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Cerebral Cortex (New York, N.Y. : 1991) Apr 2023Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the...
Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons. Here, we show that Cannabinoid type 1 receptor (CB1R)-mediated astrocyte activation by neuron-released endocannabinoids elevate astrocyte Ca2+ levels, stimulate ATP/adenosine release as gliotransmitters, and transiently depress synaptic transmission in layer 5 pyramidal neurons at relatively distant synapses (˃20 μm) from the stimulated neuron. This astrocyte-mediated heteroneuronal synaptic depression occurred between pyramidal neurons within a cortical column and was absent in neurons belonging to adjacent cortical columns. Moreover, this form of heteroneuronal synaptic depression occurs between neurons located in particular layers, following a specific connectivity pattern that depends on a layer-specific neuron-to-astrocyte signaling. These results unravel the existence of astrocyte-mediated nonsynaptic communication between cortical neurons and that this communication is column- and layer-specific, which adds further complexity to the intercellular signaling processes in the neocortex.
Topics: Astrocytes; Somatosensory Cortex; Neurons; Synaptic Transmission; Signal Transduction; Synapses
PubMed: 36124663
DOI: 10.1093/cercor/bhac357 -
Methods in Molecular Biology (Clifton,... 2022Synaptic vesicle exocytosis can be monitored with genetically encoded pH sensors in an in vitro fluorescence microscopy setup. Here, we describe a workflow starting with...
Synaptic vesicle exocytosis can be monitored with genetically encoded pH sensors in an in vitro fluorescence microscopy setup. Here, we describe a workflow starting with preparation of a primary cell culture to eventually estimate synaptic vesicle pool sizes based on electrical current-evoked vesicle release, which is reported by the synaptobrevin 2-EGFP fusion protein synapto-pHluorin (spH) that is expressed inside the synaptic vesicle membrane. The readily releasable pool and the recycling pool of synaptic vesicles are released separately in response to electrical stimulation. As vesicle reacidification is blocked in this experimental design, every released vesicle is counted only once. This spH-based approach offers different information than styryl-dye (FM dyes)-based approaches because the total synaptic pool size is measured by an alkalinization step. This provides a normalization constant for quantifying and comparing the synaptic vesicle pool sizes. In addition to investigation of basic research questions, spH-reported vesicle release is valuable to determine presynaptic effects of, e.g., pharmacological drug treatments.
Topics: Exocytosis; Green Fluorescent Proteins; Microscopy, Fluorescence; Synaptic Transmission; Synaptic Vesicles
PubMed: 35099800
DOI: 10.1007/978-1-0716-1916-2_14 -
STAR Protocols Mar 2022Spontaneous spiking activity depends on intrinsic excitability and synaptic input. Historically, synaptic activity has been mostly studied . Here, we describe a...
Spontaneous spiking activity depends on intrinsic excitability and synaptic input. Historically, synaptic activity has been mostly studied . Here, we describe a versatile and robust protocol to record field excitatory postsynaptic potentials (fEPSPs) in behaving rodents. The protocol allows estimating the input-output relationship of a specific pathway, short-term and long-term plasticity, and their modulation by pharmacological or pharmacogenetic interventions and behavioral states. However, experimenters must be aware of the protocol's specificity and interpret results with care. For complete details on the use and execution of this profile, please refer to Styr et al. (2019).
Topics: Animals; Excitatory Postsynaptic Potentials; Female; Male; Mice; Neuronal Plasticity; Synaptic Transmission
PubMed: 35118427
DOI: 10.1016/j.xpro.2021.101115 -
Handbook of Experimental Pharmacology 2015In this chapter we discuss the many recent discoveries of the mechanisms by which itch is transmitted: the neurotransmitters and the responses they trigger, the... (Review)
Review
In this chapter we discuss the many recent discoveries of the mechanisms by which itch is transmitted: the neurotransmitters and the responses they trigger, the mechanisms by which specific neuronal targets are activated, and the specificity of the pathways. Current data reveal that DRG neurons and spinal cord cells use a remarkably selective set of transmitters to convey pruritic information from the periphery to the brain: glutamate and Nppb are released from primary itch-sensory cells; these molecules activate secondary spinal cord pruriceptive-specific neurons, which in turn utilize Grp to activate tertiary pruriceptive-selective neurons. Intersecting this basic linear excitatory pathway, inhibitory input from dynorphin and neurons that express the somatostatin receptor modify itch sensation. Cumulatively, these studies paint an elegantly simple picture of how itch signals are transformed and integrated in the spinal cord and open new avenues for research efforts aimed at understanding and better treating itch.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Pruritus; Spinal Cord; Synaptic Transmission
PubMed: 25861778
DOI: 10.1007/978-3-662-44605-8_8 -
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 -
Cell Jun 2018Adamsky et al. show that stimulation of astrocytes potentiates synaptic transmission and enhances behavioral performance in memory tasks. These results demonstrate that...
Adamsky et al. show that stimulation of astrocytes potentiates synaptic transmission and enhances behavioral performance in memory tasks. These results demonstrate that astrocytes are actively involved in synaptic physiology and brain function and lend further support to the idea that animal behavior results from the coordinated activity of neurons and astrocytes.
