2019 AUG 14 (NewsRx) -- By a News Reporter-Staff News Editor at Biotech News Daily -- Data detailed on Biotechnology - Molecular Pharmacology have been presented. According to news reporting originating from Omaha, United States, by NewsRx correspondents, research stated, “The GluN2C subunit of the NMDA receptor is enriched in the neurons in the nucleus reticularis of the thalamus (nRT), but its role in regulating their function is not well understood. We found that deletion of GluN2C subunit did not affect spike frequency in response to depolarizing current injection or hyperpolarization-induced rebound burst firing of nRT neurons.”
Financial supporters for this research include National Science Foundation, National Institutes of Health National Institute of Neurologic Disorders and Stroke, National Institute of Mental Health.
Our news editors obtained a quote from the research from Creighton University, “D-Cycloserine or CIQ (GluN2C/GluN2D positive allosteric modulator) did not affect the depolarization-induced spike frequency in nRT neurons. A newly identified highly potent and efficacious coagonist of GluN1/GluN2C NMDA receptors, AICP (®-2-amino-3-(4(2-ethylpheny1)-1H-indole-2-carboxannido)propanoic acid), was found to reduce the spike frequency and burst firing of nRT neurons in wild type but not GIuN2C knockout. This effect was potentially due to facilitation of GIuN2C-containing receptors, because inhibition of NMDA receptors by AP5 did not affect spike frequency in nRT neurons. We evaluated the effect of intracerebroventricular injection of AICP. AICP did not affect basal locomotion or prepulse inhibition but facilitated MK-801-induced hyperlocomotion. This effect was observed in wild-type but not in GIuN2C knockout mice, demonstrating that AICP produces GluN2C-selective effects in vivo. Using a chemogenetic approach, we examined the role of nRT in this behavioral effect. G(q)- or G(i)-coupled DREADDs were selectively expressed in nRT neurons using Cre-dependent viral vectors and PV-Cre mouse line. We found that similar to AICP effect, activation of G(q)- but not G(i)-coupled DREADD facilitated MK-801-induced hyperlocomotion.”
According to the news editors, the research concluded: “Together, these results identify a unique role of GluN2C-containing receptors in the regulation of nRT neurons and suggest GIuN2C-selective in vivo targeting of NMDA receptors by AICP.”
For more information on this research see: Modulation of Burst Firing of Neurons In Nucleus Reticularis of the Thalamus By Glun2c-containing Nmda Receptors. Molecular Pharmacology, 2019;96(2):193-203. Molecular Pharmacology can be contacted at: Amer Soc Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA.
The news editors report that additional information may be obtained by contacting S.M. Dravid, Creighton University, Dept. of Pharmacology, Omaha, NE 68178, United States. Additional authors for this research include J.X. Liu, G.P. Shelkar, F.B. Zhao and R.P. Clausen.
The direct object identifier (DOI) for that additional information is: https://doi.org/10.1124/mol.119.116780. This DOI is a link to an online electronic document that is either free or for purchase, and can be your direct source for a journal article and its citation.
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