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Isochronic development of cortical synapses in primates and mice
How synapse development correlates with lifespan is unknown. Here, the authors show isochronic synapse development in mouse and primate despite disparate lifespans. As a result, synapse accumulation and reduction finishes in neonatal primates but spans nearly the entire life of the mouse.
- Gregg Wildenberg
- , Hanyu Li
- & Narayanan Kasthuri
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Article
| Open Access
Blazed oblique plane microscopy reveals scale-invariant inference of brain-wide population activity
Recording neuronal activity at cellular resolution across an entire adult vertebrate brain is challenging. Here, the authors develop a blazed oblique plane microscope to perform brain-wide activity measurements in an adult vertebrate at high cellular resolution.
- Maximilian Hoffmann
- , Jörg Henninger
- & Benjamin Judkewitz
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| Open Access
CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
- Melody Atkins
- , Maud Wurmser
- & Christine Métin
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Article
| Open Access
JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease
It has recently been reported a link between Alzheimer’s disease and mobilization of transposable elements (TEs) in heterochromatic regions. Here the authors demonstrate that dysregulation of the pioneer transcription factor c-JUN (AP-1) underlies aberrant transposable element mobilization, associated innate immune 2 response, and impaired neurogenesis in Alzheimer’s disease.
- Chiara Scopa
- , Samantha M. Barnada
- & Marco Trizzino
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Article
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Enhanced TARP-γ8-PSD-95 coupling in excitatory neurons contributes to the rapid antidepressant-like action of ketamine in male mice
Ketamine produces rapid antidepressant effects, but the mechanism involved is not fully understood. Here the authors show that ketamine enhances glutamatergic neurotransmission and produces rapid antidepressant-like effects though recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice.
- Shi-Ge Xue
- , Jin-Gang He
- & Jian-Guo Chen
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| Open Access
Opposing brain signatures of sleep in task-based and resting-state conditions
The associations between sleep, depression and brain activity are not well understood. Here, the authors show patterns of brain activity associated with insomnia and depression resemble those found in people who sleep less, but only under cognitive load. At rest, these activation patterns are hyperconnected and resemble those found in longer sleepers.
- Mohamed Abdelhack
- , Peter Zhukovsky
- & Daniel Felsky
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| Open Access
Emergence of the cortical encoding of phonetic features in the first year of life
To understand speech, our brains have to learn the different types of sounds that constitute words, including syllables, stress patterns and smaller sound elements, such as phonetic categories. Here, the authors provide evidence that at 7 months, the infant brain learns reliably to detect invariant phonetic categories.
- Giovanni M. Di Liberto
- , Adam Attaheri
- & Usha Goswami
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Article
| Open Access
Targeted V1 comodulation supports task-adaptive sensory decisions
Animals respond rapidly and precisely to a variety of sensory stimuli, but the neural mechanisms supporting this flexibility are not fully understood. Here the authors describe a model of adaptive sensory processing based on functionally-targeted stochastic modulation, and find evidence for this co-variability in macaque V1 and middle temporal area.
- Caroline Haimerl
- , Douglas A. Ruff
- & Eero P. Simoncelli
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| Open Access
Endogenous noise of neocortical neurons correlates with atypical sensory response variability in the Fmr1−/y mouse model of autism
Enhanced variability is a hallmark of atypical sensory processing in autism. Here, focusing on variability of neocortical tactile responses in mice, the authors explore the role of endogenous noise sources in neural processing in a model of autism.
- Arjun A. Bhaskaran
- , Théo Gauvrit
- & Andreas Frick
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| Open Access
Wake slow waves in focal human epilepsy impact network activity and cognition
Slow waves in sleep are crucial for homeostatic regulation of brain function. Here the authors show similar slow wave activity occurs during wakefulness in people with epilepsy to counter the impact of abnormal, epileptic, brain activity.
- Laurent Sheybani
- , Umesh Vivekananda
- & Matthew C. Walker
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Article
| Open Access
Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease
Alzheimer’s disease genetic risk is enriched in glial genes. Here, the authors derive cell-type-specific polygenic risk scores and link astrocytic genes with Aβ, and microglial genes with Aβ, tau, microglial activation, and cognitive decline.
- Hyun-Sik Yang
- , Ling Teng
- & Reisa A. Sperling
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Article
| Open Access
Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation
Electrical stimulation of the neuromuscular system holds promise for therapeutic biomedical applications, but is currently restricted by power. Here, the authors introduce fully implantable resonator-based designs achieving ±20 V compliance and >300 mW output, enabling multichannel, biphasic, current-controlled operation to evoke functional gate patterns for 6-weeks in freely behaving rats.
