eLife: latest articles by subject

Parkinson’s disease-associated PINK1 loss disrupts ensheathing glia and causes dopaminergic neuron synapse loss

roman.praschberger@i-med.ac.at (Ayse Kilic) — Thu, 13 Aug 2026 00:00:00 +0000

Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in the substantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear. PINK1 is mutated in familial PD, and through unbiased single-cell sequencing of the entire brain of Drosophila Pink1 models, we observed significant gene deregulation in ensheathing glia (EG), cells that share functional similarities with oligodendrocytes. We found that the loss of Pink1 leads to abnormalities in EG, similar to the reactive response of EG seen upon nerve injury. Using cell-type-specific transcriptomics, we identified deregulated genes in EG as potential functional modifiers. Specifically downregulating two trafficking factors in EG, Vps35 and Vps13, also mutated in PD, was sufficient to rescue neuronal function and protect against dopaminergic synapse loss. Our findings demonstrate that Pink1 loss in neurons triggers an injury-like response in EG, and that Pink1 loss in EG, in turn, disrupts neuronal function. Vesicle trafficking components, which may regulate membrane interactions between organelles in EG, seem to play a role in maintaining neuronal health and ultimately preventing dopaminergic synapse loss. Our work highlights the essential role of glial support cells in the pathogenesis of PD and identifies vesicle trafficking within these cells in disease progression.

Human brain-wide activation of sleep rhythms

jgao@pku.edu.cn (Haiteng Wang) — Wed, 12 Aug 2026 00:00:00 +0000

During sleep, our brain undergoes highly synchronized activity, orchestrated by distinct neural rhythms. Little is known about the associated brain activation during these sleep rhythms, and even less about their functional implications. In this study, we investigated the brain-wide activation underlying human sleep rhythms by employing simultaneous electroencephalography and functional magnetic resonance imaging in 107 participants during nocturnal naps (first half of the night). We identified robust coupling between slow oscillations (SOs) and fast spindles during deep non-rapid eye movement sleep (N2/3 stages), with spindle peaks consistently occurring just before the SO UP-state. This SO-spindle coupling was linked to elevated activation in both the thalamus and hippocampus, alongside increased functional connectivity from the hippocampus to the thalamus and from the thalamus to the medial prefrontal cortex. An open-ended cognitive state decoding analysis suggested that these activations may relate to episodic memory processes, yet were distinct from task-related networks. Together, these findings highlight the thalamus as a key coordinator of hippocampal–cortical communication during sleep and provide new insights into the mechanisms by which synchronized sleep rhythms may support memory consolidation.

In vivo mapping of striatal neurodegeneration in Huntington’s disease with Soma and Neurite Density Imaging

Metzler-BaddeleyC@cardiff.ac.uk (Anne Rosser) — Tue, 11 Aug 2026 00:00:00 +0000

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterised by progressive cognitive and motor decline driven by basal ganglia (BG) atrophy. Clinical trials of novel disease-modifying therapies are ongoing, creating a need for sensitive non-invasive imaging biomarkers. Soma and Neurite Density Imaging (SANDI) is a multi-shell diffusion MRI model that estimates intracellular signal fractions from sphere-shaped soma and shows promise as a marker of neurodegeneration. The objectives of this study were to characterise HD-related microstructural abnormalities in the BG using SANDI and to examine relationships between SANDI and volumetric measurements and motor performance. T1- and diffusion-weighted images (b-values 200–6000 s/mm²) were acquired on a 3T Siemens Connectom scanner (300 mT/m) in 56 individuals with HD and 57 age- and sex-matched controls. HD participants completed Quantitative Motor (Q-Motor) tasks, summarised using principal component analysis. SANDI estimated apparent soma and neurite density, apparent soma size, and extracellular signal fraction. Microstructural and volumetric indices were extracted from bilateral caudate, putamen, pallidum and thalamus regions, compared between groups, and correlated with Q-Motor performance. HD was associated with reduced apparent soma density and increased apparent soma size and extracellular signal fraction in the BG but not the thalami. No group differences were present for apparent neurite density. SANDI metrics correlated with Q-Motor performance and explained up to 63% of striatal atrophy in HD. SANDI indices detected HD-related striatal neurodegeneration, explained atrophy, and correlated with motor impairments, demonstrating its potential as an in vivo biomarker and surrogate clinical outcome measure for HD and other neurodegenerative diseases.

