@article{MTMT:34832654, title = {The dynamic state of a prefrontal-hypothalamic-midbrain circuit commands behavioral transitions}, url = {https://m2.mtmt.hu/api/publication/34832654}, author = {Chen, Changwan and Altafi, Mahsa and Corbu, Mihaela-Anca and Trenk, Aleksandra and van, den Munkhof Hanna and Weineck, Kristin and Bender, Franziska and Carus-Cadavieco, Marta and Bakhareva, Alisa and Korotkova, Tatiana and Ponomarenko, Alexey}, doi = {10.1038/s41593-024-01598-3}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34832654}, issn = {1097-6256}, abstract = {Innate behaviors meet multiple needs adaptively and in a serial order, suggesting the existence of a hitherto elusive brain dynamics that brings together representations of upcoming behaviors during their selection. Here we show that during behavioral transitions, possible upcoming behaviors are encoded by specific signatures of neuronal populations in the lateral hypothalamus (LH) that are active near beta oscillation peaks. Optogenetic recruitment of intrahypothalamic inhibition at this phase eliminates behavioral transitions. We show that transitions are elicited by beta-rhythmic inputs from the prefrontal cortex that spontaneously synchronize with LH 'transition cells' encoding multiple behaviors. Downstream of the LH, dopamine neurons increase firing during beta oscillations and also encode behavioral transitions. Thus, a hypothalamic transition state signals alternative future behaviors, encodes the one most likely to be selected and enables rapid coordination with cognitive and reward-processing circuitries, commanding adaptive social contact and eating behaviors. Chen et al. show that transitions to innate behaviors, such as feeding and social interaction, rely on their encoding during beta oscillations by neuron populations in the lateral hypothalamus, coordinated with the medial prefrontal cortex and ventral tegmental area.}, keywords = {DISORDERS; CORTEX; ORGANIZATION; TOP-DOWN; DOPAMINE NEURONS; Reward; LATERAL HYPOTHALAMUS; ASSEMBLIES; PROJECTION}, year = {2024}, eissn = {1546-1726}, orcid-numbers = {Altafi, Mahsa/0009-0004-8003-2930; Trenk, Aleksandra/0000-0002-5888-3550; Weineck, Kristin/0000-0003-3204-860X; Bakhareva, Alisa/0000-0001-9292-8508; Ponomarenko, Alexey/0000-0002-5185-0107} } @article{MTMT:34814708, title = {Widespread changes in alternative splicing in developing and adult mouse brain}, url = {https://m2.mtmt.hu/api/publication/34814708}, author = {A, Joglekar and HU, Tilgner}, doi = {10.1038/s41593-024-01617-3}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {2024}, unique-id = {34814708}, issn = {1097-6256}, year = {2024}, eissn = {1546-1726}, pages = {1-2} } @article{MTMT:34789419, title = {Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain}, url = {https://m2.mtmt.hu/api/publication/34789419}, author = {Joglekar, Anoushka and Hu, Wen and Zhang, Bei and Narykov, Oleksandr and Diekhans, Mark and Marrocco, Jordan and Balacco, Jennifer and Ndhlovu, Lishomwa C. and Milner, Teresa A. and Fedrigo, Olivier and Jarvis, Erich D. and Sheynkman, Gloria and Korkin, Dmitry and Ross, M. Elizabeth and Tilgner, Hagen U.}, doi = {10.1038/s41593-024-01616-4}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {2024}, unique-id = {34789419}, issn = {1097-6256}, abstract = {RNA isoforms influence cell identity and function. However, a comprehensive brain isoform map was lacking. We analyze single-cell RNA isoforms across brain regions, cell subtypes, developmental time points and species. For 72% of genes, full-length isoform expression varies along one or more axes. Splicing, transcription start and polyadenylation sites vary strongly between cell types, influence protein architecture and associate with disease-linked variation. Additionally, neurotransmitter transport and synapse turnover genes harbor cell-type variability across anatomical regions. Regulation of cell-type-specific splicing is pronounced in the postnatal day 21-to-postnatal day 28 adolescent transition. Developmental isoform regulation is stronger than regional regulation for the same cell type. Cell-type-specific isoform regulation in mice is mostly maintained in the human hippocampus, allowing extrapolation to the human brain. Conversely, the human brain harbors additional cell-type specificity, suggesting gain-of-function isoforms. Together, this detailed single-cell atlas of full-length isoform regulation across development, anatomical regions and species reveals an unappreciated degree of isoform variability across multiple axes.