- Alex Burton
- , Zhong Wang
- & Philipp Gutruf
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| Open Access
The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology
The stress etiology of depression remains elusive. Here, authors show that dynorphin/KOR signaling-mediated impairment of excitatory synaptic transmission from claustrum to prelimbic cortex PV interneurons contributes to stress-induced depression.
- Yu-Jun Wang
- , Gui-Ying Zan
- & Jing-Gen Liu
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INPP5D regulates inflammasome activation in human microglia
INPP5D/SHIP1 is a microglial-expressed gene that has been associated with Alzheimer’s disease through genetic studies. This study reveals that reduction in INPP5D activity induces activation of the NLRP3-inflammasome in human microglia.
- Vicky Chou
- , Richard V. Pearse II
- & Tracy L. Young-Pearse
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CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice
Ceramides in peripheral tissues contribute to obesity-related metabolic dysfunction. This study reveals that CerS6-derived ceramides induce hypothalamic lipotoxicity in mice via altered ER/mitochondrial homeostasis.
- Philipp Hammerschmidt
- , Sophie M. Steculorum
- & Jens C. Brüning
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Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation
How early life experience impacts adult behavior is unclear. Here, authors show that maternal immune activation remodels mouse brain methylome and selectively regulates neuronal activity genes, resulting in anxiety- and depression-like behaviors.
- Li Ma
- , Feng Wang
- & Jian-Fu Chen
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Article
| Open Access
Internal states as a source of subject-dependent movement variability are represented by large-scale brain networks
How internal states such as confidence and motivation influence motor performance remains unclear. Here, the authors explore brain networks associated with these internal states, finding that the Dorsal Attention Network encodes error states and the Default Network reflects perceived uncertainty.
- Macauley Smith Breault
- , Pierre Sacré
- & Sridevi V. Sarma
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Article
| Open Access
Introspective inference counteracts perceptual distortion
People can have perceptual illusions that they realize are not real. Here, the authors show that this type of reality testing can be explained by a Bayesian inference model that incorporates introspective knowledge.
- Andra Mihali
- , Marianne Broeker
- & Guillermo Horga
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| Open Access
The genetic relationships between brain structure and schizophrenia
Schizophrenia is considered a brain disorder. Here, authors show genetic overlap between brain structure and schizophrenia that was strongest in the hubs of structural covariance networks and concentrated three chromosomal regions.
- Eva-Maria Stauffer
- , Richard A. I. Bethlehem
- & Edward T. Bullmore
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| Open Access
Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex
How neurons represent competing values during decision making remains poorly understood. Here, the authors find evidence that context modulates value representation in the human cortex.
- Wan-Yu Shih
- , Hsiang-Yu Yu
- & Shih-Wei Wu
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| Open Access
Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity
PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.
- Anna Pagliaro
- , Roxy Finger
- & Benedetta Artegiani
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| Open Access
NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease
Oral nicotinamide riboside (NR) at a dose of 3000 mg daily for 30 days is safe and associated with a pronounced systemic augmentation of the NAD metabolome, but no methyl donor depletion.
- Haakon Berven
- , Simon Kverneng
- & Charalampos Tzoulis
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| Open Access
Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue
The mechanisms of episodic memory are not well understood. Here, the authors show that the reactivation of non-spatial information precedes the reactivation of spatial information, and that both are correlated with hippocampal sharp-wave ripples.
- HaoRan Chang
- , Ingrid M. Esteves
- & Bruce L. McNaughton
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| Open Access
Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice
Here the authors show in male mice that acute and chronic complex simulated galactic cosmic radiation exposure differentially reorganized prefrontal cortex neurotransmitter networks in vivo, which was associated with cognitive deficits.
- Rajeev I. Desai
- , Brian D. Kangas
- & Charles L. Limoli
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Resting-state global brain activity affects early β-amyloid accumulation in default mode network
Why β-amyloid plaque initially accumulates in the default mode network of the cortex before Alzheimer’s disease diagnosis is not known. Here, the authors show that this accumulation is associated with a reduction of global brain activity in these regions.
- Feng Han
- , Xufu Liu
- & Xiao Liu
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Article
| Open Access
Modular interneuron circuits control motion sensitivity in the mouse retina
Interneuron circuits in the retina allow structurally similar retinal ganglion cells to show different responses. Here the authors use an intersectional genetics approach to identify an object motion sensitive amacrine cell subtype in the mouse retina.
