Browse
Submit Data
Databases
API
Help

Dataset Information

34 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mammalian motor neurons corelease glutamate and acetylcholine at central synapses.

ABSTRACT: Motor neurons (MNs) are the principal neurons in the mammalian spinal cord whose activities cause muscles to contract. In addition to their peripheral axons, MNs have central collaterals that contact inhibitory Renshaw cells and other MNs. Since its original discovery >60 years ago, it has been a general notion that acetylcholine is the only transmitter released from MN synapses both peripherally and centrally. Here, we show, using a multidisciplinary approach, that mammalian spinal MNs, in addition to acetylcholine, corelease glutamate to excite Renshaw cells and other MNs but not to excite muscles. Our study demonstrates that glutamate can be released as a functional neurotransmitter from mammalian MNs.

SUBMITTER: Nishimaru H

PROVIDER: S-EPMC555035 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo.

Project description:Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively in dopamine neurons. The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices. Baseline motor behavior is not affected, but stimulation of locomotor activity by cocaine is impaired, apparently through a selective reduction of dopamine stores in the projection of VTA neurons to ventral striatum. Glutamate co-entry promotes monoamine storage by increasing the pH gradient that drives vesicular monoamine transport. Remarkably, low concentrations of glutamate acidify synaptic vesicles more slowly but to a greater extent than equimolar Cl(-), indicating a distinct, presynaptic mechanism to regulate quantal size.

| S-EPMC2846457 | biostudies-literature

Central synapses release a resource-efficient amount of glutamate.

Project description:Why synapses release a certain amount of neurotransmitter is poorly understood. We combined patch-clamp electrophysiology with computer simulations to estimate how much glutamate is discharged at two distinct central synapses of the rat. We found that, regardless of some uncertainty over synaptic microenvironment, synapses generate the maximal current per released glutamate molecule while maximizing signal information content. Our result suggests that synapses operate on a principle of resource optimization.

| S-EPMC3605778 | biostudies-literature

Fatty-acid-binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses.

Project description:Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the cellular mechanisms by which eCBs control synaptic function have been well characterized, the mechanisms controlling their retrograde synaptic transport remain unknown. Here, we demonstrate that fatty-acid-binding protein 5 (FABP5), a canonical intracellular carrier of eCBs, is indispensable for retrograde eCB transport in the dorsal raphe nucleus (DRn). Thus, pharmacological inhibition or genetic deletion of FABP5 abolishes both phasic and tonic eCB-mediated control of excitatory synaptic transmission in the DRn. The blockade of retrograde eCB signaling induced by FABP5 inhibition is not mediated by impaired cannabinoid receptor function or reduced eCB synthesis. These findings indicate that FABP5 is essential for retrograde eCB signaling and may serve as a synaptic carrier of eCBs at central synapses.

| S-EPMC5879704 | biostudies-literature

Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons.

Project description:Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons.

| S-EPMC6489450 | biostudies-literature

Single synapse glutamate imaging reveals multiple levels of release mode regulation in mammalian synapses.

Project description:Mammalian central synapses exhibit vast heterogeneity in signaling strength. To understand the extent of this diversity, how it is achieved, and its functional implications, characterization of a large number of individual synapses is required. Using glutamate imaging, we characterized the evoked release probability and spontaneous release frequency of over 24,000 individual synapses. We found striking variability and no correlation between action potential-evoked and spontaneous synaptic release strength, suggesting distinct regulatory mechanisms. Subpixel localization of individual evoked and spontaneous release events reveals tight spatial regulation of evoked release and enhanced spontaneous release outside of evoked release region. Using on-stage post hoc immune-labeling of vesicle-associated proteins, Ca2+-sensing proteins, and soluble presynaptic proteins we were able to show that distinct molecular ensembles are associated with evoked and spontaneous modes of synaptic release.

| S-EPMC7773578 | biostudies-literature

Chick ciliary ganglion neurons contain transcripts coding for acetylcholine receptor-associated protein at synapses (rapsyn).

