Review
Neurosciences
Jithin D. Nair, Kevin A. Wilkinson, Jeremy M. Henley, Jack R. Mellor
Summary: This article reviews the roles of kainate receptors in synaptic plasticity, focusing on their impact on postsynaptic signaling and presynaptic auto-receptor functions. It also explores the plasticity of kainate receptors themselves and their contribution to synaptic transmission plasticity.
Article
Cell Biology
Niccolo P. Pampaloni, Irene Riva, Anna L. Carbone, Andrew J. R. Plested
Summary: The study shows that in addition to the previously known fast-acting AMPA receptors, slow AMPA receptors with prolonged activity are also expressed in the hippocampal CA1 region. These slow AMPA receptors may play a significant role in synaptic transmission, short-term potentiation, and triggering of action potentials.
Article
Biochemistry & Molecular Biology
Paulina Chalupnik, Alina Vialko, Darryl S. Pickering, Markus Hinkkanen, Stephanie Donbosco, Thor C. Moller, Anders A. Jensen, Birgitte Nielsen, Yasmin Bay, Anders S. Kristensen, Tommy N. Johansen, Kamil Latka, Marek Bajda, Ewa Szymanska
Summary: A new selective antagonist for GluK3 receptors with high affinity and selectivity has been discovered. This antagonist shows a 400-fold preference for GluK3 over other homomeric receptors and does not exhibit agonist or antagonist activity in functional assays.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Zu-Cheng Shen, Zhi-Xuan Xia, Jian-Min Liu, Jie-Yan Zheng, Yu-Fei Luo, Han Yang, Meng-Die Li, Ting Cao, Hai-Ping Liu, Gui-Lin Jin, Hui-Hui Huang, Chang-Xi Yu, Jun Zhou
Summary: Palmitoylation has been found to be relevant to learning, memory, and disorders such as post-traumatic stress disorder and aging-related cognitive decline. However, the mechanisms underlying palmitoylation in these processes are not well understood. This study investigated the role of palmitoylation in hippocampal synaptic transmission and fear memory formation and identified the involvement of APT1-mediated depalmitoylation in the regulation of glutamatergic synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Jeremy M. Henley, Jithin D. Nair, Richard Seager, Busra P. Yucel, Gavin Woodhall, Benjamin S. Henley, Karolina Talandyte, Hope I. Needs, Kevin A. Wilkinson
Summary: Epilepsy is caused by abnormal neuronal network activity. The review focuses on the role and regulation of kainate and AMPA receptors in seizure activity, discussing the impact of GluK2 and GluA2 subunits on their respective receptors' properties.
Article
Clinical Neurology
Celine Boileau, Severine Deforges, Angelique Peret, Didier Scavarda, Fabrice Bartolomei, April Giles, Nicolas Partouche, Justine Gautron, Julio Viotti, Haley Janowitz, Guillaume Penchet, Cecile Marchal, Stanislas Lagarde, Agnes Trebuchon, Nathalie Villeneuve, Julie Rumi, Thomas Marissal, Roustem Khazipov, Ilgam Khalilov, Fanny Martineau, Marine Marechal, Anne Lepine, Mathieu Milh, Dominique Figarella-Branger, Etienne Dougy, Soutsakhone Tong, Romain Appay, Stephane Baudouin, Andrew Mercer, Jared B. Smith, Olivier Danos, Richard Porter, Christophe Mulle, Valerie Crepel
Summary: This study aims to reduce chronic epileptic discharges in TLE patients by downregulating KARs in the hippocampus using gene therapy. The results demonstrate that gene silencing strategy can inhibit chronic seizures in a mouse TLE model and IEDs in cultured slices derived from TLE patients.