Spine nanostructure profiling of cultured neurons from mouse models reveals a schizophrenia-linked role for Ecrg4

shigeo.okabe@riken.jp (Atsu Aiba) — Tue, 11 Aug 2026 00:00:00 +0000

Dendritic spine dysfunction may contribute to the etiology and symptom expression of neuropsychiatric disorders. The intimate relationship between spine morphology and function suggests that decoding disease-related abnormalities from spine morphology can aid in developing synapse-targeted interventions. Here, we describe a population analysis of dendritic spine nanostructure applied to the objective grouping of multiple mouse models of neuropsychiatric disorders. This method has identified two major groups of spine phenotypes linked to schizophrenia and autism spectrum disorder (ASD). An increase in spine subpopulation with small volumes characterized the spines of schizophrenia-associated mouse models, whereas a spine subset with large volumes increased in ASD models. Schizophrenia-associated mouse models showed higher similarity in spine morphology, driven by reduced size and growth of nascent spines. The expression of Ecrg4, a gene encoding small secretory peptides, was increased in schizophrenia-associated mouse models, and functional studies confirmed its critical involvement in impaired spine dynamics and shape. These results suggest that population-level spine analysis provides rich insights into heterogeneous spine pathology, facilitating the identification of new molecular targets related to core synaptic dysfunction.

Mood computational mechanisms underlying increased risk behavior in adolescent suicidal patients

hzl_811015@126.com (Bastien Blain) — Fri, 07 Aug 2026 00:00:00 +0000

Suicidal thoughts and behaviors (STB) are among the leading causes of death worldwide. Although previous research has consistently documented elevated risk-taking in individuals with STB and identified mood disturbances as central features of suicidality, the precise cognitive and affective computational mechanisms underlying this increased risky behavior remain poorly understood. Here, 83 adolescent inpatients with affective disorders—including 58 patients with STB (S⁺) and 25 without STB (S⁻)—and 118 age- and sex-matched healthy controls (HC) completed a decision-making task involving choices between certain and gamble options, alongside momentary mood ratings. Behavioral analyses showed that S⁺ exhibited greater risk-taking than both S⁻ and HC. Computational modeling of choice behavior using a prospect-theory framework augmented with value-insensitive approach–avoidance parameters indicated that this increase in risky behavior was specifically driven by an elevated approach parameter in S⁺. In addition, mood-model analyses revealed reduced sensitivity to certain rewards in S⁺ relative to S⁻ and HC. Importantly, these computational signatures predicted suicidal symptom severity and showed generalizability in an independent general-population sample (n = 747). In S⁺, lower mood sensitivity to certain rewards was associated with greater gambling, providing a computational affective account of increased risk-taking in STB. These findings remained robust after adjusting for demographic, clinical, and medication-related variables. Overall, our study identifies cognitive and affective computational mechanisms contributing to elevated risk-taking in STB and highlights their potential relevance for the early identification and prevention of suicidality.

Functional specialization of mPFC-BLA and mPFC-NAc pathways in affective state representation

huilu@gwu.edu (Chen Zeng) — Fri, 07 Aug 2026 00:00:00 +0000

Effective emotional processing, crucial for adaptive behavior, is mediated by the medial prefrontal cortex (mPFC) via connections to the basolateral amygdala (BLA), and nucleus accumbens (NAc), traditionally considered functionally similar in modulating reward and aversion responses. However, the functional specialization of the mPFC→BLA and mPFC→NAc pathways in representing affective states remains unclear. We found that while overall firing patterns appeared consistent across emotional states, deeper analysis revealed distinct variabilities. Specifically, mPFC→BLA neurons, especially ‘center-ON’ neurons, exhibited heightened activity during behaviors classically associated with anxiety-like states, suggesting their involvement in aversive behavioral regulation. Conversely, mPFC→NAc neurons were more active during exploratory and approach-related behaviors, implicating them in the processing of positively valenced behavioral states. Notably, mPFC→NAc neurons showed significant pattern decorrelation during social interactions, suggesting a pivotal role in processing social preference. Additionally, repeated win/loss outcomes in the tube test produced distinct hierarchy-dependent behavioral changes and elevated corticosterone levels in loser mice, supporting the biological relevance of these behaviorally defined states. Together, these findings reveal pathway-specific representations of affect-related behavioral states in mPFC circuits and provide a framework for understanding how prefrontal outputs organize adaptive behavior across environmental contexts.

