Neuron: March 6, 2024 (Volume 112, Issue 5)

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Featured articles --------------------------------------------------------------- [Data science opportunities of large language models for neuroscience and biomedicine](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00042-4/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/iywmmT3THRgHaVtz8-HLif87lS1B5K9Tpmz_-cv5zWs=343) Bzdok et al. [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)00052-7/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/hmbe0Iem7c5uEXcLq1agpz9TJHAsb-_-xxTDutiHM4s=343) Screven et al. [D1 and D2 medium spiny neurons in the nucleus accumbens core have distinct and valence-independent roles in learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00926-1/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/UsHMPc1acjStsa_659Uz1jyMbjB-iF4ANtjmxMKfHsE=343) Zachry et al. [Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00930-3/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/f28rCxedyGaRR0BrmZAh1lcU-cfwjc_eE5nziLGFcPU=343) Chen et al. Online now --------------------------------------------------------------- [Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00053-9/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/7txboVzrGWPvoZEnFKpC41NjYcrVhyvquUkGyZY5-TM=343) Gradwell et al. [Simultaneous, cortex-wide dynamics of up to 1 million neurons reveal unbounded scaling of dimensionality with neuron number](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00121-1/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/Z5ZX4gd4HQqZD7Cdxpjhi9fMZOhWZ9FWL38Ln2P5RIA=343) Manley et al. [An integrative, multiscale view on neural theories of consciousness](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00088-6/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/Yl2-DUxCprOJoOy0YXbEAJho3kwrRQ7mWtYxTUzsOZ4=343) Storm et al. [Excitability mediates allocation of pre-configured ensembles to a hippocampal engram supporting contextual conditioned threat in mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00091-6/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/XNiBHDmPSJQorDk_y58Okal4Vd9LeVh-aHNbbCzLFC8=343) Mocle et al. Table of Contents Previews --------------------------------------------------------------- [Rebuilding the behavioral inhibition circuit to prevent opioid relapse](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00005-9%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/9YAbxMDpPL_gUC9nW1J4RF_ZAa6sYyeJ4xxzCFEiGtI=343) Xiaoxing Liu, Tangsheng Lu, Ying Han, Lin Lu Failure in behavioral suppression is a key feature in substance use disorders, potentially leading to compulsive drug seeking and relapse. In this issue of Neuron, Paniccia et al. elucidated a heroin-damaged paraventricular thalamo (PVT)-accumbal circuit and how recovery of PVT function could prevent heroin relapse. [Building cognitive functions from distributed brain activity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00006-0%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/K2_lLrsOdD63_hLNUWuL5S-tX6d3XgU5ML92-cGWcEs=343) John Duncan With recordings from temporal, parietal, and frontal regions of the behaving monkey brain, accompanied by a powerful method for optogenetic silencing of the frontal region, Mendoza-Halliday et al. compare network functions for working memory and visual selective attention. NeuroView --------------------------------------------------------------- [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%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/jNt009RQmkgw5Mlp6WCSgYpL5diS67JF00NfZ2CijZQ=343) Laurel A. Screven, Caroline B. Pantazis, Katherine M. Andersh, Samantha Hong, Dan Vitale, Erika Lara, Ray Yueh Ku, Peter Heutink, Jason Meyer, Kelley Faber, Kwangsik Nho, Andrew J. Saykin, Tatiana M. Foroud, Mike A. Nalls, Cornelis Blauwendraat, Andrew Singleton, Priyanka S. Narayan The iDA Project (iPSCs to Study Diversity in Alzheimer’s and Alzheimer’s Disease-related Dementias) is generating 200 induced pluripotent stem cell lines from Alzheimer’s Disease Neuroimaging Initiative participants. These lines are sex balanced, include common APOE genotypes, span disease stages, and are ancestrally diverse. Cell lines and characterization data will be shared openly. Perspective --------------------------------------------------------------- [Data science opportunities of large language models for neuroscience and biomedicine](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(24)00042-4%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/rWjJ920dihfw0Bc4vD6LjcaAK-faFPMRgZRIcDSA-qM=343) Danilo Bzdok, Andrew Thieme, Oleksiy Levkovskyy, Paul Wren, Thomas Ray, Siva Reddy Open Access Bzdok et al. discuss large language models (LLMs) as a recently emerged toolkit in an age when neurobiology too has become “computable.” Primer --------------------------------------------------------------- [Lights, fiber, action! A primer on in vivo fiber photometry](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00890-5%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/ghe2IiaEMRhZG9fkvfznp8X9bb-_cG7-DiGf83pgP6E=343) Eleanor H. Simpson, Thomas Akam, Tommaso Patriarchi, Marta Blanco-Pozo, Lauren M. Burgeno, Ali Mohebi, Stephanie J. Cragg, Mark E. Walton Open Access Articles --------------------------------------------------------------- [Clearance of β-amyloid and synapses by the optogenetic depolarization of microglia is complement selective](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00931-5%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/hR8xzOn3ZZ8h2T4BmO2WsGhaMFLHOOMMqfhjyar2vnM=343) Zezhong Lv, Lixi Chen, Ping Chen, Huipai Peng, Yi Rong, Wei Hong, Qiang Zhou, Nan Li, Boxing Li, Rosa C. Paolicelli, Yang Zhan Lv et al. describe an optogenetic approach to