Corelease of Two Fast Neurotransmitters at a Central Synapse

Jónás, Péter; Bischofberger, Josef; Sandkühler, Jürgen

doi:10.1126/science.281.5375.419

Cited by 749 publications

(656 citation statements)

References 32 publications

Supporting

Mentioning

601

Contrasting

Unclassified

Order By: Relevance

“…Both antagonists at high enough concentrations will cross-react with the other receptor. However the concentrations used to isolate mIPSCs and sIPSCs in the present study are below those at which appreciable crossover block occurs (Jonas et al, 1998). In that study glycine was the dominant contributor to evoked IPSCs, with faster kinetics than GABAergic currents.…”

Section: Spontaneous Inhibitionmentioning

confidence: 58%

“…In the glycine pu experiments, unlike the experiments on release, bicuculline concentrations were in the range in which some crossover block of glycine receptors is observed (Jonas et al, 1998); however this should not have a ected anaesthetic actions on the remaining glycine currents. In some neurons amplitudes were decreased, although the decrease was signi®cant only for sIPSCs in the presence of en¯urane.…”

Section: Anaesthetic Actions: Postsynapticmentioning

confidence: 93%

See 1 more Smart Citation

Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons

Gong

Kendig

2002

British J Pharmacology

View full text Add to dashboard Cite

1 A common anaesthetic endpoint, prevention of withdrawal from a noxious stimulus, is determined primarily in spinal cord, where glycine is an important inhibitory transmitter. To de®ne pre-and postsynaptic anaesthetic actions at glycinergic snyapses, the e ects of volatile anaesthetic agents on spontaneous and evoked glycinergic currents in spinal cord motor neurons from 6 ± 14-day old rats was investigated. 2 The volatile anaesthetic agents en¯urane, iso¯urane and halothane signi®cantly increased the frequency of glycinergic mIPSCs, en¯urane to 190.4% of control+22.0 (mean+s.e.m., n=7, P50.01), iso¯urane to 199.0%+28.8 (n=7, P50.05) and halothane to 198.2%+19.5 (n=7, P50.01). However without TTX, iso¯urane and halothane had no signi®cant e ect and en¯urane decreased sIPSC frequency to 42.5% of control+12.4 (n=6, P50.01). All the anaesthetics prolonged the decay time constant (t) of both spontaneous and glycine-evoked currents without increasing amplitude. With TTX total charge transfer was increased; without TTX charge transfer was unchanged (iso¯urane and halothane) or decreased (en¯urane). 3 En¯urane-induced mIPSC frequency increases were not signi®cantly a ected by Cd 2+ (50 mM), thapsigargin (1 ± 5 mM), or KB-R7943 (5 mM). KB-R7943 and thapsigargin together abolished the en¯urane-induced increase in mIPSC frequency. 4 There are opposing facilitatory and inhibitory actions of volatile anaesthetics on glycine release dependent on calcium homeostatic mechanisms and sodium channels respectively. Under normal conditions (no TTX) the absolute amount of glycinergic inhibition does not increase. The contribution of glycinergic inhibition to anaesthesia may depend on its duration rather than its absolute magnitude.

show abstract

Section: Spontaneous Inhibitionmentioning

confidence: 58%

Section: Anaesthetic Actions: Postsynapticmentioning

confidence: 93%

Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons

Gong

Kendig

2002

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Like other examples of cotransmission (23,24), the functional consequences of having two transmitters at central spinal synapses are not completely clear. Activity in central MN synapses generate negative (MN-RC-MN) and positive (MN-MN) feedback loops that in turn regulate MN activity.…”

Section: Discussionmentioning

confidence: 95%

Mammalian motor neurons corelease glutamate and acetylcholine at central synapses