ANNALS OF NEUROLOGY
(2023)
Article
Neurosciences
Bingjie Liu, Yuxin Du, Chang Xu, Qingzhen Liu, Lidong Zhang
Summary: Through experiments on mice, it was found that repeated intermittent administration of s-ketamine nasal spray can improve depressive-like behaviors and modulate related molecular pathways, including the modification of synaptic ultrastructure. The study showed that s-ketamine can reverse the elevated phosphorylation of CaMKIIa and the decreased levels of BDNF, TrkB phosphorylation, and mTOR induced by CUMS by upregulating GluN1 and GluR1 levels and downregulating GluN2B levels. These findings provide evidence that selectively modulated glutamate receptors, CaMKIIa, and mTOR signaling play a role in repeated s-ketamine administration.
Article
Endocrinology & Metabolism
Jung Hoon Park, Yeonggwang Hwang, Yen Nhi Doan Nguyen, Hyoung-Chun Kim, Eun-Joo Shin
Summary: The neuroprotective effects of ramelteon, a selective agonist of melatonin receptors, were investigated in a mouse model of KA-induced neurotoxicity. Ramelteon attenuated oxidative stress, restored glutathione homeostasis, and inhibited neuroinflammatory changes in the hippocampus after KA treatment. The activation of melatonin receptors by ramelteon provided neuroprotection by activating Nrf2 signaling and inhibiting NF kappa B signaling.
JOURNAL OF PINEAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Amanda M. Perozzo, Jochen Schwenk, Aichurok Kamalova, Terunaga Nakagawa, Bernd Fakler, Derek Bowie
Summary: This study reveals the unique characteristics of GSG1L in terms of its spatiotemporal expression, composition, and functionality. It is expressed late during brain development in a region-specific manner and constitutes about 5% of all AMPAR complexes in adulthood. GSG1L can assemble with TARPs or CNIHs, but it also has the ability to function as the sole auxiliary subunit. Through its interaction with two evolutionarily conserved sites on the agonist-binding domain, GSG1L weakly slows desensitization at the TARP/KGK site and strongly slows recovery from desensitization at a different site. These findings provide insights into the unique signaling role of GSG1L within glutamatergic synapses.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yayan Luo, Yang Yu, Minling Zhang, Hongbo He, Ni Fan
Summary: The discovery of the rapid antidepressant effects of ketamine has been considered a significant advancement in depression treatment. However, long-term use of ketamine may lead to cognitive impairments, possibly due to reductions in glutamate receptor subunits and synaptic signaling. The study suggests that overexpression of CaMKIIβ could alleviate these impairments, while inhibition of CaMKIIβ-ERK1/2-CREB/NF-κB signaling may mediate the cognitive deficits associated with chronic ketamine use.
MOLECULAR PSYCHIATRY
(2021)
Article
Cell Biology
Jongyun Myeong, Vitaly A. Klyachko
Summary: This study identified a distinctive release-dependent form of synaptic facilitation, which dynamically amplifies multi-vesicular release and requires neuronal contact with astrocytes and astrocytic glutamate uptake.
Article
Neurosciences
Natalia A. Quijano Carde, Erika E. Perez, Richard Feinn, Henry R. Kranzler, Mariella De Biasi
Summary: Selective inhibition of GluK1*KAR has been shown to reduce ethanol intake and preference, alleviate physical manifestations of ethanol withdrawal, and influence the rewarding properties of ethanol. Additionally, this study reveals that the effects of GluK1*KAR are influenced by ethanol-dependent state.