- Andrew Jo
- , Sercan Deniz
- & Yongling Zhu
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Article
| Open Access
Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration
Synaptotagmin-1 and -7 are calcium sensors that distinctly drive vesicular exocytosis. Here, using wild-type proteins but manipulating the composition of the target membranes, the authors show that synaptotagmin-7 is unusually robust at penetrating membranes.
- Kevin C. Courtney
- , Taraknath Mandal
- & Edwin R. Chapman
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Diversity of cortical activity changes beyond depression during Spreading Depolarizations
Spreading depolarizations are classically thought to be associated with depression of cortical activity. Here, authors show variable, from depression to booming, changes in cortical activity during different types of spreading depolarizations.
- Azat Nasretdinov
- , Daria Vinokurova
- & Roustem Khazipov
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| Open Access
Three-dimensional surface motion capture of multiple freely moving pigs using MAMMAL
3D social movement capture of large-size mammals is essential for agriculture and life science yet challenging. Here, the authors introduce MAMMAL, an algorithm to enable surface motion captures of multiple freely moving animals and quantitative behaviour measurement in a non-invasive manner.
- Liang An
- , Jilong Ren
- & Yebin Liu
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Article
| Open Access
Autophagy drives the conversion of developmental neural stem cells to the adult quiescent state
Neural stem cells in the adult mammalian brain derive from proliferating precursors that are spared as dormant reservoirs during development. Here, the authors show that autophagy is required for neural stem cells to transition to the adult quiescent state.
- Isabel Calatayud-Baselga
- , Lucía Casares-Crespo
- & Helena Mira
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| Open Access
Different spectral sensitivities of ON- and OFF-motion pathways enhance the detection of approaching color objects in Drosophila
Motion vision in many animals is split into pathways for bright (ON) and dark (OFF) edges, driven by luminance changes. Here the authors show how in Drosophila color selectively contributes to ON-motion, enhancing detection of saliently colored objects.
- Kit D. Longden
- , Edward M. Rogers
- & Michael B. Reiser
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| Open Access
A synaptic corollary discharge signal suppresses midbrain visual processing during saccade-like locomotion
How the visual system differentiates between external motion and sensory input arising from self-motion is poorly understood. Here, the authors investigate how motor-related synaptic signals impact neural activity in a key visual center during locomotion.
- Mir Ahsan Ali
- , Katharina Lischka
- & Johann H. Bollmann
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Article
| Open Access
Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years
A comprehensive multi-omic analysis of the EPISTOP trial for Tuberous Sclerosis Complex (TSC). was performed. Here, authors show many differences in serum proteins and metabolites, and blood RNA species, including associations with seizure development.
- Franz Huschner
- , Jagoda Głowacka-Walas
- & David J. Kwiatkowski
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| Open Access
A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease
Mitochondrial dysfunction is a contributing factor in Parkinson’s disease. Here the authors carry out a multilayered omics analysis of Parkinson’s disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by α-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients.
- Sebastian Schmidt
- , Constantin Stautner
- & Wolfgang Wurst
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| Open Access
Motion direction is represented as a bimodal probability distribution in the human visual cortex
The visual system quickly infers an object’s direction of motion from noisy sensory signals. Here, the authors show that orientation signals are used in this process, leading to bimodal probabilistic representations of motion direction in the human cortex.
- Andrey Chetverikov
- & Janneke F. M. Jehee
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Article
| Open Access
Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
Synaptic activity controls the extinction of conditioned fear. Here the authors discovered a new way that the brain controls memories of fear: a long noncoding RNA called Gas5 that coordinates the activity of RNA granules in the synaptic compartment.
- Wei-Siang Liau
- , Qiongyi Zhao
- & Timothy W. Bredy
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Article
| Open Access
Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development
Human cerebellar development is fundamentally linked to its function. Here, the authors combine single-cell transcriptomics, spatial transcriptomics, and single-cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development.
- Suijuan Zhong
- , Mengdi Wang
- & Qian Wu
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Article
| Open Access
Heterogeneous encoding of temporal stimuli in the cerebellar cortex
The frontal cortex shows intricate feedback and feedforward connectivity, but other brain areas such as the cerebellum are thought to exhibit simpler activity profiles. Here, the authors show that rodent cerebellar cortex supports heterogeneity in task-related neuronal activity at a scale similar to that in the cerebral cortex.
