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Neuron: September 25, 2019 (Volume 103, Issue 6)

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Vol. 103, Iss. 6 Highlights Announcements ----------------------------------------------------------

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[Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30600-2/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/tSU4wY1dKPwnAHw28C8gyR3E-w4=128) Hasselmann et al. Online Now --------------------------------------------------------------- [Input-Specific Metaplasticity in the Visual Cortex Requires Homer1a-Mediated mGluR5 Signaling](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30701-9/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/5doCrUu7gPETfcX4RtVdt4nwbIM=128) Chokshi et al. [Visual Cortex Gains Independence from Peripheral Drive before Eye Opening](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30699-3/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/97Bp61UiO36-UCULun-VSvt32VQ=128) Gribizis et al. Video Abstract --------------------------------------------------------------- %2F%2Fyoutu.be%2Ff3IK1B345Lc/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/EIvYtCleOJJHYDGjO7eyHou0eFQ=128 [Cholinergic Interneurons in Parkinson’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30563-X/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/oAhDDbUrfeq9ox_CehAUu8jiSnc=128) Using a new mouse model of Parkinson’s disease, McKinley et al. found that both acetylcholine and dopamine levels decrease, but acetylcholine declines less than dopamine such that the acetylcholine-dopamine ratio increases. This finding suggests that a more effective Parkinson’s disease treatment regimen would also target acetylcholine levels. Table of Contents Previews --------------------------------------------------------------- [Enhanced Actin Dynamics: A Therapeutic Strategy for Axonal Regeneration?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30781-0%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/C8Fajicl3wbFDSZeLrb__MrIk6g=128) Hauke B. Werner, Klaus-Armin Nave Spinal cord injury causes permanent paralysis due to the inability of neurons in the central nervous system to regenerate transected axons. In this issue of Neuron, Tedeschi et al. (2019) report that axonal regrowth can be stimulated by actin-depolymerizing proteins, at least in mice. [Simplicity, Flexibility, and Interpretability in a Model of Dendritic Protein Distributions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30783-4%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/8j00wJd05NnNd5kK5d9AurRW_GA=128) Cian O’Donnell In this issue of Neuron, Fonkeu et al. (2019) present a mathematical model of mRNA and protein synthesis, degradation, diffusion, and trafficking in neuronal dendrites. The model can predict the spatial distribution and temporal dynamics of proteins along dendrites. The authors use the model to account for in situ imaging data of CaMKII⍺ mRNA and protein in hippocampal neurons. [Scratching after Stroking and Poking: A Spinal Circuit Underlying Mechanical Itch](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30782-2%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/cnoJdxFxP24RNbp5LtPr2u_JqiY=128) Zilong Wang, Christopher R. Donnelly, Ru-Rong Ji Mechanical itch is a desire to scratch due to light mechanical stimuli. In this issue of Neuron, Pan et al. (2019) identify a feedforward inhibition circuit in the spinal cord dorsal horn that processes mechanical itch as well as spontaneous itch. [Are You There, Cortex? It’s Me, Acetylcholine](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30745-7%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/OUQ73par6Dwe7IcFKBI8fOLrQFg=128) Kevin J. Monk, Marshall G. Hussain Shuler It is not well understood how associations between two temporally removed stimuli form. In this issue of Neuron, Guo et al. (2019) implicate basal forebrain cholinergic neurons as providing a link between auditory cues and the aversive outcomes they predict. [Why Are Sequence Representations in Primary Motor Cortex So Elusive?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30784-6%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/lHSc_KApq6rKZF5fVUMLuuuePAQ=128) Aaron L. Wong, John W. Krakauer In this issue of Neuron, Yokoi and Diedrichsen (2019) use a finger keyboard task to show that sequences are widely represented across cortex but that only single elements are represented in primary motor cortex. These results suggest that sequence tasks primarily probe the ability to order discreet actions rather than to execute a skilled continuous sequential action. Neuroviews --------------------------------------------------------------- [Becoming a Principal Investigator: Designing and Navigating Your Academic Adventure](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30707-X%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/aGj4MGFPWCv5y8VEuP6dIgyqYC0=128) Paul L. Greer, Melanie A. Samuel Starting your own academic lab is a wonderful opportunity to impact science through research and trainee mentoring. In this article, we share some thoughts and resources for this undertaking in the hope that they may enhance the experience of others. [Networking: Translating Neuroscience to Public Policy](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30700-7%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/qCzrHXdFsjGtodP4jfakEycJVow=128) Keith