Article
Biochemistry & Molecular Biology
Denis P. Laryushkin, Sergei A. Maiorov, Valery P. Zinchenko, Valentina N. Mal'tseva, Sergei G. Gaidin, Artem M. Kosenkov
Summary: This study investigates the role of ionotropic glutamate receptors (iGluRs) in the generation of paroxysmal depolarization shift (PDS) and the dependence of PDS pattern on neuronal membrane potential. The results show that external stimuli play a crucial role in PDS induction. AMPA receptors are necessary for PDS generation, while NMDA and kainate receptors modulate paroxysmal activity. Agonists of G(i)-coupled receptors suppress PDS generation, suggesting a potential approach for epilepsy pharmacotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ryota Fukaya, Marta Maglione, Stephan J. Sigrist, Takeshi Sakaba
Summary: This study suggests a potential mechanism for the cAMP-dependent increase in neurotransmission at hippocampal mossy fiber-CA3 synapses, involving an accumulation of active zone Ca2+ channels. Experimental results indicate an increase in the local Ca2+ concentration at the release site following potentiation, driven by rapid Ca2+ channel accumulation, rather than changes in intracellular Ca2+ sensitivity. Various microscopy techniques provide insights into the underlying mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Christian B. M. Poulie, Younes Larsen, Cindie Leteneur, Gael Barthet, Walden E. Bjorn-Yoshimoto, Fanny Malhaire, Birgitte Nielsen, Jean-Phillippe Pin, Christophe Mulle, Darryl S. Pickering, Lennart Bunch
Summary: This study reports the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. It was found that 2a showed no binding affinity or activity at all glutamate receptors and transporters, while 2b displayed selectivity for homomeric GluK3 receptors.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Psychology, Developmental
Mathilde M. Husky, Adina Bitfoi, Christine Chan-Chee, Mauro Giovanni Carta, Dietmar Goelitz, Ceren Koc, Sigita Lesinskiene, Zlatka Mihova, Roy Otten, Taraneh Shojaei, Viviane Kovess-Masfety
Summary: The number of fear subtypes is strongly associated with self-reported internalizing and externalizing problems in children. Fear of animals is less likely than other fears to be associated with psychopathology. Children who report excessive fear should be targeted for prevention measures.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2022)
Article
Clinical Neurology
Tomas Jorda-Siquier, Melina Petrel, Vladimir Kouskoff, Una Smailovic, Fabrice Cordelieres, Susanne Frykman, Ulrike Mueller, Christophe Mulle, Gael Barthet
Summary: The distribution of amyloid precursor protein (APP) and its fragments is altered in Alzheimer's disease (AD), leading to their accumulation around amyloid plaques with presynaptic proteins. This finding is associated with histopathological features and familial AD.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Adam Gorlewicz, Gael Barthet, Stefano Zucca, Peggy Vincent, Marilena Griguoli, Noelle Grosjean, Grzegorz Wilczynski, Christophe Mulle
Summary: Kainate receptors (KARs) play a crucial role in regulating synaptic circuits through ionotropic or metabotropic mechanisms. This study reveals that the acute convulsive effect of kainate is primarily dependent on GluK2/GluK5 containing KARs, while the convulsive activity induced by pilocarpine and pentylenetetrazol is not affected by the absence of KARs. Interestingly, the genetic inactivation of GluK2 increases susceptibility to acute pilocarpine-induced seizures.
Editorial Material
Cell Biology
Victor Anggono, Patricio Opazo
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Daniel Choquet, Patricio Opazo
Summary: This article reviews the evidence supporting the role of AMPAR lateral diffusion in limiting the rate of LTP and its importance in learning and memory. The authors propose multiple solutions for achieving the diffusion trapping of AMPAR during LTP, mainly through interactions with other proteins. The role of AMPAR lateral diffusion not only provides a conceptual leap in our understanding of memory, but also holds potential as a therapeutic target for memory-related disorders.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Emmanouela Kallergi, Akrivi-Dimitra Daskalaki, Angeliki Kolaxi, Come Camus, Evangelia Ioannou, Valentina Mercaldo, Per Haberkant, Frank Stein, Kyriaki Sidiropoulou, Yannis Dalezios, Mikhail M. Savitski, Claudia Bagni, Daniel Choquet, Eric Hosy, Vassiliki Nikoletopoulou
Summary: Autophagy is required for pruning dendritic spines and long-term depression (LTD), a major form of synaptic plasticity. LTD induces the biogenesis of autophagic vesicles in dendrites to facilitate the degradation of postsynaptic proteins. Autophagy plays a crucial role in dendritic spine pruning and synaptic plasticity.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Christian B. M. Poulie, Younes Larsen, Cindie Leteneur, Gael Barthet, Walden E. Bjorn-Yoshimoto, Fanny Malhaire, Birgitte Nielsen, Jean-Phillippe Pin, Christophe Mulle, Darryl S. Pickering, Lennart Bunch
Summary: This study reports the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. It was found that 2a showed no binding affinity or activity at all glutamate receptors and transporters, while 2b displayed selectivity for homomeric GluK3 receptors.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biology
Andrea Toledo, Mathieu Letellier, Giorgia Bimbi, Beatrice Tessier, Sophie Daburon, Alexandre Favereaux, Ingrid Chamma, Kristel Vennekens, Jeroen Vanderlinden, Matthieu Sainlos, Joris De Wit, Daniel Choquet, Olivier Thoumine
Summary: This study reveals the mechanism of interaction between MDGA and neuroligins and shows that MDGA can delay the assembly of functional excitatory synapses containing AMPA receptors.
