Article
Biochemistry & Molecular Biology
Rohini Subrahmanyam, Deepanjali Dwivedi, Zubin Rashid, Katherine Bonnycastle, Michael A. Cousin, Sumantra Chattarji
Summary: This study reveals that FMRP represses spontaneous presynaptic SV fusion, while mGlu receptor activation increases this event, with reciprocal control likely mediated through their regulation of intrinsic neuronal excitability.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Sang S. Seo, Susana R. Louros, Natasha Anstey, Miguel A. Gonzalez-Lozano, Callista B. Harper, Nicholas C. Verity, Owen Dando, Sophie R. Thomson, Jennifer C. Darnell, Peter C. Kind, Ka Wan Li, Emily K. Osterweil
Summary: Dysregulated protein synthesis is a key contributing factor to the development of Fragile X syndrome. The authors of this study have identified a relationship between ribosome expression and the translation of long mRNAs, which is responsible for synaptic weakening in Fragile X syndrome.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Giselle Fernandes, Pradeep K. Mishra, Mohammad Sarfaraz Nawaz, Paul G. Donlin-Asp, Mohammed Mostafizur Rahman, Anupam Hazra, Sonal Kedia, Aiman Kayenaat, Dheeraj Songara, David J. A. Wyllie, Erin M. Schuman, Peter C. Kind, Sumantra Chattarji
Summary: In a rat model of Fragile X syndrome (FXS), it was observed that activation rather than inhibition of mGluRs in the basolateral amygdala reversed impairments in fear learning. Activation of presynaptic mGluR5 in the amygdala reversed deficient synaptic transmission and plasticity, restoring normal fear learning in FXS rats. This highlights the importance of considering circuit-specific differences in FXS pathophysiology when developing therapeutic strategies.
Article
Neurosciences
Anna Bodzeta, Nicky Scheefhals, Harold D. MacGillavry
Summary: The various functions of glutamate in the brain are mediated by ionotropic and metabotropic glutamate receptors, which modulate synaptic transmission and plasticity. mGluRs play roles at both presynaptic and postsynaptic sites, acting as essential signal integrators that couple mechanisms of transmission and plasticity.
Article
Cell Biology
Sara G. Susco, Sulagna Ghosh, Patrizia Mazzucato, Gabriella Angelini, Amanda Beccard, Victor Barrera, Martin H. Berryer, Angelica Messana, Daisy Lam, Dane Z. Hazelbaker, Lindy E. Barrett
Summary: Down syndrome and fragile X syndrome may share underlying mechanisms, as evidenced by overlapping transcriptional perturbations and increased expression of select target proteins. Furthermore, upregulation of FMRP in Down syndrome patient cells can significantly reduce expression levels of candidate proteins and reverse global transcriptional perturbations.
Article
Biochemistry & Molecular Biology
James Robert Brasic, Ayon Nandi, David S. Russell, Danna Jennings, Olivier Barret, Samuel D. Martin, Keith Slifer, Thomas Sedlak, John P. Seibyl, Dean F. Wong, Dejan B. Budimirovic
Summary: Research suggests that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR(5)) plays a role in the pathogenesis of autism spectrum disorder (ASD). Contradictory findings about mGluR(5) expression in different subtypes of ASD have been reported. A study using a novel PET ligand found increased mGluR(5) expression in the cortical regions of participants with IASD, and reduced expression in all regions of men with FXS. This protocol shows promise as a valuable tool for measuring mGluR(5) expression in clinical trials for individuals with ASD and FXS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Ananth Prasad Burada, Rajesh Vinnakota, Bertrand Lambolez, Ludovic Tricoire, Janesh Kumar
Summary: Enigmatic orphan glutamate delta receptors (GluD) are a type of ionotropic glutamate receptors (iGluRs) that do not bind glutamate or evoke currents when binding glycine and D-serine. They are believed to function as structural proteins that facilitate synapse formation, maturation, and maintenance in the hippocampus and cerebellum. Recent research suggests that GluD receptors have interactions with metabotropic glutamate receptors (mGlus) and are gated by their activation, with new tools and structures helping to define their role in synaptic physiology.
