Neuron
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A neural circuit framework for economic choice: From building blocks of valuation to compositionality in multitasking
Battista et al. use biologically plausible RNNs to uncover the circuit mechanisms of economic choice. They propose a two-stage framework where feedforward inputs compute offer values and recurrent inhibition drives comparison. This architecture explains how the brain generalizes preferences and multitasks using compositional neural codes, offering a unified theory of decision-making.dlvr.itC9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes
Liu et al. demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form HQ structures with DNA. These structures obstruct key transcription machinery, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD.dlvr.itSynapse-specific and plasticity-regulated AMPA receptor mobility tunes synaptic integration
Short-term plasticity (STP) filters synaptic inputs across rapid timescales. Nowacka et al. show that postsynaptic AMPAR desensitization and diffusion-trapping, shaped by auxiliary subunits and activity-dependent signaling, generate synapse-specific gain control. By broadening temporal filtering and adjusting short-term depression, receptor mobility emerges as a central regulator of circuit information processing.dlvr.it- New issue of Neuron is out today. On the cover, a group from Fourth Military Medical University in Xi’an, China identify a novel C5aR1+ microglial subtype in human cerebral edema after brain injury.
Issue: Neuron
cell.comHippocampal estrogen levels, receptor types, and epigenetics contribute to sex-specific memory vulnerabilities to concurrent acute stresses
Acute concurrent stresses provoke lasting, sex-dependent memory problems. Hokenson, Rodríguez-Acevedo, et al. find that high hippocampal estrogen levels in mice generate permissive chromatin states, allowing both adaptive plasticity and vulnerability to acute concurrent stresses. Stress vulnerability involves estrogen receptor (ER)α in males and ERβ in females.dlvr.itIdentification of an engram ensemble mediating memory forgetting in the dentate gyrus
Hu et al. show that the dentate gyrus engram comprises two neuronal ensembles: one supports remembering, and the other promotes forgetting. By shifting the balance between these ensembles via Rac1 signaling, the brain flexibly controls recall. Dysfunctions of the forgetting ensemble contribute to memory abnormalities in models of Alzheimer’s disease and autism.dlvr.itGranular motivational interaction and behavioral choice during feeding
Liu et al. propose the theoretical framework “granular motivational interaction orchestrates real-time behavioral choice,” exploring the dynamic interactions of granular motivational states in the feeding process, their neural bases, disrupting factors, and implications for understanding intelligence and psychiatric disorders.dlvr.itConverging dopamine pathways onto basolateral amygdala neurons encode exploration decisions
Using mouse models, Zheng et al. show that social engagement promotes both innate and experience-dependent exploration. Dopaminergic neurons in the ventral tegmental area (VTA) encode risk assessment and exploratory motivation through firing pattern-biased DA transmission, thereby shaping exploration decisions via competing VTADA pathways that converge onto basolateral amygdala neurons.dlvr.itA mesoscale optogenetics system for precise and robust stimulation of the primate cortex
Li et al. present a microLED-based mesoscale optogenetic system for centimeter-scale, million-pixel primate cortical stimulation. Optogenetically evoked saccades with accurate retinotopic organization remain stable for over a year, demonstrating precise, robust, and durable neuromodulation and charting a path toward next-generation optical brain-computer interfaces and visual prostheses.dlvr.itRunx1 transcription factor modulates opioid analgesia and withdrawal in humans and rodents
Opioid responses differ across individuals. Runt-related transcription factor 1 (Runx1) modulates the microglial transcriptome, influencing opioid analgesia and withdrawal. RUNX1 variants may underlie inter-individual differences in opioid responses, guiding personalized strategies to optimize opioid pain management and minimize adverse outcomes.dlvr.itCB1R and GlyT2 interaction in spinal glycinergic circuits drives neuropathic mechanical pain
Wang et al. reveal how nerve injury causes mechanical allodynia. It triggers endocannabinoid release, which disables the spinal Gly-PKCγ “allodynia gate” by disrupting inhibitory control. They develop a peptide that reverses this process, offering a promising strategy to alleviate chronic pain.dlvr.itThe neuroimmune axis: Integrating two systems to decipher itch