LRRK2 regulates synaptic function through modulation of actin cytoskeletal dynamics

Beccano-KellyD@cardiff.ac.uk (Adriano Lama) — Thu, 06 Aug 2026 00:00:00 +0000

Parkinson’s disease (PD) is a multisystemic disorder that manifests through motor and non-motor symptoms. Motor dysfunction results from the degeneration of dopamine-producing neurons in the substantia nigra pars compacta. Increasing evidence suggests that synapse dysfunction precedes neuronal loss by years. Still, early synaptic alterations in PD remain poorly understood. Here, we integrate literature meta-analysis and multi-omics with biochemical, imaging, and electrophysiological measurements in Lrrk2 mouse models and human iPSC-derived neurons lacking LRRK2. We demonstrate that brain-derived neurotrophic factor (BDNF) activates LRRK2 in differentiated SH-SY5Y cells and primary mouse neurons, reshaping the LRRK2 interactome toward a network of actin cytoskeleton-related proteins. Gene-ontology analyses of both literature-curated LRRK2 interactors and phospho-proteome from striatal tissues with elevated LRRK2 activity highlight synapse-actin remodeling as major affected pathways. We further observed that loss of LRRK2 impairs BDNF signaling and alters postsynaptic density architecture. Young Lrrk2 knockout mice display structural alterations in dendritic protrusions, a phenotype that normalizes with age. In human iPSC-derived neurons, LRRK2 knockout affects maturation and BDNF-dependent regulation of spontaneous synaptic activity. Taken together, our study discloses a critical role of LRRK2 in BDNF-dependent synaptic modulation and identifies the synaptic actin cytoskeleton as a convergent site of LRRK2-associated pathophysiological processes in PD.

Brainstem neurons coordinate the bladder and urethral sphincter for urination

jiahb@sibet.ac.cn (Chunhui Yuan) — Thu, 06 Aug 2026 00:00:00 +0000

Urination, a vital and conserved process of emptying urine from the urinary bladder in mammals, requires precise coordination between the bladder and external urethral sphincter (EUS) that is tightly controlled by a complex neural network. However, the specific subpopulation of neurons that accounts for such coordination remains unidentified, limiting the development of target-specific therapies for certain urination disorders, for example, detrusor–sphincter dyssynergia. Here, we find that cells expressing estrogen receptor 1 (ESR1⁺) in the pontine micturition center (PMC) initiate voiding when activated and suspend ongoing voiding when suppressed, each at 100% reliability. Transection of the pelvic nerve does not impair PMC^ESR1+ neurons’ control of the EUS via the pudendal nerve, whereas transection of the pudendal nerve does not impair their control of the bladder via the pelvic nerve. Anatomically, PMC^ESR1+ neurons consist of three distinct spinal-projection-based subpopulations: one targeting the sacral parasympathetic nucleus, one innervating the dorsal gray commissure, and a third that projects to both regions, thereby enforcing the coordination of bladder contraction and sphincter relaxation in a rigid temporal sequence. Thus, we identify a cell type in the brainstem that controls the bladder–urethra coordination for urination.

Efficient and reproducible pipelines for spike sorting large-scale electrophysiology data

alessio.buccino@alleninstitute.org (Alessio Paolo Buccino) — Wed, 05 Aug 2026 00:00:00 +0000

The scale of in vivo electrophysiology has expanded in recent years, with simultaneous recordings across thousands of electrodes now becoming routine. These advances have enabled a wide range of discoveries, but they also impose substantial computational demands. Spike sorting, the procedure that extracts spikes from extracellular voltage measurements, remains a major bottleneck: a dataset collected in a few hours can take days to spike sort on a single machine, and the field lacks rigorous validation of the many spike sorting algorithms and preprocessing steps that are in use. Advancing the speed and accuracy of spike sorting is essential to fully realize the potential of large-scale electrophysiology. Here, we present an end-to-end spike sorting pipeline that leverages parallelization to scale to large datasets. The same workflow can run reproducibly on individual workstations, high-performance computing clusters, or cloud environments, with computing resources tailored to each processing step to reduce costs and execution times. In addition, we introduce a benchmarking pipeline, also optimized for parallel processing, that enables systematic comparison of multiple sorting pipelines. Using this framework, we show that Kilosort4, a widely used spike sorting algorithm, outperforms Kilosort2.5. We also show that 7× lossy compression, which substantially reduces the cost of data storage, has minimal impact on spike sorting performance. Together, these pipelines address the urgent need for scalable and transparent spike sorting of electrophysiology data, preparing the field for the coming flood of multi-thousand-channel experiments.

