A coronavirus protease activates sensory neurons via TRPA1 to drive sneeze, cough, and pain

Mali et al. show that coronaviruses, including SARS-CoV-2, trigger sneezing, coughing, and pain hypersensitivity by directly activating nociceptors. The viral protein PLpro alone is sufficient to produce these effects, revealing a mechanism by which the virus drives hallmark respiratory symptoms and may promote viral spread.

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A consensus spinal cord cell-type atlas across mouse, macaque, and human

Schmitz, Johansen, et al. build a consensus cell type atlas of the mammalian spinal cord, integrating gene expression, chromatin accessibility, and spatial data across human, macaque, and mouse. Cell identity and laminar position are broadly conserved, while the dorsal horn emerges as the main site of neuronal expression divergence.

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Slow-timescale regulation of dopamine release governs recovery of a motivational drive over days

Sunkavalli et al. show that, after sexual satiation in male mice, dopamine transmission in the medial preoptic area falls and recovers over days, acting as a timer for mating-drive recovery. Changes in the neuronal firing rate and in the capacity for dopamine synthesis control the early and late phases of recovery, respectively.

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Antisense oligonucleotide silencing rescues neurodevelopmental deficits in AMPA receptor gain-of-function mice

Chen et al. show that a recurrent ASD/ID-associated GRIA1-A636T variant disrupts the postnatal restriction of AMPAR Ca2+ permeability. In knock-in mice, persistent Ca2+-permeable AMPAR activity leads to synaptic hyperexcitability, hippocampus-biased degeneration, and behavioral impairments. A single neonatal allele-selective ASO prevents pathology and improves behavior.

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Glial progenitor-like state is preferentially co-opted in glioblastoma and sustained by POU3F3

Ramos and Khan et al. assess oncofetal biology in glioblastoma and discover a conserved developmental state preferentially co-opted in primary and recurrent tumor cells, which is reminiscent of late-gestation glial intermediate progenitor cells (gIPCs). They uncover POU3F3 as a gIPC-lineage regulator that is critical for glioblastoma stem-like maintenance, proliferation, and invasion, exposing a potentially broadly targetable GBM vulnerability.

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An astrocyte-microglia MFG-E8 axis promotes synapse engulfment in early amyloid pathology

Early synapse loss tracks cognitive decline in Alzheimer’s disease. Sokolova, Puletti, et al. identify a regional perisynaptic astrocyte state in early amyloid pathology and show that astrocyte-derived MFG-E8 promotes microglial synapse engulfment via β3 integrin. Suppressing astrocytic Mfge8 limits synapse loss, reduces plaque burden, and improves memory, suggesting therapeutic potential.

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Parvalbumin cell state dynamics regulate gamma oscillations and are disrupted in Alzheimer’s disease

Ma et al. find that parvalbumin (PV) interneurons dynamically transition between cell states rather than acting as a uniformly synchronized population during spontaneous gamma oscillations. PV cell st...

cell.com

Glioma regulates GABAergic signaling to drive hyperactivity and tumor progression

We find that knockout of the GABA transporter Slc6a1 facilitates glioma growth with decreased tumoral GABA release. Activity of inhibitory neurons affects glioma proliferation, which can be altered ph...

tinyurl.com

Neural geometry in the human hippocampus enables generalization across spatial position and gaze

Chericoni et al. show that neurons in the human hippocampus track the positions of multiple agents in a simple pursuit-based video game. They identified place codes for each agent and for gaze. The co...

cell.com

Opposing excitatory and inhibitory synaptic pathologies drive ZC4H2-associated intellectual disability

Ma et al. demonstrate that ZC4H2 mutations underlying intellectual disability stratify into two opposing pathomechanisms disrupting excitatory-inhibitory balance—either reduced GABAA receptor stability and synaptic hypo-inhibition or enhanced AMPA receptor stability and synaptic hyper-excitation. Notably, targeting the respective receptor with muscimol or perampanel rescues cognitive deficits in corresponding mouse models.

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P2RX7 drives inflammatory microglia and pathogenic extracellular vesicle secretion in tauopathy

Bodart-Santos et al. identify P2RX7 as a microglial checkpoint that drives inflammatory-state transition and pathogenic extracellular vesicle release in tauopathy. P2RX7 promotes EV-mediated tau propagation and mitochondrial danger signaling, linking microglial activation to neurodegeneration and highlighting the P2RX7-EV axis as a therapeutic target.

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Redox-dependent remodeling of mitochondrial nucleoids contributes to bioenergetic decline during neuronal aging

Cheng, Gao, et al. reveal that oxidative stress remodels mitochondrial DNA organization in aging neurons, disrupting mitochondrial gene expression and bioenergetics. Species-specific TFAM redox mechanisms converge on mt-nucleoid decompaction. Expression of redox-resistant TFAM restores mt-nucleoid compaction and ATP production, revealing a conserved mechanism linking oxidative stress to mitochondrial dysfunction.

