eLife: latest articles by subject

Starvation transforms signal encoding in C. elegans thermoresponsive neurons and suppresses heat avoidance via bidirectional glutamatergic and peptidergic signaling

dominique.glauser@unifr.ch (Dominique A Glauser) — Fri, 09 Oct 2026 00:00:00 +0000

Animals must continuously adapt their behavioral outputs in response to changes in internal state, including nutritional state. Here, we show that starvation induces a profound and progressive suppression of thermonociceptive behavior in Caenorhabditis elegans. During early food deprivation (1 hr without food), the thermoresponsive AWC sensory neurons mediate robust heat-evoked reversals over a broad range of stimulus intensities via glutamate and FLP-6 neuropeptide signaling, each covering distinct heat intensity ranges. After 6 hr of food deprivation (prolonged starvation), heat-evoked reversal responses are nearly abolished, independently of external food odor cues. Starvation shifts the distribution of AWC heat-evoked calcium response polarity, from mostly excitatory responses to a heterogeneous pattern combining excitatory and inhibitory activities. This switch relies on ASI neurons, proposed to sense internal state. INS-32 and NLP-18 neuropeptide signals from ASI switch from reversal-promoting to reversal-inhibiting effects. In addition, reversal-promoting glutamatergic transmission by AWC is antagonized by glutamatergic transmission from non-AWC neurons that suppress FLP-6-dependent reversals. Our findings define a circuit logic by which gating of nociceptive responsiveness by internal nutritional state is linked to dynamic modulation of sensory neuron activity patterns and orchestrated by bidirectional glutamatergic and neuropeptidergic signals.

Circadian photoreceptor CRYPTOCHROME promotes wakefulness under short winter-like days via a GABAergic circuitry

zhangluoying@hust.edu.cn (Chang Su) — Thu, 08 Oct 2026 00:00:00 +0000

A cardinal symptom of seasonal affective disorder (SAD, also known as winter depression) is hypersomnolence, while the cause of this ‘winter sleepiness’ is not known. Here, we found that lack of the circadian photoreceptor cryptochrome (cry) leads to increased sleep under short winter-like days in the fruit fly Drosophila, reminiscent of the hypersomnolence in SAD. CRY functions in neurons that synthesize the major inhibitory neurotransmitter GABA, including the small ventral lateral neurons, which are known to be circadian pacemakers, and downregulates the GABAergic tone. This, in turn, leads to increased neural activity of the wake-promoting large ventral lateral neurons, a subset of circadian neurons that are inhibited by GABA-A receptors. CRY protein is known to be degraded by light, thus rendering CRY to be functional within this GABAergic circuitry to enhance wakefulness only under short-day length. Taken together, we demonstrate a mechanism that specifically regulates wakefulness under short winter-like days, which may provide insights regarding the winter sleepiness in SAD.

Mapping human visual contrast sensitivity and vision loss across the visual field with model-based fMRI

hugo.chow-wing-bom.15@ucl.ac.uk (Frederic Dick) — Fri, 02 Oct 2026 00:00:00 +0000

Peripheral vision is crucial for daily activities and quality of life, yet traditional measures of visual function like visual acuity primarily assess central vision. Visual field tests can evaluate peripheral vision but require extended focus and precise fixation, often challenging for patients with severe sight loss. Functional MRI (fMRI) with population receptive field (pRF) mapping offers a non-invasive way to map scotomas but relies on single contrast levels and accurate fixation. We developed an fMRI-based approach to measure contrast sensitivity across the visual field without requiring precise fixation. Combining large-field stimulation with varying spatial frequencies and contrast levels, and either pRF mapping or a structure-based retinotopic atlas, we modeled contrast sensitivity in the primary visual cortex (V1) over a large (40 deg) expanse of the visual field. In seven normally sighted participants, we characterized differences in V1 sensitivity across eccentricities and visual quadrants, finding reliable and reproducible patterns at individual and session levels. To test robustness to fixation variability, we investigated how varying levels of eye movement affected V1 sensitivity patterns in two participants: cortical sensitivity patterns were largely preserved despite eye movements, particularly at low spatial frequencies. This suggests our approach can accommodate several degrees of fixation instability, making it suitable for populations with unstable or biased fixation for whom visual field maps are harder to acquire behaviorally (e.g., patients with dense central scotoma or strabismus). Additionally, our method effectively visualized simulated and disease-linked sensitivity loss at the cortical level. Crucially, these results could be largely recovered using the structure-based retinotopic atlas, eliminating the need for pRF mapping and precise fixation, although with reduced sensitivity. This approach, integrating large-field stimulation with a retinotopic atlas, offers a promising tool for monitoring vision loss and recovery across a range of visual impairments, addressing a significant challenge in current clinical assessments.

