Review
Neurosciences
Stuart G. Cull-Candy, Mark Farrant
Summary: CP-AMPARs are important regulators of synaptic plasticity, with their functional characteristics being modulated by auxiliary subunits and involved in various forms of central synaptic plasticity. Maladaptive synaptic plasticity and neurological disorders often involve changes in CP-AMPAR expression, such as those induced by inflammatory pain, fear conditioning, and cocaine exposure.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Cell Biology
Wenrui Qu, Baoming Yuan, Jun Liu, Qianqian Liu, Xi Zhang, Ranji Cui, Wei Yang, Bingjin Li
Summary: The role of GluA1-mediated synaptic plasticity in the early development of AD is well established, but the complex mechanisms involved are not fully understood. Deficits in synaptic plasticity are a central factor of AD etiology, and understanding the role of GluA1 and its regulatory mechanisms is crucial for developing disease-modifying therapies.
CELL PROLIFERATION
(2021)
Article
Neurosciences
S. Murat Durakoglugil, R. Catherine Wasser, H. Connie Wong, Theresa Pohlkamp, Xunde Xian, Courtney Lane-Donovan, Katja Fritschle, Lea Naestle, Joachim Herz
Summary: Alzheimer's disease is characterized by the accumulation of Aβ plaques and neurofibrillary tangles, leading to synaptic dysfunction. Reelin protects synapses against Aβ toxicity through ApoE receptors. Experiments showed that Reelin modulates mGluR-LTD, potentially impacting memory consolidation or neurodegeneration.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Jose Afonso Correa da Silva, Nadja Schroeder
Summary: It is believed that neurological diseases caused by degenerative conditions may have abnormal influx of Ca2+ through glutamate receptors. In addition to the NMDAR, AMPARs can also mediate neurotoxic Ca2+ influx, especially when the GluA2 subunit is absent or disrupted. The increase of Ca2+-permeable AMPA receptors (CP-AMPARs) is associated with behavioral changes and various neurodegenerative, neuroinflammatory, and neurotoxic conditions, suggesting a potential role in the emergence and evolution of central nervous system (CNS) pathological conditions. This article summarizes and discusses studies on changes in the composition of AMPARs and their effects, aiming to understand the therapeutic potential of CP-AMPAR in neurological diseases.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Review
Biochemistry & Molecular Biology
Yuya Sakimoto, Paw Min-Thein Oo, Makoto Goshima, Itsuki Kanehisa, Yutaro Tsukada, Dai Mitsushima
Summary: The hippocampus plays a key role in contextual memory, with long-term strengthening of glutamatergic transmission and enhancement of GABA(A) receptor-mediated inhibitory synapses after learning. Rapid plasticity at inhibitory synapses following contextual learning may facilitate encoding of memories and prevent cognitive dysfunction in hippocampal pathologies such as Alzheimer's disease, autism spectrum disorders, and epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Maria Italia, Elena Ferrari, Monica Di Luca, Fabrizio Gardoni
Summary: AMPARs play a crucial role in excitatory synaptic transmission in the mammalian brain, with the GluA3 subunit being widely expressed and functionally relevant. Modulation of GluA3 through pharmacological means may offer a new approach for addressing altered glutamatergic synapses associated with neurodegenerative and neurodevelopmental disorders.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Jee-Yeon Hwang, Hannah R. Monday, Jingqi Yan, Andrea Gompers, Adina R. Buxbaum, Kirsty J. Sawicka, Robert H. Singer, Pablo E. Castillo, R. Suzanne Zukin
Summary: This study reveals that in a mouse model of Fragile X syndrome (FXS), the transcription of GluA2, a subunit of AMPA receptor, is upregulated, which is associated with intellectual disability and autism. The researchers also identify CPEB3 protein as a critical regulator of GluA2 mRNA expression. Increased GluA2 mRNA leads to an increase in GluA2 subunits at synapses, potentially contributing to an excitatory/inhibitory imbalance, a common theme in FXS and other autism spectrum disorders.
Article
Biochemistry & Molecular Biology
Daniel B. Dorman, Kim T. Blackwell
Summary: Synaptic plasticity, the experience-induced change in connections between neurons, plays a crucial role in learning and memory. This study investigates how spatiotemporal synaptic input patterns produce plasticity under in vivo-like conditions. The findings reveal the robustness of plasticity to trial-to-trial variability of spike timing and derive general rules describing the control of plasticity by spatiotemporal patterns of synaptic inputs.
