Neuron: December 18, 2019 (Volume 104, Issue 6)

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[Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30969-9/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/w2sjXNGEn1XioWKVujFB1aTAW-M=140) Tran et al. Featured Article --------------------------------------------------------------- [Trans-Synaptic Signaling through the Glutamate Receptor Delta-1 Mediates Inhibitory Synapse Formation in Cortical Pyramidal Neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30801-3/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/rweZnpmsG4-ZDq7IQw9xjsI8MAE=140) Fossati et al. Online Now --------------------------------------------------------------- [A Discrete Presynaptic Vesicle Cycle for Neuromodulator Receptors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30979-1/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/7IN90oy32aCOKMSkk33gxElsyys=140) Jullié et al. [Dorsal and Ventral Hippocampal Sharp-Wave Ripples Activate Distinct Nucleus Accumbens Networks](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)31008-6/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/963lpv4IYFGo9WB1ZtjWgwK1rLI=140) Sosa et al. [Molecular Tuning of the Axonal Mitochondrial Ca2+ Uniporter Ensures Metabolic Flexibility of Neurotransmission](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30984-5/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/doikUin929o9kUb3sH1jz113-IM=140) Ashrafi et al. [Nicotinamide Pathway-Dependent Sirt1 Activation Restores Calcium Homeostasis to Achieve Neuroprotection in Spinocerebellar Ataxia Type 7](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30983-3/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/a4f5nOOPmSdt6O2lkXxxJ20y3uk=140) Stoyas et al. Video Abstract --------------------------------------------------------------- %2F%2Fyoutu.be%2Fwv8z7387A6A/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/vRegQOo3DA5XqUS7sGTdVRI7Zak=140 [Cortico-tecto-pulvinar Circuits for Top-Down Visual Modulation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30792-5/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/0Q5n9tz6qR9Ij_zSXt2RUl7w8o0=140) Hu et al. show that corticotectal neurons in mouse prefrontal cortex exert powerful top-down modulation of visual processing through two pathways–prefrontal projection to the superior colliculus, which in turn projects to posterior pulvinar, and direct prefrontal projection to anterior pulvinar. Table of Contents Previews --------------------------------------------------------------- [Glutamate Receptors: Not Just for Excitation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)31011-6%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/giaVQoLYbAm2ysgg_46MtGoaFns=140) Katherine L. Villa, Elly Nedivi In this issue of Neuron, Fossati et al. (2019) report a new constellation of players regulating inhibitory synaptogenesis. They show that GluD1, through a non-canonical ionotropic-independent mechanism, controls GABAergic synapse formation via trans-synaptic interactions mediated by extracellular cerebellin-4. They identify ARHGEF12 and PPP1R12A as GluD1 intracellular interactors and downstream effectors. [Insulin-like Peptides as Agents of Social Change](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)31043-8%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/UG0GMJ8slRbSQ9bM-ur-kYUeBrU=140) Benjamin Brissette, Niels Ringstad Many behaviors promote reproduction or food finding. These critical functions of behavior can conflict; successful reproductive strategies can grow populations to the point where food is depleted. In this issue of Neuron, Wu et al. (2019) show how the nematode C. elegans detects crowding to change feeding behavior by coupling pheromone sensing to signaling via insulin-like peptides. [The Dialog of Primary and Non-primary Auditory Cortex at the ‘Cocktail Party’](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)31040-2%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/HG22WDp7wV9rC7-I5KFHUHcBdDI=140) Elia Formisano, Lars Hausfeld In this issue of Neuron, O’Sullivan et al. (2019) measured electro-cortical responses to “cocktail party” speech mixtures in neurosurgical patients and demonstrated that the selective enhancement of attended speech is achieved through the adaptive weighting of primary auditory cortex output by non-primary auditory cortex. Spotlight --------------------------------------------------------------- [Therapeutic Targeting of mTORC2 in mTORopathies](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)31035-9%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/zFSSqkugtN7CVEs8jG6_VZaD2nY=140) Brianne Dentel, Christine Ochoa Escamilla, Peter T. Tsai Dysregulated mTOR contributes to neurodevelopmental dysfunction. A new study (Chen et al., 2019) demonstrates that suppression of mTORC2, not mTORC1, ameliorates survival, seizures, and abnormal behaviors in a Pten mutant model, highlighting mTORC2 as a potential therapeutic target in mTORopathies. Letters --------------------------------------------------------------- [Are HHV-6A and HHV-7 Really More Abundant in Alzheimer’s Disease?