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Hypothalamus-driven brain health through metabolic flexibility

Horvath et al. propose that hypothalamus-controlled metabolic flexibility coordinates body-brain communication, enabling physiological state to shape cognition and behavior, while its deterioration during aging and metabolic disease promotes inflammation, cognitive decline, and vulnerability to neurodegeneration.

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The neurobiology of menopause: Implications for brain aging and Alzheimer’s risk

Mosconi reviews how neuroendocrine transitions across the female lifespan, particularly menopause, shape brain aging and Alzheimer’s disease vulnerability, integrating mechanistic, biomarker, and hormone-therapy evidence to define priorities for risk stratification and prevention research.

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Trait-linked brainstem circuit resilience balances tau pathology-induced cellular vulnerability in Alzheimer’s disease

Zheng et al. show that tau pathology suppresses Edinger-Westphal CART+ neurons to impair early attention, whereas exploratory behavior recruits a medial parabrachial circuit that sustains these vulnerable neurons through substance P signaling. This balance between cellular vulnerability and circuit compensation shapes cognitive resilience in Alzheimer’s disease.

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Glioma regulates GABAergic signaling to drive hyperactivity and tumor progression

We find that knockout of the GABA transporter Slc6a1 facilitates glioma growth with decreased tumoral GABA release. Activity of inhibitory neurons affects glioma proliferation, which can be altered pharmacologically with FDA-approved drugs. Gliomas secrete the GABA-A negative allosteric modulator DBI to further facilitate growth and hyperactivity.

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Remak bundle size, structure, and function are regulated by the Schwann cell basal lamina

Lillis et al. find that collagen IV in the Schwann cell (SC) extracellular matrix is required for SC proliferation and Remak bundle formation, but not myelination. They test Remak bundle function, finding an association with mechanosensitivity: large abnormal bundles have decreased mechanosensation, which is rescued by increasing SC number/decreasing bundle size.

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A vagal gut-brain axis for feeding-induced gastric secretion in mice

Wang et al. define a vagal gut-brain-enteric circuit for feeding-induced gastric secretion. Food-derived mechanical and chemical cues recruit vagal sensory neurons, defined DMV motor outputs, and local cholinergic enteric relays to drive acid and enzyme secretion, revealing how meal signals are transformed into digestive physiology.

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A GABAergic preoptic-raphe circuit mediates paradoxical coupling of anxiety and social preference after comparative social deficit

Zhang et al. show that relative social exclusion can simultaneously heighten anxiety and social preference in male mice. They identify an mPOA-DRN brain pathway and a potassium-channel molecule that mediate this paradoxical state, offering insight into how social disconnection may increase vulnerability to anxiety disorders.

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More than just accuracy: A pathway-level framework for implementing blood and digital biomarkers for Alzheimer’s disease care

This work by Perneczky et al. provides an overview of recent developments in blood biomarkers and digital cognitive tests for Alzheimer’s disease. The authors discuss issues to be addressed for successful combined implementation and clinically relevant evaluation criteria beyond accuracy.

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Distinct patterns of whole-body coding in human motor cortex and posterior parietal cortex

Kadlec et al. record single neurons from two human brain regions long thought to control the hand and find that neurons in both areas respond to movements across the entire body. Overall effector specificity is observed in the motor cortex, while the parietal cortex represents every body part equally.

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An acetylcholine-inhibited sleep-active hippocampal interneuron orchestrates memory consolidation

Sleep is crucial for long-term memory formation. Feng et al. now show that a unique population of hippocampal interneurons is preferentially active during NREM sleep and plays a critical role in driving hippocampal ripples and sleep-dependent memory consolidation.

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Raphe nuclei in cognition: A network-level framework for behavioral-state control

Khalighinejad and Rushworth propose that raphe nuclei regulate behavioral-state transitions by integrating environmental statistics within distributed cortico-subcortical networks. Their framework links diverse serotonergic functions and predicts when motivational and cognitive states persist, update, or switch.

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A Genome-wide Screen Identifies PAPP-AA-Mediated IGFR Signaling as a Novel Regulator of Habituation Learning

(Neuron 85, 1200–1211; March 18, 2015)

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A brainstem module for backward locomotion reveals direction-selective premotor circuits

Liu et al. identify a brainstem module that drives backward locomotion and show that distinct premotor circuits control forward movement, turning, locomotor arrest, and backward movement. The findings reveal a direction- and action-selective organization of brainstem locomotor control.

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Recovery sleep induces analgesia via sleep ensembles of the zona incerta acting through distinct neural circuits in mice

Haiyan Sun and Liu et al. identify sleep-activated zona incerta neuronal ensembles mediating NREM sleep and analgesia. Chronic pain suppresses these neurons, whereas their activation promotes NREM sleep and alleviates pain. Their divergent projections to the lateral hypothalamus and posterior thalamus separately control sleep and nociception.

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