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--------------------------------------------------------------- [Design of complex neuroscience experiments using mixed-integer linear programming](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00119-7/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/A9HyEjeu6aaXhAmSqovoMHPrS_zwpHQwuWVE5U5vbiQ=191)
Slivkoff et al. Featured neuroview
--------------------------------------------------------------- [Human cells and networks of pain: Transforming pain target identification and therapeutic development](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00235-X/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/8Me5YregouQ_yGHiOKPT_pPhueAEGeeNMmT4peWUVRg=191)
Renthal et al. Article
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Norman et al. Online now
--------------------------------------------------------------- [A cortical circuit mechanism for structural knowledge-based flexible sensorimotor decision-making](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00280-4/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/L8EHGkcRVTHdBsQvBBxf3smLQ0XSJA7_x8Fe4XMt2W0=191)
Liu et al. [Brainhack: Developing a culture of open, inclusive, community-driven neuroscience](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00231-2/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/e-Sl42YzMSA9PF2dJ9phuO3hLUP2VEYTUqNEDY6dq5c=191)
Gau et al. [Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00238-5/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/F7HwcVcZjVzsUTU9_2wTmV2AmETJ8arZ6s8_H032cVA=191)
Sans-Dublanc et al. [Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00236-1/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/mdZLFWYPkw3oJ4-BKp6dpulXLBCDnswJ0I391qMR9tI=191)
Leinwand et al. Table of Contents Previews
--------------------------------------------------------------- [A tipping point in neuropsychiatric genetics](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00232-4%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/t01tzbHejGJ9yk087eFzIKG94NKdRZ53oZuZeDkrTco=191)
Jon M. McClellan, Mary-Claire King Severe neuropsychiatric disorders are so genetically heterogeneous that virtually every unrelated patient harbors different clinically significant alleles. By studying schizophrenia in the Ashkenazi Jewish founder population, Lencz and co-authors identified rare severe alleles each shared by a few patients. Experimental evaluation of an implicated protocadherin allele revealed failure to form homophilic cellular aggregates as a possible mechanism for defective development of neural circuits. [Locus revealed: Painlessness via loss of NaV1.7 at central terminals of sensory neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00261-0%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/Cfke5FiJJybuwsnrVBFWU1Eemp2HeYd28Op-vRkxsIA=191)
Manuela Simonetti, Rohini Kuner How genetic loss of the sodium channel NaV1.7 results in painlessness is puzzling. MacDonald et al. (2021) demonstrate that instead of impairing peripheral excitability, NaV1.7 channels at central terminals of pain-sensing afferents play a pivotal role in the balance between pain and analgesia. [On location for cannabinoid control of multimodal behavior](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00263-4%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/9IFoxZSAIigxsjju2t3WXrvIEot_OLcMDuNmRBn4bDk=191)
Paige N. McKeon, Brian N. Mathur In this issue of Neuron, Soria-Gomez et al. (2021) investigate whether activation of the type 1 cannabinoid receptor at specific subcellular within a single neural circuit produces multimodal behavior. Their results demonstrate that location matters: striatonigral mitochondrial CB1 drives catalepsy while striatonigral plasma membrane CB1 receptors enable antinociception. [Keep both eyes on the prize: Hunting mice use binocular vision and specialized retinal neurons to capture prey](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00284-1%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/49NebdZwAuc3h5_DjkQG1zz8BjTS6IoUpgMNQXrSE7E=191)
David Berson In this issue of Neuron, Johnson et al. show that mice rely on binocular vision when hunting insect prey. Specific types of retinal output neurons support this behavior. They have functional properties and brain connections well-suited to their role. [Anger management: pSI has a say in it](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00262-2%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/AlOcnbRSqzy9qmnur-Oz3sB452xvR0J-IxF75_GIteI=191)
Xi Zha, Xiao-Hong Xu In this issue of Neuron, Zhu et al. (2021) reveal that activities in posterior substantia innominate (pSI) neurons that project to the periaqueductal gray (PAG) are both necessary and sufficient to drive aggressive attacks in mice under various conditions. Spotlight
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Lisa Johann, Ari Waisman In a recent issue of Nature, Sanmarco et al. reveal a novel mechanism by which astrocytes maintain an anti-inflammatory state in the central nervous system (CNS). IFNγ released by gut-licensed meningeal NK cells was found to induce TRAIL expression on astrocytes, causing effector T cell apoptosis. NeuroViews
