scholarly journals Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula

Science ◽  
2019 ◽  
Vol 366 (6462) ◽  
pp. 250-254 ◽  
Author(s):  
Y. Otsu ◽  
E. Darcq ◽  
K. Pietrajtis ◽  
F. Mátyás ◽  
E. Schwartz ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Glial Cells ◽  
Neuronal Activity ◽  
The Other ◽  
Place Aversion ◽  
Nmda Receptor Subunits ◽  
Medial Habenula ◽  
Aversion Conditioning ◽  
Binding Subunit

The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.

Differential Roles of NMDA and Non-NMDA Receptors in Synaptic Responses of Neurons in Nucleus Tractus Solitarii of the Rat

1999 ◽  
Vol 81 (6) ◽  
pp. 3034-3043 ◽  
Author(s):  
J. C. Yen ◽  
Julie Y. H. Chan ◽  
Samuel H. H. Chan
Keyword(s):  
Nmda Receptor ◽  
Action Potential ◽  
Nmda Receptors ◽  
Nucleus Tractus Solitarii ◽  
The Other ◽  
Synaptic Response ◽  
Nmda Receptor Subunits ◽  
Single Action ◽  
Other Hand ◽  
Synaptic Responses

Differential roles of NMDA and non-NMDA receptors in synaptic responses of neurons in nucleus tractus solitarii of the rat. The relative role of N-methyl-d-aspartate (NMDA) and non-NMDA receptors in synaptic responses of neurons in caudal nucleus tractus solitarii (cNTS) was delineated by immunohistochemical and electrophysiologic experiments in rats. Double immunohistochemical staining in in vivo experiments revealed that ∼80% of cNTS neurons that showed Fos-like immunoreactivity induced by baroreceptor activation were generally also immunoreactive to non-NMDA receptor subunits GluR1 or GluR2. On the other hand, only 20% of Fos-labeled cNTS neurons showed immunoreactivity to NMDA receptor subunits NMDAR1 or NMDAR2. Stimulation of the ipsilateral solitary tract at suprathreshold intensity in slice preparations induced Fos expression in the cNTS and evoked either a single action potential or a complex synaptic response consisting of an initial action potential followed by a secondary slow depolarization. In a majority (70%) of cNTS neurons that exhibited the complex synaptic response, both the initial and secondary components were eliminated reversibly by 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). This non-NMDA antagonist also inhibited the single action potential manifested by the other population of cNTS neurons. On the other hand, only the secondary slow depolarization was blocked byd(−)-2-amino-5-phosphonopentanoic acid (250 μM) or potentiated by NMDA (1.7 μM). Our results suggested that NMDA and non-NMDA receptors are involved differentially in the synaptic responses of cNTS neurons. Non-NMDA receptors may be distributed predominantly on a majority of the second-order cNTS neurons that may receive primary baroreceptor afferent inputs. On the other hand, NMDA receptors are located primarily on higher-order neurons, which may be connected reciprocally with the second-order cNTS neurons.

scholarly journals Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats

2013 ◽  
Vol 305 (4) ◽  
pp. R414-R422 ◽  
Author(s):  
Javier E. Stern ◽  
Evgeniy S. Potapenko
Keyword(s):  
Heart Failure ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Neuronal Activity ◽  
Receptor Activation ◽  
Membrane Depolarization ◽  
Neurosecretory Cells ◽  
Firing Activity ◽  
Nmda Current ◽  
Intracellular Ca

An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca2+ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca2+ levels (NMDA-ΔCa2+) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa2+ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa2+ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca2+ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca2+ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa2+ signaling during HF are discussed.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Zahra Lorigooini ◽  
Ali Nouri ◽  
Faezeh mottaghinia ◽  
Shima Balali-Dehkordi ◽  
Elham Bijad ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Ferulic Acid ◽  
Nmda Receptors ◽  
Effective Dose ◽  
Life Stress ◽  
Receptor Agonist ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Central Zone

AbstractBackgroundExperiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.MethodsMice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.ResultsFindings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.ConclusionsIn deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.

scholarly journals Developmental up-regulation of NMDA receptors in the prefrontal cortex and hippocampus of mGlu5 receptor knock-out mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiziana Imbriglio ◽  
Remy Verhaeghe ◽  
Nico Antenucci ◽  
Stefania Maccari ◽  
Giuseppe Battaglia ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Adult Life ◽  
Developmental Time ◽  
Postnatal Life ◽  
Developmental Studies ◽  
Knock Out ◽  
Nmda Receptor Subunits ◽  
The Impact

AbstractmGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.

scholarly journals Biochemical and electrophysiological characterization of N- glycans on NMDA receptor subunits

2016 ◽  
Vol 138 (4) ◽  
pp. 546-556 ◽  
Author(s):  
Martina Kaniakova ◽  
Katarina Lichnerova ◽  
Kristyna Skrenkova ◽  
Ladislav Vyklicky ◽  
Martin Horak
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptor Subunits ◽  
Electrophysiological Characterization

Role of adenosine in NMDA receptor modulation in the cerebral cortex of an anoxia-tolerant turtle (Chrysemys picta belli).

1995 ◽  
Vol 198 (7) ◽  
pp. 1621-1628 ◽  
Author(s):  
L T Buck ◽  
P E Bickler
Keyword(s):  
Cerebral Cortex ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Control Level ◽  
Chrysemys Picta ◽  
Receptor Modulation ◽  
A1 Receptor ◽  
Excitatory Neurotransmission ◽  
Similar Decrease

Accumulation of the neuromodulator adenosine in the anoxia-tolerant turtle brain may play a key role in a protective decrease in excitatory neurotransmission during anoxia. Since excitatory neurotransmission is mediated largely by Ca2+ entry through N-methyl-D-aspartate (NMDA) receptors, we measured the effect of adenosine on NMDA-mediated Ca2+ transients in normoxic and anoxic turtle cerebrocortical sheets. Intracellular [Ca2+] was measured fluorometrically with the Ca2+-sensitive dye Fura-2. Baseline intracellular [Ca2+] and [ATP] were also measured to assess cortical sheet viability and potential toxic effects of NMDA. Baseline [Ca2+] did not change significantly under any condition, ranging from 109 +/- 22 to 187 +/- 26 nmoll-1. Throughout normoxic and 2h anoxic protocols, and after single and multiple NMDA exposures, [ATP] did not change significantly, ranging from 16.0 +/- 1.9 to 25.3 +/- 4.9 nmol ATP mg-1 protein. Adenosine caused a reduction in the normoxic NMDA-mediated increase in [Ca2+] from a control level of 287 +/- 35 to 103 +/- 22 nmoll-1 (64%). This effect is mediated by the A1 receptor since 8-phenyltheophylline (a specific A1 antagonist) effectively blocked the adenosine effect and N6-cyclopentyladenosine (a specific A1 agonist) elicited a similar decrease in the NMDA-mediated response. Cortical sheets exposed to anoxia alone exhibited a 52% decrease in the NMDA-mediated [Ca2+] rise, from 232 +/- 30 to 111 +/- 9 nmoll-1. The addition of adenosine had no further effect and 8-phenyltheophylline did not antagonize the observed decrease. Therefore, the observed down-regulation of NMDA receptor activity during anoxia must involve additional, as yet unknown, mechanisms.

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