Negative affect influences the computations underlying food choice in bulimia nervosa

laura.berner@mssm.edu (Blair RK Shevlin) — Thu, 01 Oct 2026 00:00:00 +0000

Individuals often consume tasty, calorically dense foods in response to negative emotions, a phenomenon exemplified by notions of ‘stress eating’ and ‘comfort food’. While this link between food and mood can become pathological in binge eating, the decision-making processes underlying this link are poorly understood. Here, we investigated the impact of acute increases in negative affect on when and how strongly the perceived tastiness and healthiness of foods influence food choices in healthy adults and individuals with bulimia nervosa (BN), an eating disorder characterized by cycles of over- and under-consumption of food. In a randomized crossover design, 25 women with BN and 21 healthy controls completed two sessions where they received either a neutral or negative affect induction and then completed a food choice task. Using a time-varying diffusion decision model, we assessed how negative affect influences food choice dynamics for high- and low-fat foods. In the neutral affect condition, individuals with BN considered tastiness relative to healthiness of high-fat foods sooner than healthy controls but maintained a restrictive food choice policy by reducing the weight on tastiness. After a negative affect induction, both groups showed a stronger bias toward considering tastiness before healthiness, but this bias was exaggerated in individuals with BN. This affect-induced bias for high-fat foods predicted more frequent subjective binge episodes over 3 months. These results provide insights into how negative emotion influences food choices and may explain why binge eating in BN is more likely during high negative affect, while dietary restriction is more likely during low negative affect.

A cortical–hippocampal communication undergoes rebalancing after new learning

dw657@drexel.edu (Arron F Hall) — Thu, 01 Oct 2026 00:00:00 +0000

The brain’s ability to consolidate a wide range of memories while maintaining their distinctiveness across experiences remains poorly understood. Sharp-wave ripples, neural oscillations that occur predominantly within CA1 of the hippocampus during immobility and sleep, have been shown to play a critical role in the consolidation process. More recently, evidence has uncovered functional heterogeneity of pyramidal neurons within distinct sublayers of CA1 that display unique properties during ripples, potentially contributing to memory specificity. Despite this, it remains unclear exactly how ripples shift the activity of CA1 neuronal populations to accommodate the consolidation of specific memories and how sublayer differences manifest. Here, we studied interactions between the anterior cingulate cortex (ACC) and CA1 neurons during ripples and discovered a reorganization of their communication following learning. Specifically, using a generalized linear model decoder, we demonstrated the pre-existence of ACC-to-CA1 communication, which is weakened during post-training sleep following learning, suggesting that ACC activity reallocates the contribution of CA1 neurons during memory formation. Interestingly, the reorganization appeared unique for a subset of CA1 superficial (CA1sup) neurons that were task inactive, whereas communication between the ACC and CA1deep neurons remained largely stable across pre- and post-training sleep. Consistent with this sublayer-selective reorganization, we found that optogenetic stimulations of the ACC preferentially suppressed CA1sup neurons while activating a unique subset of CA1 interneurons. Overall, these findings highlight an important role of the ACC in rebalancing CA1 neuronal populations’ contribution in learning and memory consolidation.

Learning is a fundamental source of individuality

amjaksic@gmail.com (Alireza Modirshanechi) — Wed, 30 Sep 2026 00:00:00 +0000

Learning and memory are essential components of our individuality. While it is established that behaviour can vary across genetically identical individuals, it remains unknown how much of this variation stems from momentary experience during learning compared to genetics and its past interactions with the environment. To address this, we measured behaviour in thousands of flies from 90 genetic backgrounds while they performed tasks in conditions that either did or did not require learning. Flies that were genetically identical, raised under the same conditions, and tested simultaneously in the same environment persistently modified the extent of expressed individuality when they could learn. This learning-induced residual expression of individuality and its dynamics were subdued or absent in innate, learning-independent behaviours. We could quantify and then recreate this phenomenon in computer simulations. The emergence of in silico behaviour individuality was most consistent with the individuality of real flies once we enabled reinforced learning in simulated agents. Moreover, we showed that minor differences in initial conditions of the experiment can exacerbate the expression of individuality within a genotype in a learning-dependent manner. Our results establish that besides the classical genotype × environment (G × E) interactions shared between individuals in the past, learning from individual momentary experience further extends the expression of individuality.

Biophysically inspired mean-field model of neuronal populations driven by ion-exchange mechanisms

giovanni.rabuffo@upf.edu (Abhirup Bandyopadhyay) — Wed, 30 Sep 2026 00:00:00 +0000

Whole-brain simulations are a valuable tool for gaining insight into the multiscale processes that regulate brain activity. Due to the complexity of the brain, it is impractical to include all microscopic details in a simulation. Hence, researchers often simulate the brain as a network of coupled neural masses, each described by a mean-field model. These models capture the essential features of neuronal populations while approximating most biophysical details. However, it may be important to include certain parameters that significantly impact brain function. The concentration of ions in the extracellular space is one key factor to consider, as its fluctuations can be associated with healthy and pathological brain states. In this paper, we develop a new mean-field model of a population of Hodgkin–Huxley-type neurons, retaining a microscopic perspective on the ion-exchange mechanisms driving neuronal activity. This allows us to maintain biophysical interpretability while bridging the gap between micro- and macro-scale mechanisms. Our model is able to reproduce a wide range of activity patterns, also observed in large neural network simulations. Specifically, slow-changing ion concentrations modulate the fast neuroelectric activity, a feature of our model that we validated through in vitro experiments. By studying how changes in extracellular ionic conditions can affect whole-brain dynamics, this model serves as a foundation to measure biomarkers of pathological activity and provide potential therapeutic targets in cases of brain dysfunctions like epilepsy.

