Neuron: June 5, 2024 (Volume 112, Issue 11)

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[Webinar: Single‐cell transcriptomics of organoids for disease modeling and treatment](%2F%2Fwww.workcast.com%2Fregister%3Fcpak=4648763751232005%26referrer=etoc/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/Z1iyn144VfVUH60L_oTgTjWIJz1GXbxw0p5MhzNZxkE=356) June 5, 2024, 11:00 am ET | Register here Featured articles --------------------------------------------------------------- [Neural mechanisms of information seeking](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00246-0/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/j-8Or3ea5-pztBPr7exP9igsNYBfxqcIgPjf6eF8ktw=356) Kobayashi et al. [An implantable device for wireless monitoring of diverse physio‐behavioral characteristics in freely behaving small animals and interacting groups](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00153-3/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/ccpz6y4r5cWQN9pJuZWSbC1mGwo5QXJkdEGCH7vo4b4=356) Ouyang et al. [Single‐nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer s disease profile and possible mechanisms of disease protection](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00093-X/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/nHvgS8JE7sy4LJuwt31B0A7bI_YLeJRUmXT-ngghEMo=356) Almeida et al. [TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00126-0/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/SykVkZ8_rgA1HFxsOFWOg4mtU3w3QW-dGMcurlYMtac=356) Huang et al. Online now --------------------------------------------------------------- [Cell‐class‐specific electric field entrainment of neural activity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00356-8/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/b4yMB4n7mb2QJN5oFN0HZHOppwvsMkIMpHonxdPw_cw=356) Lee et al. [Cell‐type‐specific effects of age and sex on human cortical neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00360-X/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/yiRfAsdaANiBPctV-jqtXLXTG11kV01MsO3soxxf4W4=356) Chien et al. [Principles of cortical areas and their implications for neuroimaging](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00355-6/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/QlH0fAvcf_2p2ogvhSLo67x40SGlInzRXwrP1mVeO_8=356) Petersen et al. [Cryo‐EM structures of pathogenic fibrils and their impact on neurodegenerative disease research](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00359-3/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/ojgvNPAZ8sLSlBymgVUz2MGh5j6dCRfHG-sti3uZhUY=356) Todd et al. Table of Contents Previews --------------------------------------------------------------- [Seq-ing mechanisms behind types of Alzheimer’s disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00320-9%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/Ppug7XOZ1RAy542vwCIHcGP2KYN04OD59MrlnQ22e_Y=356) Yun Chen, Jason D. Ulrich Sporadic Alzheimer’s disease (AD) and autosomal dominant Alzheimer’s disease (ADAD) share pathological features, but differing mechanisms, leading to disease. In this issue of Neuron, Almeida, Eger, et al. uncovered molecular processes that may distinguish sporadic AD from ADAD and how the APOE-Christchurch variant may be protective. [From bile acids to melancholia](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00333-7%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/3FcTKTpqiDHXdqGHX2QsAVal4v85TWdshfm2-GL6gmU=356) Alexandra S. Klein, Mazen A. Kheirbek In this issue of Neuron, Li, Zhang, et al. find that the bile acid receptor TGR5 in the lateral hypothalamus influences neuronal dynamics underlying stress-induced depression-like behaviors. Inhibition of these neurons produces antidepressant-like effects through a circuit that includes hippocampal CA3 and dorsolateral septum, revealing a novel potential therapeutic for depression. [Turning down the body heat: A novel mechanism for TRPV1 antagonist-induced hyperthermia](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00321-0%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/AX_AKku_QkHaBX_9Z1eT1NqjazV7rVnLM2QP4mqhghA=356) Kali Esancy, Ajay Dhaka While effective analgesics, TRPV1 antagonists can dangerously alter thermoregulation. In this issue of Neuron, Huang et al. demonstrate that interaction with the S4-S5 linker of TRPV1 determines whether an antagonist affects core body temperature, with promising implications for analgesic development. Spotlight --------------------------------------------------------------- [Making sense of Timothy syndrome with 3D human neuronal models](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00363-5%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/T5o3obeRyb_n5GvpvjayofZICvPSJoGMtKOTNe45t0c=356) Ramsey Najm, Juergen A. Knoblich In a recent issue of Nature, Chen and colleagues reveal the potential for antisense oligonucleotides (ASOs) to rescue the neuropathological mechanisms underlying Timothy syndrome (TS) using three-dimensional neuronal models. Combining in vitro and in vivo approaches, the authors present a strategy to translate disease biology findings into potential therapeutics. Obituary --------------------------------------------------------------- [William A. Catterall (1946–2024)](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00283-6%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/5KbMoBDUXgdWu1LB9zJnx-SViQ81GVX69VD4lTXgPdE=356) Todd Scheuer, Ruth Westenbroek, Ning Zheng, Franck Kalume, Thuy N. Vien, Jian Payandeh, Paul G. DeCaen NeuroView --------------------------------------------------------------- [Thriving in neuroscience careers: Three lessons from 12+ years of the BRAINS Program](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00322-2%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/Tmv0uoXQzPd0kbYFO3J4pb8vIoEW72Vw4VG_BjlogIw=356) Joyce W. Yen, M. Claire Horner-Devine, Erin Carll, Rachel Talney, Sheri J.Y. Mizumori The NINDS-funded BRAINS Program for neuroscientists from underrepresented and marginalized groups has positively impacted its participants and the field. We discuss three lessons to advance excellence and diversity: center relationships, provide ongoing engagement, and leverage programmatic expertise. Review --------------------------------------------------------------- [Neural mechanisms of information seeking](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00246-0%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/9bUQ5utKWMdphnas_WXJMoa_V9N47zNwDAkO4NH2oLQ=356) Kenji Kobayashi, Joseph W. Kable Information seeking is an integral, yet often overlooked aspect of value-based decision-making. Kobayashi and Kable review recent findings on the neural mechanisms of information seeking, highlighting an emerging hypothesis that the reward system represents the subjective value of information. Case study --------------------------------------------------------------- [Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00275-7%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/Mvwhj9hTNwGKsQUhhUBb3hojc84asOQHo9bUtHcA5NU=356) Jeremias Motte, Melissa Sgodzai, Christiane Schneider-Gold, Nina Steckel, Thomas Mika, Tobias Hegelmaier, Dominic Borie, Aiden Haghikia, Dimitrios Mougiakakos, Roland Schroers, Ralf Gold Open Access Myasthenia gravis and Lambert-Eaton myasthenic syndrome are autoimmune disorders affecting neuromuscular transmission, for which effective therapies are limited. Motte et al. demonstrate safe application of anti-CD19 chimeric antigen receptor T cell therapy for two patients with these concomitant conditions, resulting in profound recovery of clinical parameters and mobility. NeuroResource --------------------------------------------------------------- [An implantable device for wireless monitoring of diverse physio-behavioral characteristics in freely behaving small animals and interacting groups](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00153-3%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/doeBsgRx0E74rv03nfPmEaXKWFHbOawYOj69GJiI4OQ=356) Wei Ouyang, Keith J. Kilner, Rachael M.P. Xavier, Yiming Liu, Yinsheng Lu, Sophia M. Feller, Kayla M. Pitts, Mingzheng Wu, Jokubas Ausra, Ian Jones, Yunyun Wu, Haiwen Luan, Jacob Trueb, Elizabeth M. Higbee-Dempsey, Iwona Stepien, Nayereh Ghoreishi-Haack, Chad R. Haney, Hao Li, Yevgenia Kozorovitskiy, Mitra Heshmati, Anthony R. Banks, Sam A. Golden, Cameron H. Good, John A. Rogers Ouyang et al. report a wireless, battery-free implant for comprehensive, continuous monitoring of physiology and behavior in freely behaving small animals and interacting groups. Demonstrations in pharmacological, locomotor, and acute and social stress tests and the implant's concurrent operation with wireless optogenetics showcase its broad utility as a tool for neuroscience. Articles --------------------------------------------------------------- [Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer’s disease profile and possible mechanisms of disease protection](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00093-X%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/docDfUKo6nWRMitWDcEH85baEBXngqaOPF4r1Zff_1A=356) Maria Camila Almeida, Sarah J. Eger, Caroline He, Morgane Audouard, Arina Nikitina, Stella M.K. Glasauer, Dasol Han, Barbara Mejía-Cupajita, Juliana Acosta-Uribe, Nelson David Villalba-Moreno, Jessica Lisa Littau, Megan Elcheikhali, Erica Keane Rivera, Daniel Carneiro Carrettiero, Carlos Andrés Villegas-Lanau, Diego Sepulveda-Falla, Francisco Lopera, Kenneth S. Kosik Almeida, Eger, and colleagues find specific autophagy and chaperone gene signatures that distinguish autosomal dominant Alzheimer’s disease (ADAD) from sporadic cases. Protection from dementia due to the APOE3-Christchurch variant may arise from increased LRP1 