during high-frequency AP firing. We found that the stability of the calyceal AP waveform requires KCNQ (K7) K channel activation during high-frequency spiking activity. High-frequency presynaptic spikes gradually led to accumulation of KCNQ channels in open states which kept interspike membrane potential sufficiently negative to maintain Na channel availability. Blocking KCNQ channels during stimulus trains led to inactivation of presynaptic Na, and to a lesser extent K1 channels, thereby reducing the AP amplitude and broadening AP duration. Moreover, blocking KCNQ channels disrupted the stable calcium influx and glutamate release required for reliable synaptic transmission at high frequency. Thus, while KCNQ channels are generally thought to prevent hyperactivity of neurons, we find that in axon terminals these channels function to facilitate reliable high-frequency synaptic signaling needed for sensory information processing. The presynaptic spike results in calcium influx required for neurotransmitter release. For this reason, the spike waveform is crucial in determining the timing and strength of synaptic transmission. Auditory information is encoded by spikes phase locked to sound frequency at high rates. The calyx of Held nerve terminals in the auditory brainstem show minimum changes in spike waveform during high-frequency spike firing. We found that activation of KCNQ K channel builds up during high-frequency firing and its activation helps to maintain a stable spike waveform and reliable synaptic transmission. While KCNQ channels are generally thought to prevent hyperexcitability of neurons, we find that in axon terminals these channels function to facilitate high-frequency synaptic signaling during auditory information processing.
Topics: Action Potentials; Animals; Calcium; Neurotransmitter Agents; Presynaptic Terminals; Rats; Sodium; Synaptic Transmission
PubMed: 35256530
DOI: 10.1523/JNEUROSCI.0363-20.2022