PKD2L1 channels segregated to the apical compartment are the dual-mode pH sensor in cerebrospinal fluid-contacting neurons

federico.trigo@pedeciba.edu.uy (Daniel Prieto) — Tue, 29 Sep 2026 00:00:00 +0000

Cerebrospinal fluid-contacting neurons (CSFcNs) are GABAergic cells that surround the central canal (cc) of the spinal cord. Their soma is located sub-ependymally and they have a dendritic-like process that ends as a bulb (the so-called ‘apical process’; ApPr) inside the cc. It remains unclear how this unique anatomical organization, with the soma and the ApPr located in different extracellular environments, relates to their function as a multimodal sensor of cerebrospinal fluid (CSF) composition. One of the main physiological features of CSFcNs is a prominent spontaneous electrical activity mediated by PKD2L1 channels, a non-selective cation channel of the TRP family. PKD2L1 channels have a high single-channel conductance (around 200 pS) and can be modulated by protons and mechanical forces. In this work, we investigate PKD2L1 channel sensitivity to pH and its effects on CSFcNs excitability. We demonstrate that PKD2L1 spontaneous activity generates not only phasic inward currents, but also a sustained current, both of which are modulated bidirectionally by pH with a high sensitivity around physiological values. By combining electrophysiology (direct recordings from intact and isolated ApPrs) with optical methods (laser photolysis of protons), we further show that functional PKD2L1 channels are specifically localized in the ApPr. The spatial segregation of PKD2L1 channels, along with their biophysical properties (high single-channel conductance and pH sensitivity) and the ApPr’s unique membrane properties (very high input resistance), renders CSFcN excitability exquisitely sensitive to PKD2L1 modulation. Altogether, our findings illustrate how the ApPr’s properties are finely tuned to support its sensory role.

Dissociable roles of reward prediction error in the contrasting mood dynamics of depression and anxiety

yunzhe.liu@bnu.edu.cn (André Aleman) — Tue, 29 Sep 2026 00:00:00 +0000

Mood fluctuations, central to human experience, are profoundly influenced by reward prediction errors (RPE). Although depression and anxiety traditionally exhibit contrasting mood fluctuations, their interrelated nature has made it challenging to pinpoint their specific roles in RPE-induced mood variations. In this study, we employed a computational model of momentary mood within a gambling task, involving 2043 participants across five experiments. Participants also completed a battery of questionnaires designed to allow us to dissociate anxiety- and depression-specific traits through bifactor modeling. Results showed that depression was associated with dampened mood fluctuations due to mood hyposensitivity to RPE. Importantly, this pattern was also found in patients with affective disorders. In contrast, anxiety correlated with heightened mood fluctuations stemming from mood hypersensitivity to RPE in non-clinical participants. Moreover, the shared depression/anxiety component was linked to lower affective baseline and greater risk aversion. Collectively, our results uncover computational dissociation of depression vs. anxiety using RPE-based mood modeling and present multi-dimensional computational signatures for these symptoms, with clinical relevance for management of mood disorders.

Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons

daniel.beaudet@mcgill.ca (Adam G Hendricks) — Mon, 28 Sep 2026 00:00:00 +0000

Tau, a neuronal microtubule-associated protein (MAP), organizes the axonal cytoskeleton, and regulates intracellular transport. Tau hyperphosphorylation is linked to neurodegeneration in tauopathies, including Alzheimer’s disease. Tau binds microtubules cooperatively to form cohesive envelopes, which are thought to control access to the microtubule lattice and regulate the activity of motor proteins and other MAPs. However, how disease-related perturbations affect tau dynamics and its function as a selective barrier to intracellular transport remains unclear. Using tau phospho-variants in vitro and in live neurons, we show that tau hyperphosphorylation disrupts cooperative microtubule binding and dysregulates lysosome transport. Hyperphosphorylated tau does not form envelopes, distributes more uniformly along the axon, and dissociates faster from microtubules. Tau weakly inhibits KIF5C motility, but strongly inhibits KIF1A. Hyperphosphorylation reduces KIF5C inhibition but increases KIF1A inhibition by decreasing processivity and accelerating detachment. Consistent with these effects, hyperphosphorylated tau alters lysosome transport in neurons. While phospho-resistant tau inhibits processive lysosome motility, hyperphosphorylated tau weakens tau-mediated regulation of lysosome transport, mimicking tau knockout neurons that exhibit enhanced processivity. Altogether, these findings show that hyperphosphorylation disrupts tau envelopes and impairs lysosome trafficking, likely contributing to early defects in degradative pathways that drive neurodegeneration.

