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Neuron: February 21, 2024 (Volume 112, Issue 4)

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Vol. 112, Iss. 4 Highlights Announcements ----------------------------------------------------------

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Featured articles --------------------------------------------------------------- [STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00795-X/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/UtZsZAXLA68EobRsncHt8R1mw4gLY8QAZJKWt4EyU5s=341) Yang et al. [Advances in structure-based drug design: The potential for precision therapeutics in psychiatric disorders](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00004-7/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/vXiUruoqvBDnO10a7cuE3R-wUjABchRBI0OrTZpKzsA=341) Cao et al. [Primate neocortex performs balanced sensory amplification](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00880-2/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/icje56UFIn1tD_8o_uMhAXWzRuXrJ-UgitlYy95DGFY=341) Pattadkal et al. [Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00881-4/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/xLo0870izoEtrDiqVDUTfvDIJSbfDgbwF_0vJ2JuHPg=341) Piantadosi et al. Online now --------------------------------------------------------------- [Harnessing diversity to study Alzheimer's disease: A new iPSC resource from the NIH CARD and ADNI](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00052-7/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/eiOVIKMokAodtXXNDx7GxkfixZvK8xEmWKq7DD149FU=341) Screven et al. [Tuned geometries of hippocampal representations meet the computational demands of social memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00047-3/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/32FUPSph_tTiay1XfDvLXwVPdymhTtsxOPa7vtbJ1EQ=341) Boyle et al. [Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00049-7/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/kNB6Nd1yFjrlwadVqJmVbuRL54DK9qABJLVcSv264PA=341) Kawatake-Kuno et al. [Cell-type-specific expression of tRNAs in the brain regulates cellular homeostasis](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00054-0/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/ldT3hs31qYjsezgXibTudNe6Ca3mKYlyU-IH45rimfk=341) Kapur et al. Table of Contents Previews --------------------------------------------------------------- [Driving valence-specific behavior through single-cell resolution control in the amygdala](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00045-X%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/h-xXzUf-x1WK9tWta6XnhSkwuZSPhskdTLyO0gVdJDw=341) Leonardo Jared Ramirez Sanchez, Bo Li In this issue of Neuron, Piantadosi et al. demonstrate that by precisely controlling the activity of individual negative-valence neurons and positive-valence neurons in the basolateral amygdala, one can alter animals’ appetitive or aversive responses, respectively, establishing a causal role of these neurons in valence-specific behavior. [Transcriptional programming of social hierarchy](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00056-4%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/9QPNCLL3HtmgZ3vrYrNRDPlxaRXoRhV6VFsyc3eREiE=341) Yoh Isogai In this issue of Neuron, Choi and colleagues uncover the direct role of the transcription factor Pou3f1 in regulating dominance hierarchy in mice. Pou3f1 accomplishes this role via its action in specific prefrontal projection neurons that regulate behaviors associated with low social status. Primer --------------------------------------------------------------- [Advances in structure-based drug design: The potential for precision therapeutics in psychiatric disorders](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00004-7%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/eKX9OFinWz1HvRvv3ZKX-In1VYj77XEgNBVO1IRuiJQ=341) Dongmei Cao, Pei Zhang, Sheng Wang Cao et al. outline the iterative development, challenges, and opportunities in structure-based drug design (SBDD) for GPCRs, emphasizing the impact of SBDD on translational research for psychiatric disorders and offering insights for future GPCR drug design. Review --------------------------------------------------------------- [STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00795-X%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/pViCL65k0SP-At9ta2MO2MYjmD5xQxfwCTy9ubSqrLA=341) Kun Yang, Zhen Tang, Cong Xing, Nan Yan Yang et al. review the current state of knowledge about innate immune system STING signaling in neurological diseases and discuss mechanisms of STING signaling activation, activities in different brain cell types, human relevance, and development of STING antagonists. Articles --------------------------------------------------------------- [Cortical somatostatin long-range projection neurons and interneurons exhibit divergent developmental trajectories](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00887-5%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/RmactGkJH_PavOXG6Dd8FsNd9CmUNX4kONetRLtJ_EQ=341) Josephine Fisher, Marieke Verhagen, Zhen Long, Monika Moissidis, Yiming Yan, Chenyi He, Jingyu Wang, Elia Micoli, Clara Milían Alastruey, Rani Moors, Oscar Marín, Da Mi, Lynette Lim Open Access Fisher et al. reveal that cortical GABAergic neurons expressing somatostatin are highly diverse during embryonic development. However, the timing of cell fate acquisition among these cells varies depending on their identity. Fisher