Nishimaru

Restrepo

Ryge

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

220

201

View full text Add to dashboard Cite

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.synaptic transmission ͉ spinal cord M otor neurons (MNs) are the output neurons from the central nervous system. Their activity directly leads to muscle contraction. By the 1940s, it was generally accepted that MNs release acetylcholine (ACh) at the neuromuscular junction (1). Shortly thereafter, it was shown that ACh also is released from MNs' central axonal branches contacting Renshaw cells (RCs) (2). As was found at the neuromuscular junction, this transmission was shown to be nicotinic (3, 4). The collaterals contacting other MNs (5) are also thought to be mediated by ACh, although this has not been shown directly (6). Since these initial discoveries and after many later investigations, it has been a general dogma that mammalian MNs contain and release one neurotransmitter, ACh, both centrally and peripherally. It has been suggested recently, based on anatomical data, that MNs might contain glutamate as a neurotransmitter (7,8). There has been, however, no direct electrophysiological evidence to support this. Here, we examine this question directly by investigating the transmission in central and peripheral MN synapses (Fig. 1a). Materials and MethodsRecordings from RCs and MNs. All procedures followed Swedish federal guidelines for animal care. Postnatal heterozygote glutamic acid decarboxylase (GAD) 67-GFP mice [postnatal day (P) 0 to P4] were anaesthetized with isoflurane and eviscerated, and spinal cords were removed with ventral laminectomy, as described in ref. 9. The spinal cord was placed in a recording chamber perfused with oxygenated Ringer's solution (128 mM NaCl͞4.69 mM KCl͞25 mM NaHCO 3 ͞1.18 mM KH 2 PO 4 ͞1.25 mM MgSO 4 ͞2.5 mM CaCl 2 ͞22 mM glucose aerated with 5% CO 2 in O 2 ) at room temperature. Whole-cell tight-seal recording of RCs and MNs were performed with patch electrodes pulled from thick-walled borosilicate glass (o.d. of 1.5 mm, i.d. of 1.0 mm; Harvard Instruments) to a final resistance of 5-8 M⍀. The electrode tips were filled with 138 mM K-gluconate, 10 mM Hepes, 0.0001 mM CaCl 2 , 5 mM ATP-Mg, and 0.3 mM GTP-Li. After filling of the tip, the electrodes were back-filled with the same solution, and to label the recorded cell, Alexa Fluor dye (0.15-0.20%; Molecular Probes) or neurobiotin (1-2%) was diluted into the electrode solution. Cells were filled during recording. Signals wer...

show abstract

“…ten Bruggencate and Sonnhof (1972) demonstrated that iontophoretic application of glycine and GABA generates IPSPs in hypoglossal motoneurons, and this hyperpolarization can be blocked by glycine and GABA antagonists, strychnine and picrotoxin, respectively. Studies using intracellular recording in rodent in vitro preparation showed that glycine and GABA are either colocalized and coreleased from the same presynaptic vesicle or released from the separate terminals onto spinal and cranial motoneurons (Jonas et al, 1998;O'Brien and Berger, 1999;Russier et al, 2002). Anatomical studies also demonstrated that input terminals on spinal motoneurons contain GABA, glycine, or both (Taal and Holstege, 1994;Ornung et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: AnIn VivoMicrodialysis Study

2003

View full text Add to dashboard Cite

We hypothesized that cessation of brainstem monoaminergic systems and an activation of brainstem inhibitory systems are both involved in pontine inhibitory area (PIA) stimulation-induced muscle atonia. In our previous study (Lai et al., 2001), we found a decrease in norepinephrine and serotonin release in motoneuron pools during PIA stimulation-induced muscle tone suppression. We now demonstrate an increase in inhibitory amino acid release in motor nuclei during PIA stimulation in the decerebrate cat using in vivo microdialysis and HPLC analysis techniques. Microinjection of acetylcholine into the PIA elicited muscle atonia and simultaneously produced a significant increase in both glycine and GABA release in both the hypoglossal nucleus and the lumbar ventral horn. Glycine release increased by 74% in the hypoglossal nucleus and 50% in the spinal cord. GABA release increased by 31% in the hypoglossal nucleus and 64% in the spinal cord during atonia induced by cholinergic stimulation of the PIA. As with cholinergic stimulation, 300 msec train electrical stimulation of the PIA elicited a significant increase in glycine release in the hypoglossal nucleus and ventral horn. GABA release was significantly increased in the hypoglossal nucleus but not in the spinal cord during electrical stimulation of the PIA. Glutamate release in the motor nuclei was not significantly altered during atonia induced by electrical or acetylcholine stimulation of the PIA. We suggest that both glycine and GABA play important roles in the regulation of upper airway and postural muscle tone. A combination of decreased monoamine and increased inhibitory amino acid release in motoneuron pools causes PIA-induced atonia and may be involved in atonia linked to rapid eye-movement sleep.

show abstract

Corelease of Two Fast Neurotransmitters at a Central Synapse

Cited by 749 publications

References 32 publications

Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons

Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons

Mammalian motor neurons corelease glutamate and acetylcholine at central synapses

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: AnIn VivoMicrodialysis Study

Contact Info

Product

Resources

About