Crosstalk between the nervous and immune systems is imperative to maintain homeostasis, and disruptions to this balance can drive pathology. In this review, Kothari and Dong discuss neuroimmune mechanisms that regulate itch, with an emphasis on pruritic diseases and therapies.dlvr.itSpontaneous behavior is a succession of self-directed tasks
Weinreb et al. reveal a hierarchy of timescales in mouse behavior, including low-level syllables and high-level behavioral states. States and syllables are encoded in different brain areas. Prefrontal encoding of behavioral states identifies principles common to both structured tasks and spontaneous behavior.dlvr.itTranscranial focused ultrasound in the human brain
Transcranial focused ultrasound is emerging as a possible novel therapeutic tool for neurological and psychiatric disorders. This review covers three promising applications of this technology in human brain disorders based on high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU).dlvr.itThe layer 6b theory of attention
Zolnik et al. propose that the long-overlooked neocortical layer 6b (L6b) supports a key circuit for attention and related cognitive functions. L6b integrates neuromodulatory and cortical feedback to trigger, sustain, and precisely control higher-order thalamocortical loops needed for attentive processing.dlvr.itIntestinal interoception: A nexus of environment-body-brain interactions
Salvador, Golynker, et al. discuss anatomical and functional principles of intestinal interoception. They explore how environmental factors impact interoceptive signaling, how interoceptive dysfunction contributes to disease pathogenesis, and how molecular enhancement of interoceptive function may restore organismal homeostasis.dlvr.itThe cerebellar components of the human language network
Casto et al. systematically examine language-responsive regions of the cerebellum with precision fMRI. They find one region that closely resembles the neocortical language network in its selectivity for language and response to linguistic manipulations. They also find three mixed-selective regions that respond to language but also to non-linguistic inputs.dlvr.itMacaque prefrontal cortex integrates multiple components for metacognitive judgments of working memory
Ning et al. show that macaque prefrontal neurons encode remembered spatial locations along with uncertainty and combine them with cues, such as trial history and arousal, to generate a meta-working-memory signal guiding opt-out decisions. The findings reveal how the prefrontal cortex integrates multiple components for metacognitive judgments of working memory.dlvr.it- New issue out today: A group from Sun Yat-sen University Cancer Center uncover how pancreatic cancer remotely rewires brain circuits to drive neurological comorbidity. Artwork depicts the Monkey King guarding the celestial peach tree.
A multi-region recurrent circuit for evidence accumulation in rats
Gupta et al. demonstrate that the rat prefrontal cortex and striatum jointly accumulate sensory evidence through recurrent, bidirectional communication rather than a feedforward hierarchy. Combining multi-region recordings, projection-specific perturbations, and biologically constrained recurrent neural network modeling, the study reveals distributed cortico-striatal mechanisms for decision-making that recover in the face of perturbations.dlvr.itCLN3 mediates chloride efflux from lysosomes
Wang et al. identify CLN3 as a conserved lysosomal protein that regulates lysosomal chloride homeostasis, pH, and protein degradation. Transcription factor EB (TFEB) activation enhances CLN3 function, revealing the TFEB-CLN3 signaling axis as a promising therapeutic target for lysosomal storage disorders.dlvr.itGut-brain cholinergic signaling mediates the antiseizure effects of Bacteroides fragilis
Jia et al. show that the antiseizure effects of Bacteroides fragilis are mediated by enhanced cholinergic signaling along the gut-vagus-brain axis and reinforced by the gut colonization of Lactobacillus. These findings reveal a microbiota-neural circuit interaction with translational implications for pediatric refractory epilepsy.dlvr.itTachykinin signaling defines distinct populations of glia in the enteric nervous system
To date, glial cells in the enteric nervous system have been categorized by spatial location and morphology. Here, Muppirala et al. define distinct subtypes of enteric glia that align with this spatial classification and identify tachykinin signaling as a key mediator of glial diversification and subtype-specific function in intestinal motility.dlvr.it- Reposted by Neuron[Not loaded yet]
- New issue out today at: cell.com/neuron/current The cover features a collaboration from several groups at the Chinese Academy of Sciences mapping thousands of single-neuron projectomes in the mouse cortex, providing novel insights into cortical networks.
