TY - JOUR AU - Joglekar, Anoushka AU - Hu, Wen AU - Zhang, Bei AU - Narykov, Oleksandr AU - Diekhans, Mark AU - Marrocco, Jordan AU - Balacco, Jennifer AU - Ndhlovu, Lishomwa C. AU - Milner, Teresa A. AU - Fedrigo, Olivier AU - Jarvis, Erich D. AU - Sheynkman, Gloria AU - Korkin, Dmitry AU - Ross, M. Elizabeth AU - Tilgner, Hagen U. TI - Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI VL - 2024 PY - 2024 SP - 1 SN - 1097-6256 DO - 10.1038/s41593-024-01616-4 UR - https://m2.mtmt.hu/api/publication/34789419 ID - 34789419 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Duszkiewicz, A.J. AU - Orhan, P. AU - Skromne, Carrasco S. AU - Brown, E.H. AU - Owczarek, E. AU - Vite, G.R. AU - Wood, E.R. AU - Peyrache, A. TI - Local origin of excitatory–inhibitory tuning equivalence in a cortical network JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 SN - 1097-6256 DO - 10.1038/s41593-024-01588-5 UR - https://m2.mtmt.hu/api/publication/34768956 ID - 34768956 N1 - Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom Department of Psychology, University of Stirling, Stirling, United Kingdom Ecole normale supérieure, PSL University, CNRS, Paris, France Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, United Kingdom Export Date: 4 April 2024 CODEN: NANEF Correspondence Address: Duszkiewicz, A.J.; Montreal Neurological Institute and Hospital, Canada; email: aduszkie@ed.ac.uk Correspondence Address: Peyrache, A.; Montreal Neurological Institute and Hospital, Canada; email: adrien.peyrache@mcgill.ca AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Haynes, P.R. AU - Pyfrom, E.S. AU - Li, Y. AU - Stein, C. AU - Cuddapah, V.A. AU - Jacobs, J.A. AU - Yue, Z. AU - Sehgal, A. TI - A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 SN - 1097-6256 DO - 10.1038/s41593-023-01568-1 UR - https://m2.mtmt.hu/api/publication/34734030 ID - 34734030 N1 - Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, United States Chronobiology and Sleep Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA, United States Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States Export Date: 12 March 2024 CODEN: NANEF Correspondence Address: Sehgal, A.; Department of Neuroscience, United States; email: amita@pennmedicine.upenn.edu LA - English DB - MTMT ER - TY - JOUR AU - Cregg, Jared M. AU - Sidhu, Simrandeep K. AU - Leiras, Roberto AU - Kiehn, Ole TI - Basal ganglia-spinal cord pathway that commands locomotor gait asymmetries in mice JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 26 SN - 1097-6256 DO - 10.1038/s41593-024-01569-8 UR - https://m2.mtmt.hu/api/publication/34658461 ID - 34658461 LA - English DB - MTMT ER - TY - JOUR AU - Oldenburg, Ian Anton AU - Hendricks, William D. AU - Handy, Gregory AU - Shamardani, Kiarash AU - Bounds, Hayley A. AU - Doiron, Brent AU - Adesnik, Hillel TI - The logic of recurrent circuits in the primary visual cortex JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 32 SN - 1097-6256 DO - 10.1038/s41593-023-01510-5 UR - https://m2.mtmt.hu/api/publication/34615663 ID - 34615663 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Tome, Douglas Feitosa AU - Zhang, Ying AU - Aida, Tomomi AU - Mosto, Olivia AU - Lu, Yifeng AU - Chen, Mandy AU - Sadeh, Sadra AU - Roy, Dheeraj S. AU - Clopath, Claudia TI - Dynamic and selective engrams emerge with memory consolidation JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 38 SN - 1097-6256 DO - 10.1038/s41593-023-01551-w UR - https://m2.mtmt.hu/api/publication/34614999 ID - 34614999 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Jin, Lei AU - Sullivan, Heather A. AU - Zhu, Mulangma AU - Lavin, Thomas K. AU - Matsuyama, Makoto AU - Fu, Xin AU - Lea, Nicholas E. AU - Xu, Ran AU - Hou, Yuanyuan AU - Rutigliani, Luca AU - Pruner, Maxwell AU - Babcock, Kelsey R. AU - Ip, Jacque Pak Kan AU - Hu, Ming AU - Daigle, Tanya L. AU - Zeng, Hongkui AU - Sur, Mriganka AU - Feng, Guoping AU - Wickersham, Ian R. TI - Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 33 SN - 1097-6256 DO - 10.1038/s41593-023-01545-8 UR - https://m2.mtmt.hu/api/publication/34614705 ID - 34614705 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Looser, Zoe J. AU - Faik, Zainab AU - Ravotto, Luca AU - Zanker, Henri S. AU - Jung, Ramona B. AU - Werner, Hauke B. AU - Ruhwedel, Torben AU - Moebius, Wiebke AU - Bergles, Dwight E. AU - Barros, L. Felipe AU - Nave, Klaus-Armin AU - Weber, Bruno AU - Saab, Aiman S. TI - Oligodendrocyte-axon metabolic coupling is mediated by extracellular K+ and maintains axonal health JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 35 SN - 1097-6256 DO - 10.1038/s41593-023-01558-3 UR - https://m2.mtmt.hu/api/publication/34614702 ID - 34614702 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Fleming, Elizabeth A. AU - Field, Greg D. AU - Tadross, Michael R. AU - Hull, Court TI - Local synaptic inhibition mediates cerebellar granule cell pattern separation and enables learned sensorimotor associations JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 20 SN - 1097-6256 DO - 10.1038/s41593-023-01565-4 UR - https://m2.mtmt.hu/api/publication/34610473 ID - 34610473 AB - The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell population responses contribute to behavior have remained unclear. To address these questions, we have used in vivo calcium imaging and granule cell-specific pharmacological manipulation of synaptic inhibition in awake, behaving mice. These experiments indicate that inhibition sparsens and thresholds sensory responses, limiting overlap between sensory ensembles and preventing spiking in many granule cells that receive excitatory input. Moreover, inhibition can be recruited in a stimulus-specific manner to powerfully decorrelate multisensory ensembles. Consistent with these results, granule cell inhibition is required for accurate cerebellum-dependent sensorimotor behavior. These data thus reveal key mechanisms for granule cell layer pattern separation beyond those envisioned by classical models.Using in vivo calcium imaging and cell-type-specific pharmacology, we reveal that synaptic inhibition in the cerebellar granule cell layer supports pattern separation and cerebellum-dependent behavior. LA - English DB - MTMT ER - TY - JOUR AU - Li, Jiaxing AU - Monk, Kelly R. TI - Synapses shape oligodendrocyte precursor cell development and predict myelination location JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI PY - 2024 PG - 2 SN - 1097-6256 DO - 10.1038/s41593-023-01555-6 UR - https://m2.mtmt.hu/api/publication/34602281 ID - 34602281 AB - Using in vivo imaging in zebrafish, we unveiled critical components (PSD-95, gephyrin and neuroligin-3) and dynamic properties of synapses between neurons and oligodendrocyte precursor cells (OPC). Furthermore, we showed that neuron-OPC synapses have a pivotal role in regulating OPC development and CNS myelination. LA - English DB - MTMT ER -