}, year = {2024}, eissn = {1546-1726}, pages = {1}, orcid-numbers = {Hu, Wen/0000-0002-0604-2119; Diekhans, Mark/0000-0002-0430-0989; Marrocco, Jordan/0000-0001-8357-5288; Ndhlovu, Lishomwa C./0000-0001-5427-4187; Milner, Teresa A./0000-0002-0458-6569; Jarvis, Erich D./0000-0001-8931-5049; Sheynkman, Gloria/0000-0002-4223-9947; Korkin, Dmitry/0000-0002-3875-9085; Ross, M. Elizabeth/0000-0001-6440-8089; Tilgner, Hagen U./0000-0002-7058-3606} } @article{MTMT:34768956, title = {Local origin of excitatory–inhibitory tuning equivalence in a cortical network}, url = {https://m2.mtmt.hu/api/publication/34768956}, author = {Duszkiewicz, A.J. and Orhan, P. and Skromne, Carrasco S. and Brown, E.H. and Owczarek, E. and Vite, G.R. and Wood, E.R. and Peyrache, A.}, doi = {10.1038/s41593-024-01588-5}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34768956}, issn = {1097-6256}, abstract = {The interplay between excitation and inhibition determines the fidelity of cortical representations. The receptive fields of excitatory neurons are often finely tuned to encoded features, but the principles governing the tuning of inhibitory neurons remain elusive. In this study, we recorded population of neurons in the mouse postsubiculum (PoSub), where the majority of excitatory neurons are head-direction (HD) cells. We show that the tuning of fast-spiking (FS) cells, the largest class of cortical inhibitory neurons, was broad and frequently radially symmetrical. By decomposing tuning curves using the Fourier transform, we identified an equivalence in tuning between PoSub-FS and PoSub-HD cell populations. Furthermore, recordings, optogenetic manipulations of upstream thalamic populations and computational modeling provide evidence that the tuning of PoSub-FS cells has a local origin. These findings support the notion that the equivalence of neuronal tuning between excitatory and inhibitory cell populations is an intrinsic property of local cortical networks. © The Author(s) 2024.}, keywords = {Male; ARTICLE; MOUSE; Therapy; controlled study; nonhuman; nerve cell; cell population; Thalamus; computer model; tuning curve}, year = {2024}, eissn = {1546-1726} } @article{MTMT:34734030, title = {A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis}, url = {https://m2.mtmt.hu/api/publication/34734030}, author = {Haynes, P.R. and Pyfrom, E.S. and Li, Y. and Stein, C. and Cuddapah, V.A. and Jacobs, J.A. and Yue, Z. and Sehgal, A.}, doi = {10.1038/s41593-023-01568-1}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34734030}, issn = {1097-6256}, year = {2024}, eissn = {1546-1726} } @article{MTMT:34658461, title = {Basal ganglia-spinal cord pathway that commands locomotor gait asymmetries in mice}, url = {https://m2.mtmt.hu/api/publication/34658461}, author = {Cregg, Jared M. and Sidhu, Simrandeep K. and Leiras, Roberto and Kiehn, Ole}, doi = {10.1038/s41593-024-01569-8}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34658461}, issn = {1097-6256}, year = {2024}, eissn = {1546-1726} } @article{MTMT:34615663, title = {The logic of recurrent circuits in the primary visual cortex}, url = {https://m2.mtmt.hu/api/publication/34615663}, author = {Oldenburg, Ian Anton and Hendricks, William D. and Handy, Gregory and Shamardani, Kiarash and Bounds, Hayley A. and Doiron, Brent and Adesnik, Hillel}, doi = {10.1038/s41593-023-01510-5}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34615663}, issn = {1097-6256}, abstract = {Recurrent cortical activity sculpts visual perception by refining, amplifying or suppressing visual input. However, the rules that govern the influence of recurrent activity remain enigmatic. We used ensemble-specific two-photon optogenetics in the mouse visual cortex to isolate the impact of recurrent activity from external visual input. We found that the spatial arrangement and the visual feature preference of the stimulated ensemble and the neighboring neurons jointly determine the net effect of recurrent activity. Photoactivation of these ensembles drives suppression in all cells beyond 30 mu m but uniformly drives activation in closer similarly tuned cells. In nonsimilarly tuned cells, compact, cotuned ensembles drive net suppression, while diffuse, cotuned ensembles drive activation. Computational modeling suggests that highly local recurrent excitatory connectivity and selective convergence onto inhibitory neurons explain these effects. Our findings reveal a straightforward logic in which space and feature preference of cortical ensembles determine their impact on local recurrent activity.Using two-photon (2P) optogenetics and computational modeling, the authors find that neither space-based nor feature-based rules are sufficient to describe cell-cell interactions within the primary visual cortex (V1). Instead, models must include interactions between these cardinal axes.