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30972-9%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/PuC_lLpVvBk-JaVIBniGS_eXDvg=140) Hyun-Hwan Jeong, Zhandong Liu [Clarifying the Potential Role of Microbes in Alzheimer’s Disease](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30971-7%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/wXbb1D_OoGi-7Go_mPJ7QjXLXV8=140) Ben Readhead, Jean-Vianney Haure-Mirande, Michelle E. Ehrlich, Sam Gandy, Joel T. Dudley Neuroresources --------------------------------------------------------------- [Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30969-9%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/vTliPQndqSSwaiPF_8Y9TV2nw2Q=140) Nicholas M. Tran, Karthik Shekhar, Irene E. Whitney, Anne Jacobi, Inbal Benhar, Guosong Hong, Wenjun Yan, Xian Adiconis, McKinzie E. Arnold, Jung Min Lee, Joshua Z. Levin, Dingchang Lin, Chen Wang, Charles M. Lieber, Aviv Regev, Zhigang He, Joshua R. Sanes High-throughput single-cell RNA-seq characterizes 46 types of adult mouse retinal ganglion cells and documents dramatic differences among them in their ability to survive axotomy. Manipulation of genes differentially expressed between resilient and vulnerable types enhances survival and axon regeneration. [Holographic Reconstruction of Axonal Pathways in the Human Brain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30832-3%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/I9ZHL0HsdM6AkOAAN2f0nuC9EEU=140) Mikkel V. Petersen, Jeffrey Mlakar, Suzanne N. Haber, Martin Parent, Yoland Smith, Peter L. Strick, Mark A. Griswold, Cameron C. McIntyre Petersen et al. use group-based holographic visualization to construct axonal pathway trajectories in the human brain via interactive collaboration by world expert neuroanatomists. They blend advanced visualization hardware, software development, and neuroanatomy data to overcome the limitations of tractography. Articles --------------------------------------------------------------- [The RAB3-RIM Pathway Is Essential for the Release of Neuromodulators](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30788-3%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/bD1Wu0Zur5ndxyihKT_SNJnAU3U=140) Claudia M. Persoon, Rein I. Hoogstraaten, Joris P. Nassal, Jan R.T. van Weering, Pascal S. Kaeser, Ruud F. Toonen, Matthijs Verhage Neurons secrete neuromodulators/neuropeptides from dense-core vesicles (DCVs) by a largely unknown mechanism. Persoon et al. identify RAB3 and RIM1/2 as essential factors. RAB3’s indispensable role is the first distinct feature of DCV secretion as compared to synaptic vesicle secretion. [Trans-Synaptic Signaling through the Glutamate Receptor Delta-1 Mediates Inhibitory Synapse Formation in Cortical Pyramidal Neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30801-3%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/QpuBoVQgzV2DQSaje6RyNCBoatk=140) Matteo Fossati, Nora Assendorp, Olivier Gemin, Sabrina Colasse, Florent Dingli, Guillaume Arras, Damarys Loew, Cécile Charrier Open Access Fossati et al. show that, in stark contrast to other iGluRs, the glutamate receptor delta-1 (GluD1) operates at inhibitory, rather than excitatory, synapses in the cortex. GluD1 mediates trans-synaptic signaling governing the formation of synapses between specific interneurons and pyramidal neurons. [Pheromones Modulate Learning by Regulating the Balanced Signals of Two Insulin-like Peptides](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30779-2%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/LC-BTv8iHsuC5Z0ZBVC1GgTq3uw=140) Taihong Wu, Fengyun Duan, Wenxing Yang, He Liu, Antonio Caballero, Diana Andrea Fernandes de Abreu, Abdul Rouf Dar, Joy Alcedo, QueeLim Ch’ng, Rebecca A. Butcher, Yun Zhang Wu et al. show that social signals of crowding inhibit worms from learning to avoid low-quality pathogenic food by disrupting balanced signals of two insulin-like peptides that are critical for learning to facilitate food intake when population density is high. [Dynamics of Awake Hippocampal-Prefrontal Replay for