Selective lifelong suppression of an odor processing channel in response to critical period experience

htb@case.edu (Abigail J Wilkov) — Mon, 28 Sep 2026 00:00:00 +0000

Sensory circuits undergo experience-dependent plasticity during early-life critical periods, attuning the nervous system to levels of key environmental stimuli. During a critical period in the Drosophila olfactory system, we found that exposure to ethyl butyrate (EB) induces glial phagocytosis of odorant receptor Or42a-positive olfactory sensory neuron (OSN) axon terminals which terminate in the VM7 glomerulus (Leier et al., 2025). Here, we extend these findings by establishing functional significance and circuit selectivity in this critical period paradigm. First, using a combination of two-photon Ca²⁺ imaging and the genetically-encoded voltage indicator ASAP5, we find that Or42a OSN odor-evoked responses are permanently suppressed in animals with critical period odor exposure. Thus, critical period odor exposure results in long-term changes to odor sensitivity in Or42a OSNs. Second, to establish the selectivity of glial pruning for Or42a axon terminals, we examined projection neurons (PNs) postsynaptic to Or42a OSNs as well as a second population of highly EB-responsive OSNs, called Or43b OSNs. We find that (1) within VM7, glial pruning is selective for Or42a terminals, and (2) while Or43b OSNs appear modestly pruned, they maintain their sensitivity to EB. To elucidate this difference, we turned to the Drosophila connectome. We identify striking differences in the scale of inhibitory connectivity to Or42a and Or43b OSNs, although disruption of GABA A receptor expression in both OSN types enhanced pruning. This study expands our understanding of this critical period plasticity paradigm by demonstrating lifelong suppression of pruned Or42a OSNs and establishing its specificity within and between sensory circuits.

Retinal curl as a functional signal for heading estimation beyond the focus of expansion

j.lopezmoliner@ub.edu (Joan López-Moliner) — Fri, 25 Sep 2026 00:00:00 +0000

Prevailing models aiming at explaining heading assume that humans need to recover the Focus of Expansion (FoE) while accounting for eye-movement-induced rotation. We propose an alternative: the visual system utilizes mean retinal curl from fixations as a surrogate signal for heading, rendering the explicit recovery of the FoE unnecessary. Stationary participants viewed simulated walking paths on a large screen while fixating on points on the projected ground texture at varying eccentricities – a natural behavior inducing sustained retinal curl. Participants continuously reported perceived heading in 3D scene coordinates. To isolate the role of retinal curl, we employed a real-time manipulation that kept translational flow constant while the foveal curl component was either unaltered, canceled, or over-canceled. Under natural conditions (unaltered), participants exhibited systematic heading biases opposite the direction of gaze. Crucially, these biases vanished when we canceled the expected curl and flipped when we over-canceled it, identifying retinal curl as the specific driver of perceptual bias. We modeled these results using a simple feedback controller and a ring-attractor neural network featuring gaze-contingent inhibition and a ‘straight-ahead’ prior. These findings suggest that the brain exploits the geometry of gaze stabilization to simplify navigation, treating retinal curl as a functional signal rather than noise to be filtered.

Opening the black box toward a modular approach to spike sorting

samuel.garcia@cnrs.fr (Alessio Paolo Buccino) — Fri, 25 Sep 2026 00:00:00 +0000

Spike sorting is an algorithmic process that extracts the activity of individual neurons from extracellular electrophysiology recordings. With the ballooning use of high-density probes, such as Neuropixels, this essential processing step is increasingly becoming time-consuming and computationally expensive. Although many software tools have been proposed to address spike sorting, they are usually constructed and benchmarked as monolithic ‘black boxes’, making it difficult to factor out the effects of individual algorithmic steps on the final outcome, especially when varying datasets and parameters. To address this issue, we developed a modular and common framework to develop, benchmark, and assemble the key computational steps that are used in state-of-the-art spike sorting algorithms. Relying on fast and efficient ground truth generation of biophysically plausible recordings, we show that we are able to individually benchmark and precisely quantify the performance of different steps in a spike sorting pipeline (i.e. peak detection, feature extraction, clustering, and template matching). We then leverage these results to create a modular, component-based spike sorter that can outperform Kilosort4 on dense and large simulated recordings, and produce similar quantitative results on real data. In addition, we find that the major bottleneck of all modern spike sorting pipelines is in the physical motion of probes, regardless of the drift-correction strategy. The component-based spike sorting framework presented here has the potential to foster community engagement in the field by lowering the barrier to contributions and providing a flexible yet powerful framework to construct end-to-end spike sorting solutions.