Humphreys Neuroscientific findings are rarely translated into public policies that improve the health and well-being of people experiencing serious disorders. In this NeuroView, Humphreys advocates for investment in policymaker-scientist networks dedicated to such translation for a range of diseases. Perspective --------------------------------------------------------------- [Engineering a Less Artificial Intelligence](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30740-8%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/oDFg0e-xC2zQ8j0OP0mYJRRRHY8=128) Fabian H. Sinz, Xaq Pitkow, Jacob Reimer, Matthias Bethge, Andreas S. Tolias Artificial neural networks still lag behind brains in their ability to generalize beyond their training conditions. In this review, Sinz et al. discuss several ideas for how neuroscience can guide the search for better inductive biases by providing useful constraints on representations and network architecture. Review --------------------------------------------------------------- [Development and Arealization of the Cerebral Cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30635-X%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/bfM_oNTVrekt6oAt-KkWYQyKQBc=128) Cathryn R. Cadwell, Aparna Bhaduri, Mohammed A. Mostajo-Radji, Matthew G. Keefe, Tomasz J. Nowakowski Cadwell et al. review the early developmental processes that underlie arealization of the cerebral cortex, with a focus on recent single-cell transcriptomic studies, the interplay of intrinsic genetic programs and extrinsic signals, and implications for developmental of functional circuits. Viewpoint --------------------------------------------------------------- [Can One Concurrently Record Electrical Spikes from Every Neuron in a Mammalian Brain?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30695-6%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/wXDM6jIUL1zswU6BRjyZ_3xMAi8=128) David Kleinfeld, Lan Luan, Partha P. Mitra, Jacob T. Robinson, Rahul Sarpeshkar, Kenneth Shepard, Chong Xie, Timothy D. Harris Understanding cognition can, in principle, require simultaneous records of spikes from every neuron in cortex. Can this be achieved? The results from back-of-the-envelope calculations show that such measurements may be obtained using electrodes fabricated with existing yet nontraditional materials and procedures. Neuroresource --------------------------------------------------------------- [Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30600-2%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/AwSaFV0DkyjtYKZb72tD7aT8-g0=128) Jonathan Hasselmann, Morgan A. Coburn, Whitney England, Dario X. Figueroa Velez, Sepideh Kiani Shabestari, Christina H. Tu, Amanda McQuade, Mahshad Kolahdouzan, Karla Echeverria, Christel Claes, Taylor Nakayama, Ricardo Azevedo, Nicole G. Coufal, Claudia Z. Han, Brian J. Cummings, Hayk Davtyan, Christopher K. Glass, Luke M. Healy, Sunil P. Gandhi, Robert C. Spitale, Mathew Blurton-Jones Hasselmann, Coburn, et al. validate a new xenotransplantation paradigm to study iPSC-derived human microglia in vivo. This chimeric approach rectifies many of the deficits observed in culture models, providing new insight into the functional and transcriptional responses of human microglia to inflammatory insults and Alzheimer’s disease pathology. Report --------------------------------------------------------------- [Distinct Contributions of Whisker Sensory Cortex and Tongue-Jaw Motor Cortex in a Goal-Directed Sensorimotor Transformation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30634-8%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/-8KdmwYcAlJj8IrPjJgqrMNphf4=128) Johannes M. Mayrhofer, Sami El-Boustani, Georgios Foustoukos, Matthieu Auffret, Keita Tamura, Carl C.H. Petersen Open Access Mayrhofer et al. map the location of mouse tongue-jaw motor cortex, finding that its neuronal activity encodes licking direction and is necessary for contralateral goal-directed licking but does not encode which sensory cue initiates licking, in contrast to sensory cortex. Articles --------------------------------------------------------------- [A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30652-X%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/xPq1mGFJCrr1bCNd13WOfvTela4=128) Guangsen Shi, Lijuan Xing, David Wu, Bula J. Bhattacharyya, Christopher R. Jones, Thomas McMahon, S.Y. Christin Chong, Jason A. Chen, Giovanni Coppola, Daniel Geschwind, Andrew Krystal, Louis J. Ptáček, Ying-Hui Fu A mutation in ADRB1 was found in humans who sleep fewer hours than most. Using mouse modeling and calcium imaging experiments, Shi et al. demonstrate that dorsal pons ADRB1+ neuron activity is increased in the mutant, correlating with increased wakefulness. [Dopamine Deficiency Reduces Striatal Cholinergic Interneuron Function in Models of Parkinson’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30563-X%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/7ZFaSOt0gN0mLotlK0DcAevk-IM=128) Jonathan W. McKinley, Ziqing Shi, Ivana Kawikova, Matthew Hur, Ian J. Bamford, Suma Priya Sudarsana Devi, Annie Vahedipour, Martin Darvas, Nigel S. Bamford McKinley et al. use a new model of Parkinson’s disease to show that a reduction in dopamine modifies the availability of acetylcholine within the striatum, suggesting that treatment of the disease requires restoration of the balance between these