Boosting hyperalignment performance with age-specific templates

james.v.haxby@dartmouth.edu (James V Haxby) — Wed, 05 Aug 2026 00:00:00 +0000

Hyperalignment aligns individual brain activity and functional connectivity patterns to a common, high-dimensional model space, resolving idiosyncrasies in functional–anatomical correspondence and revealing shared information encoded in fine-grained spatial patterns. Given that the brain undergoes significant developmental and functional changes over the lifespan, certain features in brain functional organization may be more prominent in certain age groups than others. In this study, we examined whether age-specific functional templates, compared with a canonical template, could enhance alignment accuracy across diverse age groups. We used the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) dataset (18–87 years old) to build age-specific templates and tested their performance in young and old brains in both the Cam-CAN dataset and the Dallas Lifespan Brain Study dataset (20–90 years old). We found the congruent age-specific template outperforms the incongruent template for various analyses, including inter-subject correlation of hyperaligned connectivity profiles and predictions of individualized connectomes and brain responses to the movie. The results are consistent across both datasets. This work enhances our understanding of age-related differences in brain function, highlights the benefits of age-specific templates to refine hyperalignment model performance, and may contribute to the development of age-sensitive diagnostic tools and interventions for neurological disorders.

Heritability of movie-evoked brain activity and connectivity

david.gruskin@columbia.edu (Daniel J Vieira) — Tue, 04 Aug 2026 00:00:00 +0000

The neural bases of sensory processing are conserved across people but no two individuals experience the same stimulus in exactly the same way. Recent work has established that the idiosyncratic nature of subjective experience is underpinned by individual variability in brain responses to sensory information. However, the fundamental origins of this individual variability have yet to be systematically investigated. Here, we establish a genetic basis for individual differences in sensory processing by quantifying (1) the heritability of high-dimensional brain responses to movies and (2) the extent to which this heritability is grounded in lower-level aspects of brain function. Specifically, we leverage 7T fMRI data collected from a twin sample to first show that movie-evoked brain activity is heritable across the cortex, and that this heritability is greater for information encoded in lower temporal frequencies, especially in more associative cortical areas. Next, we use hyperalignment to decompose this heritability into genetic similarity in where vs. how sensory information is processed. We also show that the heritability of brain activity patterns can be partially explained by the heritability of the neural timescale, a one-dimensional measure of local circuit functioning. Finally, we generalize our findings by illustrating a similar pattern of results for the heritability of movie-evoked functional connectivity. These results demonstrate that brain responses to complex stimuli are heritable, and that this heritability is due, in part, to genetic control over stable aspects of brain function.

Deletion of neuroligins from astrocytes does not detectably alter synapse numbers or astrocyte cytoarchitecture by maturity

samgolf@uab.edu (George Nakahara) — Tue, 04 Aug 2026 00:00:00 +0000

Astrocytes perform multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved are incompletely understood. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that function as synaptic organizers by binding to presynaptic neurexins. Here, we examined the function of neuroligins in astrocytes with a rigorous genetic approach that uses the conditional deletion of all major neuroligins (Nlgn1–3) in astrocytes in vivo in mice and complemented this approach by a genetic deletion of neuroligins in glial cells that are co-cultured with human neurons. Our results show that early postnatal deletion of neuroligins from astrocytes in vivo has no detectable effect on cortical or hippocampal excitatory or inhibitory synapses, and does not alter the cytoarchitecture of astrocytes when evaluated in young adult mice. Moreover, deletion of astrocytic neuroligins in co-cultures of human neurons produced no detectable consequences for the formation and function of synapses. Thus, astrocytic neuroligins are unlikely to fundamentally shape synapse formation or astrocyte morphogenesis, but likely perform other important roles that remain to be discovered.

Thalamo-accumbal circuit adaptations following extended oxycodone abstinence

alonsocy@umn.edu (Elena Chartoff) — Tue, 04 Aug 2026 00:00:00 +0000

Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.