expression in astrocytes and, consequently, their increased TAU uptake. [TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00152-1%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/juTuVr-4snPvZZaNn25X19qoddJ0cNLE-9seJtEMprw=356) Xu-Yi Li, Shi-Ya Zhang, Yi-Zhou Hong, Zhi-Gang Chen, Yan Long, Dan-Hua Yuan, Jia-Jia Zhao, Su-Su Tang, Hao Wang, Hao Hong Li et al. uncover that the increase in bile acid TGR5 membrane-type receptor in the lateral hypothalamic area improves depressive-like behavior and reveal a potential therapeutic strategy, activating TGR5 by supplementing bile acids for depression. [TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00126-0%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/DQge3eqEmqz27asTKcpejnlo3h3X4Nh-0nOkneCwgAs=356) Yi-Zhe Huang, Jing-Xian Ma, Yu-Jing Bian, Qin-Ru Bai, Yu-Hao Gao, Shu-Ke Di, Yun-Tao Lei, Hui Yang, Xiao-Na Yang, Chang-Yan Shao, Wen-Hui Wang, Peng Cao, Chang-Zhu Li, Michael X. Zhu, Meng-Yang Sun, Ye Yu Development of analgesics targeting TRPV1 receptors has been hampered by undesirable hypo- or hyperthermic effects induced by TRPV1 agonists/antagonists. Huang et al. suggest that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, which may be selectively targeted for developing non-opioid analgesics without the confounding CBT alterations. [Glial KCNQ K+ channels control neuronal output by regulating GABA release from glia in C. elegans](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00123-5%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/Wlgh8bgBaexNock5kvQYNvCzxcs5dYx4besa7Shr8jw=356) Bianca Graziano, Lei Wang, Olivia R. White, Daryn H. Kaplan, Jesus Fernandez-Abascal, Laura Bianchi Graziano et al. report that in C. elegans KCNQ K+ channels control the glial membrane potential, thereby regulating voltage-gated Ca2+ channels responsible for Ca2+ influx, which mediates GABA release from glia. Human KCNQ pathogenic mutations associated with epilepsy and autism spectrum disorder alter GABA release from glia. [Simple spike patterns and synaptic mechanisms encoding sensory and motor signals in Purkinje cells and the cerebellar nuclei](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00124-7%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/CslGlctWDEOLfTs_yl-tXMzKu_ZVABO_jv7ECThVbdA=356) Spencer T. Brown, Mauricio Medina-Pizarro, Meghana Holla, Christopher E. Vaaga, Indira M. Raman Brown et al. find that differential short-term plasticity of excitatory and inhibitory synapses lets Purkinje cells encode touch and whisking with a dual simple spike code. Sensory onset evokes well-timed spike suppression. Motor-related signals evoke slow spike rate increases. CbN targets fire strongly during the former but filter the latter. [Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00154-5%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/sj05Y5JXrAx1yqUquy8ydsWCFL4piRs2efgVxFG-FOs=356) Yiyao Zhang, Mursel Karadas, JingJing Liu, Xinyi Gu, Mihály Vöröslakos, Yulong Li, Richard W. Tsien, György Buzsáki Zhang and Karadas et al. use GRAB sensors and electrophysiology to unravel the interaction of acetylcholine and oxytocin at slow and fast timescales across brain states. Perturbation experiments reveal that acetylcholine modulates oxytocin through the hippocampus-lateral septum path, demonstrating how their cooperative actions enable specific functions. [Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00092-8%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/CFBT-VH-Xz6CqmbnxGBZobsWHeU_o8O7g9f37nTl4s8=356) Alex Piet, Nick Ponvert, Douglas Ollerenshaw, Marina Garrett, Peter A. Groblewski, Shawn Olsen, Christof Koch, Anton Arkhipov Open Access Individuals may adopt unique strategies to find rewards, but it is unclear how strategy choice affects neural activity. Piet et al. find that mice solve a visual change detection task using two strategies and that strategy choice influences the activity of cortical neurons in cell-type-specific ways. Corrections --------------------------------------------------------------- [Global and subtype-specific modulation of cortical inhibitory neurons regulated by acetylcholine during motor learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00358-1%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/oDyxta1uIeWFG9l7Qhhwdn2SKIi_SuXJ8hESzYrnGvk=356) Chi Ren, Kailong Peng, Ruize Yang, Weikang Liu, Chang Liu, Takaki Komiyama [Social Control of Hypothalamus-Mediated Male Aggression](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00357-X%3Fdgcid=raven_jbs_etoc_email/1/0100018fe95744a0-576ac317-cbbd-4e11-b5d2-55edf5e17027-000000/c_pWbQJwdp8Ap7kp-bx-GUvIYAMsTe2VusnmZ1N0j28=356) Taehong Yang, Cindy F. Yang, M. Delara Chizari, Niru Maheswaranathan, Kenneth J. Burke Jr., Maxim Borius, Sayaka Inoue, Michael C. Chiang, Kevin J. Bender, Surya Ganguli, Nirao M. 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