Developmental synchrony of retinal waves, apoptosis, and angiogenesis in postnatal retina

michael.savage2@newcastle.ac.uk (Cori Bertram) — Thu, 24 Sep 2026 00:00:00 +0000

Postnatal mouse retinal development is a multi-faceted process involving the coordinated interaction of spontaneous neural activity as retinal waves, vascular plexus growth, and programmed cell death. While these processes are known to interact at a coarse scale, the specific mechanisms integrating them have remained elusive. Using large-scale, wide-field calcium imaging, high-density multielectrode array recordings, single-cell RNA sequencing, and immunohistochemistry, we characterise a tightly aligned centrifugal expansion pattern during retinal development. This pattern is common to stage II retinal wave onsets, vascular development, Heme oxygenase-1 (Hmox1) expressing microglia, apoptotic cell markers, and a novel set of auto-fluorescent cluster complexes (ACCs) identified in this study. Apoptotic cells are known to upregulate functional pannexin-1 (PANX-1) hemichannels. These voltage-gated channels release purinergic molecules which act as ‘eat me’ signals to neighbouring microglia. PANX-1 hemichannel blockade with the drug probenecid results in a profound decrease in spontaneous wave frequency and strength, suggesting that retinal waves are indeed triggered by these apoptotic cells. Taken together, our observations suggest that spontaneous waves are initially triggered in hotspots by hyperactive apoptotic retinal ganglion cells (RGCs) in unvascularised retinal areas. These apoptotic cells release purinergic molecules via PANX-1 hemichannels, leading to wave generation. This hyperactivity leads to local hypoxic conditions, which, coupled with high extracellular ATP concentrations, promotes angiogenesis. Once blood vessels reach a particular hotspot, ATP release activates Hmox1-positive microglia, which engulf the dying RGCs, creating the auto-fluorescent clusters. Herein, we present a unified mechanism linking causally linking early neural activity, programmed cell death, and angiogenesis in the mammalian retina.

Real-time closed-loop feedback system for mouse mesoscale cortical signal and movement control

thmurphy@mail.ubc.ca (Pankaj Kumar Gupta) — Thu, 24 Sep 2026 00:00:00 +0000

Increasingly, experiments designed to provide practical perturbations to circuits or behavior are required for hypothesis testing in various disciplines ranging from motor learning to recovery after injury. We present the implementation and efficacy of an open-source closed-loop neurofeedback (CLNF) and closed-loop movement feedback (CLMF) system. In CLNF, we measure mm-scale cortical mesoscale activity with GCaMP6s and provide graded auditory feedback (within ~63 ms) based on changes in dorsal-cortical activation within regions of interest (ROIs) and with a specified rule. Single or dual ROIs (ROI1, ROI2) on the dorsal cortical map were selected as targets. Both motor and sensory regions supported closed-loop training in male and female mice. Mice modulated activity in rule-specific target cortical ROIs to get increasing rewards over days (repeated-measures ANOVA [RM-ANOVA], p=2.83e-5) and adapted to changes in ROI rules (RM-ANOVA, p=8.3e-10, Table 4 for different rule changes). In CLMF, feedback (within ~67 ms) was based on tracking a specified body movement, and rewards were generated when the behavior reached a threshold. For movement training, the group that received graded auditory feedback performed significantly better (RM-ANOVA, p=9.6e-7) than a control group (RM-ANOVA, p=0.49) within 4 training days. Additionally, mice can learn a change in task rule from left forelimb to right forelimb within a day, after a brief performance drop on day 5. Offline analysis of neural data and behavioral tracking revealed changes in the overall distribution of Ca²⁺ fluorescence values in CLNF and body-part speed values in CLMF experiments. Increased CLMF performance was accompanied by a decrease in task latency and cortical ΔF/F₀ amplitude during the task, indicating lower cortical activation as the task gets more familiar.

Region-specific mechanosensation modulates Drosophila postural control behaviour

c.alonso@sussex.ac.uk (Claudio R Alonso) — Wed, 23 Sep 2026 00:00:00 +0000

The relation between regional morphological features derived from the bilaterian body plan and the behaviours necessary to extract utility from such structures is not well understood. Here, we use the Drosophila larva to investigate this ‘form-function’ problem focusing on the mapping of the regional stimuli that trigger an adaptive and evolutionarily conserved behaviour termed self-righting: a postural control system that allows the animal to restore its natural position if turned upside-down. Through the development of new methodologies that allow regionally restricted mechanical stimulation and zonal-specific neuronal optogenetics, we find that multidendritic sensory neuron inhibition in anterior areas (thoracic/anterior abdominal) has a profound effect on self-righting performance, while inhibition of posterior sensory elements (mid and posterior abdomen) produces no effects. To gain insight into how regional neuronal inhibition affects the different subcomponents of the self-righting sequence we applied a deep neural network tracking method which revealed that reduction of neural activity in anterior sensory neurons primarily increases head casting behaviour and that this, in turn, is strongly correlated with abnormally long self-righting times. Furthermore, to explore the mechanistic bases of our behavioural observations, we considered the hypothesis that the Hox genes – well known for their roles in axial developmental patterning – might play a role in the functional specification of multidendritic sensory neurons along the body axis. Molecular expression analysis of FACS-sorted neural populations, fluorescent immunolabelling and neuron-specific knockdown experiments demonstrate that normal sensory neuron expression of the Hox genes Antennapedia and Abdominal-b is necessary for self-righting in the Drosophila larva. Altogether, our work shows that region-specific mechanosensory processes mediated by multidendritic sensory neurons and instructed via Hox gene inputs are essential for self-righting, providing a link between regional structural features and an adaptive and widely evolutionarily conserved postural control behaviour.

