Neuron: April 17, 2024 (Volume 112, Issue 8)

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Featured articles --------------------------------------------------------------- [Cross-hemispheric communication: Insights on lateralized brain functions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00120-X/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/0ySVrXWXMZLM2omgPDcFCNjEaaRXm0XcpgBTOFBWzoM=349) Ocklenburg et al. [Mechanisms of sex differences in Alzheimer's disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00050-3/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/Q0QgoQAvxc9JWa_mjnzJWulD76ByMJnV1SboGILXWcU=349) Lopez-Lee et al. [Epigenetic dysregulation in Alzheimer's disease peripheral immunity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00039-4/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/T57cTtNShSZwQZSLgA975fAv_EZ37RB6Tzmiez72C4Y=349) Ramakrishnan et al. [Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00040-0/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/IVRtyiT2zSg79WC7MndULvXUqjiv06Vhgy-GlPGCyP8=349) Li et al. Online now --------------------------------------------------------------- [Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00197-1/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/6wQmKanCUVPNqgNF76V9ZW6qFmAa2lmA9mWVcTg4hao=349) Rangel Guerrero et al. [Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00193-4/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/gzvdj1clIaJ6k2570XSxR0d1LFwva_HvqXNuMDi8dUA=349) Wang et al. [Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00195-8/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/MgJ3a9o9B3rb1TFKe_OexvPOTmzzz_tM8Tg0IMv6ie4=349) Umpierre et al. [Modeling proprioception with task-driven neural network models](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00199-5/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/sIOrZIhUF2DDfcreFd9jFJmKy5KpHqaTajRsSOQbWMA=349) Hansjörg Scherberger Table of Contents Previews --------------------------------------------------------------- [14-3-3θ, a novel player in TDP-43 pathophysiology: Implications for ALS/FTD](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00203-4%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/7UBECs-XotdthK9VVZMfi_DIfhkC1WO7b9u16z9ZPBM=349) Bilal Khalil, Sandrine Da Cruz In this issue of Neuron, Ke et al. report a novel non-canonical interaction between 14-3-3θ and TDP-43 that impacts loss-of-function and gain-of-toxic pathology in TDP-43 proteinopathies. The authors further provide proof of principle for a 14-3-3θ-targeted gene therapy to reduce TDP-43-induced deficits in transgenic TDP-43 mutant mice. [pHeeling the pHorce](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00201-0%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/PG1it-hRx2KCrm-A-ppkjyCfQFP70zKlNM-HJJJE7fQ=349) Sang-Min Jeon, Michael J. Caterina In this issue of Neuron, Yamada et al.1 show that fast excitatory neurotransmission by protons acting at acid-sensing ion channels (ASICs) mediates mechanical force-evoked signaling at the Merkel cell-neurite complex (MNC), contributing to mammalian tactile discrimination. [Anterior cingulate cortex and insomnia: A cingulate-striatum connection](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00194-6%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/kTH7hiEPCcEqp1EENdBmbWMUgJ5blsG2YUQLXRguIHY=349) Qi-Yu Chen, Min Zhuo Insomnia is an important comorbidity of chronic pain. In this issue of Neuron, Li et al. report that chronic-pain-induced insomnia is mediated by the pyramidal neurons in the anterior cingulate cortex and their dopaminergic projections to the dorsal medial striatum. Spotlight --------------------------------------------------------------- [Interferons: Invited guests at the brain’s gala banquet](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00164-8%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/bDe0jJsPFsF0AGTyLaq_GTOyVD5S6KXUnJS6ZBmSypo=349) Mar Márquez-Ropero, Amanda Sierra Removal of toxic debris that can hinder brain function is performed primarily by microglia, the brain’s professional phagocytes. A recent study in Cell 1 identified that viral response interferons are required for priming microglia, ensuring competent phagocytosis and proper circuit wiring. Reviews --------------------------------------------------------------- [Mechanisms of sex differences in Alzheimer’s disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00050-3%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/FT-XFPPlEk_8BHimBzyPxWEF4sTUKC6smC4u0mBFaqw=349) Chloe Lopez-Lee, Eileen Ruth S. Torres, Gillian Carling, Li Gan Open Access This review by Lopez-Lee and Torres et al. summarizes sex-specific differences in AD and potential biological mechanisms and discusses how sex hormones and chromosomes may influence inflammation, metabolism, and autophagy in aging, contributing to distinct disease patterns in men and women. [Cross-hemispheric communication: Insights on lateralized brain functions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00120-X%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/s8dB9MHU7j5AMPX1EOHljiA0OpF4SHBd-4BfLkJcZYU=349) Sebastian Ocklenburg, Zengcai V. Guo Ocklenburg and Guo review the current state of knowledge on cross-hemispheric communication in the vertebrate brain, with a focus on recent research in rodents. They discuss how lateralization in sensory, memory, and motor functions can emerge from asymmetric cross-hemispheric communication. NeuroResource --------------------------------------------------------------- [Epigenetic dysregulation in Alzheimer’s disease peripheral immunity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00039-4%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/Vy5JN4ClI7Qj1OzpcvNsSAumev68eHiqval_Zs1RjK8=349) Abhirami Ramakrishnan, Natalie Piehl, Brooke Simonton, Milan Parikh, Ziyang