Neuron: April 3, 2024 (Volume 112, Issue 7)

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Featured articles --------------------------------------------------------------- [The neuroscience of lucid dreaming: Past, present, future](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00162-4/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/9YYEuiWewRvUXQel2jHWQGZsALadWPJVUdgxGp6CXWE=347) Zerr et al. [Episodic memory development: Bridging animal and human research](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00046-1/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/h8qJTyPxmPx9YmyRi0iN1rZvST1kSLeaLoVjXnD89ok=347) Bevandic et al. [Beyond hippocampus: Thalamic and prefrontal contributions to an evolving memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00980-7/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/-K9wDKLBRQoVrO-ubXZ9KRj24XLMUBeAbcUZ9PVPHOE=347) Yadav et al. [APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's disease pathology](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00008-4/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/nyPrAPE2XtF_5nv7ZmjLq8CPpe3fU6O2wRBcVB_aKzo=347) Chemparathy et al. Online now --------------------------------------------------------------- [Astrocyte-secreted neurocan controls inhibitory synapse formation and function](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00161-2/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/2DK_RIANIPqXe7AAxek02eoipQxyGgaNtj6JdMqP0IQ=347) Irala et al. [Monitoring norepinephrine release in vivo using next-generation GRABNE sensors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00155-7/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/2eZ9chaACBV6FdW36joWUnxhzIj4JflPQAuk8Teq0vs=347) Feng 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)00153-3/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/G4R63h1855FLN1d_QtDUlSpAnGItV8tIgIH04SdUIcw=347) Ouyang et al. [Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00154-5/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/G85uomax1ZUqztbr4qdWnX5c4j-qySZUWYXFJQ9ntYU=347) Zhang et al. Table of Contents Previews --------------------------------------------------------------- [APOE loss of function: A genetic shield against Alzheimer’s disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00157-0%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/njQmjZCKhLCd8YAIssSUSVD1GbOyVOKppLKFMy54QB8=347) Mason D. Tate, Hande Karahan, Jungsu Kim In this issue of Neuron, Chemparathy et al. provide human genetics data suggesting that APOE loss-of-function mutations may confer resistance to Alzheimer’s disease (AD) without compromising longevity. These data strongly support the APOE toxic gain-of-function hypothesis for AD. [Ignorance is bliss: Inhibition of proteomic stress sensing improves direct neuronal conversion](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00158-2%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/gA8XbvVVRos9enqfC4YhvjUmLzsgJTu_sNB8bf7fSUQ=347) Larissa Traxler, Oliver Borgogno, Jerome Mertens Direct conversion of non-neuronal cells to neurons offers opportunities for disease modeling and therapy. In this issue of Neuron, Sonsalla et al. reveal the unfolded protein response (UPR) pathway as a “proteomic roadblock” to direct neuronal conversion; overcoming this roadblock enhances reprogramming. [The cerebellum tells the amygdala, “Nothing diminishes anxiety faster than action”](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00166-1%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/SuzSBhM8kwBLitsDGY87Fr5UCMN2pV4Dq8kRL8RDr5w=347) Ludovic Spaeth, Kamran Khodakhah In this issue of Neuron, Zhang et al. question the neural substrates of exercise-based alleviation of anxiety in rodents. In brief, they propose a model where physical activity provides an anxiolytic effect by recruiting specific cerebello-limbic circuits. NeuroView --------------------------------------------------------------- [The neuroscience of lucid dreaming: Past, present, future](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00162-4%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/jFvxnPfYtRa216jkHdx4TUX3wUdUcipqC5prKmLuYMc=347) Paul Zerr, Nico Adelhöfer, Martin Dresler Lucid dreaming allows conscious awareness