Retrotrapezoid nucleus glutamate receptors: control of CO2-sensitive phrenic and sympathetic output

1993 ◽  
Vol 74 (6) ◽  
pp. 2958-2968 ◽  
Author(s):  
E. E. Nattie ◽  
M. Gdovin ◽  
A. Li
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Kynurenic Acid ◽  
Nmda Receptor Antagonist ◽  
Initial Slope ◽  
Xanthurenic Acid ◽  
Retrotrapezoid Nucleus ◽  
Nerve Signal ◽  
Kynurenic Acid Analogue

In decerebrate cats, we asked whether endogenous glutamate in the region of the retrotrapezoid nucleus (RTN) was involved in the control of CO2-sensitive phrenic and phrenic-related sympathetic output and, if so, which type of glutamate receptor was predominant. We made unilateral 10-nl injections into the RTN of the nonspecific glutamate receptor antagonist kynurenic acid (100 and 250 mM), the N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 1 and 10 mM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX; 1 and 10 mM), and the inactive kynurenic acid analogue xanthurenic acid (100 mM). Each antagonist resulted in a significant dose-dependent decrease in the amplitude of the integrated phrenic nerve signal (PNA) over 30 min (CNQX > AP5 > kynurenic acid). The duration of the phrenic cycle was also decreased because of a shortening of expiratory time (CNQX > kynurenic acid > AP5). All three antagonists significantly decreased the initial slope of the PNA response to increased CO2 by 70–80% with no clear distinction in efficacy. The amplitude of the respiratory-related integrated cervical sympathetic nerve signal (SNA) was significantly decreased after kynurenic acid and CNQX but not AP5. In each case, the decrease in respiratory-related SNA accompanied a decrease in PNA and, at high levels of CO2, the decrease in respiratory-related SNA was greater than that of PNA. Endogenous glutaminergic input to neurons in the RTN via both NMDA and non-NMDA receptors is involved in the control of eucapneic PNA and timing, PNA-related SNA, and the response to increased CO2.

NMDA Receptor-Mediated Differential Laminar Susceptibility to the Intracellular Ca2+ Accumulation Induced by Oxygen-Glucose Deprivation in Rat Neocortical Slices

1998 ◽  
Vol 79 (1) ◽  
pp. 430-438 ◽  
Author(s):  
Atsuo Fukuda ◽  
Kanji Muramatsu ◽  
Akihito Okabe ◽  
Yasunobu Shimano ◽  
Hideki Hida ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Kynurenic Acid ◽  
Pyramidal Cells ◽  
Glucose Deprivation ◽  
Nmda Receptor Antagonist ◽  
Oxygen Glucose Deprivation ◽  
Glutamate Receptor Antagonist ◽  
Intracellular Ca ◽  
Cellular Ca

Fukuda, Atsuo, Kanji Muramatsu, Akihito Okabe, Yasunobu Shimano, Hideki Hida, Ichiro Fujimoto, and Hitoo Nishino. NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices. J. Neurophysiol. 79: 430–438, 1998. Slices of somatosensory cortex taken from immature rats on postnatal day (P)7–14 were labeled with fura-2. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in identified pyramidal cells as the ratio of fluorescence intensities (RF340/F380) during oxygen-glucose deprivation. The RF340/F380 ([Ca2+]i) of individual pyramidal cells was monitored in each of the cortical layers II–VI simultaneously. Neurons in all neocortical layers exhibited significant increases in [Ca2+]i that varied with the duration of oxygen-glucose deprivation. Individual neurons responded to oxygen-glucose deprivation with abrupt increases in [Ca2+]i after various latencies. The ceiling level of the [Ca2+]i increase differed from cell to cell. Neurons in layer II/III showed significantly greater increases in [Ca2+]i than those in layers IV, V, or VI. Kynurenic acid, a nonselective glutamate receptor antagonist, and bicuculline, a selective γ-aminobutyric acid (GABA)A receptor antagonist, suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in all neocortical layers examined. After kynurenic acid, but not after bicuculline, there was no longer a differential [Ca2+]i increases in layer II/III. Both 2-amino-5-phosphonopentanoic acid (AP5), a selective N-methyl-d-aspartate (NMDA) receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, strongly suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in all layers. The laminar difference in terms of the [Ca2+]i increases was abolished by AP5, but not by CNQX. These results indicate that layer II/III cells are the most prone to oxygen-glucose deprivation-induced intracellular Ca2+ accumulation, and that this is primarily mediated by NMDA receptors. Thus, layer II/III neurons would be more likely to suffer cellular Ca2+ overload and excitotoxicity during ischemia than layer IV–VI cells. Such a differential laminar vulnerability might play an important role in determining the pathological characteristics of the immature cortex and its sequelae later in life.

