Simultaneous, real-time tracking of many neuromodulatory signals with multiplexed optical recording of sensors on a micro-endoscope

Kalugin et al. present multiplexed optical recording of sensors on a micro-endoscope (MORSE), an approach to tracking many molecular signals simultaneously in brain extracellular fluids using spatial multiplexing of fluorescent sensors. They use this to quantitatively capture combinatorial neuromodulatory states in brain slices and cerebrospinal fluid of awake, behaving mice.

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Tunneling nanotubes in the nervous system: The fourth pillar of brain connectivity

Budinger and Heneka review how tunneling nanotubes represent an underappreciated layer of brain connectivity, shaping intercellular communication in health and disease and highlighting their implications for neurodegeneration, neuroinflammation, repair, and future research.

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HCN1 channels in GABAergic amygdalar neurons underpin male-biased aggressive behaviors

By elucidating the intricate molecular and functional architecture of the pSI, Li et al. reveal that testosterone hyperexcites pSIVgat neurons via HCN1 upregulation to drive male-biased aggression in mice. These insights open new avenues for exploring how the pSI governs sexually dimorphic aggression.

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Single-neuron resolution mapping of dopaminergic connectivity across development, adulthood, and degeneration

Using a novel intersectional genetic strategy for sparse neuronal labeling, Grossouw, Heijmink, et al. reconstruct individual midbrain dopamine neurons throughout development, adulthood, and degeneration. They reveal previously unrecognized morphological diversity, developmental wiring principles, and subtype-specific connectivity, providing a comprehensive framework for understanding how dopaminergic circuits are assembled, maintained, and disrupted.

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A cortical-hypothalamic neural circuit for compulsive eating in mice

Leow et al. identify a prefrontal-hypothalamic circuit that drives compulsive eating despite negative consequences. In mice, binge eating reshapes prefrontal neural dynamics into persistent food-seeking states, while human imaging links stronger coupling between prefrontal and hypothalamic circuits to obesity and binge-eating traits, revealing a conserved brain pathway for maladaptive feeding.

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Transcriptional regulation of disease-relevant microglial activation programs

McQuade et al. identified transcriptional regulators for six microglial activation states associated with brain disorders. They deeply characterized complex, multi-state regulators and identified common functions downstream of activation. These data support our understanding of these states and provide a toolkit to identify and selectively direct microglial activation.

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Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development

Using a combination of microglia-specific conditional mouse knockout and knockin approaches and xenotransplantation of human iPSC-derived microglia, Diaz-Salazar et al. demonstrate that the human-specific genes SRGAP2B/C, which downregulate the ancestral SRGAP2A, are necessary and sufficient to induce neotenic features of microglial structural maturation, leading to delayed timing of synaptic development in cortical pyramidal neurons.

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A sync state in the midbrain dopamine network for interoceptive nutrient learning

Yang et al. show that a subpopulation of VTA dopamine neurons enters a distinct low-frequency synchronous state during novel food consumption. Emerging during oral-gastric overlap, this state mediates interoceptive credit assignment by linking delayed nutrient signals to immediate tastes. Disrupting this impairs value updating, whereas synchrony-mimicking stimulation enhances future consumption.

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Advancing NeuroAI through developmental alignment

Ayzenberg et al. describe how principles from child development can be used to improve the capacities and biological plausibility of AI models. These principles can be incorporated into every stage of the modeling process, from the architectures to the benchmarks.

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Senescent cell heterogeneity in brain aging and neurodegenerative disease

This review by Graves et al. synthesizes emerging evidence that senescent brain cells are heterogeneous, dynamic, and context dependent, highlighting determinants of diverse programs and emphasizing integration of single-cell- and spatial-omics with mouse studies to facilitate mechanistic insights and possible therapeutics.

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Neural traveling waves in cortex: Network mechanisms and potential roles in neural computation

Muller et al. review how spiking and synaptic activity are often organized as traveling waves in single cortical areas that modulate excitability, perception, and behavior. Specific features of these waves support spatiotemporal, dynamics-based computations, such as short-term prediction and generative processing.

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Neurexin-1γ drives synaptic transmission through structural integration of neurotransmitter release machinery and postsynaptic receptor nanodomains

Padmanabhan et al. identify neurexin1-γ as a presynaptic organizer that anchors a vesicle-priming subassembly to the active zone and physically bridges release machinery to AMPAR nanodomains through its heparan sulfate modification. Neurexin1-γ loss disrupts synaptic nanoarchitecture, causing deficits in excitatory and inhibitory synaptic transmission, synaptic plasticity, and cognitive function.

