Review
Neurosciences
Ege T. Kavalali, Lisa M. Monteggia
Summary: Neuronal and synaptic plasticity are common concepts in the field of psychiatry. Two broad classes of plasticity, Hebbian and homeostatic, have been identified by cellular neurophysiologists. Homeostatic plasticity, which can be rapidly engaged by fast-acting antidepressants like ketamine, may provide novel targets for neuropsychiatric treatment. There is evidence that neuropsychiatric compounds can directly or indirectly trigger changes in synaptic activity, leading to homeostatic plasticity and subsequent behavioral effects.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Esther Park, Anthony G. Lau, Kristin L. Arendt, Lu Chen
Summary: Fragile X syndrome is a neurodevelopmental disorder caused by inactivation of the FMR1 gene and loss of the FMRP protein, with defective synaptic RA signaling playing a key role in synaptic plasticity. The interaction between FMRP and RAR alpha is crucial for proper RA signaling and homeostatic synaptic plasticity, providing insights into the synaptic pathophysiology of FXS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Shruti Thapliyal, Kristin L. Arendt, Anthony G. Lau, Lu Chen, Dion K. Dickman
Summary: Homeostatic synaptic plasticity is a mechanism that adjusts synaptic strength to maintain network stability. This study reveals that synaptic signaling through retinoic acid and its receptor, RAR alpha, regulates presynaptic neurotransmitter release to achieve homeostatic adjustment.
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
Cell Biology
Kira Gromova, Edda Thies, Philipp C. Janiesch, Felix P. Lutzenkirchen, Yipeng Zhu, Daniele Stajano, Celine D. Duerst, Michaela Schweizer, Anja Konietzny, Marina Mikhaylova, Christine E. Gee, Matthias Kneussel
Summary: Homeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Kif21b, a microtubule-dependent kinesin motor, binds GKAP and regulates actin dynamics in dendritic spines. This study reveals that Kif21b controls homeostatic synaptic downscaling by promoting actin turnover and decreasing the number of AMPARs in spines.
Article
Neurosciences
Shu-Ling Chiu, Chih-Ming Chen, Richard L. Huganir
Summary: The study revealed a novel function of ICA69 in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 regulates the distribution and stability of PICK1 in neurons, which impacts AMPAR function in the brain. The genetic deletion of ICA69 selectively impairs NMDAR-dependent LTP and leads to behavioral deficits in spatial and associative learning and memory.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Endocrinology & Metabolism
Gregg Duester
Summary: It is well established that retinoic acid receptors (RARs) control gene expression in response to retinoic acid (RA) binding. However, there is evidence suggesting that RAR-alpha (RARa) may also impact synaptic plasticity through non-genomic effects outside the nucleus. Nevertheless, there is a lack of mutation studies and genetic research removing endogenous ligand RA to support this non-genomic mechanism.
FRONTIERS IN NEUROENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Paola Muttathukunnel, Patrick Frei, Sarah Perry, Dion Dickman, Martin Mueller
Summary: Robust neural information transfer relies on the delicate molecular nano-architecture of chemical synapses. This study reveals the alignment of presynaptic nanorings with postsynaptic glutamate receptor rings and the formation of nanocolumn rings by presynaptic proteins and glutamate receptors. The impairment of glutamate receptors triggers the formation of transsynaptic nanocolumns on a minute timescale during homeostatic plasticity. This research uncovers the regulatory mechanism of synaptic nano-architecture and highlights its importance in stabilizing synaptic transmission.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Miranda Mele, Pasqualino De Luca, Ana Rita Santos, Marta Vieira, Ivan L. Salazar, Paulo S. Pinheiro, Carlos B. Duarte
Summary: This study investigated the regulation of the synaptic protein GRASP1 by ubiquitin-dependent mechanisms, revealing an impact on the surface distribution and activity of AMPA receptors. Ubiquitination was found to decrease dendritic levels of GRASP1 and surface expression of GluA1 subunits, leading to a reduction in mEPSC amplitudes, effects that were partially reversed by cotransfection with GRASP1.
Article
Cell Biology
Zikai Zhou, Guiqin He, Xiaoyun Zhang, Xin Lv, Xiaolin Zhang, An Liu, Shuting Xia, Hao Xie, Rui Dang, Lifang Han, Junxia Qi, Yanghong Meng, Shunying Yu, Wei Xie, Zhengping Jia
Summary: Synaptic scaling, a form of homeostatic plasticity, is initiated by the release of neurite growth-promoting factor 2 (NGPF2) following TTX treatment, leading to actin reorganization and stabilization of AMPARs at the synapse via the ALK-LIMK-cofilin signaling pathway.
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
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
Li Chen, Hanjie Wang, Shuhan Cha, Jiong Li, Jiaqi Zhang, Jiaming Wu, Guoqing Guo, Jifeng Zhang
Summary: Synaptic plasticity is crucial for cognitive functions, and mutations in the SPAST gene can lead to hereditary spastic paraparesis and cognitive impairment. Phosphorylation of the Spastin protein enhances the delivery of AMPA receptor GluA2 subunit to the synaptic surface, increasing the amplitude and frequency of synaptic currents.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Thomas P. Cast, Daniel J. Boesch, Kim Smyth, Alisa E. Shaw, Michael Ghebrial, Soham Chanda
Summary: The amino acid substitution mutation (R101Q) in the NLGN4 gene impairs the maturation and surface trafficking of NLGN4 protein, leading to reduced synaptic localization and functional impact on neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Trey Polvadore, Malcolm Maden
Summary: This study reveals the impact of retinoic acid treatment on the control of positional information during axolotl limb regeneration. Through RNA sequencing, the genes interacting with RAR alpha were identified, shedding light on the mechanism of action for future research.