Zhang, Victoria Teregulova, Lynn van Olst, David Gate Ramakrishnan et al. provide a single-cell genomics resource for exploring the peripheral immune system in Alzheimer’s disease. Their extrapolated findings provide novel insights into the complex relationship between epigenetics and genetic risk factors in Alzheimer’s disease peripheral immunity. Articles --------------------------------------------------------------- [Targeting 14-3-3θ-mediated TDP-43 pathology in amyotrophic lateral sclerosis and frontotemporal dementia mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00048-5%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/5P0LGQr_ajuMauSRVq08YFfiC26WGMLhde27RAm_Y8k=349) Yazi D. Ke, Annika van Hummel, Carol Au, Gabriella Chan, Wei Siang Lee, Julia van der Hoven, Magdalena Przybyla, Yuanyuan Deng, Miheer Sabale, Nicolle Morey, Josefine Bertz, Astrid Feiten, Stefania Ippati, Claire H. Stevens, Shu Yang, Amadeus Gladbach, Nikolas K. Haass, Jillian J. Kril, Ian P. Blair, Fabien Delerue, Lars M. Ittner TDP-43 forms neuronal deposits in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) due to unknown causes. Ke et al. identified the TDP-43 interactor 14-3-3θ, which promotes TDP-43 deposition. They devised a treatment harnessing 14-3-3θ’s affinity for TDP-43, mitigating deficits and neurodegeneration in ALS/FTD models with implications for future therapy. [Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00049-7%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/GgUrXMnsE-6_PirHMTKZe1xyGj0Ttj0V47xQ61QM9Ts=349) Ayako Kawatake-Kuno, Haiyan Li, Hiromichi Inaba, Momoka Hikosaka, Erina Ishimori, Takatoshi Ueki, Yury Garkun, Hirofumi Morishita, Shuh Narumiya, Naoya Oishi, Gen Ohtsuki, Toshiya Murai, Shusaku Uchida Kawatake-Kuno, Li, Inaba, et al. considered a midline thalamic structure, the aPVT, a crucial brain region involved in the sustained antidepressant-like effects of the ketamine metabolite (2S,6S)-HNK. Moreover, they uncover the mechanisms whereby this drug drives its antidepressant-like effects via modulation of GABAergic-inhibition-mediated epigenetic regulations in the aPVT. [ASICs mediate fast excitatory synaptic transmission for tactile discrimination](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00044-8%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/8Dq_-kE-uUv5PVlUWxSS9FCeZ9b05Q7Q4ZeazAMIT1U=349) Akihiro Yamada, Jennifer Ling, Ayaka I. Yamada, Hidemasa Furue, Jianguo G. Gu Yamada et al. show that acid-sensing ion channels (ASICs) mediate fast excitatory synaptic transmission at the tactile end organs, Merkel cell-neurite complexes (MNCs), with protons serving as the principal transmitters. This suggests the unique role of ASICs in the sense of touch and tactile discrimination in mammals. [Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00053-9%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/qvbPn7Y1L1YSIM-jJ90dt6357wwiLq7FVqODkUUzCEY=349) Mark A. Gradwell, Nofar Ozeri-Engelhard, Jaclyn T. Eisdorfer, Olivier D. Laflamme, Melissa Gonzalez, Aman Upadhyay, Laura Medlock, Tara Shrier, Komal R. Patel, Adin Aoki, Melissa Gandhi, Gloria Abbas-Zadeh, Olisemaka Oputa, Joshua K. Thackray, Matthew Ricci, Arlene George, Nusrath Yusuf, Jessica Keating, Zarghona Imtiaz, Simona A. Alomary, Manon Bohic, Michael Haas, Yurdiana Hernandez, Steven A. Prescott, Turgay Akay, Victoria E. Abraira Gradwell et al. highlight the medial deep dorsal horn as a hub for sensory convergence in the spinal cord. Within this region, they identify a population of glycinergic inhibitory interneurons providing broad ipsilateral inhibition to pre-motor and motor networks to gate cutaneous-evoked muscle activity, ensuring smooth movement transitions. [Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00040-0%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/iIzodyeSaH5zjIvpAQuEiT7eWlAJvRXAjxkhs5S67S8=349) Ya-Dong Li, Yan-Jia Luo, Wei-Kun Su, Jing Ge, Andrew Crowther, Ze-Ka Chen, Lu Wang, Michael Lazarus, Zi-Long Liu, Wei-Min Qu, Zhi-Li Huang Over 50% of chronic pain patients experience insomnia. Li et al. reveal that heightened activity of anterior cingulate cortex excitatory neurons precisely governs chronic-pain-induced insomnia via the dorsal medial striatum pathway. This effect relies on enhanced plasticity in dopamine D1-receptor-positive medium spiny neurons. [Cell-type-specific optogenetic fMRI on basal forebrain reveals functional network basis of behavioral preference](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00043-6%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/6WTVU09yomb9NW_FGEMxuA8nB0JNngXKM7Mh2HGsm1s=349) Yijuan Zou, Chuanjun Tong, Wanling Peng, Yue Qiu, Jiangxue Li, Ying Xia, Mengchao Pei, Kaiwei Zhang, Weishuai Li, Min Xu, Zhifeng Liang Open Access Zou et al. uncover basal forebrain (BF)-modulated, cell-type-specific whole-brain BOLD activations and corresponding behavioral preferences. A decoding model is developed to link optogenetic fMRI (opto-fMRI) activation inside the magnet and behavioral preference outside the magnet, revealing the functional network basis of behavioral preference. [Tuned geometries of hippocampal representations meet the computational demands of social memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00047-3%3Fdgcid=raven_jbs_etoc_email/1/0100018eecf7de1b-f470c0a1-4b63-4c37-a8ab-4474655dfd43-000000/bKp_T8L2l76BGL7q4MfqrI2wGkW0q8Sy0ABHgpDZ6WA=349) Lara M. Boyle, Lorenzo Posani, Sarah Irfan, Steven A. Siegelbaum, Stefano Fusi Social memory consists of both familiarity detection and recollection of past social episodes. Whether and how the hippocampus fulfills these roles is unclear. Boyle, Posani, et al. find that the hippocampal CA2 region meets the distinct computational demands of these processes through tuning the geometry of structured neural activity. 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