--------------------------------------------------------------- [Human cells and networks of pain: Transforming pain target identification and therapeutic development](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00235-X%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/DROSeJetRA7QjKU8xHOuwjIIqk2QMtwUfFFtjrw4vuY=191)
William Renthal, Alexander Chamessian, Michele Curatolo, Steve Davidson, Michael Burton, Sulayman Dib-Hajj, Patrick M. Dougherty, Allison D. Ebert, Robert W. Gereau IV, Andre Ghetti, Michael S. Gold, Gwendolyn Hoben, Daniela Maria Menichella, Philippe Mercier, Wilson Z. Ray, Daniela Salvemini, Rebecca P. Seal, Stephen Waxman, Clifford J. Woolf, Cheryl L. Stucky, Theodore J. Price Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this challenge. [Building brain capital](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00237-3%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/G8X2A8m2BrT2_4nO2mUuLZLKgNbOLKT6V6EWG2fpjWs=191)
Harris A. Eyre, Rym Ayadi, William Ellsworth, Gowri Aragam, Erin Smith, Walter D. Dawson, Agustin Ibanez, Cara Altimus, Michael Berk, Husseini K. Manji, Eric A. Storch, Marion Leboyer, Naoko Kawaguchi, Michael Freeman, Patrick Brannelly, Facundo Manes, Sandra B. Chapman, Jeffrey Cummings, Carol Graham, Benjamin F. Miller, Zoltan Sarnyai, Retsina Meyer, William Hynes Brains are indispensable drivers of human progress. Why not invest more heavily in them? We seek to place Brain Capital at the center of a new narrative to fuel economic and societal recovery and resilience. Primer
--------------------------------------------------------------- [Design of complex neuroscience experiments using mixed-integer linear programming](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00119-7%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/4NPzzKMW83jqsRqx299hCS-wszQP7Ed9n_ZD1VVOEs8=191)
Storm Slivkoff, Jack L. Gallant Neuroscience experimental design can be challenging. In this review, the authors show how mixed-integer linear programming (MILP) can assist the experimental design process. The article compares MILP to other methods and provides four experimental design case studies. NeuroResource
--------------------------------------------------------------- [Enhancer viruses for combinatorial cell-subclass-specific labeling](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00159-8%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/tprqSgfDrqhDvWD9ceOgG16rjorUUG10IMfqDbUmHsw=191)
Lucas T. Graybuck, Tanya L. Daigle, Adriana E. Sedeño-Cortés, Miranda Walker, Brian Kalmbach, Garreck H. Lenz, Elyse Morin, Thuc Nghi Nguyen, Emma Garren, Jacqueline L. Bendrick, Tae Kyung Kim, Thomas Zhou, Marty Mortrud, Shenqin Yao, Laâ Akea Siverts, Rachael Larsen, Bryan B. Gore, Eric R. Szelenyi, Cameron Trader, Pooja Balaram, Cindy T.J. van Velthoven, Megan Chiang, John K. Mich, Nick Dee, Jeff Goldy, Ali H. Cetin, Kimberly Smith, Sharon W. Way, Luke Esposito, Zizhen Yao, Viviana Gradinaru, Susan M. Sunkin, Ed Lein, Boaz P. Levi, Jonathan T. Ting, Hongkui Zeng, Bosiljka Tasic Graybuck et al. generated a single-cell chromatin accessibility dataset for adult mouse cortex and identified functional enhancer elements. They created a suite of enhancer-containing adeno-associated viruses to label genetically defined cell populations in the mouse brain. Articles
--------------------------------------------------------------- [Novel ultra-rare exonic variants identified in a founder population implicate cadherins in schizophrenia](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00152-5%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/PtyHZ2gMOXLLZ7KBS2cBqcEso3wmOGzojAiDwGlDubU=191)
Todd Lencz, Jin Yu, Raiyan Rashid Khan, Erin Flaherty, Shai Carmi, Max Lam, Danny Ben-Avraham, Nir Barzilai, Susan Bressman, Ariel Darvasi, Judy H. Cho, Lorraine N. Clark, Zeynep H. GümüÅ, Joseph Vijai, Robert J. Klein, Steven Lipkin, Kenneth Offit, Harry Ostrer, Laurie J. Ozelius, Inga Peter, Anil K. Malhotra, Tom Maniatis, Gil Atzmon, Itsik Peâer Lencz et al. demonstrate that the Ashkenazi Jewish population has an enhanced power for genetic discovery in schizophrenia. Cases had excess missense or loss-of-function ultra-rare variants, enriched in cadherins and neurodevelopmental genes. A recurrent case mutation in PCDHA3 results in the formation of cytoplasmic aggregates and failure to engage in membrane homophilic interactions. [Akt-mTOR hypoactivity in bipolar disorder gives rise to cognitive impairments associated with altered neuronal structure and function](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00156-2%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/rZTy3c2gqX6uwlRrEp-YtT0q6f7hEEoP3hYj1RTc9jU=191)