and control of vivid dream states; however, its rarity and instability make neuroscientific experimentation challenging. Recent advances in wearable neurotechnology, large-scale collaborations, citizen neuroscience, and artificial intelligence increasingly facilitate the decoding of this intriguing phenomenon. Perspective --------------------------------------------------------------- [Beyond hippocampus: Thalamic and prefrontal contributions to an evolving memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00980-7%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/HHU-ogdAazL0df6h5ZpZiLj1Yzc4sHoz853fUTr1HBw=347) Nakul Yadav, Andrew Toader, Priya Rajasethupathy Yadav et al. discuss how memory representations initially formed in hippocampus continually reorganize across the brain. They propose a model where parallel memory representations emerge in prefrontal cortex but require sustained support from limbic, then diencephalic, then cortical circuits, each with longer time constants, for continuous stabilization into long-term storage. Review --------------------------------------------------------------- [Episodic memory development: Bridging animal and human research](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00046-1%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/gmncXJ1JCVKjroUAFJjmDF-0Sa5_9mfG6s4Qs7TSHYM=347) Juraj Bevandić, Loïc J. Chareyron, Jocelyne Bachevalier, Francesca Cacucci, Lisa Genzel, Nora S. Newcombe, Faraneh Vargha-Khadem, H. Freyja Ólafsdóttir Open Access Bevandić et al. review human, non-human primate, and rodent studies on the ontogeny of episodic and episodic-like memory. They identify theoretical and methodological obstacles that currently limit cross-species insights and propose a common research framework to facilitate comparative studies. NeuroResource --------------------------------------------------------------- [Single-neuron projectomes of mouse paraventricular hypothalamic nucleus oxytocin neurons reveal mutually exclusive projection patterns](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)01010-3%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/94pc059u2JQApyWXUQbiG0_omGP1KuVuPeddCNAoHZM=347) Humingzhu Li, Tao Jiang, Sile An, Mingrui Xu, Lingfeng Gou, Biyu Ren, Xiaoxue Shi, Xiaofei Wang, Jun Yan, Jing Yuan, Xiaohong Xu, Qing-Feng Wu, Qingming Luo, Hui Gong, Wen-Jie Bian, Anan Li, Xiang Yu Li et al. 3D reconstructed the complete axon, dendrite, and soma morphologies of individual OXT neurons in the mouse paraventricular hypothalamic nucleus at submicron resolution. They identified two main clusters, which project to mutually exclusive targets and possess distinct morphological features. These results provide a structural foundation for understanding OXT function. Reports --------------------------------------------------------------- [Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00977-7%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/-irR1IkXiXfrFSy22kYmpARSHxvwsg-E3aFAJxsrtK8=347) Michael R. Strickland, Michael J. Rau, Brock Summers, Katherine Basore, John Wulf II, Hong Jiang, Yun Chen, Jason D. Ulrich, Gwendalyn J. Randolph, Rui Zhang, James A.J. Fitzpatrick, Anil G. Cashikar, David M. Holtzman Apolipoprotein E (ApoE) is the largest genetic risk factor for late-onset Alzheimer’s disease. Utilizing cryo-EM, Strickland et al. demonstrate important insights into the structure of lipidated ApoE. ApoE was found to adopt an antiparallel dimer in discoidal lipoproteins secreted by astrocytes and in artificially lipidated recombinant ApoE. [APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer’s disease pathology](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00008-4%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/pvFtQsHITdNNePxsPPbz4JVkhPFFCa1QCOuHU3OzalI=347) Augustine Chemparathy, Yann Le Guen, Sunny Chen, Eun-Gyung Lee, Lesley Leong, John E. Gorzynski, Tanner D. Jensen, Alexis Ferrasse, Guangxue Xu, Hong Xiang, Michael E. Belloy, Nandita Kasireddy, Andrés Peña-Tauber, Kennedy Williams, Ilaria Stewart, Lia Talozzi, Thomas S. Wingo, James J. Lah, Suman Jayadev, Chadwick M. Hales, Elaine Peskind, Daniel D. Child, Sigrun Roeber, C. Dirk Keene, Le Cong, Euan A. Ashley, Chang-En Yu, Michael D. Greicius The apolipoprotein