eLife: latest articles by subject

Bilateral equalization of synaptic output in olfactory glomeruli of Xenopus tadpoles

allobet@ub.edu (Artur Llobet) — Fri, 15 May 2026 00:00:00 +0000

Odorants stimulate olfactory sensory neurons (OSNs) to create a bilateral sensory map defined by a set of glomeruli present in the left and right olfactory bulbs. Using Xenopus tropicalis tadpoles, we challenged the notion that glomerular activation is exclusively determined ipsilaterally. Glomerular responses evoked by unilateral stimulation were potentiated following transection of the contralateral olfactory nerve. The gain of function was observed as early as 2 hr after injury and faded away with a time constant of 4 days. Potentiation was mediated by the presence of larger and faster calcium transients driving glutamate release from OSN axon terminals. The cause was the reduction of the tonic presynaptic inhibition exerted by dopamine D₂ receptors. Inflammatory mediators generated by injury were not involved. These findings reveal the presence of a bilateral modulation of glomerular output driven by dopamine that compensates for imbalances in the number of operative OSNs present in the two olfactory epithelia. Considering that the constant turnover of OSNs is an evolutionarily conserved feature of the olfactory system and determines the innervation of glomeruli, the compensatory mechanism described here may represent a general property of the vertebrate olfactory system to establish an odor map.

Adrenomedullin restores the human cortical interneurons migration defects induced by hypoxia

apasca@stanford.edu (Alyssa Puno) — Fri, 15 May 2026 00:00:00 +0000

Extremely preterm birth (at <28 postconceptional weeks) leads to brain injury and represents the leading cause of childhood-onset neuropsychiatric diseases. No effective therapeutics exist to reduce the incidence and severity of brain injury of prematurity. Hypoxic events are the most important environmental factor, along with inflammation. Among other developmental processes, the second half of in utero fetal development coincides with the migration of cortical interneurons from the ganglionic eminences into the cortex; this process is thus prone to disruptions following extremely preterm birth. To date, no studies have directly investigated the migration of human cortical inhibitory neurons under hypoxic conditions. Using multi-day confocal live imaging in human forebrain assembloids (hFA) derived from human-induced pluripotent stem cells (hiPSCs) and ex vivo developing human brain tissue, we found a substantial reduction in the migration of hypoxic interneurons. Using transcriptomics, we identified adrenomedullin (ADM) as the gene with the highest fold change increase in expression. Based on previous literature about the protective role of supplemental ADM for other injuries, here, we demonstrated that addition of exogenous ADM to the hypoxic media restores the migration defects of interneurons. Lastly, we showed that one of the mechanisms of protection by ADM is through the activation of the cAMP/PKA pathway and subsequent pCREB-dependent rescued expression of a subset of GABA receptors, which are known to promote migration. Overall, in this manuscript, we provide the first direct evidence for hypoxia-induced deficits in the migration of human cortical interneurons and identify ADM as a possible target for therapeutic development.

Drug-induced changes in connectivity to midbrain dopamine cells revealed by rabies monosynaptic tracing

kbeier@uci.edu (Cindy M Yamamoto) — Fri, 15 May 2026 00:00:00 +0000

Addictive drugs cause long-lasting changes in connectivity from inputs onto ventral tegmental area dopamine cells (VTA^DA) that contribute to drug-induced behavioral adaptations. However, it is not known which inputs are altered. Here, we used a rabies virus (RABV)-based mapping strategy to quantify RABV-labeled inputs to VTA cells after a single exposure to one of a variety of misused drugs – cocaine, amphetamine, methamphetamine, morphine, and nicotine – and compared the relative global input labeling across conditions. We observed that all tested addictive drugs elicited similar input changes onto VTA^DA cells, in particular onto DA cells projecting to the lateral shell of the nucleus accumbens and amygdala. In addition, repeated administration of ketamine/xylazine to induce anesthesia induces a change in inputs to VTA^DA cells that is similar to but different from those elicited by a single exposure to addictive drugs, suggesting that caution should be taken when using ketamine/xylazine-based anesthesia in rodents when assessing motivated behaviors. Furthermore, comparison of viral tracing data to an atlas of gene expression in the adult mouse brain showed that the basal expression patterns of several gene classes, especially calcium channels, were highly correlated with the extent of both addictive drug- or ketamine/xylazine-induced changes in RABV-labeled inputs to VTA^DA cells. Reducing expression levels of the voltage-gated calcium channel Cacna1e in cells in the nucleus accumbens lateral shell reduced RABV-mediated input labeling of these cells into VTA^DA cells. These results directly link genes controlling cellular excitability and the extent of input labeling by RABV.