Issue: Neuron
cell.com A small population of stress-responsive neurons in the hypothalamus-habenula circuit mediates development of depression-like behavior in mice
(Neuron 112, 3924–3939.e1–e5; December 4, 2024)dlvr.itOligodendrocyte mechanotransduction channel TMEM63A regulates myelin sheath geometry
Dereddi, Djannatian, and colleagues show that oligodendrocytes use mechanical cues to measure axon size. The stretch-activated channel TMEM63A converts membrane tension into calcium signals, which calibrate myelin sheath growth via MYO5A-dependent Mbp mRNA transport. Loss of TMEM63A causes mis-sizing of myelin sheaths and hypomyelination linked to transient infantile leukodystrophy.dlvr.itHow heterogeneity shapes dynamics and computation in the brain
No two neurons are the same, yet models often treat neural populations as pools of identical and interchangeable elements. Here, Dahmen et al. highlight recent theoretical advances that reveal the impact of neural heterogeneity on brain dynamics and function.dlvr.itAberrant nuclear pore complex degradation contributes to neurodegeneration in VCP disease
Dubey et al. found that the AAA+ATPase valosin-containing protein (VCP) is required for nuclear pore complex quality control in neurons and muscle. Loss of VCP leads to nucleoporin aggregation, whereas neurodegenerative-disease-associated mutations cause excessive nucleoporin degradation and the disruption of nucleocytoplasmic transport, highlighting potential therapeutic approaches for these diseases.dlvr.itNeurons undergo IFNγ-driven persistent epigenetic shifts and synaptopathy in encephalitis
Shammas et al. show a neuronal epigenetic remodeling during CNS encephalitis. This program involves IFNγ-driven persistent reduction in TF-binding site accessibility, linked to long-lasting reduction of synaptic gene expression and associated synaptopathy. Parallel findings in Rasmussen encephalitis patient neurons point toward a conserved cross-species mechanism.dlvr.itIdentification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch
(Neuron 103, 1135–1149.e1–e6; September 25, 2019)dlvr.itThe Alzheimer’s disease risk genes MS4A4A and MS4A6A cooperate to negatively regulate TREM2 and microglia states
The Alzheimer’s risk genes at the MS4A locus have poorly described function. Rosner et al. show that MS4A4A and MS4A6A cooperate to negatively regulate the TREM2 and TYROBP risk genes and microglia activity. MS4A4A antibodies increase TREM2 and beneficial microglia functions, suggesting therapeutic potential for this axis.dlvr.itImmune-brain plasticity underpins stress and affective behaviors
Lee and Wheeler review the interface of neuroimmune interactions, stress, and affective behaviors. They highlight anatomical and cellular mechanisms controlling immune-brain plasticity as well as therapeutic opportunities and new technologies that could be used to modulate and discover relevant pathways.dlvr.itNeural population activity for memory: Properties, computations, and codes
Dupret et al. synthesize recent advances linking neural population activity to the properties, computations, and codes of memory, proposing that memory circuits achieve efficient function by balancing trade-offs within a safe zone of population-activity space.dlvr.itSynchrony timescales underlie irregular neocortical spiking
Variable spiking is a ubiquitous neuronal feature. Pattadkal et al. show that physiological spiking variability is reflective of input drive characteristics. They demonstrate that weak input synchrony induces physiological variability and identify synchrony timescales to be critical in regulating variability shifts, using in vivo, in vitro, and in silico approaches.dlvr.it- New issue out today at: www.cell.com/neuron/current The cover highlights a paper from Karunesh Ganguly's group examining how activity in the premotor cortex supports recovery of reach-to-grasp behaviors. Art by Milan and Leela Ganguly.