Brief disruption of activity in a subset of dopaminergic neurons during consolidation impairs long-term memory by fragmenting sleep

szmchlyt@hbmu.edu.cn (Chang Liu) — Wed, 23 Sep 2026 00:00:00 +0000

Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, using both male and female flies, Drosophila melanogaster, we show that, during the first few hours of memory consolidation, disruption of basal activity of a small subset of protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition of the two dorsal posterior medial (DPM) neurons, impairs 24 hr LTM. Interestingly, these brief changes in activity using female flies result in sleep loss and fragmentation, especially at night. Importantly, pharmacological rescue of sleep after manipulation restores LTM. A specific subset of PAM-DANs (PAM-α1) that synapse onto DPM neurons specify the microcircuit that links sleep and memory. MBON-α1 also contributes to the integration of sleep and memory by acting as an additional parallel circuit. PAM-DANs, including PAM-α1, form functional synapses onto DPM mainly via two dopamine receptor subtypes. Dop1R1 primarily mediates the link between sleep and memory. This PAM-α1 to DPM microcircuit exhibits a synchronized, transient, post-training change in activity during the critical memory consolidation window, suggesting an effect of this microcircuit on maintaining the sleep necessary for LTM consolidation. Our results provide a new molecular and circuit basis for the complex relationship between sleep and memory.

Machine learning of honey bee olfactory behavior identifies repellent odorants in free-flying bees in the field

anand.ray@ucr.edu (Anandasankar Ray) — Wed, 23 Sep 2026 00:00:00 +0000

Preventing beneficial insects like honey bees (Apis mellifera) from contacting pesticides on crops using odorants could counter current pollinator declines. However, the discovery of behaviorally aversive odorants is impeded by the complexity of the honey bee olfactory system where >170 olfactory receptors detect volatiles and generate valence. To solve this systems-level challenge, we generated a machine-learning model to predict aversive valence from chemical structure using published olfactory behavior data in honey bees. We refine the predictive model by generating species-level behavioral data for honey bees and Drosophila on an initial set of novel predicted repellents. The improved second computational model was then used to screen a chemical space of >50 million compounds and identify >130 repellent candidates. Behavioral validation using honey bees in the laboratory shows a high predictive success. Additional testing of the top seven candidates using freely foraging honey bees in a field assay confirmed strong repellency, thus predicting a high probability to repel foraging bees from pesticide-treated crops. Machine learning, with iterative testing and modeling, therefore provides a powerful approach for rational discovery of aversive volatiles for control of insects for which limited data is available.

Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity

daan@mbg.au.dk (Asad Jan) — Tue, 22 Sep 2026 00:00:00 +0000

Missense variants in the O-GlcNAc transferase (OGT) gene have recently been shown to segregate with a syndromic form of intellectual disability (OGT-ID), underscoring the importance of protein O-GlcNAcylation in brain function. However, the underlying pathophysiological mechanisms linking ID to potential OGT malfunction—whether developmental, neurophysiological, or both – remain unclear. Here, we present comprehensive analyses encompassing behaviour and brain architecture of a rodent model carrying the pathogenic C921Y OGT-ID variant. These mice show a range of behavioural deficits, including hyperactivity, impulsivity, and associative learning phenotypes. Structural studies, using micro-computed tomography and magnetic resonance imaging, revealed reduced skull size, microcephaly, reduced cortical thickness and hypoplastic corpus callosum. Detailed histological analyses revealed dysplastic changes in the neocortex, predominantly affecting the superficial layers of the cingulate cortex. Mechanistically, quantitative proteomic analyses revealed O-GlcNAc dyshomeostasis associated with distinct perturbed molecular pathways involved in brain development. Taken together, these data reveal neurodevelopmental defects associated with O-GlcNAc dyshomeostasis and provide a platform for dissecting mechanism and treatments of OGT-ID.

Retinotopic coding organizes the interaction between internally and externally oriented brain networks