Review
Biochemistry & Molecular Biology
Tomasz Boczek, Ludmila Zylinska
Summary: The activity of specific populations of neurons in different brain areas plays a critical role in decision-making processes related to synaptic transmission, adaptations to external signals, and the maintenance of neural function. The endocannabinoid system (ECS) is identified as a vital control system in the central nervous system (CNS), allowing for rapid responses to synaptic processes and inducing long-term changes. Endocannabinoids are bioactive lipid mediators that act primarily through two receptors, CB1R and CB2R, which can regulate downstream Ca2+ signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Magdalena Chojnacka, Anna Beroun, Marta Magnowska, Aleksandra Stawikowska, Dominik Cysewski, Jacek Milek, Magdalena Dziembowska, Bozena Kuzniewska
Summary: Fragile X syndrome (FXS) is a common genetic cause of intellectual disability and autism. The Fmr1 KO mouse model of FXS exhibits increased translation of synaptic proteins, leading to abnormalities in circuit formation and synaptic properties. Proteomics analysis of synaptoneurosomes from adult Fmr1 KO mice shows differential abundance of proteins regulating glutamatergic synapse activity. Further experiments reveal impaired activity-dependent synaptic delivery of AMPARs and an increased number of Ca(2+-)impermeable receptors in Fmr1 KO synapses.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Neurosciences
Ian D. Coombs, Stuart G. Cull-Candy
Summary: The functional properties of AMPA receptors are crucial in shaping excitatory synaptic signaling in the brain. Understanding the behavior and regulation of single AMPAR channels is essential in unraveling how central synapses carry, process, and store information. Auxiliary subunits play a key role in regulating AMPAR channel properties and adding diversity, while single-channel studies reveal the unique behavior of AMPAR channels.
Article
Neurosciences
Aoi Jitsuki-Takahashi, Susumu Jitsuki, Naoya Yamashita, Meiko Kawamura, Manabu Abe, Kenji Sakimura, Akane Sano, Fumio Nakamura, Yoshio Goshima, Takuya Takahashi
Summary: The semaphorin family of proteins regulates formation of contextual memory by driving AMPA receptors into hippocampal synapses. This signaling process involves alteration of the phosphorylation status of collapsin response mediator protein 2, affecting Hebbian synaptic plasticity.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Xin Qin, Michael G. Zaki, Zhicheng Chen, Elisabet Jakova, Zhi Ming, Francisco S. Cayabyab
Summary: Experimental results show that during hypoxia/reperfusion, protein kinase casein kinase 2 (CK2) regulation of A1R and A2AR, as well as AMPAR endocytosis, play important roles in APSPs and neuronal damage.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Changyong Guo, Di Wen, Yihong Zhang, Richie Mustaklem, Basil Mustaklem, Miou Zhou, Tao Ma, Yao-Ying Ma
Summary: This study suggests that the synaptic insertion mechanism of CP-AMPARs in the nucleus accumbens is crucial for mediating synaptic degeneration in Alzheimer's Disease. Blocking CP-AMPARs can prevent Aβ O-associated spine loss and reduced synaptic transmission.
MOLECULAR PSYCHIATRY
(2022)
Article
Biology
Anastasiya Zaytseva, Evelina Bouckova, McKennon J. Wiles, Madison H. Wustrau, Isabella G. Schmidt, Hadassah Mendez-Vazquez, Latika Khatri, Seonil Kim
Summary: Ketamine enhances neuronal activity and synaptic strength by reducing calcineurin activity, leading to rapid antidepressant effects.