Issue: Neuron
cell.com Linguistic coupling between neural systems for speech production and comprehension during real-time dyadic conversations
Zada et al. use fMRI hyperscanning to simultaneously record dyads engaging in free-form, interactive conversations. They find that speech production and comprehension rely on highly overlapping neural representations across the cortical language network. Brain-to-brain coupling is strongest in areas associated with social cognition.dlvr.itElevated calneuron-1, an accessory subunit of muscarinic receptors, induces frontotemporal dysconnectivity and schizophrenia-like deficits
Oelschlegel et al. report that the schizophrenia-risk gene calneuron-1 is elevated in schizophrenia, elicits schizophrenia-like behavior, and impairs network communication in mice. Calneuron-1 is an accessory subunit of muscarinic M1R that inhibits G-protein coupling and shuts off M1R signaling in schizophrenia. The M1R agonist xanomeline interrupts calneuron-1/M1R interaction and rescues schizophrenia-related deficits.dlvr.itAberrant hypothalamic neuronal activity blunts glucocorticoid diurnal rhythms in murine breast cancer
Gomez, Wu, et al. demonstrate that breast cancer promotes blunted glucocorticoid diurnal rhythms via disinhibition of PVNCRH neurons. Restoration of normal glucocorticoid rhythms via endogenous activation of the HPA axis reduces tumor progression and boosts anti-tumor immunity. This neural mechanism offers a novel target for potential anti-cancer therapy.dlvr.itTDP-43 dysfunction compromises UPF1-dependent mRNA metabolism in ALS
Alessandrini et al. map UPF1-mediated RNA decay in human motor neurons and show that TDP-43 dysfunction impairs RNA surveillance. UPF1 and TDP-43 proteins interact and co-aggregate in pathological inclusions; they also co-regulate alternative polyadenylation of specific transcripts extending 3′ UTRs, revealing a shared pathway underlying ALS-related RNA dysregulation.dlvr.itSemaphorin–Neuropilin Interactions Underlying Sympathetic Axon Responses to Class III Semaphorins
(Neuron 21, 1283–1290; December, 1998)dlvr.itSympathetic functional units encoded by genetically defined postganglionic neurons
Wei et al. found two CG-SMG sympathetic subpopulations: Calb2-positive neurons project to gut muscle, forming endings at myenteric ganglia to regulate motility, and Nxph4-positive neurons innervate organ blood vessels, forming perivascular endings that act as visceral vasoconstrictors controlling blood flow.dlvr.itModulation of metastable ensemble dynamics explains the inverted-U relationship between tone discriminability and arousal in auditory cortex
Papadopoulos et al. report an inverted-U relationship between tone discriminability and arousal in mouse auditory cortex. A spiking network model with clustered connectivity explains the effects via modulations of metastable attractor dynamics. The model suggests that transitions in dynamical regimes mediate state-dependent sensory processing and induce changes in neural variability.dlvr.itThe hologenome in brain health and disease
The perspective by Dooling and Costa-Mattioli highlights how the hologenome, the collective genomes of the host and associated microbes and their interactions, modulates brain health and recommends a roadmap for studying the hologenome in complex behaviors.dlvr.it- New issue: www.cell.com/neuron/current The cover highlights a Review article from 24 co-authors that discusses the principles of brain clearance, including the role of CSF influx, sleep-dependent waste removal, and connections to the immune system. Art by Nadia Alzoubi.
Protective ApoE variants support neuronal function by effluxing oxidized phospholipids
Ralhan et al. show that ApoE2 and ApoE3 Christchurch on lipid particles efflux oxidized phospholipids from neurons via the ABCA7 transporter. This reduces the burden of oxidized lipids, which improves lysosomal function and protects neurons from ferroptosis.dlvr.itBiased histamine signaling selectively gates fat preference
Zheng et al. uncover the neural basis for specific food preferences, showing that separate thalamic populations mediate intake of high-fat and high-sugar diets. They identify a histamine H3 receptor-mediated circuit that specifically regulates fat consumption in response to orosensory cues, suggesting potential targets for precise weight management.dlvr.itExploiting correlations across trials and behavioral sessions to improve neural decoding
Animals share common patterns of brain activity across trials and sessions. Exploiting this shared structure improves the prediction of behavior from neural activity, scales across many sessions and brain regions, and offers interpretable alternatives to deep-learning-based foundation models.dlvr.itDistinct roles of prefrontal subregion feedback to the primary visual cortex across behavioral states
Ährlund-Richter et al. show that in mice, discrete subregions of the prefrontal cortex send distinct feedback signals to the primary visual cortex. These pathways differentially modulate visual processing depending on behavioral state, revealing how higher-order cortical areas dynamically influence sensory representations to integrate perception with internal state.dlvr.itResolving the mysteries of brain clearance and immune surveillance
This review by Kipnis et al. explores recent advances in brain fluid dynamics, emphasizing CSF flow’s role in waste clearance, the glymphatic and meningeal lymphatic systems, and neuroimmune interactions, with implications for neurodegenerative and neuroimmune disorders.dlvr.it