neurotransmitters. [ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30633-6%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/ADr8BUo6JzuaBUgpU2RIMJzqZn8=128) Andrea Tedeschi, Sebastian Dupraz, Michele Curcio, Claudia J. Laskowski, Barbara Schaffran, Kevin C. Flynn, Telma E. Santos, Sina Stern, Brett J. Hilton, Molly J.E. Larson, Christine B. Gurniak, Walter Witke, Frank Bradke Tedeschi et al. identify ADF/cofilin as a key driver of axon regeneration in adult dorsal root ganglion neurons. Specifically, enhanced actin turnover by the ADF/cofilin severing function controls axon regeneration in the adult CNS. [Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30693-2%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/HDbSFqQvPr787qDTON-g6HQrsXc=128) Nicola Mattugini, Riccardo Bocchi, Volker Scheuss, Gianluca Luigi Russo, Olof Torper, Chu Lan Lao, Magdalena Götz Open Access Neurons dying after brain injury cannot be replaced. Mattugini, Bocchi, et al. show that local astrocytes can be converted into functional neurons acquiring appropriate layer identity and connectivity by expression of neurogenic factors in a mouse model of traumatic brain injury. [Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30597-5%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/izy7-gwNSMGTRRVI3jx28F-UebY=128) Jerome Bonnefont, Luca Tiberi, Jelle van den Ameele, Delphine Potier, Zachary B. Gaber, Xionghui Lin, Angéline Bilheu, Adèle Herpoel, Fausto D. Velez Bravo, François Guillemot, Stein Aerts, Pierre Vanderhaeghen Open Access Bonnefont et al. show that Bcl6 promotes neurogenesis by directly repressing genes belonging to the major signaling pathways promoting cortical progenitor self-renewal. These data indicate that a single cell-intrinsic factor represses multiple extrinsic signaling pathways to ensure irreversible neurogenic commitment. [How mRNA Localization and Protein Synthesis Sites Influence Dendritic Protein Distribution and Dynamics](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30572-0%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/2bCToNH_toTLIjkdvQ60O9oFUu4=128) Yombe Fonkeu, Nataliya Kraynyukova, Anne-Sophie Hafner, Lisa Kochen, Fabio Sartori, Erin M. Schuman, Tatjana Tchumatchenko A steady protein supply is critical to synaptic function. Here, Fonkeu et al. present a theoretical framework, validated by experimental data, that details how local and dendritic mRNAs shape dendritic protein dynamics across short and long timescales. [Convergent Temperature Representations in Artificial and Biological Neural Networks](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30601-4%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/E3zAY3FQ_u-PoFa3U4E6O7nBLyQ=128) Martin Haesemeyer, Alexander F. Schier, Florian Engert Haesemeyer et al. train convolutional neural networks to navigate temperature gradients to reveal shared representations and processing in artificial and biological networks. Constrained by zebrafish behavior, artificial networks critically rely on fish-like units and make testable predictions about the brain. [Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30566-5%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/JFLfxtWMkJc-4XliPtjCf_Tdgos=128) Haili Pan, Mahar Fatima, Alan Li, Hankyu Lee, Wei Cai, Lorraine Horwitz, Chia Chun Hor, Nizam Zaher, Mitchell Cin, Hannah Slade, Tianwen Huang, X.Z. Shawn Xu, Bo Duan Pan et al. identify a microcircuit in the dorsal spinal cord that transmit mechanically evoked itch. Sensitization of this pathway is required for chronic itch development. [Persistent Gamma Spiking in SI Nonsensory Fast Spiking Cells Predicts Perceptual Success](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30564-1%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/a3QKT4XEb7oN7XxjSTY70q6EVnY=128) Hyeyoung Shin, Christopher I. Moore Gamma oscillations are hypothesized to temporally coordinate sensory encoding. Shin and Moore found a distinct subtype of fast spiking interneurons (FS) in SI that are nonsensory responsive and spike regularly at gamma intervals. These “gamma regular nonsensory FS” could potentially mediate perceptually relevant oscillations, independent of the LFP and sensory drive. [The Cholinergic Basal Forebrain Links Auditory Stimuli with Delayed Reinforcement to Support Learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30594-X%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/cj7g7lZ_9-G1GE_FLFYgERv2ie8=128) Wei Guo, Blaise Robert, Daniel B. Polley Sensory stimuli and behavioral reinforcement can be separated by long silent intervals. Guo et al. characterize a distributed neural circuit in the mouse forebrain that supports auditory fear learning by linking brief sounds with aversive events that occur many seconds later. [Neural Organization of Hierarchical Motor Sequence Representations in the Human Neocortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30567-7%3Fdgcid=raven_jbs_etoc_email/1/0100016d6961df7c-08d40867-f579-4ba6-8abf-fe5d61472f00-000000/W4iICqS0Jod8LteGnmCeDKmVeQU=128) Atsushi Yokoi, Jörn Diedrichsen Hierarchical movement sequences are often assumed to mirror an anatomical hierarchy of brain regions. Using representational fMRI analysis, Yokoi and Diedrichsen challenge this common assumption. Although the primary motor cortex represents elementary movements, chunk and sequence representations coexist in the premotor and parietal cortices. 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