Subregional activity in the dentate gyrus is amplified during elevated cognitive demands

a-contractor@northwestern.edu (Anis Contractor) — Thu, 14 May 2026 00:00:00 +0000

Neural activity in the dentate gyrus (DG) supports the detection and discrimination of novelty, context, and patterns. Granule cell activation differs between the supra- and infrapyramidal blades across hippocampal-dependent tasks, yet how excitatory dynamics shape this blade-specific bias under varying cognitive demands remains unclear. Here, we combined an automated touchscreen pattern separation task in mice with temporally controlled tagging of active neurons to determine how increasing cognitive demand influences spatial activity patterns in the DG. As task difficulty increased, activation became progressively biased toward the suprapyramidal blade and was accompanied by structured distributions of active mature granule cells (mGCs) along both the radial and transverse axes. Selective inhibition of mGCs did not alter these spatial patterns, but profoundly impaired performance, as mice were no longer able to discriminate between closely spaced locations. In contrast, chemogenetic inhibition of adult-born dentate granule cells (abDGCs) beyond a critical maturation window impaired performance under high-demand conditions, increased overall mGC activity, and disrupted blade-specific organization even in animals that successfully completed the task. These findings demonstrate that high cognitive demand recruits spatially organized mGC activity and support a modulatory role for abDGCs in shaping dentate circuit dynamics.

A meta-analysis suggests that TMS targeting the hippocampal network selectively improves episodic memory

joelvoss@uchicago.edu (Arantzazu San Agustin) — Thu, 14 May 2026 00:00:00 +0000

Episodic memory is critically dependent on the hippocampal network and is frequently impaired in many clinical disorders. Recent findings highlight Hippocampal Indirectly Targeted Stimulation (HITS) as a promising, network-guided non-invasive transcranial magnetic stimulation (TMS) procedure to enhance episodic memory performance. Here, we report the first comprehensive meta-analysis of HITS effects on episodic memory, encompassing both healthy individuals and clinical populations. HITS using parieto-occipital network targets robustly improved episodic memory, with effects selective for episodic memory versus other non-memory cognitive domains. Efficacy was significantly greater when memory performance was assessed using memory tasks sensitive to recollection, which is strongly linked to hippocampal network function, compared to recognition or other types of episodic memory tasks. Efficacy was also significantly greater when HITS was delivered before the memory tasks were administered versus in the period between study and test phases of tasks. No serious adverse events were reported. These findings establish HITS as a robust approach for episodic memory enhancement, suggesting potential for clinical translation in memory disorders. Selectivity of effects for episodic memory generally and for recollection-format tests in particular indicates cognitive and mechanistic specificity, supporting the potential for targeted and selective neuromodulation of hippocampal networks and their associated functions.

Effort produces after-effects costly for others but valued for self

zhengya1982@gmail.com (Rumeng Tang) — Thu, 14 May 2026 00:00:00 +0000

Engaging in prosocial behavior requires effort, yet people are often averse to exerting effort for others’ benefit. However, it remains unclear how effort exertion affects subsequent reward evaluation during prosocial acts. Here, we combined high-temporal-resolution electroencephalography with a paradigm that independently manipulated physical effort and monetary reward for self and others to elucidate the neural mechanisms underlying the reward after-effect of prosocial effort expenditure. We found dissociable reward after-effects for self-benefiting and other-benefiting effort. For self-benefiting rewards, the reward positivity (RewP) increased with effort demand, suggesting an effort-enhancement effect. In contrast, for other-benefiting rewards, the RewP decreased as effort increased, demonstrating an effort-discounting effect. Critically, this dissociation was contingent upon high reward magnitude and modulated by individual differences in effort discounting, yet remained distinct from performance evaluation. Our findings reveal distinct neural computations for self- and other-benefiting efforts, offering new insights into how prior effort expenditure shapes reward evaluation during prosocial behavior.