Inactivation of amino acid receptors in medullary reticular formation modulates and suppresses ingestion and rejection responses in the awake rat

2003 ◽  
Vol 285 (1) ◽  
pp. R68-R83 ◽  
Author(s):  
Zhixiong Chen ◽  
Joseph B. Travers
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Reticular Formation ◽  
Glutamate Receptor ◽  
Nmda Receptor Antagonist ◽  
Receptor Subtype ◽  
Consummatory Behavior ◽  
Medullary Reticular Formation ◽  
Amino Acid Receptors

The lateral medullary reticular formation (RF) is the source of many preoromotor neurons and is essential for generation of ingestive consummatory responses. Although the neurochemistry mediating these responses is poorly understood, studies of fictive mastication suggest that both excitatory and inhibitory amino acid receptors play important roles in the generation of these ororhythmic behaviors. We tested the hypothesis that amino acid receptors modulate the expression of ingestion and rejection responses elicited by natural stimuli in awake rats. Licking responses were elicited by either intraoral (IO) gustatory stimuli or sucrose presented in a bottle. Oral rejection responses (gaping) were elicited by IO delivery of quinine hydrochloride. Bilateral microinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist d-[(3)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (D-CPP) suppressed licking and gape responses recorded electromyographically from a subset of orolingual muscles. Likewise, infusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) significantly reduced licking and gape responses but was accompanied by spontaneous gasping responses. Rats still actively probed the bottle, indicating an intact appetitive response. Neither D-CPP nor CNQX differentially affected ingestion or rejection, suggesting that the switch from one behavior to the other does not simply rely on one glutamate receptor subtype. Nevertheless, a glutamate receptor-mediated switch from consummatory behavior to gasps after CNQX infusions suggests a multifunctional substrate for coordinating the jaw and tongue in different behaviors. Bilateral infusions of the GABAA receptor antagonist bicuculline or the glycine receptor antagonist strychnine enhanced the amplitude of IO stimulation-induced oral responses. These data suggest that the neural substrate underlying ingestive consummatory responses is under tonic inhibition. Release of this inhibition may be one mechanism by which aversive oral stimuli produce large-amplitude mouth openings associated with the rejection response.

scholarly journals Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

2011 ◽  
Vol 300 (2) ◽  
pp. R501-R510 ◽  
Author(s):  
Ana C. Takakura ◽  
Eduardo Colombari ◽  
José V. Menani ◽  
Thiago S. Moreira
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Metabotropic Glutamate Receptor ◽  
Nmda Receptor Antagonist ◽  
Ventrolateral Medulla ◽  
Metabotropic Receptors ◽  
Gaba A ◽  
Metabotropic Glutamate ◽  
Retrotrapezoid Nucleus ◽  
Nerve Discharge

A rise in arterial Pco2 stimulates breathing and sympathetic activity to the heart and blood vessels. In the present study, we investigated the involvement of the retrotrapezoid nucleus (RTN) and glutamatergic mechanisms in the Bötzinger/C1 region (Bötz/C1) in these responses. Splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded in urethane-anesthetized, sino-aortic-denervated, vagotomized, and artificially ventilated rats subjected to hypercapnia (end-expiratory CO2 from 5% to 10%). Phrenic activity was absent at end-expiratory CO2 of 4%, and strongly increased when end-expiratory CO2 reached 10%. Hypercapnia also increased sSND by 103 ± 7%. Bilateral injections of the GABA-A agonist muscimol (2 mM) into the RTN eliminated the PND and blunted the sSND activation (Δ = +56 ± 8%) elicited by hypercapnia. Injections of NMDA receptor antagonist AP-5 (100 mM), non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mM) or metabotropic glutamate receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100 mM) bilaterally into the Bötz/C1 reduced PND (Δ = +43 ± 7%, +52 ± 6% or +56 ± 11%, respectively). MCPG also reduced sSND (Δ = +41 ± 7%), whereas AP-5 and DNQX had no effect. In conclusion, the increase in sSND caused by hypercapnia depends on increased activity of the RTN and on metabotropic receptors in the Bötz/C1, whereas PND depends on increased RTN activity and both ionotropic and metabotropic receptors in the Bötz/C1.

EAA receptors in the dorsomedial hypothalamic area mediate the cardiovascular response to activation of the amygdala

1998 ◽  
Vol 275 (2) ◽  
pp. R624-R631 ◽  
Author(s):  
Robert P. Soltis ◽  
Jennifer C. Cook ◽  
Adam E. Gregg ◽  
James M. Stratton ◽  
Kathleen A. Flickinger
Keyword(s):  
Receptor Antagonist ◽  
Kynurenic Acid ◽  
Basolateral Amygdala ◽  
Excitatory Amino Acid ◽  
Cardiovascular Response ◽  
Nmda Receptor Antagonist ◽  
Xanthurenic Acid ◽  
Receptor Subtypes ◽  
Hypothalamic Area ◽  
Cardiovascular Changes

The role of excitatory amino acid (EAA) receptors in the dorsomedial hypothalamus (DMH) in mediating the cardiovascular response to activation of the basolateral amygdala (BLA) was examined using conscious rats. Microinjection of the nonselective EAA receptor antagonist kynurenic acid (0.1–10 nmol) into the DMH blocked or reversed the increases in heart rate and arterial pressure resulting from injection of the GABAA receptor antagonists bicuculline methiodide (BMI; 100 pmol) and picrotoxin (100 pmol) into the BLA. Similar injections of kynurenic acid at sites lateral or dorsal to the DMH or injection of the inactive analog xanthurenic acid into the DMH were less effective in blocking the cardiovascular changes resulting from intra-amygdalar injection of BMI. Hypothalamic injection of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 pmol) or thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (50 pmol) at doses shown to be selective for their respective EAA receptor subtypes attenuated the cardiovascular changes associated with intra-amygdalar injection of BMI. Therefore, EAA receptors in the area of the DMH appear to be involved in mediating the cardiovascular changes resulting from activation of the amygdala.

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