Neuron: July 20, 2022 (Volume 110, Issue 14)

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[The translational revolution of itch](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00267-7/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/AExuaObSiSNNNt2K4w1H2V49_l0337NiDkjIyR1Ht4Y=258) Brian S. Kim [5-hydroxytryptamine produced by enteric serotonergic neurons initiates colorectal cancer stem cell self-renewal and tumorigenesis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00369-5/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/GZ8KNb_UAo7J66d-kg4Zzs8Rxju34h8gCc_weFbe1Hw=258) Zhu et al. [Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00411-1/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/tZHgt_XkPOe_82gUulijrSkil0nBYLLDlJlqmPRcmT8=258) Chen et al. Online now --------------------------------------------------------------- [Not so spontaneous: Multi-dimensional representations of behaviors and context in sensory areas](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00588-8/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/-Z_bzhHuYGSNNGJzTsIWuq5I68JuRZhzch2L9ckNVrA=258) Avitan et al. [Sequential inhibitory plasticities in hippocampal area CA2 and social memory formation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00551-7/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/UR79DhGZ9sL8XHS9WfIc8L47Dc4nTUji2TTgRsR9lJE=258) Loisy et al. [Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00555-4/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/Ge77qlBiLLd1ceLUUvBo5vH9ulRGkQeXItfw96HueV4=258) Bowles et al. [Novelty and uncertainty regulate the balance between exploration and exploitation through distinct mechanisms in the human brain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00502-5/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/UNlAPCHmjd-uR0svTcT7NX34wvyi9H6rgbjUM-NiawU=258) Cockburn et al. Table of Contents Previews --------------------------------------------------------------- [Evolution gone wrong: Enteric serotonergic neurons and colorectal cancer](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00554-2%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/dhhXj5F74y7EfG1joUYJJ6J9K0WQipcaOC5VGcReVGU=258) Michael D. Gershon Serotonin is a multifunctional signaling molecule. In this issue of Neuron, Zhu et al. (2022) demonstrate, surprisingly, that despite the diminutive size of the enteric serotonin neuronal pool, it is serotonin from these neurons that drives proliferation of colorectal cancer stem cells. [The role of hippocampal KCNQ2 channel in antidepressant actions of ketamine](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00504-9%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/MAMaKp5hoIf2xEq89_5ZmuxYHzcsBkpWRk7zVTSmgkg=258) Li Ma, Kenji Hashimoto In this issue of Neuron, Lopez et al. report that KCNQ2 (potassium voltage-gated channel subfamily Q member 2) is essential for the sustained antidepressant-like effects of ketamine in glutamatergic neurons of the ventral hippocampus. This study implies that KCNQ2 activators can be novel antidepressants without the ketamine side effects. [Cracking the combinatorial code of neuronal wiring](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00505-0%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/_oI-Hktf7Uj2I-dXSmA1i69kbIQoq_H5wpkoGcOeTv0=258) Andrew Kovalenko, Avraham Yaron How transcription factors orchestrate the combinatorial expression of cell-surface proteins that, in turn, specify the wiring of the nervous system is an open question. In this issue of Neuron, Xie et al. reveal a new, unexpected layer of complexity. [ErbB4+ spinal cord dorsal horn neurons process heat pain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00552-9%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/QC-pZfYA4nAp_ChZAvP5m7PgGx-3vx2bUMXi6EqumUY=258) Huasheng Yu, Suna L. Cranfill, Wenqin Luo How the spinal cord transmits heat signals from the periphery to the brain remains unclear. In this issue of Neuron, Wang et al. (2022) identify a population of spinal cord neurons functioning in this pathway. Perspective --------------------------------------------------------------- [The translational revolution of itch](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00267-7%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/wCcAsr9b7jhNLC1H8lCuIxF3fqYN9XHf5ngV7fc4TpA=258) Brian S. Kim Open Access In this perspective by Kim, the historically overlooked neurobiology and medicine of itch are reviewed to show how unexpected breakthroughs have put forth new paradigms of sensation, neuroimmunology, and therapy extending beyond itch. Review --------------------------------------------------------------- [Cross-translational models of late-onset cognitive sequelae and their treatment in pediatric brain tumor survivors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00348-8%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/HtR_XlD8wFy2VkfFiDgmeeBGz2c7HOqQlSsISGEnSWk=258) Noor Z. Al Dahhan, Elizabeth Cox, Brian J. Nieman, Donald J. Mabbott In this review, Al Dahhan et al. discuss forward and reverse translational studies of treatment-induced cognitive sequelae in pediatric brain tumor patients and animal models. They highlight treatment modifications, pharmacological agents, and lifestyle/environmental interventions that can improve cognition in brain cancer survivors. NeuroResource --------------------------------------------------------------- [Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00411-1%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/mOalpDO7qI-AWrhY09bEuYS5FcYpkQ1UpwtqOaxPzg0=258) Xinhong Chen, Sripriya Ravindra Kumar, Cameron D. Adams, Daping Yang, Tongtong Wang, Damien A. Wolfe, Cynthia M. Arokiaraj, Victoria Ngo, Lillian J. Campos, Jessica A. Griffiths, Takako Ichiki, Sarkis K. Mazmanian, Peregrine B. Osborne, Janet R. Keast, Cory T. Miller, Andrew