Article
Neurosciences
Peggy Rentsch, Sandy Stayte, Gary P. Morris, Bryce Vissel
Review
Clinical Neurology
I. A. Clark, B. Vissel
EXPERT REVIEW OF NEUROTHERAPEUTICS
(2019)
Article
Neurosciences
Sandy Stayte, Kathryn J. Laloli, Peggy Rentsch, Aimee Lowth, Kong M. Li, Russell Pickford, Bryce Vissel
EXPERIMENTAL NEUROLOGY
(2020)
Article
Neurosciences
Peggy Rentsch, Sandy Stayte, Timothy Egan, Ian Clark, Bryce Vissel
NEUROBIOLOGY OF DISEASE
(2020)
Article
Neurosciences
Lyndsey M. Konen, Amanda L. Wright, Gordon A. Royle, Gary P. Morris, Benjamin K. Lau, Patrick W. Seow, Raphael Zinn, Luke T. Milham, Christopher W. Vaughan, Bryce Vissel
Article
Multidisciplinary Sciences
David Goodman-Meza, Akos Rudas, Jeffrey N. Chiang, Paul C. Adamson, Joseph Ebinger, Nancy Sun, Patrick Botting, Jennifer A. Fulcher, Faysal G. Saab, Rachel Brook, Eleazar Eskin, Ulzee An, Misagh Kordi, Brandon Jew, Brunilda Balliu, Zeyuan Chen, Brian L. Hill, Elior Rahmani, Eran Halperin, Vladimir Manuel
Article
Neurosciences
Franklin B. Krasne, Raphael Zinn, Bryce Vissel, Michael S. Fanselow
Summary: The study focuses on the extinction of contextual fear in exposure therapy for fear disorders, introducing a new neurocomputational model BaconX. The model explains how contextual representations are formed and associated with fear, and predicts factors influencing successful extinction, such as session length and context change.
Article
Immunology
Hui Chen, Baoming Wang, Gerard Li, Joel R. Steele, Sandy Stayte, Bryce Vissel, Yik Lung Chan, Chenju Yi, Sonia Saad, Rita Machaalani, Brian G. Oliver
Summary: Research shows that exposure to e-cigarettes impairs short-term memory independently of diet and nicotine, and is associated with systemic inflammation, decreased synaptic protein levels, and increased astrogliosis in chow-fed mice, but decreased astrogliosis and increased microglia in HFD-fed mice.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Health Care Sciences & Services
Faysal G. Saab, Jeffrey N. Chiang, Rachel Brook, Paul C. Adamson, Jennifer A. Fulcher, Eran Halperin, Vladimir Manuel, David Goodman-Meza
Summary: A retrospective study found no association between fever, oxygen requirement, and laboratory abnormalities upon admission with the need for acute care within 30 days after discharge for patients with severe COVID-19.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2021)
Article
Neurosciences
Jessica Leake, Raphael Zinn, Laura H. Corbit, Michael S. Fanselow, Bryce Vissel
Summary: Memories formed under inadequate learning time display maladaptive properties, with differences in neuronal activation impacting memory specificity. Larger memory engrams support better neuronal and behavioral discrimination, showing the influence of previous learning and present experience on behavior.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Behavioral Sciences
Sandy Stayte, Amolika Dhungana, Bryce Vissel, Laura A. Bradfield
Summary: Recent evidence suggests that the parafascicular nucleus of the thalamus and the lateral orbitofrontal cortex play roles in representing internal state/context and guiding action selection in partially observable tasks, possibly through inputs onto cholinergic interneurons in the dorsomedial striatum. This function may be achieved interdependently through direct projections or the convergence of independent inputs onto striatal targets.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Neurosciences
Amolika Dhungana, Serena Becchi, Jessica Leake, Gary Morris, Nesli Avgan, Bernard W. Balleine, Bryce Vissel, Laura A. Bradfield
Summary: A comprehensive investigation of goal-directed action in a transgenic mouse model of Alzheimer's disease reveals deficits in behavior control and a correlation with neuroinflammation in the dorsal CA1 hippocampal region.
Article
Biochemistry & Molecular Biology
Peggy Rentsch, Timothy Egan, Andrea Kuriakose, Sandy Stayte, Bryce Vissel
Summary: L-Dopa treatment for Parkinson's disease can cause dyskinesias, and this study suggests that the increased ratio of M1 to M2 microglia in the striatum is a contributing cause of dyskinesias. Anti-inflammatory drugs can alleviate dyskinesias and reduce the M1/M2 microglia ratio.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Ian A. Clark, Bryce Vissel
Summary: Over a decade's experience of post-stroke rehabilitation by etanercept indicates that excess TNF contributes to chronically diminished neurological function. Treatment with etanercept can revert chronically activated microglia to their normal state, offering potential for treating various chronic neurological illnesses characterized by activated microglia.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Article
Clinical Neurology
Hui Zhong, Chunni Zhu, Yoshihiko Minegishi, Franziska Richter, Sharon Zdunowski, Roland R. Roy, Bryce Vissel, Parag Gad, Yury Gerasimenko, Marie-Francoise Chesselet, V. Reggie Edgerton
NEUROREHABILITATION AND NEURAL REPAIR
(2019)