Properties of amino acid neurotransmitter receptors of embryonic cortical neurons when activated by exogenous and endogenous agonists

1992 ◽  
Vol 67 (5) ◽  
pp. 1185-1200 ◽  
Author(s):  
M. G. Blanton ◽  
A. R. Kriegstein
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Cortical Neurons ◽  
Nmda Receptor Antagonist ◽  
Chloride Ions ◽  
Negative Slope ◽  
Equilibrium Potential ◽  
Slow Response ◽  
Postmitotic Neurons

1. The properties of receptors for amino acid neurotransmitters expressed by developing cortical neurons were studied with the use of whole-cell recording in the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally applied to single cells under voltage clamp, and the ionic dependence, voltage dependence, and pharmacological sensitivity of the responses were characterized. The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and by evoked release of an endogenous excitatory agonist, were compared further. Fluctuation analysis was used to characterize the properties of the NMDA channels and the mechanism of action of receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all neurons tested responded to GABA with a current that reversed at the equilibrium potential for chloride ions and that was sensitive to the GABAA receptor antagonist bicuculline methiodide (BMI). As development proceeded, an increasing proportion of neurons also responded with a BMI-insensitive current that reversed near the equilibrium potential for potassium ions. This current was blocked by the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The GABAB agonist baclofen, however, failed to produce a detectable postsynaptic current. 3. Neurons at stage 15 showed a biphasic response to glutamate that reversed at the equilibrium potential for cations. All neurons tested showed a slow, sustained response associated with an increase in current variance compared with background, and, as development proceeded, an increasing proportion also exhibited a fast, transient response. Both fast and slow responses varied linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions to the bathing medium attenuated the slow response at hyperpolarized potentials. As a result, the current-voltage relation of the slow response in the presence of Mg2+ ions exhibited a region of negative slope conductance, like that of currents mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed in their pharmacological sensitivity. The fast responses were sensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a fluctuating current consisting of channel currents with a mean open time, tau, of 4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)

NMDA-induced burst discharge in guinea pig trigeminal motoneurons in vitro

1995 ◽  
Vol 74 (1) ◽  
pp. 334-346 ◽  
Author(s):  
Y. I. Kim ◽  
S. H. Chandler
Keyword(s):  
Nmda Receptor ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Negative Slope ◽  
Plateau Potentials ◽  
Perfusion Medium ◽  
Spike Discharge ◽  
Trigeminal Motoneurons

1. The responses of guinea pig trigeminal motoneurons (TMNs) to N-methyl-D,L-aspartate (NMA) were studied using brain stem slice preparations and whole cell patch-clamp (n = 89) or conventional microelectrode (n = 22) recording techniques. The primary goals of this study were to determine whether N-methyl-D-aspartate (NMDA) receptor activation would produce spontaneous bursting activity in TMNs and, if so, the underlying mechanisms responsible for the generation of these bursts. 2. Bath-applied NMA (100-300 microM, n = 80) in standard perfusion medium elicited depolarization, increase in apparent input resistance (Rinp), and rhythmic burst discharges (1-90 s in duration) from TMNs. These effects were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5, 30 microM, n = 6), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM, n = 10). Furthermore, the burst-inducing effect of NMA was not mimicked by the non-NMDA receptor agonists kainate (KA, 5-10 microM, n = 6) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 5-10 microM, n = 5). 3. In tetrodotoxin (TTX) treatment conditions (n = 13), NMA elicited depolarization, an increase in apparent Rinp, and rhythmic membrane potential oscillations without action potential bursts (i.e., plateau potentials), suggesting that the effects of NMA observed in the TTX-free condition resulted from activation of postsynaptic NMDA receptors. 4. Graded depolarization of neurons (n = 20) by intracellular direct current injection generally led to a graded increase in frequency and duration of the NMA-induced bursts and plateau potentials until these rhythmic events eventually became transformed into continuous spike discharge and maintained depolarization, respectively. Removal of Mg2+ from the perfusion medium (n = 11) also turned the bursts and plateau potentials into continuous spike discharge and maintained depolarization, respectively. 5. The effects of NMA on the current-voltage (I-V) curve after a depolarizing ramp voltage-clamp command (15-20 mV/s) were examined (n = 40). Under NMA (100-300 microM) conditions, the I-V relationship exhibited a region of negative slope conductance (NSC) between -60 and -35 mV, thus making the I-V relationship N-shaped. The NSC was abolished by AP5 (30 microM, n = 8), but not by CNQX (5-10 microM, n = 6). The I-V relationship in AMPA (3-10 microM, n = 5) or KA (3-10 microM, n = 5) was almost linear between -80 and -30 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Efficacy of prophylactic versus therapeutic administration of the NMDA receptor antagonist MK-801 on the acute neurochemical response to a concussion in a rat model combining force and rotation

2021 ◽  
pp. 1-10
Author(s):  
Ian Masse ◽  
Luc Moquin ◽  
Caroline Bouchard ◽  
Alain Gratton ◽  
Louis De Beaumont
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Rat Model ◽  
Nmda Receptor Antagonist ◽  
Cerebral Microdialysis ◽  
Secondary Outcome ◽  
Mk 801 ◽  
Amino Acid Concentrations ◽  
Therapeutic Administration