and colleagues also identify distinct molecular programs governing the diversification of GABAergic long-range projection neurons and interneurons. [Delayed maturation and migration of excitatory neurons in the juvenile mouse paralaminar amygdala](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00884-X%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/Mzp75e4ph8gim1QTF3E1mCz1BmfXc0fKNz5ADHzVG28=341) Pia J. Alderman, David Saxon, Lucía I. Torrijos-Saiz, Malaz Sharief, Chloe E. Page, Jude K. Baroudi, Sean W. Biagiotti, Vladimir A. Butyrkin, Anna Melamed, Chay T. Kuo, Stefano Vicini, Jose M. García-Verdugo, Vicente Herranz-Pérez, Joshua G. Corbin, Shawn F. Sorrells Similar to humans, mice have a paralaminar amygdala region containing immature excitatory neurons. These neurons are not produced by ongoing neurogenesis but are born embryonically and delay their maturation. In juvenile-adolescent ages, some migrate into the nearby cortex, and others begin to mature locally, developing selective responses to olfactory stimuli. [Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00881-4%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/VjBGuV0vSEvDFeNMMhpbR1g7G5AUUHmEmW_OEzYz1GI=341) Sean C. Piantadosi, Zhe Charles Zhou, Carina Pizzano, Christian E. Pedersen, Tammy K. Nguyen, Sarah Thai, Garret D. Stuber, Michael R. Bruchas The amygdala is a critical brain locus for valence encoding and the expression of valence-specific behavior. Piantadosi et al. report that optically separable valence-encoding ensembles are mutually inhibitory and can be precisely manipulated via multiphoton holographic stimulation producing bidirectional changes in consummatory behavior. [Distinct prefrontal projection activity and transcriptional state conversely orchestrate social competition and hierarchy](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00886-3%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/EyvNEws8aQj2ZsJTbjrf3IPvEq_u6mweKOxutku87Tc=341) Tae-Yong Choi, Hyoungseok Jeon, Sejin Jeong, Eum Ji Kim, Jeongseop Kim, Yun Ha Jeong, Byungsoo Kang, Murim Choi, Ja Wook Koo Choi et al. find that distinct neuronal populations in the medial prefrontal cortex (mPFC) oppositely drive social hierarchy: mPFC neurons projecting to the nucleus accumbens (mPFC-NAc) for winning and those projecting to the ventral tegmental area (mPFC-VTA) for losing. Pou3f1 expression level in mPFC-VTA neurons regulates social hierarchy. [Disinhibition by VIP interneurons is orthogonal to cross-modal attentional modulation in primary visual cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00879-6%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/uNv66ELPXvTcDNH7dn3jGn2SYz8M3Vxr8OMAipA6zO0=341) Dylan Myers-Joseph, Katharina A. Wilmes, Marian Fernandez-Otero, Claudia Clopath, Adil G. Khan Open Access Attentional modulation of sensory processing is a critical aspect of cognition, but its neural circuit basis is poorly understood. Previous work implicates VIP interneurons as critical to this modulation. Myers-Joseph et al. demonstrate that modulations by VIP interneurons and attention are in fact orthogonal, allowing multiplexing diverse signals in V1. [Egocentric processing of items in spines, dendrites, and somas in the retrosplenial cortex](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00892-9%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/jUCyV67yQYzocIUkjPjd48M5xWSTSiqh0JlYjOi59xc=341) Ning Cheng, Qiqi Dong, Zhen Zhang, Li Wang, Xiaojing Chen, Cheng Wang To study how distinct items are represented by the egocentric representation system, Cheng et al. show that retrosplenial cortex neurons demonstrated microscopic clustering of functional inputs at the synaptic level, and independent populations of cells were recruited to represent items in sufficiently different contexts. [Primate neocortex performs balanced sensory amplification](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00880-2%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/qmGN2kRtVWwu3NH46Sn086qEPdaAQITVPvJMc0Dsh8g=341) Jagruti J. Pattadkal, Boris V. Zemelman, Ila Fiete, Nicholas J. Priebe Sensory circuits show high sensitivity to signals of interest even in noisy, changing environments. Pattadkal et al. place constraints on the circuitry for amplification using calcium imaging and electrophysiology in marmoset area MT. Different circuits for amplification are characterized by distinct dynamics. Area MT dynamics match a balanced amplification circuit. [Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00888-7%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/Q0ii7FqBEZASFHR5d6FkuWxmz8GBSWcaeOZv3VkNVdQ=341) Joseph Giorgio, Jenna N. Adams, Anne Maass, William J. Jagust, Michael Breakspear Open Access The core pathologies of Alzheimer’s disease (AD) arise in spatially distinct areas of the brain. We provide a mechanistic account for how this occurs, showing that local AD pathology impacts the function of brain networks. This dysfunction in cortical processing cascades across the brain, precipitating further pathological changes. Correction --------------------------------------------------------------- [Primate neocortex performs balanced sensory amplification](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00051-5%3Fdgcid=raven_jbs_etoc_email/1/0100018dcca07225-18d7928f-49d4-4858-b4f7-b3aa1076297a-000000/C5QUkEr4LkmsU2AGvwHOCxfkOdLT5b-1L1q5xEmDJYc=341) Jagruti J. Pattadkal, Boris V. Zemelman, Ila Fiete, Nicholas J. 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