}, year = {2024}, eissn = {1546-1726}, orcid-numbers = {Handy, Gregory/0000-0003-4432-080X; Shamardani, Kiarash/0000-0002-2548-705X} } @article{MTMT:34614999, title = {Dynamic and selective engrams emerge with memory consolidation}, url = {https://m2.mtmt.hu/api/publication/34614999}, author = {Tome, Douglas Feitosa and Zhang, Ying and Aida, Tomomi and Mosto, Olivia and Lu, Yifeng and Chen, Mandy and Sadeh, Sadra and Roy, Dheeraj S. and Clopath, Claudia}, doi = {10.1038/s41593-023-01551-w}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34614999}, issn = {1097-6256}, abstract = {Episodic memories are encoded by experience-activated neuronal ensembles that remain necessary and sufficient for recall. However, the temporal evolution of memory engrams after initial encoding is unclear. In this study, we employed computational and experimental approaches to examine how the neural composition and selectivity of engrams change with memory consolidation. Our spiking neural network model yielded testable predictions: memories transition from unselective to selective as neurons drop out of and drop into engrams; inhibitory activity during recall is essential for memory selectivity; and inhibitory synaptic plasticity during memory consolidation is critical for engrams to become selective. Using activity-dependent labeling, longitudinal calcium imaging and a combination of optogenetic and chemogenetic manipulations in mouse dentate gyrus, we conducted contextual fear conditioning experiments that supported our model's predictions. Our results reveal that memory engrams are dynamic and that changes in engram composition mediated by inhibitory plasticity are crucial for the emergence of memory selectivity.This paper shows that memory engrams are dynamic: neurons drop in and out as engrams become selective during memory consolidation. Inhibition and inhibitory plasticity are crucial for the expression and emergence of memory selectivity, respectively.}, year = {2024}, eissn = {1546-1726} } @article{MTMT:34614705, title = {Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses}, url = {https://m2.mtmt.hu/api/publication/34614705}, author = {Jin, Lei and Sullivan, Heather A. and Zhu, Mulangma and Lavin, Thomas K. and Matsuyama, Makoto and Fu, Xin and Lea, Nicholas E. and Xu, Ran and Hou, Yuanyuan and Rutigliani, Luca and Pruner, Maxwell and Babcock, Kelsey R. and Ip, Jacque Pak Kan and Hu, Ming and Daigle, Tanya L. and Zeng, Hongkui and Sur, Mriganka and Feng, Guoping and Wickersham, Ian R.}, doi = {10.1038/s41593-023-01545-8}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34614705}, issn = {1097-6256}, abstract = {Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans in postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.Rabies-virus-based tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has limited its applications. Here Jin et al. present a second-generation system with minimal toxicity, using double-deletion-mutant rabies viruses.}, year = {2024}, eissn = {1546-1726}, orcid-numbers = {Jin, Lei/0000-0002-7264-4409; Fu, Xin/0009-0001-7478-0244} } @article{MTMT:34614702, title = {Oligodendrocyte-axon metabolic coupling is mediated by extracellular K+ and maintains axonal health}, url = {https://m2.mtmt.hu/api/publication/34614702}, author = {Looser, Zoe J. and Faik, Zainab and Ravotto, Luca and Zanker, Henri S. and Jung, Ramona B. and Werner, Hauke B. and Ruhwedel, Torben and Moebius, Wiebke and Bergles, Dwight E. and Barros, L. Felipe and Nave, Klaus-Armin and Weber, Bruno and Saab, Aiman S.}, doi = {10.1038/s41593-023-01558-3}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, unique-id = {34614702}, issn = {1097-6256}, abstract = {The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca2+) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K+) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K+ signaling, making acute metabolic coupling possible and adjusting the axon-OL metabolic unit to promote axonal health.}, year = {2024}, eissn = {1546-1726} }