S. Fox, Isaac M. Chiu, Viviana Gradinaru Open Access Chen et al. evolved a family of AAV capsid variants, including MaCPNS1 and MaCPNS2, that efficiently transduced the PNS in rodents following systemic administration, enabling functional readout and non-invasive modulation of PNS. Both vectors could also enable efficient gene delivery to both PNS and CNS in macaque and marmoset. Report --------------------------------------------------------------- [Prelimbic cortex drives discrimination of non-aversion via amygdala somatostatin interneurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00256-2%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/Xl8EATnoNxlyXY6Sayc9_Q61I8hvchb7tapgLm_q82E=258) Joseph M. Stujenske, Pia-Kelsey O'Neill, Carolina Fernandes-Henriques, Itzick Nahmoud, Samantha R. Goldburg, Ashna Singh, Laritza Diaz, Margarita Labkovich, William Hardin, Scott S. Bolkan, Thomas R. Reardon, Timothy J. Spellman, C. Daniel Salzman, Joshua A. Gordon, Conor Liston, Ekaterina Likhtik Overgeneralization of fear to non-aversive stimuli is observed in several psychiatric disorders. Using a mouse model, Stujenske et al. identify the dorsomedial prefrontal cortex acting via somatostatin interneurons in the basolateral amygdala as the mechanism that desynchronizes sensory activation of the amygdala during non-aversive stimuli, thereby suppressing generalized fear responses. Articles --------------------------------------------------------------- [5-hydroxytryptamine produced by enteric serotonergic neurons initiates colorectal cancer stem cell self-renewal and tumorigenesis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00369-5%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/bHT8F9zrxPkS88pjT_GjYceWWWsvrQuj3vWJYhmYonA=258) Pingping Zhu, Tiankun Lu, Zhenzhen Chen, Benyu Liu, Dongdong Fan, Chong Li, Jiayi Wu, Luyun He, Xiaoxiao Zhu, Ying Du, Yong Tian, Zusen Fan The enteric nervous system regulates various physiological and pathological processes. Zhu et al. investigated the cross talk between enteric serotonergic neurons and colorectal tumorigenesis in mice and revealed the critical role of neurotransmitter 5-HT in colorectal tumor initiation. These observations provide an additional layer for tumor regulation by the enteric nervous system. [Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00409-3%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/qI1xDOb9Q_UjUdVE4KuWh13wlhVPXbehOfQC84Omp1o=258) Juan Pablo Lopez, Malte D. Lücken, Elena Brivio, Stoyo Karamihalev, Aron Kos, Carlo De Donno, Asaf Benjamin, Huanqing Yang, Alec L.W. Dick, Rainer Stoffel, Cornelia Flachskamm, Andrea Ressle, Simone Roeh, Rosa-Eva Huettl, Andrea Parl, Carola Eggert, Bozidar Novak, Yu Yan, Karin Yeoh, Maria Holzapfel, Barbara Hauger, Daniela Harbich, Bianca Schmid, Rossella Di Giaimo, Christoph W. Turck, Mathias V. Schmidt, Jan M. Deussing, Matthias Eder, Julien Dine, Fabian J. Theis, Alon Chen Lopez et al. identify cell-type-specific changes associated with the sustained antidepressant effects of ketamine. They demonstrate that the combined treatment of ketamine with a KCNQ activator leads to stronger effects. Their findings provide a deeper understanding of the complex mechanisms underlying the antidepressant effects of ketamine, with important clinical implications. [Transcription factor Acj6 controls dendrite targeting via a combinatorial cell-surface code](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00403-2%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/QqVwEyTSIUB9KamCDdZ26eT8TqkkwPtOjfhz8iVWWu0=258) Qijing Xie, Jiefu Li, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, Daniel Orlin, Sayeh Kohani, Ricardo Guajardo, D.R. Mani, Chuanyun Xu, Tongchao Li, Shuo Han, Wei Wei, S. Andrew Shuster, David J. Luginbuhl, Stephen R. Quake, Swetha E. Murthy, Alice Y. Ting, Steven A. Carr, Liqun Luo Open Access How do transcription factors control neuronal wiring specificity? Xie and Li et al. combine in situ cell-surface proteomics and genetic analyses to investigate the “transcription factor → cell-surface executor → neuronal wiring” axis and find that lineage-defining transcription factor Acj6 uses unique combinations of cell-surface proteins to specify distinct dendrite targeting of different neuron types. [A novel spinal neuron connection for heat sensation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00366-X%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/RvcnoFiJ_dNmYJBtSPf4RywH8L9Q8jRoy7zPbBWtfcU=258) Hongsheng Wang, Wenbing Chen, Zhaoqi Dong, Guanglin Xing, Wanpeng Cui, Lingling Yao, Wen-Jun Zou, Heath L. Robinson, Yaoyao Bian, Zhipeng Liu, Kai Zhao, Bin Luo, Nannan Gao, Hongsheng Zhang, Xiao Ren, Zheng Yu, James Meixiong, Wen-Cheng Xiong, Lin Mei How heat signals are processed in the spinal cord remains unclear. Wang et al. found that ErbB4+ excitatory interneurons are activated by noxious heat, and they participate in heat sensation in mice. In addition, the neuregulin-ErbB4 signaling regulates heat sensation and contributes to heat hypersensitivity under pathological conditions. [Global and subtype-specific modulation of cortical inhibitory neurons regulated by acetylcholine during motor learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)00408-1%3Fdgcid=raven_jbs_etoc_email/1/010001821c672878-b7bcaf35-0d3e-423b-b469-bde9f8f91829-000000/mveSgJbf481murUOfAHPFjg_czKBBni8TEteQ7CUf1s=258) Chi Ren, Kailong Peng, Ruize Yang, Weikang Liu, Chang Liu, Takaki Komiyama With longitudinal calcium imaging at both macroscale and microscale in behaving mice, Ren et al. uncover a global and subtype-specific modulation of cortical inhibitory neuron activity regulated by the basal forebrain cholinergic system during motor learning. Correction --------------------------------------------------------------- [What’s familiarity got to do with it? 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