- Chris. I. De Zeeuw
- , Julius Koppen
- & Devika Narain
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Article
| Open Access
Distinct value computations support rapid sequential decisions
How animals determine the value of the environment for motivation and error-based learning remains unclear. Here, the authors found that rats use multiple distinct algorithms to compute the value of the environment for rapid sequential actions on single trials.
- Andrew Mah
- , Shannon S. Schiereck
- & Christine M. Constantinople
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| Open Access
Synaptic mechanisms for associative learning in the cerebellar nuclei
The role of the cerebellar nuclei (CN) during associative learning remains debated. Here, the authors show that well-timed conditioned responses can result from stimulating CN inputs, and that learning coincides with structural and synaptic activity changes in vivo.
- Robin Broersen
- , Catarina Albergaria
- & Chris I. De Zeeuw
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Article
| Open Access
Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction
Inhibiting 2-AG synthesis in ventral tegmental area dopamine neurons may impair cue-driven motivated behavior and dopamine release. Here the authors report this, showing the role of endocannabinoid signaling in dopamine-based predictive associations.
- Miguel Á. Luján
- , Dan P. Covey
- & Joseph F. Cheer
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Article
| Open Access
Behavioral representational similarity analysis reveals how episodic learning is influenced by and reshapes semantic memory
Pre-existing semantic knowledge provides an organizational structure for episodic memories. Here, the authors show that episodic learning systematically shapes this semantic space depending on how learners engage with material and the strength of prior associations.
- Catherine R. Walsh
- & Jesse Rissman
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Article
| Open Access
Dopamine receptor activation regulates reward expectancy signals during cognitive control in primate prefrontal neurons
Dopamine responds to reward-predicting cues and is also linked to cognitive control. Here the authors examine the role of dopamine receptor subtypes in the neuromodulation of reward-related activity in the macaque prefrontal cortex.
- Torben Ott
- , Anna Marlina Stein
- & Andreas Nieder
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Article
| Open Access
Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females
Men are at a greater risk to develop Parkinson’s disease (PD). However, Hefeng and team revealed enhanced cytotoxicity and terminal differentiation in CD8 T cells of early-to-mid stage idiopathic PD, especially for females, using systems immunology.
- Christophe M. Capelle
- , Séverine Ciré
- & Feng Q. Hefeng
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Article
| Open Access
Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly
The soluble neurotrophic factor GDNF promotes trans-synaptic adhesion through its co-receptor GFRα1. Here, the authors describe the structural basis for GDNF-GFRα1 adhesion and reconstitute assemblies bridging membranes, demonstrating that binding of either the RET receptor or proteoglycans can disrupt this adhesive function.
- F. M. Houghton
- , S. E. Adams
- & N. Q. McDonald
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Article
| Open Access
A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson’s disease
Using animal models to mimic Parkinson’s disease can advance our understanding of pathogenesis. Here, the authors combine single-cell genomics with a primate model of parkinsonism to provide insights into neuronal vulnerability and resilience.
- Lei Tang
- , Nana Xu
- & Sheng Liu
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Article
| Open Access
The homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Synapse elimination is a critical process in the maturation of brain circuitry. Here the authors identify a key transcriptional program in Caenorhabditis elegans that directs the elimination of juvenile synapses during developmental circuit rewiring.
- Kellianne D. Alexander
- , Shankar Ramachandran
- & Michael M. Francis
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Article
| Open Access
GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21
How excitatory neurons (EN) acquire senescence is unclear. Here, the authors show that GDF11 in ENs slows EN senescence, brain ageing, cognitive decline and maintains lifespan, revealing a mechanism underlying EN senescence and brain ageing.
- Di-Xian Wang
- , Zhao-Jun Dong
- & Jing-Wei Zhao
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Article
| Open Access
Topographic axonal projection at single-cell precision supports local retinotopy in the mouse superior colliculus
Retinotopy can arise from axons or their targets; however, the underlying connectivity pattern remains elusive. Here, the authors use two-photon calcium imaging of retinal ganglion cell axon terminals in the female mouse superior colliculus to identify a high precision of retinotopic tiling at single-cell resolution.
- Dmitry Molotkov
- , Leiron Ferrarese
- & Hiroki Asari
Longitudinal development of category representations in ventral temporal cortex predicts word and face recognitionBrowse broader subjects
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- Auditory system
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- Cell death in the nervous system
- Cellular neuroscience
- Circadian rhythms and sleep
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- Development of the nervous system
- Diseases of the nervous system
- Emotion
- Epigenetics in the nervous system
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- Motor control
- Myelin biology and repair
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- Reward
- Sensorimotor processing
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