Article
Cell Biology
Xin Yang, Ru Gong, Linwei Qin, Yifei Bao, Yi Fu, Shan Gao, Hui Yang, Jinfei Ni, Ti-Fei Yuan, Wei Lu
Summary: NMDAR trafficking plays a crucial role in the modulation of synaptic functions and information processing. It can regulate the trafficking of AMPAR and AMPAR-mediated LTP, while AMPAR trafficking does not impact NMDAR-mediated LTP. Additionally, impaired NMDAR trafficking results in deficits in fear memory consolidation.
Review
Neurosciences
Julien P. Dupuis, Olivier Nicole, Laurent Groc
Summary: N-Methyl-D-aspartate ionotropic glutamate receptors (NMDARs) have crucial roles in various neuronal functions and are implicated in neurological and psychiatric disorders. Understanding the molecular mechanisms underlying the physiological and pathological contributions of NMDARs is an important area of research. Recent studies have revealed new dimensions of postsynaptic NMDAR signaling, including the nanoscale organization of NMDAR complexes, their activity-dependent redistributions, and non-ionotropic signaling capacities, which contribute to neural plasticity and cognition. Dysregulations in these processes may directly contribute to NMDAR-dysfunction-related brain diseases.
Article
Multidisciplinary Sciences
Shuo Li, Sumana Raychaudhuri, Stephen Alexander Lee, Marisa M. Brockmann, Jing Wang, Grant Kusick, Christine Prater, Sarah Syed, Hanieh Falahati, Raul Ramos, Tomas M. Bartol, Eric Hosy, Shigeki Watanabe
Summary: Neurotransmitter release in synapses is influenced by action potentials, with synchronous and asynchronous release sites segregated within active zones, aligned with AMPA and NMDA receptor clusters respectively. This organization leads to efficient activation of NMDA receptors, enhancing membrane depolarization through AMPA receptors.
NATURE COMMUNICATIONS
(2021)
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
Aliza A. Le, Julie C. Lauterborn, Yousheng Jia, Weisheng Wang, Conor D. Cox, Christine M. Gall, Gary Lynch
Summary: Multiple studies indicate that adult male rodents perform better than females on spatial problems and have a lower threshold for long-term potentiation (LTP) of hippocampal CA3-to-CA1 synapses. In prepubescent rodents, females rapidly encode spatial information and express low-threshold LTP, while age-matched males do not. However, the loss of low-threshold LTP across female puberty was associated with increased densities of alpha 5 subunit-containing GABA(A)Rs at inhibitory synapses, greater shunting of burst responses used to induce LTP, and a reduction of NMDAR-mediated synaptic responses. In contrast, the reasons for the gain of functions with male puberty do not involve these mechanisms. In summary, puberty has opposing consequences for plasticity in the two sexes, albeit through different routes.
NATURE NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Jake F. Watson, Alexandra Pinggera, Hinze Ho, Ingo H. Greger
Summary: Changes in AMPAR localization can regulate synaptic transmission strength. The interactions between TARP gamma 8 and AMPAR N-terminal domain are crucial for receptor accumulation and positioning at post-synapses. The study demonstrates that AMPAR C-termini only play a modulatory role, while N-terminal domain and PDZ interactions are essential for controlling transmission.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Seok Heo, Taewook Kang, Alexei M. Bygrave, Martin R. Larsen, Richard L. Huganir
Summary: This study investigated the global dynamics of the hippocampal PSD proteome and phosphoproteome in mice following different types of experience, revealing the crucial role of PSD in synaptic plasticity and identifying molecular mechanisms associated with experience-dependent synaptic remodeling.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Neurosciences
Musa Iyiola Ajibola, Jei-Wei Wu, Wahab Imam Abdulmajeed, Cheng-Chang Lien
Summary: The study demonstrates that subcortical input from the SuM selectively regulates the activities of different DG neurons through distinct synaptic mechanisms in mice. While SuM activation leads to synaptic excitation and inhibition in all post-synaptic cells, the ratio of these components varies depending on cell type. Specifically, dendrite-targeting interneurons primarily receive synaptic excitation, soma-targeting interneurons and granule cells mainly receive synaptic inhibition.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Alexandra Tzilivaki, John J. Tukker, Nikolaus Maier, Panayiota Poirazi, Rosanna P. Sammons, Dietmar Schmitz
Summary: This article explores the brain's ability to capture and store information, focusing on the types, plasticity, and activity patterns of interneurons in the hippocampus and their impact on memory processing.
Article
Neurosciences
Delia N. Chiu, Brett C. Carter
Summary: NMDA receptors (NMDARs) play a crucial role in glutamatergic synaptic signaling in the mammalian central nervous system. The unique biophysical properties of NMDARs, including their ligand- and voltage-dependence, allow them to function as synaptic coincidence detectors, controlling the influx of synaptic Ca2+. Experimental results show that NMDARs contribute to synaptic currents and Ca2+ influx even in the presence of extracellular Mg2+ and absence of AMPAR depolarization. This suggests that NMDARs have an important role in synaptic signaling.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Jonathan D. Lautz, Kaleb B. Tsegay, Zhiyi Zhu, Edward P. Gniffke, John P. Welsh, Stephen E. P. Smith
Summary: The study found that the activity-dependent dynamics of the glutamatergic post-synapse exhibit remarkable stimulus-specific and brain-region-specific diversity, with different input stimuli triggering different responses in PIN parameters. This diversity may help explain the challenges in developing molecule-specific drug therapies for neurological disorders.
Article
Biochemistry & Molecular Biology
Kunwei Wu, Wenyan Han, Wei Lu
Summary: Sleep is an essential process for memory consolidation, and this study reveals the daily rhythmic alterations of GABAergic synapses in hippocampal CA1 pyramidal neurons. Wake promotes tonic inhibition and inhibits phasic inhibition compared to sleep. The study also demonstrates that inhibitory inputs from parvalbumin-expressing interneurons contribute to dynamic iLTP during sleep and wake. Additionally, synaptic insertion of alpha 5-GABA(A) receptors is found to underlie the wake-specific enhancement of iLTP at parvalbumin synapses, independent of the time of the day.
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
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)
Article
Neurosciences
Alvaro Nuno-Perez, Sarah Mondoloni, Anna Tchenio, Salvatore Lecca, Manuel Mameli
Summary: The lateral habenula is involved in encoding aversive stimuli and affective states through excitatory synaptic transmission, partly mediated by Habenular glutamatergic synapses and AMPA receptors. However, the role of NMDA receptors in the LHb remains unknown, hindering their study in mental health contexts. Using mice, researchers discovered that Habenular NMDAR currents are sensitive to specific inhibitors, with region-specific differences in current-voltage relationship and decay time. Inspired by in vivo LHb neuron firing, a burst protocol was designed to induce calcium-dependent long-term potentiation of habenular NMDAR transmission ex vivo, providing new avenues for studying plasticity processes in both physiological and pathological contexts.