Spatial Learning and Memory-Guided Decision Making](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30785-8%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/2Bq_jE5aQFadHLvHH3qHveqqv88=140) Justin D. Shin, Wenbo Tang, Shantanu P. Jadhav Shin, Tang, and Jadhav use continuous activity tracking to show that awake CA1 reverse- and forward-replay events predict past and future choices, respectively, with opposing spatial learning gradients. CA1-PFC replay supports recall and planning for spatial working memory tasks. [Corticostriatal Flow of Action Selection Bias](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30802-5%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/pOOA7I83Yi8gRfLp4STfSiqyzM4=140) Eun Jung Hwang, Trevor D. Link, Yvonne Yuling Hu, Shan Lu, Eric Hou-Jen Wang, Varoth Lilascharoen, Sage Aronson, Keelin O’Neil, Byung Kook Lim, Takaki Komiyama The posterior parietal cortex (PPC) is important for both action selection and sensorimotor control. Using projection-specific anatomical tracing, activity recording, and perturbation, Hwang et al. identified two parallel subsystems in PPC, each involved in action selection and motor control, respectively. [Prefrontal Corticotectal Neurons Enhance Visual Processing through the Superior Colliculus and Pulvinar Thalamus](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30792-5%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/VpydQPvLTqXb5O8UVPjUIylLE-U=140) Fei Hu, Tsukasa Kamigaki, Zhe Zhang, Siyu Zhang, Usan Dan, Yang Dan Hu et al. show that corticotectal pyramidal neurons in the mouse anterior cingulate cortex exert powerful top-down modulation of visually guided behavior and visual cortical responses through collateral projections to two subcortical targets: the motor layers of the superior colliculus and pulvinar thalamus. [Thalamic Input to Orbitofrontal Cortex Drives Brain-wide, Frequency-Dependent Inhibition Mediated by GABA and Zona Incerta](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30797-4%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/6kEC1B8PSZNQXVx41Mf9y1Bbri8=140) Andrew J. Weitz, Hyun Joo Lee, ManKin Choy, Jin Hyung Lee Weitz et al. find that thalamic input to ventrolateral orbital cortex can result in widespread decreases in brain activity. Zona incerta mediates this effect. These findings help explain how VLO supports diverse sensory and cognitive processes. [Targeted Cortical Manipulation of Auditory Perception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30846-3%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/OQg-quVnXxay6JVULmr3xEMevnQ=140) Sebastian Ceballo, Zuzanna Piwkowska, Jacques Bourg, Aurélie Daret, Brice Bathellier Open Access In this study, Ceballo et al. show that targeted activation of specific neural ensembles in auditory cortex changes perceptual decisions in a difficult auditory discrimination task, although auditory cortex is not involved in easier decisions. [A Critical Role for Neocortical Processing of Threat Memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30799-8%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/Ihfm8spwKOP12j8VKTF_5FQBHZo=140) Tamas Dalmay, Elisabeth Abs, Rogier B. Poorthuis, Jan Hartung, De-Lin Pu, Sebastian Onasch, Yave R. Lozano, Jérémy Signoret-Genest, Philip Tovote, Julijana Gjorgjieva, Johannes J. Letzkus Dalmay et al. demonstrate that the neocortex plays a key role in learning and memory, particularly when auditory stimuli are complex and naturalistic. Memory is mediated by plasticity in neurons projecting to the amygdala, the brain’s hub for emotions. [Hierarchical Encoding of Attended Auditory Objects in Multi-talker Speech Perception](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(19)30780-9%3Fdgcid=raven_jbs_etoc_email/1/0100016f1a72209c-7f4cefca-1ea9-45a8-a198-e3627eba9ebe-000000/qZ1tN6OssMA1PZD38XVyvT5qUHI=140) James O’Sullivan, Jose Herrero, Elliot Smith, Catherine Schevon, Guy M. McKhann, Sameer A. Sheth, Ashesh D. Mehta, Nima Mesgarani How different areas of the human auditory cortex (AC) represent mixed speech is unclear. O’Sullivan et al. obtained invasive recordings from subjects listening to multi-talker speech. They found that the primary AC represented the individual speakers and was unchanged by attention. In contrast, the nonprimary AC selectively represented the attended speaker, was invariant to the acoustic overlap with unattended speaker, and was linearly predictable from the primary AC. These results reveal the neural underpinnings of the hierarchical formation of auditory objects in human AC. 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