In-situ glial cell-surface proteomics identifies pro-longevity factors in Drosophila

hongjie.li@bcm.edu (Amogh Varanasi) — Tue, 04 Aug 2026 00:00:00 +0000

Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the critical roles glial cells play in maintaining brain health. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins is hypothesized to play an important role in age-related neurodegeneration. However, it remains technically difficult to profile glial cell-surface proteins in intact brains. Here, we applied an in-situ cell-surface proteomic profiling method to glial cells from intact fly brains. Applying this platform to young and old flies, we identified candidate genes predicted to be involved in brain aging. Through a genetic screen, we identified one surface protein, DIP-β, which is down-regulated in old flies and can increase fly lifespan when overexpressed in adult glial cells. We performed whole-head single-nucleus RNA-seq and revealed that DIP-β overexpression mainly impacts glial and fat cells. We also found that glial DIP-β overexpression was associated with improved cell-cell communication. Our study is the first to apply in-situ cell-surface proteomics to glial cells in Drosophila, and to identify DIP-β as a potential glial regulator of brain aging.

Pupil size reveals the perceptual quality and effortless nature of synesthesia

c.strauch@uu.nl (Casper Leenaars) — Tue, 04 Aug 2026 00:00:00 +0000

Synesthesia describes cross-over processes that can generate ‘extra’ conscious percepts, such as seeing additional color when reading numbers. While existing research focuses on the mechanisms and effects of synesthetic associations, it often overlooks its most distinctive feature: unique sensory phenomenology. Here, we introduce pupillometry as an objective physiological measure of synesthetic color phenomenology. Across 16 grapheme-color synesthetes and two matched control groups, pupil responses tracked the brightness of synesthetic colors under constant physical visual input, scaling with self-reported strength. Synesthetic colors elicited pupil dynamics comparable to real colors, dissociating synesthetes from non-synesthetes. These responses emerged too rapidly to reflect imagery and scaled with reported color brightness, revealing cross-over caused genuine perceptual processing. Controls required to generate color associations showed greater effort-linked pupil dilation than synesthetes or controls who did not report colors, providing evidence for the effortless nature of synesthesia. Synesthesia thus provides a tractable human model for studying physiologically measurable phenomenology.

Concurrent category-selective neural activity across the ventral occipito-temporal cortex supports a non-hierarchical view of human visual recognition

bruno.rossion@univ-lorraine.fr (Bruno Rossion) — Tue, 04 Aug 2026 00:00:00 +0000

Visual recognition is a fundamental human brain function, supported by a network of regions in the ventral occipito-temporal cortex (VOTC). This network is thought to be organized hierarchically, with definite processing stages increasing in invariance and time-course from posterior to anterior cortical regions. Here, we provide a stringent test of this view by measuring category-selective neural activity to natural images of faces across the VOTC with electrophysiological intracerebral recordings in a large human sample (N=140; >11,000 recording sites). Face-selective high frequency broadband (30–160 Hz) neural activity is distributed across the VOTC, with right-hemispheric dominance and regional peaks of activity. Crucially, while a progressive increase in degree of category-selectivity is found along the postero-anterior axis, neural activity occurs largely concurrently (~100 ms onset – ~450 ms offset) across all VOTC regions. These observations challenge the standard hierarchical view of neural organization of visual object recognition in the human association cortex, supporting alternative models of this key brain function.

Correction: cxcl18b-defined transitional state-specific nitric oxide drives injury-induced Müller glia cell-cycle re-entry in the zebrafish retina