E (APOE) ε4 allele strongly increases the risk for Alzheimer’s disease. Chemparathy et al. identified seven carriers of APOE loss-of-function (LoF) variants, including two controls with LoF variants on ε4 and normal amyloid at ages 76 and 90 years. The knockdown of ε4 may protect against Alzheimer’s disease. Articles --------------------------------------------------------------- [Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00978-9%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/xvfbBXjHUQrx5lzBGupYxtQY-prAimNPbhKnwfxzvIM=347) Giovanna Sonsalla, Ana Belen Malpartida, Therese Riedemann, Mirjana Gusic, Ejona Rusha, Giorgia Bulli, Sonia Najas, Aleks Janjic, Bob A. Hersbach, Pawel Smialowski, Micha Drukker, Wolfgang Enard, Jochen H.M. Prehn, Holger Prokisch, Magdalena Götz, Giacomo Masserdotti Open Access Sonsalla, Malpartida, et al. investigated the direct neuronal reprogramming of human astrocytes and fibroblasts carrying mutations in NDUFS4. This led to the discovery of the unfolded protein response as a major hurdle whose inhibition improved the conversion rate, leading to more mature neurons. [Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00003-5%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/nn0FWSPc5x37wLFlW8YZpx-IvMJwdCrpZvuGut9h9cM=347) Andrew D. Nelson, Amanda M. Catalfio, Julie P. Gupta, Lia Min, René N. Caballero-Florán, Kendall P. Dean, Carina C. Elvira, Kimberly D. Derderian, Henry Kyoung, Atehsa Sahagun, Stephan J. Sanders, Kevin J. Bender, Paul M. Jenkins Autism spectrum disorder (ASD) is associated with dysfunction in hundreds of genes. How dysfunction in ASD-associated genes converges on shared biological mechanisms remains an open question. Here, Nelson et al. show that one ASD-associated gene, Ank2, scaffolds another, Scn2a, in neocortical pyramidal cell dendrites, with shared effects on dendritic integration. [The Calmodulin-interacting peptide Pcp4a regulates feeding state-dependent behavioral choice in zebrafish](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00001-1%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/5J3cAilwoeHZYzzb7ihF0fDfdzUStUP8s26t4TiFkBg=347) Margherita Zaupa, Nagarjuna Nagaraj, Anna Sylenko, Herwig Baier, Suphansa Sawamiphak, Alessandro Filosa Open Access Zaupa et al. identify the intracellular peptide Pcp4a as a mediator of the modulatory action of feeding state on behavioral choice. Food intake represses expression of pcp4a via activation of dopamine D2 receptors, leading to disinhibition of CaMKII and possibly increased CaMKII-dependent weakening of responses to small visual stimuli. [A role for the cerebellum in motor-triggered alleviation of anxiety](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00007-2%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/4gNJGFtfj3pXvXV3JeNm03xupABRyO4CcKPWMWVz3kY=347) Xiao-Yang Zhang, Wen-Xia Wu, Li-Ping Shen, Miao-Jin Ji, Peng-Fei Zhao, Lei Yu, Jun Yin, Shu-Tao Xie, Yun-Yong Xie, Yang-Xun Zhang, Hong-Zhao Li, Qi-Peng Zhang, Chao Yan, Fei Wang, Chris I. De Zeeuw, Jian-Jun Wang, Jing-Ning Zhu Open Access The brain mechanisms by which exercise improves mood remain unclear. Zhang et al. dissect a hypothalamo-cerebello-amygdalar circuit bridging the subcortical motor and limbic systems, through which motor activity quickly regulates anxiety at two levels of intensity, and shed light on developing challenging exercise strategies and cerebellar-targeted interventions for anxiety. [Amygdala-hippocampus somatostatin interneuron beta-synchrony underlies a cross-species biomarker of emotional state](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00976-5%3Fdgcid=raven_jbs_etoc_email/1/0100018ea5083a7b-c79bf8bb-61e3-4310-b4a3-8b68d6d5ed82-000000/84eFWakVr3R4WslQraTmE8ahi9uknHXipYv6Fzq_oqo=347) Adam D. Jackson, Joshua L. Cohen, Aarron J. Phensy, Edward F. Chang, Heather E. Dawes, Vikaas S. Sohal Open Access Examining a synchrony-based biomarker for emotional state previously identified in humans, Jackson et al. validate the same biomarker in mice, finding that it depends on amygdala and hippocampus somatostatin neurons, which are linked by direct connections. They show that this biomarker is a causal driver (not just readout) of behavior. 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