Article
Neurosciences
Diego Castillo-Rolon, Enrique Ramirez-Sanchez, Gabina Arenas-Lopez, Julieta Garduno, Omar Hernandez-Gonzalez, Stefan Mihailescu, Salvador Hernandez-Lopez
Summary: The rostromedial tegmental nucleus (RMTg) is a bilateral structure in the brainstem mainly composed of GABAergic neurons, which regulates dopamine neurons through glutamatergic and cholinergic inputs. Nicotine was found to induce the persistent release of glutamate in RMTg neurons through the activation of alpha 7 nicotinic acetylcholine receptors and calcium release. This mechanism increases excitability and synchronizes activity of RMTg neurons, suggesting RMTg as a potential therapeutic target for tobacco addiction.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Ananth Prasad Burada, Rajesh Vinnakota, Pratibha Bharti, Priyanka Dutta, Neelima Dubey, Janesh Kumar
Summary: GluD receptors are a subfamily of ionotropic glutamate receptors that play a crucial role in synapse formation, maturation, and maintenance of central nervous system functions. Despite the lack of knowledge about their endogenous ligands, significant discoveries have been made regarding their role in mediating trans-synaptic interactions and their unique non-swapped architecture. Additionally, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Cell Biology
Kexin Li, Meng Lu, Mengxu Cui, Xiaoming Wang, Yang Zheng
Summary: This study investigated the changes in NAAG, Glu, and mGluR expression, as well as the effects on synaptic plasticity in the brain after HI injury. The results showed an increase in NAAG and mGluR3 expression levels after HI, with a correlation between Glu content and mGluR1/mGluR5 expression. NAAG was found to maintain cortical synaptic plasticity and neurotransmitter homeostasis. Hibernated NAAG levels after 12-24 h of HI injury were associated with mGluR3 receptor expression, thus indicating their role in preserving synaptic function.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Neurosciences
Benjamin D. Auerbach, Senthilvelan Manohar, Kelly Radziwon, Richard Salvi
Summary: The study characterized auditory hypersensitivity in a Fmr1 knockout transgenic rat model of FX, revealing perceptual evidence of excessive loudness growth and altered integration of sound duration and bandwidth in Fmr1 KO rats. Antagonism of mGlu5 selectively and dose-dependently restored normal loudness growth in Fmr1 KO rats, suggesting a pharmacologic approach for alleviating sensory hypersensitivity associated with FX. Leveraging the tractable nature of the auditory system and unique behavioral advantages of rats, this study provides important insights into an understudied aspect of FX and ASD.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Neurosciences
Jessica C. Pressey, Melanie A. Woodin
Summary: Kainate receptors (KARs) mediate both ionotropic currents and metabotropic signalling. They regulate GABA release in the hippocampus bidirectionally through ionotropic and metabotropic pathways, affecting the strength of inhibition. This evidence suggests that KARs play a crucial role in regulating the balance between excitation and inhibition in neural circuits.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Clinical Neurology
Roghayeh Mozafari, Saeideh Karimi-Haghighi, Mojdeh Fattahi, Peter Kalivas, Abbas Haghparast
Summary: Psychostimulant Use Disorder is a chronic relapsing disorder with high motivation for drug abuse and is associated with various physical and mental health issues. There is currently no FDA-approved medication for treating psychostimulant abuse, making it crucial to understand the cellular and molecular changes involved in the disorder for developing effective medications.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Johnathan M. M. Borland, Desarae A. A. Dempsey, Anna C. C. Peyla, Megan A. L. Hall, Abigail L. L. Kohut-Jackson, Paul G. G. Mermelstein, Robert L. L. Meisel
Summary: Aggression can be rewarding and lead to behavioral plasticity. This study identified ERK1/2 and mTOR as potential signaling pathways for regulating the rewarding consequences of aggressive interactions. These pathways have distinct recruitment profiles in different brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)