adamdanielsteel@gmail.com (Adam Steel) — Tue, 22 Sep 2026 00:00:00 +0000

The human brain seamlessly integrates internally generated thoughts with incoming sensory information, yet the large-scale networks that support these functions – the internal default network (DN) and external dorsal attention network (dATN) – are traditionally viewed as functionally independent. This raises a crucial question: how does the brain integrate information across these seemingly noninteractive systems? Here, using densely sampled 7T fMRI, individualized resting-state parcellations, and voxel-wise population-receptive-field mapping, we show that these internal/external networks are more interlocked than previously thought. Spontaneous DN and dATN activity during rest is uncorrelated at the network level. However, voxel-scale functional coupling across networks is shaped by the latent visual field preferences of individual voxels in each network, as measured during independent retinotopic mapping. Voxels that share visual field preferences exhibit stronger spontaneous coupling than those with divergent preferences. These retinotopically specific interactions are bivalent: DN voxels with negative (suppressive) visual response amplitudes are anticorrelated with matched (positive) dATN voxels, while those DN voxels with positive response amplitudes are positively correlated. Thus, distinct subpopulations of visually tuned DN voxels participate in spatially specific interactions with the dATN. Further, retinotopic coding is intrinsic to the DN, persisting even during periods when the DN signal is elevated. These findings reveal a latent, voxel-level architecture of retinotopically grounded interactions between the DN and dATN. Taken together, our results suggest that retinotopic coding underpins the dynamic coordination of perception and thought in the human brain.

Enhanced tactile coding in rat neocortex under darkness

nobuyoshi@matsumoto.ac (Kotaro Yamashiro) — Mon, 21 Sep 2026 00:00:00 +0000

Sensory systems are known for their adaptability, responding dynamically to changes in environmental conditions. A key example of this adaptability is the enhancement of tactile perception in the absence of visual input. Despite behavioral studies showing visual deprivation can improve tactile discrimination, the underlying neural mechanisms, particularly how tactile neural representations are reorganized during visual deprivation, remain unclear. In this study, we explore how the absence of visual input alters tactile neural encoding in the rat primary somatosensory cortex (S1). Rats were trained on a custom-designed treadmill with distinct tactile textures (rough and smooth), and local field potentials (LFPs) were recorded from S1 under light and dark conditions. Machine learning techniques, specifically a convolutional neural network, were used to decode the high-dimensional LFP signals. We found that the neural representations of tactile stimuli became more distinct in the dark, indicating a reorganization of sensory processing in S1 when visual input was removed. Notably, conventional amplitude-based analyses failed to capture these changes, highlighting the power of deep learning in uncovering subtle neural patterns. These findings offer new insights into how the brain rapidly adapts tactile processing in response to the loss of visual input, with implications for multisensory integration.

Infants at high and low likelihood for autism show different EEG developmental trajectories in speech tracking and statistical learning

michel.godel@unige.ch (Ana Fló) — Mon, 21 Sep 2026 00:00:00 +0000

Delayed onset of canonical babbling and first words is often reported in infants later diagnosed with autism spectrum disorder. Identifying the neural mechanisms underlying language acquisition in autism is therefore critical to inform early diagnosis, prognosis, and intervention strategies. In this study, we investigated two speech processing mechanisms previously identified as atypical in children and adults with autism: the neural ability to track syllables, and statistical learning, the capacity to detect speech regularities beneath surface variability. We recorded 83 longitudinal high-density electroencephalograms from 44 infants (2.5–22.6 months) at high (HL) and low (LL) likelihood for autism and assessed their verbal outcomes at 20 months. Neural entrainment was measured at syllable and word frequencies during exposure to a multi-speaker stream of concatenated tri-syllabic words, followed by a word recognition test using evoked response potential (ERP) recording. Our findings revealed reduced tracking abilities at the syllabic level in HL infants, a measure that correlated with verbal outcomes. While HL infants did not exhibit deficits in statistical learning itself, they displayed reduced novelty orientation during the word recognition test, indicated by a reduced late ERP. By contrast, multi-talker variability temporarily disrupted word segmentation around 12 months in LL infants, but not in HL infants, potentially reflecting decreased sensitivity to human voices variability in the HL group. These results emphasize the importance of longitudinal protocols employing online, implicit measures to track the hierarchical stages of speech processing in both HL and LL infants.

An applicable and efficient retrograde monosynaptic circuit mapping tool for larval zebrafish

forestdu@ion.ac.cn (Fu-Qiang Xu) — Fri, 18 Sep 2026 00:00:00 +0000

The larval zebrafish is a vertebrate model for in vivo monitoring and manipulation of whole-brain neuronal activity. Tracing its neural circuits remains challenging. Here, we report an applicable methodology tailored for larval zebrafish to achieve efficient retrograde trans-monosynaptic tracing from genetically defined neurons via EnvA-pseudotyped glycoprotein-deleted rabies viruses. By combinatorially optimizing multiple factors involved, we identified the CVS strain trans-complemented with advanced expression of N2cG at 36 °C as the optimal combination. It yielded a tracing efficiency of up to 20 inputs per starter cell. Its low cytotoxicity enabled the viable labeling and calcium imaging of infected neurons 10 days post-infection, spanning larval ages commonly used for functional examination. Cre-dependent labeling was further developed to enable cell-type-specific input tracing and circuit reconstruction. We mapped cerebellar circuits and uncovered the ipsilateral preference and subtype specificity of granule cell-to-Purkinje cell connections. Our method offers an efficient way for tracing neural circuits in larval zebrafish.