Intravital calcium imaging of meningeal macrophages reveals niche-specific dynamics and aberrant responses to brain hyperexcitability

dlevy1@bidmc.harvard.edu (Anna Gutterman) — Wed, 13 May 2026 00:00:00 +0000

The meninges, which envelop and protect the brain, host a dense network of resident macrophages with diverse roles in regulating homeostasis and neuroinflammation. Despite their importance, we have a limited understanding of their behavior in vivo. Many dynamic cellular functions of macrophages involve intracellular Ca²⁺ signaling. However, virtually nothing is known about the spatiotemporal Ca²⁺ dynamics of meningeal macrophages in vivo. We developed a chronic intravital two-photon imaging approach and related computational analysis tools to interrogate meningeal macrophage Ca²⁺ dynamics, at subcellular resolution, in a novel Pf4-Cre:Ai162 conditional GCaMP6s reporter mouse model. Using imaging in awake mice, we characterized Ca²⁺ activity in meningeal macrophages at steady state and in response to cortical spreading depolarization (CSD), an aberrant pro-inflammatory brain hyperexcitability event implicated in migraine, traumatic brain injury, and stroke. In homeostatic meninges, macrophages in the dural perivascular niche exhibited several Ca²⁺ dynamic features, including event duration and signal frequency spectrum, distinct from those localized to the interstitial, non-perivascular niche. Simultaneous tracking of macrophage Ca²⁺ dynamics and local vasomotion revealed a subset of dural perivascular macrophages whose activity was coupled to locomotion-driven diameter fluctuations of their associated vessels. Most perivascular and non-perivascular meningeal macrophages displayed propagating intracellular Ca²⁺ activity and synchronized intercellular Ca²⁺ elevations, potentially driven by extrinsic factors. In response to CSD, the majority of perivascular and non-perivascular meningeal macrophages showed a persistent decrease in Ca²⁺ activity, while a smaller subset displayed Ca²⁺ elevations. Mechanistically, calcitonin gene-related peptide receptor signaling mediated the increase but not the decrease in CSD-mediated Ca²⁺ signaling. Collectively, our results highlight a previously unknown diversity of Ca²⁺ dynamics in meningeal macrophages at steady state and in response to an aberrant brain hyperexcitability event linked to neuroinflammation.

Locus coeruleus modulation of prefrontal dynamics during attentional switching in mice

hongdian@ucr.edu (Hongdian Yang) — Wed, 13 May 2026 00:00:00 +0000

Behavioral flexibility, the ability to adjust behavioral strategies in response to changing environmental contingencies and internal demands, is fundamental to cognitive functions. Despite a large body of pharmacology and lesion studies, the precise neurophysiological mechanisms that underlie behavioral flexibility are still under active investigations. This work is aimed to determine the role of a brainstem-to-prefrontal cortex circuit in flexible rule switching. We trained mice to perform a set-shifting task in which they learned to switch attention to distinguish complex sensory cues. Using chemogenetic inhibition, we selectively targeted genetically defined locus coeruleus (LC) neurons or their input to the medial prefrontal cortex (mPFC). We revealed that suppressing either the LC or its mPFC projections severely impaired switching behavior, establishing the critical role of the LC-mPFC circuit in supporting attentional switching. To uncover the neurophysiological substrates of the behavioral deficits, we paired endoscopic calcium imaging of the mPFC with chemogenetic inhibition of the LC in task-performing mice. We found that mPFC prominently responded to attentional switching and that LC inhibition not only enhanced the engagement of mPFC neurons but also broadened single-neuron tuning in the task. At the population level, LC inhibition disrupted mPFC dynamic changes and impaired the encoding capacity for switching. Our results highlight the profound impact of the ascending LC input on modulating prefrontal dynamics and provide new insights into the cellular and circuit-level mechanisms that support behavioral flexibility.

An altered cell-specific subcellular distribution of translesion synthesis DNA polymerase kappa (POLK) in aging mouse neurons

amp7167@psu.edu (Anirban Paul) — Wed, 13 May 2026 00:00:00 +0000

Genomic stability is critical for cellular function; however, in the central nervous system, highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role, if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in mouse neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons (INs) compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. INs associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which will help design strategies for longevity, healthspan, and prevention of neurodegeneration.

A context-free model of savings in motor learning

pgribble@uwo.ca (Jonathan A Michaels) — Wed, 13 May 2026 00:00:00 +0000

Learning to adapt voluntary movements to an external perturbation, whether mechanical or visual, is faster during a second encounter than during the first. The mechanisms underlying this phenomenon, known as savings, remain unclear. Recent studies propose that the high dimensionality of neural control enables the retention of learning traces that may facilitate savings. To test this idea, we used MotorNet, a framework for training recurrent neural networks (RNNs) to control biomechanical models of the human upper limb. RNNs were trained to perform reaching movements with a velocity-dependent force field (FF) and without (NF) in the sequence NF1 (baseline), FF1 (adaptation), NF2 (washout), and FF2 (re-adaptation). RNNs showed behaviural signatures of savings in the absence of any explicit contextual input signalling the presence or absence of the FF. Savings was more robust in RNNs with larger numbers of units. We identified a component of RNN activity associated with savings—a shift in preparatory activity that persisted even after washout. Displacing this preparatory activity in the direction of the shift enhanced savings, whereas perturbations in the opposite direction reduced or eliminated savings. These findings suggest a potential neural basis for motor memory retention underlying savings that is reliant on the high dimensionality of neural circuits for control, and is independent of cognitive or strategic learning.