Mon, 03 Aug 2026 00:00:00 +0000

Comprehensive characterization of human color discrimination thresholds

fh862@sas.upenn.edu (Alex H Williams) — Fri, 31 Jul 2026 00:00:00 +0000

Color discrimination thresholds—the smallest detectable color differences—provide a benchmark for models of color vision, enable quantitative evaluation of eye diseases, and inform the design of display technologies. Despite their importance, a comprehensive characterization of these thresholds has long been considered intractable due to the psychophysical curse of dimensionality. Here, we address this challenge using a novel semiparametric Wishart process psychophysical model (WPPM), which leverages the feature that the internal noise limiting color discrimination varies smoothly across stimulus space. The model was fit to data collected with a nonparametric adaptive trial-placement procedure, enabling efficient stimulus selection. Together, through the combination of adaptive trial placement and post hoc WPPM fitting, we achieved a comprehensive characterization of color discrimination in the isoluminant plane with only ∼6000 trials per participant (N = 8). Once fit, the WPPM allows readouts of discrimination performance for any stimulus pair. We validated these readouts against 25 probe psychometric functions, measured with an additional 6000 trials per participant held out from model fitting. In conclusion, our study provides a foundational dataset for color vision, and our approach generalizes beyond color to any domain in which the internal noise limiting performance varies smoothly across stimulus space, offering a powerful and efficient method for comprehensively characterizing various perceptual discrimination thresholds.

Dichotomy between extracellular signatures of active dendritic chemical synapses and gap junctions

rishi@iisc.ac.in (Richa Sirmaur) — Thu, 30 Jul 2026 00:00:00 +0000

Local field potentials (LFPs) are compound signals that represent the dynamic flow of information across the brain, which have been historically associated with chemical synaptic inputs. How do gap junctional inputs onto active compartments shape LFPs? We developed a methodology to record extracellular potentials associated with different patterns of gap junctional inputs onto conductance-based models. We found that synchronous inputs through chemical synapses yielded a negative deflection in proximal extracellular electrodes whereas those onto gap junctions manifested a positive deflection. Importantly, we observed extracellular dipoles only when inputs arrived through chemical synapses but not with gap junctions. Remarkably, hyperpolarization-activation cyclic nucleotide-gated channels, which typically conduct inward currents, mediated outward currents triggered by the fast voltage transition caused by synchronous inputs. With rhythmic inputs at different frequencies arriving through gap junctions, we found strong suppression of LFP power at higher frequencies as well as frequency-dependent differences in the spike phase associated with the LFP when compared to respective chemical synaptic counterparts. All observed differences in LFP were mediated by the relative dominance of synaptic currents vs. voltage-driven transmembrane currents with chemical synapses vs. gap junctions, respectively. Our analyses unveil a hitherto unknown role for active dendritic gap junctions in shaping extracellular potentials.

Neural correlates of perceptual consciousness from within: A narrative review of human intracranial research

nathan.faivre@univ-grenoble-alpes.fr (Alexis Robin) — Thu, 30 Jul 2026 00:00:00 +0000

Despite many years of research, the quest to identify neural correlates of perceptual consciousness (NCC) remains unresolved. One major obstacle lies in methodological limitations: most studies rely on non-invasive neural measures with limited spatial or temporal resolution, making it difficult to disentangle proper NCCs from concurrent cognitive processes. Additionally, the relatively low sensitivity of non-invasive neural measures limits the interpretation of null findings in studies targeting proper NCCs. In this review, we discuss how human intracranial recordings can advance the search for NCCs by offering high spatiotemporal resolution, improved signal sensitivity, and broad cortical and subcortical coverage. We review studies that have examined NCCs at the level of single neurons and populations of neurons, and evaluate their implications on the debates between cognitive and sensory theories of consciousness. Finally, we highlight the limits of current intracranial human recordings and propose future directions based on emerging technologies and novel experimental paradigms.

Acute opioid responses are modulated by dynamic interactions of Oprm1 and Fgf12

labwilliams@gmail.com (Alexander S Hatoum) — Wed, 29 Jul 2026 00:00:00 +0000

We generated time-series data for 105 morphine- and naloxone-related traits across ~700 BXD mice (64 diverse strains for both sexes) for 3 hr after a single morphine injection. Variations in responses were mapped using genome sequencing-based genotypes. The locomotor responses to morphine mapped to the µ opioid receptor gene (Oprm1) on chromosome (Chr) 10 with a peak linkage of 12.4 (–logp). The B allele inherited from C57BL/6J was associated with up to 60% higher activity. This effect climaxed at 75 min but was exhausted by 160 min. A second major modulator of locomotion emerged after approximately 100 min. This locus was located on Chr 16 with peak linkage of 10.6 in females and included one compelling candidate, fibroblast growth factor 12 (Fgf12). A strong and transient epistatic interaction existed between the Oprm1 and Fgf12 loci during a short time window (45–75 min). In heterogeneous stock rats, we demonstrated that Oprm1 and Fgf12 were co-expressed in one subtype of Drd1⁺ medium spiny neuron. A Bayesian network analysis supported an Oprm1-to-Fgf12 network that involves a MAP kinase cascade that modulates FGF12 phosphorylation and locomotor activation. OPRM1 and FGF12 networks in human genome-wide association study (GWAS) data highlight enrichment of signals associated with substance use disorder. This study represents the first demonstration of a time-dependent epistatic interaction modulating drug response in mammals and the first linkage of Fgf12 to opioid-induced behavior.