Larger language models better align with neural representations of natural language

kw1166@princeton.edu (Adeen Flinker) — Wed, 16 Sep 2026 00:00:00 +0000

Recent research has used large language models (LLMs) to study the neural basis of naturalistic language processing in the human brain. LLMs have rapidly grown in complexity, leading to improved language processing capabilities. Here, we utilized several families of transformer-based LLMs to investigate the relationship between model size and their ability to capture linguistic information in the human brain. Crucially, a subset of LLMs were trained on a fixed training set, enabling us to dissociate model size from architecture and training set size. We used electrocorticography (ECoG) to measure neural activity in epilepsy patients while they listened to a 30 min naturalistic audio story. We fit electrode-wise encoding models using contextual embeddings extracted from each hidden layer of the LLMs to predict word-level neural signals. In line with prior work, we found that larger LLMs better capture the structure of natural language and better predict neural activity. We also found a logarithmic relationship where the encoding performance peaks in relatively earlier layers as model size increases. We also observed variations in the best-performing layer across different brain regions, corresponding to an organized language processing hierarchy.

Modulating task-outcome value to mitigate real-world procrastination via noninvasive brain stimulation

chenzhiyi@tmmu.edu.cn (Bernhard Hommel) — Wed, 16 Sep 2026 00:00:00 +0000

Procrastination is a prevalent behavioral problem associated with individual health and societal productivity. A leading model posits that procrastination reflects an imbalance between task aversiveness and the pursuit of positive task outcomes, yet this theoretical framework has neither been validated in real-world settings nor effectively applied to guide interventions. To address this gap, we conducted a double-blind, randomized, sham-controlled trial. Adults with chronic procrastination received seven sessions of high-definition transcranial direct current stimulation (HD-tDCS) to the left dorsolateral prefrontal cortex (DLPFC). Using the intensive experience sampling method, we assessed the effect of anodal HD-tDCS on real-world procrastination behavior at offline after-effect (2-day interval) and long-term after-effect (6-month follow-up). This neuromodulation produced a lasting reduction in real-world procrastination, with effects sustained at a 6-month follow-up. The mediation analysis indicated that increased outcome value, but not reduced task aversiveness, statistically accounted for variation in behavioral improvement. These findings are consistent with the hypothesis that enhancing DLPFC function may reduce procrastination by selectively amplifying the valuation of future rewards, not by reducing negative feelings about the task, which also suggests a targeted, theory-informed avenue for future behavioral interventions.

Correction: Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation

Tue, 15 Sep 2026 00:00:00 +0000

Rank- and threat-dependent social modulation of innate defensive behaviors

lingyunli@ccmu.edu.cn (Jun Zhang) — Tue, 15 Sep 2026 00:00:00 +0000

Fear and defense are among the most fundamental survival behaviors and are profoundly influenced by the social environment in group-living animals. However, it remains poorly understood how social context—and particularly dominance hierarchy, a defining feature of many social species—modulates defensive strategies under naturalistic conditions. To address this question, we investigated the social modulation of innate fear in mice exposed to two ethologically relevant threats: a transient visual looming stimulus and a sustained predatory threat posed by a live rat. We found that social presence alleviated threat-induced stress and modulated defensive behaviors in a rank- and threat-specific manner. During looming exposure, it reduced immediate defensive responses and alleviated post-looming anxiety, with dominants deriving greater benefit. During rat exposure, it promoted a shift from passive to active defense, again most prominently in dominants. These behavioral changes were accompanied by reorganization of transitions between defensive states, indicating that dominance hierarchy shapes both the expression and temporal organization of innate defensive behaviors. Conversely, threat exposure strengthened social engagement, with dominant mice exhibiting more proactive social behaviors and subordinate mice responding more readily to dominant social initiations. Together, these findings demonstrate how dominance hierarchy modulates defensive responses to distinct naturalistic threats and, in turn, how threat experience shapes social behavior, providing a behavioral framework for probing the neural basis of socially modulated innate fear.

PRRT2 as an auxiliary regulator of Nav channel slow inactivation

lubin@ion.ac.cn (Bin Lu) — Fri, 11 Sep 2026 00:00:00 +0000

During sustained activity, voltage-gated sodium (Nav) channels enter a slow-inactivated state to limit cellular hyperexcitability. Disruption of this regulatory process has been implicated in skeletal, cardiac, and neurological disorders. While the kinetics of this process are well characterized, its endogenous modulators remain unclear. Here, we identify Proline-Rich Transmembrane Protein 2 (PRRT2) as a native regulator of Nav channel slow inactivation. We show that PRRT2 facilitates the entry of Nav channels into the slow-inactivated state and delays their recovery, a regulatory effect conserved from zebrafish to humans. PRRT2 forms molecular complexes with Nav channels both in vitro and in vivo. In the mouse cortex, PRRT2 deficiency impairs the slow inactivation of Nav channels in neuronal axons, leading to reduced cortical resilience in response to hyperexcitable challenges. Together, these findings establish PRRT2 as a physiological modulator of Nav channel slow inactivation and reveal a mechanism that supports cortical resilience to pathological perturbations.