Characterisation of cold-selective lamina I spinal projection neurons in the mouse

Andrew.Todd@glasgow.ac.uk (Aimi N Razlan) — Wed, 13 May 2026 00:00:00 +0000

Skin cooling is detected by primary afferents that express the Trpm8 channel, but how this information is conveyed to the brain remains poorly understood. We have previously identified a population of lamina I projection neurons belonging to the anterolateral system (ALS) that receive numerous contacts from Trpm8-expressing primary afferents. Here, using a semi-intact somatosensory preparation, we provide evidence that these cells correspond to the cold-selective ALS neurons identified in previous physiological studies. We also confirm the presence of synapses from Trpm8 afferents onto these cells at the ultrastructural level and with optogenetics. Based on our previous transcriptomic findings, we identify calbindin as a molecular marker, and show that this can be used to target the cold-selective ALS neurons for anterograde tracing studies. We provide evidence that they project to brain regions that have been implicated in thermosensation: the rostralmost part of the lateral parabrachial area, the caudal part of the periaqueductal grey matter, and the posterior triangular and ventral posterolateral nuclei of the thalamus. Our findings provide important insights into the organisation of neuronal circuits that underlie thermoregulation and the perception of cold stimuli applied to the skin.

Examining the role of lipids in hearing

Angela.Ballesteros@nih.gov (Angela Ballesteros) — Wed, 13 May 2026 00:00:00 +0000

The asymmetry of lipid membranes is tightly regulated in eukaryotic cells, and auditory hair cells are no exception.

Dissociable neural substrates of integration and segregation in exogenous attention

xhe@bournemouth.ac.uk (Ai-Su Li) — Wed, 13 May 2026 00:00:00 +0000

The integration-segregation theory proposes that early facilitation and later inhibition (i.e. inhibition of return [IOR]) in exogenous attention arises from the competition between cue-target event integration and segregation. Although widely supported behaviorally, the theory lacked direct neural evidence. Here, we used event-related functional magnetic resonance imaging (fMRI) in human participants with an optimized cue-target paradigm to test this account. Cued targets elicited stronger activation in the frontoparietal attention networks, including the bilateral frontal eye field (FEF), intraparietal sulcus (IPS), right temporoparietal junction (TPJ), and left dorsal anterior cingulate cortex (dACC), consistent with the notion of attentional demand of reactivating the cue-initiated representations for integration. In contrast, uncued targets engaged the medial temporal cortex, particularly the bilateral parahippocampal gyrus (PHG) and superior temporal gyrus (STG), reflecting the segregation processes associated with new object-file creation and novelty encoding. These dissociable activations provide the first direct neuroimaging evidence for the integration-segregation theory. Moreover, we observed neural interactions between IOR and cognitive conflict, suggesting a potential modulation of conflict processing by attentional orienting. Taken together, these findings provide new insights into exogenous attention by clarifying the neural underpinnings of integration and segregation and uncovering the interaction between spatial orienting and conflict processing.

Modeling flexible behavior with remapping-based hippocampal sequence learning

yito@nips.ac.jp (Taro Toyoizumi) — Wed, 13 May 2026 00:00:00 +0000

Animals flexibly change their behavior depending on context. It is reported that the hippocampus is one of the most prominent regions for contextual behaviors, and its sequential activity shows context dependency. However, how such context-dependent sequential activity is established through reorganization of neuronal activity (remapping) remains unclear. To better understand the formation of hippocampal activity and its contribution to context-dependent flexible behavior, we present a novel biologically plausible reinforcement learning model. In this model, Context selector promotes the formation of context-dependent sequential activity and allows for flexible switching of behavior in multiple contexts. This model reproduces a variety of findings from neural activity, optogenetic inactivation, human fMRI, and clinical research. Furthermore, our model predicts that imbalances in the ratio between sensory and contextual representations in Context selector account for schizophrenia and autism spectrum disorder-like behaviors.