Behavioral signatures of post-decisional attention in preferential choice

ariel.zylberberg@gmail.com (Ariel Zylberberg) — Tue, 28 Jul 2026 00:00:00 +0000

Attention plays a key role in decision-making by directing limited cognitive resources to relevant information. It has been proposed that attention also biases the decision process, due to a multiplicative interaction between attention and subjective value (e.g., Krajbich et al., 2010). We tested two predictions of models that posit a causal multiplicative effect of attention on decision formation: (i) the last fixation should be more informative about the choice when the overall value of the alternatives is high, and (ii) more attention should be directed to the chosen option when choices conflict with stated preferences than when they do not. Reanalyzing several datasets from a food-choice task, we found no evidence supporting these predictions. An alternative model where attention reflects choices after the decision has completed explains key observations, including the last-fixation bias, the gaze-cascade effect, and the effect of the overall value of the alternatives on response times. However, this model does not fully account for the association between dwell time and choice. We conclude that gaze behavior prior to the choice report likely reflects both decisional and post-decisional processes.

Excitatory cholecystokinin neurons in the CA3 area regulate the navigation learning and neuroplasticity

fwhuang2@stanford.edu (Abdul Baset) — Tue, 28 Jul 2026 00:00:00 +0000

Hippocampus, a key hub of neural circuits for spatial learning and memory, has attracted tremendous studies. Neuronal information processing in the hippocampus can be regulated by many types of neuropeptides. Cholecystokinin (Cck), the most abundant neuropeptide in the central nervous system that is involved in modulating neuronal functions, such as cognition, memory, and neuroplasticity, is widely expressed in the hippocampus. However, whether local excitatory Cck neurons modulate hippocampal function is still unclear. In this study, we showed that CA1 pyramidal neurons receive projections from excitatory Cck neurons in area CA3 (CA3^Cck neurons) in adult mice. Subsequently, activation of the CA1-projecting CA3^Cck neurons triggers the release of Cck. Then, we found that the activity of CA3^Cck-CA1 neurons supports the hippocampal-dependent tasks. Furthermore, inhibition of CA3^Cck-CA1 projections or knockdown of CA3^Cck gene expression markedly impaired the behavioral tasks and neuroplasticity. Taken together, these results may add to a better understanding of how neuromodulators regulate the neural functions in the central nervous system.

CellCover defines marker gene panels capturing developmental progression in neocortical neural stem cell identity

ccolantu@jhmi.edu (An Wang) — Tue, 28 Jul 2026 00:00:00 +0000

Defining cell classes is central to the analysis of growing single-cell RNA sequencing (scRNA-seq) atlases. Marker genes are most often identified by differential expression (DE) methods that assess genes one at a time, ignoring the redundancy and complementarity revealed when genes are considered jointly. Working with binarized expression data, we instead seek discriminating panels of genes that together are specific to a cell type, framing marker-panel selection as a variant of the minimal set-covering problem in combinatorial optimization. This formulation efficiently searches the vast space of candidate panels, exploits the large cell numbers typical of scRNA-seq, and is robust to zero-inflation. Using blood and brain data, we show that our method, CellCover, reduces gene redundancy and captures cell-class-specific signals distinct from those found by DE. Transfer-learning experiments across mouse, primate, and human data demonstrate that CellCover identifies conserved cell classes in neocortical neurogenesis and tracks developmental progression in progenitors and neurons. Examining outer radial glia markers across mammals, we find that transcriptomic elements of this key cell type likely arose in rodent gliogenic precursors before the full program emerged in the primate lineage.