Amanda M. Vanderplow, Andrew L. Eagle, Bailey A. Kermath, Kathryn J. Bjornson, Alfred J. Robison, Michael E. Cahill The biochemical changes that contribute to bipolar disorder pathophysiology remain largely unknown. Cahill et al. reveal a reduction in the activation of the Akt-mTOR pathway in the prefrontal cortex of bipolar disorder subjects. Cahill et al. demonstrate that reduced activity of this pathway causes cognitive and synaptic phenotypes. [A central mechanism of analgesia in mice and humans lacking the sodium channel NaV1.7](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00160-4%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/zZJqginSgv9MZu8tcqA6-rCwnwPl7XiYgEr9EMVpo1c=191)
Donald Iain MacDonald, Shafaq Sikandar, Jan Weiss, Martina Pyrski, Ana P. Luiz, Queensta Millet, Edward C. Emery, Flavia Mancini, Gian D. Iannetti, Sascha R.A. Alles, Manuel Arcangeletti, Jing Zhao, James J. Cox, Robert M. Brownstone, Frank Zufall, John N. Wood
Open Access Loss of the peripheral sodium channel NaV1.7 causes profound insensitivity to pain. MacDonald et al. show that nociceptor activity is unaffected by NaV1.7 deletion but that synaptic input to the dorsal horn is compromised by an opioid-dependent mechanism. Blocking central opioid receptors reverses analgesia in mice and humans lacking NaV1.7. [Subcellular specificity of cannabinoid effects in striatonigral circuits](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00155-0%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/eXZZ4T_XfP8Nq5rdCvFpYpJVzi2mnZktVfbtEtr56yY=191)
Edgar Soria-Gomez, Antonio C. Pagano Zottola, Yamuna Mariani, Tifany Desprez, Massimo Barresi, Itziar Bonilla-del Río, Carolina Muguruza, Morgane Le Bon-Jego, Francisca Julio-KalajziÄ, Robyn Flynn, Geoffrey Terral, Ignacio Fernández-Moncada, Laurie M. Robin, José F. Oliveira da Cruz, Simone Corinti, Yasmine Ould Amer, Julia Goncalves, Marjorie Varilh, Astrid Cannich, Bastien Redon, Zhe Zhao, Thierry Lesté-Lasserre, Peggy Vincent, Tarson Tolentino-Cortes, Arnau Busquets-García, Nagore Puente, Jaideep S. Bains, Etienne Hebert-Chatelain, Gabriel Barreda-Gómez, Francis Chaouloff, Alexander W. Lohman, Luis F. Callado, Pedro Grandes, Jerome Baufreton, Giovanni Marsicano, Luigi Bellocchio Soria-Gomez et al. show that CB1 receptors in the striatonigral circuit mediate both adverse cataleptic and clinically relevant antinociceptive effects of cannabinoids. These effects clearly involve distinct subcellular and molecular mechanisms in the same neuronal circuit, resulting in the respective control of neurotransmitter and neuropeptide release. [Cell-type-specific binocular vision guides predation in mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00158-6%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/8MnBmJ9HZmwY7zaIu1NWJEf-LzCeGuwXkEq1bssXdbU=191)
Keith P. Johnson, Michael J. Fitzpatrick, Lei Zhao, Bing Wang, Sean McCracken, Philip R. Williams, Daniel Kerschensteiner Johnson et al. show that mice track prey with their binocular visual field and discover that a small subset of retinal ganglion cell types innervates ipsilateral brain targets to support binocular vision and guide predation. [A substantia innominata-midbrain circuit controls a general aggressive response](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00150-1%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/aUlCAbX7P1k_jyLT3BPGhOF60EvC4X8_TNZcxHT0ORY=191)
Zhenggang Zhu, Qingqing Ma, Lu Miao, Hongbin Yang, Lina Pan, Kaiyuan Li, Ling-Hui Zeng, Xiaoxing Zhang, Jintao Wu, Sijia Hao, Shen Lin, Xiulin Ma, Weihao Mai, Xiang Feng, Yizhe Hao, Li Sun, Shumin Duan, Yan-qin Yu Zhu et al. find that a subset of neurons in a brain area called the posterior substantia innominata promote arousal and universally drive aggressive behaviors in an activity-level-dependent manner in mice. [Single-trial decoding of movement intentions using functional ultrasound neuroimaging](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00151-3%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/-Lib4BQEDBKMitBH-P6_u7L5NFfgP3s6nmY6Wqg7cn4=191)
Sumner L. Norman, David Maresca, Vassilios N. Christopoulos, Whitney S. Griggs, Charlie Demene, Mickael Tanter, Mikhail G. Shapiro, Richard A. Andersen Norman et al. use functional ultrasound (fUS) neuroimaging to record brain activity while animals perform motor tasks. They use fUS signals to predict movement timing, direction, and effector (hand or eye). This is a critical step toward brain recording and interface tools that are less invasive, high resolution, and scalable. [Optimal anticipatory control as a theory of motor preparation: A thalamo-cortical circuit model](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(21)00157-4%3Fdgcid=raven_jbs_etoc_email/1/010001793da0e267-26dc9327-6ec0-4f65-85b5-b42d423d1955-000000/ge1RvziidCx36Sh5LrfpcsuzlX4Bk6nS3DtPPZvE-KU=191)
Ta-Chu Kao, Mahdieh S. Sadabadi, Guillaume Hennequin
Open Access Optimal control theory has successfully explained aspects of motor cortex activity during but not before movement. Kao et al. formalize movement preparation as optimal feedback control of cortex. They show that optimal preparation can be realized in a thalamo-cortical loop, enables fast preparation, and explains prominent features of pre-movement activity. Correction
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