Article
Multidisciplinary Sciences
Angela M. Getz, Mathieu Ducros, Christelle Breillat, Aurelie Lampin-Saint-Amaux, Sophie Daburon, Urielle Francois, Agata Nowacka, Monica Fernandez-Monreal, Eric Hosy, Frederic Lanore, Hanna L. Zieger, Matthieu Sainlos, Yann Humeau, Daniel Choquet
Summary: This study presents a new method to track and modify synaptic neurotransmitter receptor content using biotin acceptor peptide (AP) tagging. By generating knock-in mice expressing GluA2 receptors with AP tags, it becomes possible to control receptor mobility and achieve target-specific control of synaptic plasticity and animal behavior.
Article
Neurosciences
Gael Barthet, Ana Moreira-de-Sa, Pei Zhang, Jorge Castanheira, Adam Gorlewicz, Christophe Mulle
Summary: Kainate receptors (KARs) play a role in regulating neuronal networks and have been implicated in epilepsy. This study investigates the role of KARs in Alzheimer's disease (AD) and finds that the synaptic expression and function of KARs are impaired in mouse models of AD. The study also suggests that the protein APP stabilizes KARs at synapses through a transsynaptic mechanism, and this interaction is regulated by the c-secretase proteolytic activity of presenilin.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Maxime Malivert, Fabrice Harms, Cynthia Veilly, Jerome Legrand, Ziqiang Li, Emmanuelle Bayer, Daniel Choquet, Mathieu Ducros
Summary: Lattice light-sheet microscopy (LLSM) is an efficient technique for high resolution 3D imaging of dynamic phenomena in biological samples. However, optical aberrations caused by refractive index mismatch limit the depth of LLSM imaging. To address this issue, we propose a simple and low-cost active image optimization (AIO) method to recover high resolution imaging in thick biological samples.
BIOMEDICAL OPTICS EXPRESS
(2022)
Article
Neurosciences
Pushpa Khanal, Zoran Boskovic, Lauri Lahti, Aruna Ghimire, Rimante Minkeviciene, Patricio Opazo, Pirta Hotulainen
Summary: The brain stores new information by modifying connections between neurons. Dendritic spines are the protrusions along neuronal dendrites where synapses are located and they play a crucial role in the formation of new connections. However, the molecular mechanisms linking neuronal activity to spine initiation are not well understood.
Article
Multidisciplinary Sciences
Zengmin Li, Dilsher Athwal, Hsu-Lei Lee, Pankaj Sah, Patricio Opazo, Kai-Hsiang Chuang
Summary: Memory consolidation after learning involves spontaneous, brain-wide network reorganization during rest and sleep, but how this is achieved is still poorly understood. Using fMRI in male mice, the authors identified a different set of spontaneous networks and their hubs that are instrumental in consolidating memory during post-learning rest. Chemogenetic suppression of each hub confirmed their behavioral significance in memory consolidation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Asuncion Carmona, Si Chen, Florelle Domart, Daniel Choquet, Richard Ortega
Summary: Neurons form growth cones during neurodevelopment to establish synaptic connections, and the distributions of F-actin and various biologically active elements in the growth cones play important roles. Calcium is crucial in this process, but other elements are also involved. Deficiencies in these elements, such as iron or zinc, may lead to learning and memory deficits in children.