GABA-mediated neurotransmission in the ventrolateral  NTS plays a role in respiratory regulation in the rat

Wasserman, Adam M.; Ferreira, Manuel; Sahibzada, Niaz; Hernandez, Y. M.; Gillis, Richard A.

doi:10.1152/ajpregu.00488.2001

Cited by 36 publications

(39 citation statements)

References 46 publications

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“…Subsequent to ipsilateral vagotomy and two reproducible responses of L-glutamate microinjection into the unilateral mNTS, bicuculline methiodide (BMI; 20 pmol/30 nl) was microinjected at the same site into the mNTS. This dose of BMI was chosen on the basis of our previous studies of GABAA receptor blockade in the rat NTS (38). Unilateral microinjection of BMI could be repeated following a 30-min period.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…Muscimol (100 pmol/30 nl) was unilaterally microinjected into the mNTS and could be repeated following a 30-min interval to allow complete recovery to baseline activity. This dose was chosen on the basis of our previous work (38).…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…Kynurenic acid (Kyn; 1 nmol/30 nl) was then microinjected into the mNTS at the same site. This dose was chosen on the basis of our previous studies (38). Microinjection of Kyn was not repeated.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

Herman

Cruz²,

Sahibzada³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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It has been proposed that there is an "apparent monosynaptic" connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes (6). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release L-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABA A receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (Ϫ1.6 Ϯ 0.2 mmHg, P Ͻ 0.05, n ϭ 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABA A receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or N G -nitro-L-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABA A receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABA A receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit. gastric; vagus; afferent; inhibition; rat THE IMPORTANCE OF THE VAGOVAGAL reflexes in the regulation of gastrointestinal (GI) function has been highlighted in a recent series of articles published under the theme "Musings on the Wanderer: What's New in Our Understanding of Vagovagal Reflexes?" (6, 37). The central nervous system component of this reflex circuit is located in the hindbrain and consists of a sensory nucleus, the nucleus tractus solitarius (NTS), and a motor nucleus, the dorsal motor nucleus of the vagus (DMV). Currently it is thought that signals from sensory receptors in the GI tract are received in the NTS and conveyed to DMV preganglionic vagal nerves (28, 36). These impulses produce functional changes in thoracic and abdominal viscera (28, 36). Critical to conveying sensory signals to vagal efferent impulses are synaptic connections between NTS and DMV neurons. There is considerable evidence that GABAergic neurons are responsible for a significant part of this communication (9, 35). There is also evidence that noradrenergic neurons take part in this communication process (10,11,18,26,29). Both the GABAergic and noradrenergic neurons are considered...

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Section: Experimental Protocolsmentioning

confidence: 99%

Section: Experimental Protocolsmentioning

confidence: 99%

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GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

Herman

Cruz²,

Sahibzada³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

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“…The GABA A receptor is widely expressed in the medulla and is involved in diverse aspects of autonomic function, including control of breathing (Wasserman et al, 2002;Lujan et al, 2005). At P5, GABA A receptors were found on neurons in the LRt, IO, nTS, and Cu nuclei.…”

Section: Characteristics Of Plp-egfp Neuronsmentioning

confidence: 99%

Neuronal expression of the proteolipid protein gene in the medulla of the mouse

Miller¹,

Kangas²,

Macklin³

2009

J of Neuroscience Research

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The proteolipid protein (PLP) gene (Plp) encodes the major myelin proteins, PLP and DM20. Expression of Plp occurs predominantly in oligodendrocytes, but evidence is accumulating that this gene is also expressed in neurons. In earlier studies, we demonstrated that myelin-deficient (MD) rats, which carry a mutation in the Plp gene, exhibit lethal hypoxic ventilatory depression. Furthermore, we found that, in the MD rat, PLP accumulated in neuronal cell bodies in the medulla oblongata. In the current study, we sought to determine which neurons expressed the Plp gene in the medulla oblongata and whether Plp gene expression changed in neurons with maturation. A transgenic mouse expressing the Plp promoter driving expression of enhanced green fluorescent protein (Plp-EGFP) was used to identify neurons expressing this gene. Plp expression in neurons was confirmed by immunostaining EGFP-positive cells for NeuN and by in situ hybridization for PLP mRNA. The numbers of neurons expressing Plp-EGFP and their distribution increased between P5 and P10 in the medulla. Immunostaining for surface receptors and classes of neurons expressing Plp-EGFP revealed that Plp gene expression in brainstem neurons was restricted to neurons expressing specific ligand-gated channels and biosynthetic enzymes, including glutamatergic NMDA receptors, GABA(A) receptors, and ChAT in defined areas of the medulla. Plp gene expression was rarely found in interneurons expressing GABA and was never found in AMPA receptor- or tyrosine hydroxylase-expressing neurons. Thus, Plp expression in the mouse caudal medulla was found to be developmentally regulated and restricted to specific groups of neurons.

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“…The neurons responsible for propofol depression of cardiorespiratory control are unknown, but most likely homeostatic depression involves autonomic pathways within the brainstem that are compromised by general anesthetics (Lee et al, 2002). Indeed modulation of GABA neurotransmission within the NTS may alter multiple homeostatic processes within the gastrointestinal (Travagli et al, 2006), respiratory (Wasserman et al, 2002) and cardiovascular systems. Propofol likely enhances solitary tract driven GABAergic inputs as well as other major sources of inhibitory input to NTS from the forebrain (Saha, 2005).…”

Section: Propofol Actions In Nts In Vitro and Autonomic Controlmentioning

confidence: 99%

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

et al. 2008

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The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter" <200 µs), "all-or-none" glutamatergic excitatory postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol prolonged miniature IPSC decay time constants by 50% above control at 1.8 µM. Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher concentrations, propofol (30 µM) induced a gabazine-insensitive tonic current that was blocked by picrotoxin or bicuculline. In contrast, total propofol concentrations up to 30 µM had no effect on EPSCs. Thus, propofol enhanced phasic GABA events in NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.

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GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat

Cited by 36 publications

References 46 publications

GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit

Neuronal expression of the proteolipid protein gene in the medulla of the mouse

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

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