Article
Neurosciences
Esther Park, Michelle Tjia, Yi Zuo, Lu Chen
JOURNAL OF NEUROSCIENCE
(2018)
Article
Neurosciences
Jie Li, Esther Park, Lei R. Zhong, Lu Chen
CURRENT OPINION IN NEUROBIOLOGY
(2019)
Article
Multidisciplinary Sciences
Yu-Tien Hsu, Jie Li, Dick Wu, Thomas C. Sudhof, Lu Chen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
Ying Yang, Yang Geng, Dongyun Jiang, Lin Ning, Hyung Joon Kim, Noo Li Jeon, Anthony Lau, Lu Chen, Michael Z. Lin
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Review
Behavioral Sciences
Omid Miry, Jie Li, Lu Chen
Summary: This review summarizes theories and experimental evidence on hippocampal memory engram formation and function, discussing the latest advances in the field and highlighting the mechanisms of engram allocation. Unanswered questions for future investigations are identified to achieve a more comprehensive understanding of memory formation and retrieval.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Biology
Jie Li, Rena Y. Jiang, Kristin L. Arendt, Yu-Tien Hsu, Sophia R. Zhai, Lu Chen
Article
Cell Biology
Nisha Raj, Zachary T. McEachin, William Harousseau, Ying Zhou, Feiran Zhang, Megan E. Merritt-Garza, J. Matthew Taliaferro, Magdalena Kalinowska, Samuele G. Marro, Chadwick M. Hales, Elizabeth Berry-Kravis, Marisol W. Wolf-Ochoa, Veronica Martinez-Cerdeno, Marius Wernig, Lu Chen, Eric Klann, Stephen T. Warren, Peng Jin, Zhexing Wen, Gary J. Bassell
Summary: The transcriptional silencing of the FMR1 gene in FXS leads to the loss of FMRP, which is important for regulating mRNA translation and protein synthesis. Abnormal protein synthesis in FXS is related to altered cell fate decisions favoring proliferation over neurogenesis during early development. Pharmacologic inhibition of elevated PI3K signaling can correct excess protein synthesis and cell proliferation in a subset of patient neural cells.
Article
Biochemistry & Molecular Biology
Esther Park, Anthony G. Lau, Kristin L. Arendt, Lu Chen
Summary: Fragile X syndrome is a neurodevelopmental disorder caused by inactivation of the FMR1 gene and loss of the FMRP protein, with defective synaptic RA signaling playing a key role in synaptic plasticity. The interaction between FMRP and RAR alpha is crucial for proper RA signaling and homeostatic synaptic plasticity, providing insights into the synaptic pathophysiology of FXS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ju Lu, Michelle Tjia, Brian Mullen, Bing Cao, Kacper Lukasiewicz, Sajita Shah-Morales, Sydney Weiser, Lindsay P. Cameron, David E. Olson, Lu Chen, Yi Zuo
Summary: The study shows that TBG can reduce anxiety levels and rescue deficits in sensory processing and cognitive flexibility in mice under stress. Furthermore, TBG promotes the regrowth of excitatory neuron dendritic spines and enhances neural activity in the somatosensory cortex.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Cheng-Hui Lin, Yue Sun, Candace S. Y. Chan, Man-Ru Wu, Lei Gu, Alexander E. Davis, Baokun Gu, Wenlin Zhang, Bogdan Tanasa, Lei R. Zhong, Mark M. Emerson, Lu Chen, Jun B. Ding, Sui Wang
Summary: Adeno-associated viruses (AAVs) can be used as powerful tools to study specific cell types in the central nervous system (CNS). Chromatin accessibility data can be utilized to identify active cis-regulatory modules (CRMs) for AAV-based cell-type specific labeling and manipulation. Strategies such as prescreening based on cell-type-specific transcription factor binding sites (TFBSs) density and generation of synthetic CRMs can improve the efficiency of identifying active CRMs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Lu Chen, Xiling Li, Michelle Tjia, Shruti Thapliyal
Summary: This review discusses the significance of the synaptic E/I balance in homeostatic plasticity and its association with neurological diseases and sensory deafferentation.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Article
Neurosciences
Bing Cao, Gregory Scherrer, Lu Chen
Summary: Mechanical allodynia in neuro-pathic pain is caused by spinal disinhibition through the homeostatic reduction of inhibitory outputs from dorsal horn parvalbumin-positive (PV+) interneurons. Retinoic acid receptor RARa is the key molecular mediator for this synaptic disinhibition.
Article
Biology
Shruti Thapliyal, Kristin L. Arendt, Anthony G. Lau, Lu Chen, Dion K. Dickman
Summary: Homeostatic synaptic plasticity is a mechanism that adjusts synaptic strength to maintain network stability. This study reveals that synaptic signaling through retinoic acid and its receptor, RAR alpha, regulates presynaptic neurotransmitter release to achieve homeostatic adjustment.
Editorial Material
Neurosciences
Fereshteh S. S. Nugent, Ka Wan Li, Lu Chen
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Lu Chen, Michelle Tjia, Kristin L. Arendt
JOURNAL OF NEUROCHEMISTRY
(2022)