Topics: Animals; Astrocytes; Neurons; Synaptic Transmission
PubMed: 29958102
DOI: 10.1016/j.cell.2018.06.023 -
Journal of Neurophysiology Aug 2023Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from... (Review)
Review
Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from literature published before August 2022 about the effects of cannabinoids on quantifiable measures of motoneuron output. Four databases (MEDLINE, Embase, PsycINFO, and Web of Science CoreCollection) were queried and 4,237 unique articles were retrieved. Twenty-three studies met the inclusion criteria, and the findings from these studies were grouped according to four emergent themes: rhythmic motoneuron output, afferent feedback integration, membrane excitability, and neuromuscular junction transmission. This synthesis of evidence suggests that CB1 agonists can increase the frequency of cyclical patterns of motoneuron output (i.e., fictive locomotion). Furthermore, a majority of the evidence indicates that activating CB1 receptors at motoneuron synapses promotes excitation of motoneurons by enhancing excitatory synaptic transmission and depressing inhibitory synaptic transmission. The collated study results reveal variable effects of cannabinoids on acetylcholine release at the neuromuscular junction, and the influence of cannabinoids in this area requires more work to ensure precision of findings for CB1 agonist and antagonist impact. Altogether, these reports indicate that the endocannabinoid system is integral within the final common pathway and can impact motor output. This review contributes to understanding the effects of endocannabinoids on synaptic integration at the motoneuron and modulation of motor output.
Topics: Cannabinoids; Motor Neurons; Synapses; Synaptic Transmission; Neuromuscular Junction
PubMed: 37283484
DOI: 10.1152/jn.00460.2022 -
Current Protocols Apr 2022Synaptic modulation and plasticity are key mechanisms underlying pain transmission in the spinal cord and supra-spinal centers. The study and understanding of these...
Synaptic modulation and plasticity are key mechanisms underlying pain transmission in the spinal cord and supra-spinal centers. The study and understanding of these phenomena are fundamental to investigating both acute nociception and maladaptive changes occurring in chronic pain. This article describes experimental protocols and analytical methods utilized in electrophysiological studies to investigate synaptic modulation and plasticity at the first station of somatosensory processing, the spinal cord dorsal horn. Protocols useful for characterizing the nature of synaptic inputs, the site of modulation (pre- versus postsynaptic), and the presence of short-term synaptic plasticity are presented. These methods can be employed to study the physiology of acute nociception, the pathological mechanisms of persistent inflammatory and neuropathic pain, and the pharmacology of receptors and channels involved in pain transmission. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Spinal cord dissection and acute slice preparation Basic Protocol 2: Stimulation of the dorsal root and extracellular recording (compound action potentials and field potentials) Basic Protocol 3: Patch-clamp recording from dorsal horn neurons: action potential firing patterns and evoked synaptic inputs Basic Protocol 4: Analysis of parameters responsible for changes in synaptic efficacy Basic Protocol 5: Recording and analysis of currents mediated by astrocytic glutamate.
Topics: Animals; Excitatory Postsynaptic Potentials; Neuralgia; Rats; Rats, Sprague-Dawley; Rodentia; Spinal Cord Dorsal Horn; Synaptic Transmission
PubMed: 35435326
DOI: 10.1002/cpz1.409 -
International Journal of Molecular... Feb 2024One of the most biologically relevant functions of astrocytes within the CNS is the regulation of synaptic transmission, i.e., the physiological basis for information... (Review)
Review
One of the most biologically relevant functions of astrocytes within the CNS is the regulation of synaptic transmission, i.e., the physiological basis for information transmission between neurons. Changes in the strength of synaptic connections are indeed thought to be the cellular basis of learning and memory. Importantly, astrocytes have been demonstrated to tightly regulate these processes via the release of several gliotransmitters linked to astrocytic calcium activity as well as astrocyte-neuron metabolic coupling. Therefore, astrocytes seem to be integrators of and actors upon learning- and memory-relevant information. In this review, we focus on the role of astrocytes in learning and memory processes. We delineate the recognized inputs and outputs of astrocytes and explore the influence of manipulating astrocytes on behaviour across diverse learning paradigms. We conclude that astrocytes influence learning and memory in various manners. Appropriate astrocytic Ca dynamics are being increasingly identified as central contributors to memory formation and retrieval. In addition, astrocytes regulate brain rhythms essential for cognition, and astrocyte-neuron metabolic cooperation is required for memory consolidation.
Topics: Astrocytes; Learning; Synaptic Transmission; Neurons; Memory
PubMed: 38339177
DOI: 10.3390/ijms25031899 -
Current Opinion in Structural Biology Aug 2019Chemical and electrical signaling at the synapse is a dynamic process that is crucial to neurotransmission and pathology. Traditional pharmacotherapy has found countless... (Review)
Review
Chemical and electrical signaling at the synapse is a dynamic process that is crucial to neurotransmission and pathology. Traditional pharmacotherapy has found countless applications in both academic labs and the clinic; however, diffusible drugs lack spatial and temporal precision when employed in heterogeneous tissues such as the brain. In the field of photopharmacology, chemical attachment of a synthetic photoswitch to a bioactive ligand allows cellular signaling to be controlled with light. Azobenzenes have remained the go-to photoswitch for biological applications due to their tunable photophysical properties, and can be leveraged to achieve reversible optical control of numerous receptors and ion channels. Here, we discuss the most recent advances in photopharmacology which will improve the use of azobenzene-based probes for neuroscience applications.
Topics: Azo Compounds; Drug Design; Light; Molecular Probes; Signal Transduction; Synaptic Transmission
PubMed: 30825844
DOI: 10.1016/j.sbi.2019.01.022