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Common DISC1 Polymorphisms Disrupt Wnt/GSK3β Signaling and Brain Development

(Neuron 72, 545–558, November 17, 2011)

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Population encoding of cool and warm by thermoreceptors

In vivo calcium imaging and modeling identify encoding principles of innocuous temperature by thermoreceptors in mouse lumbar DRG. The majority of thermoreceptors encode temperature bidirectionally, with enhanced response to cool and suppression to warm. TRPM8 is involved in the thermoreceptor encoding of both warm and cool.

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Optogenetic mimicry of drug action: Tools and models to dissect the dopamine-dependent core of addiction

Lüscher et al. review optogenetic mimicry mouse models that leverage the shared effect of addictive drugs to elevate mesolimbic dopamine. These models replicate key addiction-like behaviors and synaptic adaptations, enabling cell-type- and circuit-specific dissection of reinforcement and compulsive reward seeking.

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Ethological learning during the critical period resets synaptic setpoints in mouse binocular visual cortex

Bissen et al. show that prey capture learning profoundly reshapes visual cortical circuitry and function during developmental critical periods, but not in adulthood. These learning-induced structural and functional changes are stabilized by homeostatic mechanisms that reset synaptic setpoints, thus facilitating learning and retention of this naturalistic, vision-dependent behavior.

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Receptor and cell-type-specific mechanisms in mesocortical dopamine circuits gate chronic pain and comorbid anxiodepression

(Neuron 114, ◼◼◼–◼◼◼. e1-e7; October 21, 2026)

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Autonomic C1 neurons promote anxiety via activation of vlPAG

Fernández-Peña et al. used viral intersectional tools to selectively target epinephrine-expressing C1 neurons in mouse rostral ventrolateral medulla (RVLM). Adjusting their activity altered the severity of fear- and anxiety-related behaviors, emphasizing a role for these cells in the integration of autonomic signals and modulation of complex behaviors.

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Recurrent connectivity shapes spatial coding in hippocampal CA3 subregions

Using in vivo two-photon imaging, genetic perturbation, and computational modeling, Kong et al. show that gradients in recurrent connectivity along the transverse axis of hippocampal CA3 organize distinct coding strategies for location and context. The study highlights how local circuit architecture shapes neural computations during active behavior.

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Fast-conducting mechanonociceptors uniquely engage reflexive and affective pain circuitry to drive protective responses

Nociceptors are neurons mediating acute pain in healthy animals. Lezgiyeva et al. conduct a screen of sensory neuron types in the mouse paw skin and identify two fast-conducting nociceptors that are distinct in their physiological, morphological, synaptic, and functional properties from slow-conducting nociceptors and other somatosensory neuron types.

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Sparse component analysis: A method that uncovers separable computations within neural population activity

Zimnik et al. provide a new, interpretable, unsupervised dimensionality approach for neural population activity. Their approach, sparse component analysis (SCA), reveals the latent factors corresponding to distinct computations without users needing to provide behavioral labels or known timing of computations.

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TGF-β1-induced endothelial transcytosis drives blood-brain barrier leakage during aging

Fang et al. show that BBB leakage during aging begins in midlife and results from increased endothelial caveolar transcytosis rather than tight junction disruption. Elevated TGF-β1 suppresses Mfsd2a via Tgfbr2-Smad2/4 signaling, promoting endothelial transcytosis. Genetic or pharmacological inhibition of this pathway improves BBB integrity and neurological function in aged mice.

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Spatiomolecular mapping reveals anatomical organization of heterogeneous cell types in the human nucleus accumbens

The nucleus accumbens (NAc) is implicated in several neuropsychiatric disorders. Ravichandran, Bach, et al. integrate single-nucleus and spatial transcriptomics in the human NAc, revealing continuous spatial organization of medium spiny neuron (MSN) subtypes and OPRM1+ D1 islands, establishing a spatiomolecular framework for linking molecular identity, anatomical organization, and neuropsychiatric risk.

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Dynamic coordination and segregation mechanisms in higher cortex for parallel task processing

Wang et al. show that mice can perform multiple tasks in parallel by dynamically allocating brain resources. Initially, task-shared and non-shared neurons in M2 mediate resource competition and coordination. With training, M2 recruits specialized neurons and separates task representations, illustrating how the higher cortex balances flexibility with specialization in complex behaviors.

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Composing trajectories for rapid inference of navigational goals

AbdelRahman et al. develop a learning algorithm that captures structured exploration and rapid navigational learning in animals. The algorithm combines path integration with vector computations to flexibly compose navigational trajectories that explain the speed and structure of learning as mice infer hidden targets, avoid obstacles, and adapt to context switches.

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