Expression of N-methyl-D-aspartate receptor subunits in the rat parabrachial and K�lliker-Fuse nuclei and in selected pontomedullary brainstem nuclei

Guthmann, Axel; Herbert, Horst

doi:10.1002/(sici)1096-9861(19991227)415:4<501::aid-cne6>3.0.co;2-9

Cited by 39 publications

(7 citation statements)

References 51 publications

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“…Numerous experiments illustrate that IOS is disrupted after local blockade of NMDA-R in the KF-area or following systemic application of NMDA-R antagonists (34,43,48,71,79,99,120,121,125,127,160,161, 226,266,291–293,355). These findings are consistent with the dense expression of NMDA-Rs in KF neurons (151,207,259). Because NMDA-Rs commonly expressed postsynaptically, it is most likely that local NMDA-R blockade is suppressing glutamatergic input to KF neurons.…”

Section: The Parabrachial Complex and Kölliker-fuse Nuclei Of The Dorsupporting

confidence: 89%

“…Furthermore, AMPA-receptor blockade did not affect vagally mediated reflex apnea induced by intravenous infusion of serotonin (187), while pharmacological blockade of metabotropic glutamate receptors exacerbated apneic responses to intravenous serotonin (365). Thus, functional apneic responses from the ITR may be mediated via NMDA-R, which are reported to be densely expressed in this pontine brain region (151). Yet, ironically unilateral lesioning of the ITR region increases the incidence of sleep apnea (302).…”

Section: Intertrigeminal Region Of the Mediolateral Ponsmentioning

confidence: 99%

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Pontine Mechanisms of Respiratory Control

Dutschmann

Dick

2012

Comprehensive Physiology

222

201

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Pontine respiratory nuclei provide synaptic input to medullary rhythmogenic circuits to shape and adapt the breathing pattern. An understanding of this statement depends on appreciating breathing as a behavior, rather than a stereotypic rhythm. In this review, we focus on the pontine-mediated inspiratory off-switch (IOS) associated with postinspiratory glottal constriction. Further, IOS is examined in the context of pontine regulation of glottal resistance in response to multimodal sensory inputs and higher commands, which in turn rules timing, duration, and patterning of respiratory airflow. In addition, network plasticity in respiratory control emerges during the development of the pons. Synaptic plasticity is required for dynamic and efficient modulation of the expiratory breathing pattern to cope with rapid changes from eupneic to adaptive breathing linked to exploratory (foraging and sniffing) and expulsive (vocalizing, coughing, sneezing, and retching) behaviors, as well as conveyance of basic emotions. The speed and complexity of changes in the breathing pattern of behaving animals implies that “learning to breathe” is necessary to adjust to changing internal and external states to maintain homeostasis and survival.

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Section: The Parabrachial Complex and Kölliker-fuse Nuclei Of The Dorsupporting

confidence: 89%

Section: Intertrigeminal Region Of the Mediolateral Ponsmentioning

confidence: 99%

Pontine Mechanisms of Respiratory Control

Dutschmann

Dick

2012

Comprehensive Physiology

222

201

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“…However, in our opinion, NMDA-R blockade largely interrupts ascending glutamatergic transmission from medullary respiratory centres to the pons and, in particular, to the KF. This suggestion is supported by the findings that local blockade of post-synaptic NMDA-R in the KF causes apneusis (Fung et al 1994;Ling et al 1994 Herbert 1999). We therefore suggest that pontine-mediated IE phase transition depends largely on excitatory glutamatergic inputs to the KF.…”

Section: Pontine-mediated Inspiratory/ Expiratory Phase Transition: a Physiological Role Revisitedsupporting

confidence: 72%

Pontine respiratory activity involved in inspiratory/expiratory phase transition

Mörschel

Dutschmann

2009

Phil. Trans. R. Soc. B

100

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Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (BreuerHering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kölliker-Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo. Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically.Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed.

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“…However, the existence of triheteromeric GluN1/GluN2A/GluN2C receptors in these cells has not been explicitly demonstrated. The GluN2A and GluN2C subunits are also co-expressed in the cortex of rodent olfactory bulb, spinal cord, and locus coeruleus (Akazawa et al, 1994; Allgaier et al, 2001; Sun et al, 2000; Sundström et al, 1997), as well as the suprachiasmatic nucleus (Clark and Kofuji, 2010; O’Hara et al, 1995), brainstem nuclei (Guthmann and Herbert, 1999), hypothalamus (Al-Ghoul et al, 1997), thalamus (Wenzel et al, 1997), and retinal ganglion cells (Lagréze et al, 2000). Despite these reports of GluN2A and GluN2C co-expression in the CNS by detecting mRNA expression and subunit-selective antibody labeling, there is only a single description of glutamate and glycine potencies in Xenopus oocytes co-expressing GluN1, GluN2A, and GluN2C, in which the authors report an intermediate EC 50 with variable Hill slopes (Wafford et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells

Bhattacharya

Khatri

Swanger

et al. 2018

Neuron

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NMDA-type glutamate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory neurotransmission in the CNS. Here we describe functional and single-channel properties of triheteromeric GluN1/GluN2A/GluN2C receptors, which contain two GluN1, one GluN2A, and one GluN2C subunits. This NMDAR has three conductance levels and opens in bursts similar to GluN1/GluN2A receptors but with a single-channel open time and open probability reminiscent of GluN1/GluN2C receptors. The deactivation time course of GluN1/GluN2A/GluN2C receptors is intermediate to GluN1/GluN2A and GluN1/GluN2C receptors and is not dominated by GluN2A or GluN2C. We show that triheteromeric GluN1/GluN2A/GluN2C receptors are the predominant NMDARs in cerebellar granule cells and propose that co-expression of GluN2A and GluN2C in cerebellar granule cells occludes cell surface expression of diheteromeric GluN1/GluN2C receptors. This new insight into neuronal GluN1/GluN2A/GluN2C receptors highlights the complexity of NMDAR signaling in the CNS.

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Expression of N-methyl-D-aspartate receptor subunits in the rat parabrachial and K�lliker-Fuse nuclei and in selected pontomedullary brainstem nuclei

Cited by 39 publications

References 51 publications

Pontine Mechanisms of Respiratory Control

Pontine Mechanisms of Respiratory Control

Pontine respiratory activity involved in inspiratory/expiratory phase transition

Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells

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