OBJECTIVE Alterations in amino acid concentrations are a major contributor to the persistent neurological and behavioral effects induced by concussions and mild traumatic brain injuries (TBIs). Glutamate, the most abundant excitatory amino acid in the CNS, has a major role in the pathophysiological process of concussion. The indiscriminate liberation of glutamate immediately after a concussion triggers an excitotoxic response that leads to cell death, neuronal damage, and the dysfunction of surviving neurons, largely by overactivation of N-methyl-d-aspartate (NMDA) glutamatergic receptors. The aim of the present study was to investigate the efficacy of prophylactic versus therapeutic administration of MK-801, a promising NMDA receptor antagonist, on the acute changes in amino acid extracellular concentrations involved in excitotoxicity resulting from a concussive trauma. METHODS The immediate neurochemical response to a concussion cannot be characterized in humans. Therefore, the authors used their previously validated combination of a weight-drop concussion rat model and in vivo cerebral microdialysis. The microdialysis probe was inserted inside the hippocampus and left inserted at impact to allow uninterrupted sampling of amino acids of interest immediately after concussion. The primary outcome included amino acid concentrations and the secondary outcome included righting time. Samples were taken in 10-minute increments for 60 minutes before, during, and 60 minutes after impact, and analyzed for glutamate, gamma-aminobutyric acid, taurine, glycine, glutamine, and serine using high-performance liquid chromatography. Righting time was acquired as a neurological restoration indicator. Physiological saline or 10 mg/kg MK-801 was administrated intraperitoneally 60 minutes before or immediately following induction of sham injury or concussion. RESULTS Following induction of concussion, glutamate, taurine, and glycine levels as well as righting times in cases from the MK-801 treatment group were comparable to those of vehicle-treated animals. In contrast, righting times and amino acid concentrations observed within the first 10 minutes after induction of concussion in cases assigned to the MK-801 prophylaxis group were comparable to those of sham-injured animals. CONCLUSIONS These results suggest that presynaptic actions and peak availability of MK-801 following prophylactic administration significantly inhibit the immediate and indiscriminate release of glutamate, taurine, and glycine in extracellular fluid after a concussion.

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.

The NMDA receptor antagonist eliprodil (SL 82.0715) blocks voltage-operated Ca2+ channels in rat cultured cortical neurons

1994 ◽  
Vol 257 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Bruno Biton ◽  
Patrick Granger ◽  
Alexandra Carreau ◽  
Henri Depoortere ◽  
Bernard Scatton ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Cortical Neurons ◽  
Nmda Receptor Antagonist ◽  
Cultured Cortical Neurons ◽  
Ca2 Channels

A reevaluation of excitatory amino acid-mediated synaptic transmission in rat dentate gyrus

1990 ◽  
Vol 64 (1) ◽  
pp. 119-132 ◽  
Author(s):  
J. D. Lambert ◽  
R. S. Jones
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Excitatory Amino Acid ◽  
Nmda Receptor Antagonist ◽  
Perforant Path ◽  
Receptor Subtypes ◽  
Excitatory Postsynaptic Potential ◽  
Small Component

1. Intracellular recordings were made from granule cells in combined slices of the hippocampus and parahippocampal cortex from adult Wistar rats. The neurons had a mean resting membrane potential (EM) of -85.1 +/- 0.7 (SE) mV, input resistance (Rin) of 30.9 +/- 1.5 M omega and action potential (AP) amplitude of 79.9 +/- 1.06 mV measured from the threshold potential. The threshold for AP generation was approximately 40 mV positive to EM. 2. The passive current-voltage relationship showed anomalous rectification, with Rin increasing by 34% on average at modest depolarizations. With large excursions of the EM (by +/- 30 mV or more), there was a marked fall in Rin. 3. With extracellular recording, a monophasic, positive-going field potential of 5–15 mV was evoked by stimulation of the perforant path (PP). Intracellularly, an excitatory postsynaptic potential (EPSP) of up to 40 mV in size was recorded. It was unusual to evoke an AP on orthodromic stimulation. Perfusion with picrotoxin (PTX, up to 20 microM) had small and variable effects on the EPSP, which implies that GABAergic inhibition does not play a major role. 4. Tonic depolarization reduced the EPSP. Hyperpolarization either had no effect or again decreased the EPSP. 5. The role of excitatory amino acid (EAA) receptor subtypes in mediation of the EPSP was investigated. Perfusion with the non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) caused a dose-dependent reduction of the EPSP with a shift to the right of the input-output relationship. The ED50 for this effect was approximately 2 microM. 6. In the presence of 5–10 microM CNQX a small component of the EPSP usually remained, which could be blocked by the NMDA receptor antagonist +/- 2-amino-5-phosphonovaleric acid (APV, 20–50 microM). This depolarizing component was markedly enhanced during perfusion with Mg2(+)-free medium. It increased in size and duration when the membrane was depolarized and decreased with hyperpolarization. These properties are consistent with the mediation of this potential via NMDA receptors. 7. These results indicate that NMDA receptors contribute to transmission at the synapse between the PP and the granule cell. This was confirmed by demonstrating that APV caused a small reduction in the size of the untreated EPSP and a shortening of the recovery phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Sign in / Sign up

Export Citation Format

Share Document