manipulate microglia and find the enhancement of Aβ clearance and synapse elimination, which are selectively modulated by the complement C1q. This study provides a synergistic strategy for targeting microglia to reduce toxic protein aggregates in neurodegenerative diseases while preserving synaptic connections. [Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00930-3%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/_-bxcmFbVmjFrZieA3JGW-2wTmK3Psadb-P5Jgsz8_w=343) Jing-Jing Chen, Walter A. Kaufmann, Chong Chen, Itaru Arai, Olena Kim, Ryuichi Shigemoto, Peter Jonas Chen et al. combine paired recordings, structural analysis, and modeling to examine the coupling between presynaptic Ca2+ channels and release sensors in an inhibitory GABAergic synapse at different developmental time points. The results reveal a developmental transformation from more random organization to precise point-to-point synaptic transmission at the nanometer scale. [Restoration of a paraventricular thalamo-accumbal behavioral suppression circuit prevents reinstatement of heroin seeking](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00928-5%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/ms0ihfxZ6axHMzAsi7coPcmMRau4q3Mf3-un_wxUiUE=343) Jacqueline E. Paniccia, Kelsey M. Vollmer, Lisa M. Green, Roger I. Grant, Kion T. Winston, Sophie Buchmaier, Annaka M. Westphal, Rachel E. Clarke, Elizabeth M. Doncheck, Bogdan Bordieanu, Logan M. Manusky, Michael R. Martino, Amy L. Ward, Jennifer A. Rinker, Jacqueline F. McGinty, Michael D. Scofield, James M. Otis Behavioral disinhibition is the cardinal feature of substance use disorders, enabling drug use and relapse despite significant consequences. Paniccia, Vollmer, Green, and colleagues discover that heroin use induces behavioral disinhibition through maladaptive plasticity in a thalamus-nucleus accumbens circuit, whereas restoration of this circuit prevents heroin seeking in mice. [Discrete prefrontal neuronal circuits determine repeated stress-induced behavioral phenotypes in male mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00934-0%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/eyj4h_wmapuoRFuSOW87uU0za_XTEKO329Xht0b6_c0=343) Haiyan Li, Ayako Kawatake-Kuno, Hiromichi Inaba, Yuka Miyake, Yukihiro Itoh, Takatoshi Ueki, Naoya Oishi, Toshiya Murai, Takayoshi Suzuki, Shusaku Uchida Although depression is a highly heterogeneous syndrome, it remains unclear how stress drives individual differences in behavioral phenotypes. Utilizing a subtyping-based approach, Li, Kawatake-Kuno, Inaba, et al. found the causal mechanism of KDM5C’s epigenetic repression of Shisa2 transcription in aPVT-projecting mPFC neurons in specific symptoms of stressed mice. [Layer 6b controls brain state via apical dendrites and the higher-order thalamocortical system](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00895-4%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/B7UhrySSm84YOH_EikDa2tJ0FEniHgVgTigLZiBgI4Q=343) Timothy Adam Zolnik, Anna Bronec, Annemarie Ross, Marcel Staab, Robert N.S. Sachdev, Zoltán Molnár, Britta Johanna Eickholt, Matthew Evan Larkum Zolnik et al. find that orexin-sensitive layer 6b subcircuits powerfully excite the cortex and drive circuit loops between L5 pyramidal neurons and higher-order thalamic neurons. The synaptic output of L6b includes highly plastic facilitating synapses and connections dependent on NMDA-receptor-dependent dendritic spikes. [Activity-dependent recruitment of inhibition and excitation in the awake mammalian cortex during electrical stimulation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00927-3%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/qqM_Il_MaKfz3sMsKL5EO5J7rE64eKiq-4dzPMexl-c=343) Maria C. Dadarlat, Yujiao Jennifer Sun, Michael P. Stryker How does cortical electrical stimulation affect different types of neurons in awake animals? The authors show that increasing stimulation amplitude recruits a distributed population of excitatory neurons but recruits inhibitory neurons closer to the electrode. Furthermore, evoked responses in excitatory neurons are strongly influenced by their pre-stimulus activity level. [D1 and D2 medium spiny neurons in the nucleus accumbens core have distinct and valence-independent roles in learning](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00926-1%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/dPDjIswdVExuAzo1ELX2Ke7JvABMaKcKjoa3a5KLGY0=343) Jennifer E. Zachry, Munir Gunes Kutlu, Hye Jean Yoon, Michael Z. Leonard, Maxime Chevée, Dev D. Patel, Anthony Gaidici, Veronika Kondev, Kimberly C. Thibeault, Rishik Bethi, Jennifer Tat, Patrick R. Melugin, Atagun U. Isiktas, Max E. Joffe, Denise J. Cai, P. Jeffrey Conn, Brad A. Grueter, Erin S. Calipari A large body of work has focused on how the nucleus accumbens (NAc) is critical to reward encoding. Zachry, Kutlu, et al. show that medium spiny neurons (MSNs) within the NAc of mice do not signal reward. Rather, D1 MSN responses are evoked by salient stimuli, while D2 MSNs track prediction errors. [Dissociable neuronal substrates of visual feature attention and working memory](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00935-2%3Fdgcid=raven_jbs_etoc_email/1/0100018e14deeadf-ee18f57e-e018-46c7-b716-6de05b95f607-000000/qpgsj2ldSDsQo-Uo41Tgpa_h12z1EfsIl_Iu2fMtcQU=343) Diego Mendoza-Halliday, Haoran Xu, Frederico A.C. Azevedo, Robert Desimone Open Access Mendoza-Halliday and colleagues show that in multiple cortical areas, neurons modulated by visual feature attention are largely different from those encoding working memories. By optogenetically inactivating LPFC-p during attention or working memory, they further show that it plays a critical role in attentional modulation, but not in working memory. 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