Sensory adaptation and pupil-linked arousal support flexible evidence accumulation during perceptual decision making

jigold@pennmedicine.upenn.edu (Joshua I Gold) — Mon, 27 Jul 2026 00:00:00 +0000

Effective decision making in dynamic environments requires flexible evidence accumulation. Although models often express this flexibility as a property of the accumulator, its implementation in the brain may involve adaptive mechanisms operating at other stages of the decision process. We examined two such mechanisms: (1) stimulus-specific sensory adaptation at the level of evidence encoding, and (2) arousal-related neuromodulation, which could, in principle, affect both evidence encoding and accumulation. We measured single-unit activity in the middle temporal (MT) area and pupil-linked arousal while monkeys performed a modified random-dot motion direction-discrimination task in which an adapting stimulus with varied temporal stability preceded a behaviorally relevant test stimulus. The monkeys’ decisions reflected adaptive evidence accumulation that depended on temporal-context stability and corresponded to context-dependent changes in both stimulus-specific sensory adaptation in MT and task-evoked pupil responses. However, adaptation and pupil adjustments were not related to each other. Together, these findings suggest that multiple mechanisms contribute to flexible, context-dependent evidence accumulation, including changes in sensory adaptation that shape evidence encoding and changes in arousal that may shape the accumulation process itself.

Active dendrites enable robust spiking computations despite timing jitter

tsjb2@cam.ac.uk (Michael E Rule) — Mon, 27 Jul 2026 00:00:00 +0000

Dendritic action potentials exhibit long plateaus of many tens of milliseconds, outliving axonal spikes by an order of magnitude. The computational role of these slow events seems at odds with the need to rapidly integrate and relay information throughout large nervous systems. We propose that the timescale of dendritic potentials allows for reliable integration of asynchronous inputs. We develop a physiologically grounded model in which the extended duration of dendritic spikes equips each dendrite with a resettable memory of incoming signals. This provides a tractable model for capturing dendritic nonlinearities observed in experiments and in more complex, detailed models. Using this model, we show that long-lived, nonlinear dendritic plateau potentials allow neurons to spike reliably when confronted with asynchronous input spikes. We demonstrate this model supports non-trivial computations in a network solving an association/discrimination task using sparse spiking that is subject to timing jitter. This demonstrates a computational role for the specific timecourse of dendritic potentials in situations where decisions occur quickly, reliably, and with a low number of spikes. Our results provide empirically testable hypotheses for the role of dendritic action potentials in cortical function, as well as a potential bio-inspired means of realising neuromorphic spiking computations in analog hardware.

Stable excitatory-inhibitory synapse balance despite dynamic turnover

richard.sando@vanderbilt.edu (Cassandra M Smith) — Mon, 27 Jul 2026 00:00:00 +0000

Diverse synaptic connections self-organize into neural circuits during brain development. A balance between excitatory and inhibitory synaptic function is required for information processing by these neural circuits. Despite the importance of this balance, the interplay between excitatory and inhibitory synaptic assembly during circuit establishment remains unclear due to a lack of means to monitor both processes simultaneously. Here, we develop imaging and analysis methods to visualize and track excitatory and inhibitory synapses. By applying these approaches, we find that despite continual dynamics, excitatory and inhibitory synaptic density remain at steady-state levels during synapse maturation. These results indicate balanced excitatory and inhibitory synapse assembly, despite continual synaptic turnover.

Two time scales of adaptation in human learning rates

tom.verguts@ugent.be (Haopeng Chen) — Wed, 22 Jul 2026 00:00:00 +0000

Different situations may require radically different information updating speeds (i.e., learning rates). Some demand fast learning rates while others benefit from using slower ones. To adjust learning rates, decision makers could rely on either global, meta-learned differences between environments, or faster but transient adaptations to locally experienced prediction errors. Here, we introduce a new paradigm that allows researchers to measure and empirically disentangle both forms of adaptation. Participants performed short blocks of trials of a continuous estimation task – fishing for crabs – on six different islands that required different optimal (initial) learning rates. Across two experiments, participants showed fast adaptations in learning rate within a block. Critically, participants also learned global environment-specific learning rates over the time course of the experiment, as evidenced by computational modelling and by the learning rates calculated on the very first trial when revisiting an environment (i.e., unconfounded by transient adaptations). Using representational similarity analyses of fMRI data, we found that differences in voxel pattern responses in the central orbitofrontal cortex (OFC) correlated with differences in these global environment-specific learning rates. Our findings show that humans adapt learning rates at both slow and fast time scales, and that the central OFC may support meta-learning by representing environment-specific task-relevant features such as learning rates.