Project description:A peripheral membrane protein of approximately 43 kDa (rapsyn) clusters muscle nicotinic acetylcholine receptors (AChRs), but molecules relevant to clustering neuronal AChRs have not been identified. Here, we have detected rapsyn transcripts in the chick nervous system, localized rapsyn mRNA in ciliary ganglion (CG) neurons, which are known to cluster AChRs, and identified three rapsyn cDNAs derived from the ganglion. Our initial Northern blots, performed using a mouse probe, revealed rapsyn-like transcripts in chick muscle and brain. To develop species-specific probes, we prepared a chick rapsyn cDNA construct, Ch43K.1, that encodes a protein having extensive homology to mouse rapsyn. Using primers designed to anneal near the 5' and 3' boundaries of Ch43K.1, three prominent cDNAs were amplified from chick muscle templates by reverse transcriptase based-PCR. Products of similar size were also amplified using cDNA prepared from neuronal tissues expected to contain clustered AChRs (CG and brain), whereas none were detected using templates from tissues not displaying clustered AChRs (sensory ganglia and liver). In situ hybridization confirmed that rapsyn mRNA is expressed both in chick muscle fibers and in CG neurons. Sequencing the three cDNAs amplified from CG templates revealed the largest to be Ch43K.1, whereas the smaller two may represent splice variants. These findings suggest that multiple rapsyn-like molecules are involved in clustering the distinct AChRs expressed by muscle fibers and neurons.

| S-EPMC6573290 | biostudies-literature

Dopamine Cells Differentially Regulate Striatal Cholinergic Transmission across Regions through Corelease of Dopamine and Glutamate.

Project description:The balance of dopamine and acetylcholine in the dorsal striatum is critical for motor and learning functions. Midbrain dopamine cells and local cholinergic interneurons (ChIs) densely innervate the striatum and have strong reciprocal actions on each other. Although dopamine inputs regulate ChIs, the functional consequences of dopamine neuron activity across dorsal striatal regions is poorly understood. Here, we find that midbrain dopamine neurons drive pauses in the firing of dorsomedial ChIs but robust bursts in dorsolateral ChIs. Pauses are mediated by dopamine D2 receptors, while bursts are driven by glutamate corelease and activation of a mGluR-mediated excitatory conductance. We find the frequency of muscarinic cholinergic transmission to medium spiny neurons is greater in the dorsomedial striatum. This regional variation in transmission is moderated by the different actions of dopamine and glutamate corelease. These results delineate a mechanism by which dopamine inputs maintain consistent levels of cholinergic activity across the dorsal striatum.

| S-EPMC6658127 | biostudies-literature

Glutamate signaling at cytoneme synapses.

Project description:We investigated the roles of components of neuronal synapses for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.

| S-EPMC7008667 | biostudies-literature

Abelson family tyrosine kinases regulate the function of nicotinic acetylcholine receptors and nicotinic synapses on autonomic neurons.

Project description:Abelson family kinases (AFKs; Abl1, Abl2) are non-receptor tyrosine kinases (NRTKs) implicated in cancer, but they also have important physiological roles that include regulating synaptic structure and function. Recent studies using Abl-deficient mice and the antileukemia drug STI571 [imatinib mesylate (Gleevec); Novartis], which potently and selectively blocks Abl kinase activity, implicate AFKs in regulating presynaptic neurotransmitter release in hippocampus and postsynaptic clustering of nicotinic acetylcholine receptors (nAChRs) in muscle. Here, we tested whether AFKs are relevant for regulating nAChRs and nAChR-mediated synapses on autonomic neurons. AFK immunoreactivity was detected in ciliary ganglion (CG) lysates and neurons, and STI571 application blocked endogenous Abl tyrosine kinase activity. With similar potency, STI571 specifically reduced whole-cell current responses generated by both nicotinic receptor subtypes present on CG neurons (?3*- and ?7-nAChRs) and lowered the frequency and amplitude of ?3*-nAChR-mediated excitatory postsynaptic currents. Quantal analysis indicated that the synaptic perturbations were postsynaptic in origin, and confocal imaging experiments revealed they were unaccompanied by changes in nAChR clustering or alignment with presynaptic terminals. The results indicate that in autonomic neurons, Abl kinase activity normally supports postsynaptic nAChR function to sustain nAChR-mediated neurotransmission. Such consequences contrast with the influence of Abl kinase activity on presynaptic function and synaptic structure in hippocampus and muscle, respectively, demonstrating a cell-specific mechanism of action. Finally, because STI571 potently inhibits Abl kinase activity, the autonomic dysfunction side effects associated with its use as a chemotherapeutic agent may result from perturbed ?3*- and/or ?7-nAChR function.

| S-EPMC3127535 | biostudies-literature

Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system.

Project description:Complexins (Cplxs) are key regulators of synaptic exocytosis, but whether they act as facilitators or inhibitors is currently being disputed controversially. We show that genetic deletion of all Cplxs expressed in the mouse brain causes a reduction in Ca(2+)-triggered and spontaneous neurotransmitter release at both excitatory and inhibitory synapses. Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery.

| S-EPMC2409395 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data