Cortical motor activity modulates respiration and reduces apnoea in neonates

caroline.hartley@paediatrics.ox.ac.uk (Caroline Hartley) — Tue, 12 May 2026 00:00:00 +0000

Respiration is governed by a widespread network of cortical and subcortical structures. This complex communication between the brain and lungs is altered in pathological conditions. Apnoea – the cessation of respiration – is a common condition in infants, particularly those born prematurely. Apnoea in infants is believed to relate to immaturity of brainstem respiratory centres; involvement of the cortex in respiration in infants has yet to be explored. We investigated if there was any evidence for cortical coupling with respiration in newborn humans and whether it relates to apnoea. Using simultaneous electroencephalography (EEG) and impedance pneumography, we investigated interactions between cortical and respiratory activity (known as cortico-respiratory coupling) using phase-amplitude coupling. We show that cortico-respiratory coupling is present in premature and term newborns (104 recordings from 68 infants; 34.5±2.6 weeks postmenstrual age), identifying an interplay between breathing phase and EEG amplitude. We further shed light on the biological meaning by revealing that the strongest coupling occurs during inspiration and that cortical activity precedes respiration, with coupling strongest over frontocentral regions. Whilst our study was limited in spatial resolution, and determining causality is challenging, we believe these findings support the notion that the cortico-respiratory coupling observed here constitutes communication between cortical motor areas and lung effectors. Moreover, we show that cortico-respiratory coupling is negatively correlated with the rate of apnoea, revealing novel insight into this common and potentially life-threatening neonatal pathology.

Drift in individual behavioral phenotype as a strategy for unpredictable worlds

rtmaloney@coloradocollege.edu (Athena Q Ye) — Tue, 12 May 2026 00:00:00 +0000

Individuals, even with matched genetics and environment, show substantial phenotypic variability. This variability may be part of a bet-hedging strategy, where populations express a range of phenotypes to ensure survival in unpredictable environments. In addition, phenotypic variability between individuals (‘bet-hedging’), individuals also show variability in their phenotype across time, even absent external cues. There are few evolutionary theories that explain random shifts in phenotype across an animal's life, which we term drift in individual phenotype. We use individuality in locomotor handedness in Drosophila melanogaster to characterize both bet-hedging and drift. We use a continuous circling assay to show that handedness spontaneously changes over timescales ranging from seconds to the lifespan of a fly. We compare the amount of drift and bet-hedging across a number of different fly strains and show independent strain-specific differences in bet-hedging and drift. We show manipulation of serotonin changes the rate of drift, indicating a potential circuit substrate controlling drift. We then develop a theoretical framework for assessing the adaptive value of drift, demonstrating that drift may be adaptive for populations subject to selection pressures that fluctuate on timescales similar to the lifespan of an animal. We apply our model to real-world environmental signals and find patterns of fluctuations that favor random drift in behavioral phenotype, suggesting that drift may be adaptive under some real-world conditions. These results demonstrate that drift plays a role in driving variability in a population and may serve an adaptive role distinct from population-level bet-hedging.

Functional imaging of nine distinct neuronal populations under a miniscope in freely behaving animals

mary.phillips@zeiss.com (Mary L Phillips) — Tue, 12 May 2026 00:00:00 +0000

Head-mounted miniscopes have enabled functional fluorescence imaging in freely moving animals. However, current technology is limited to recording at most two spectrally distinct fluorophores, severely restricting the number of identifiable cell types. Here, we introduce multiplexed neuronal imaging (Neuroplex), a pipeline combining miniscope Ca²⁺ recordings with in vivo multiplexed confocal spectral imaging to distinguish nine projection-defined neuronal subtypes through the same GRIN lens. By co-registering defined neurons with fluorophore-specific spectral fingerprints via linear unmixing, we link projection-defined identities to behaviorally relevant neuronal activity. This approach overcomes spectral constraints of miniscopes, enabling circuit-level dissection of behavior in single animals.

Endogenous corazonin signaling modulates the post-mating switch in behavior and physiology in females of the brown planthopper and Drosophila

wusf@njau.edu.cn (Congfen Gao) — Tue, 12 May 2026 00:00:00 +0000

Mating in insects typically triggers a post-mating response (PMR) in females, characterized by reduced receptivity to re-mating and increased oviposition, which ensures numerous and viable offspring and male paternity. This PMR is induced by male seminal factors, such as sex peptide in Drosophila melanogaster, as well as intrinsic female signaling components. The latter signaling remains poorly understood in most insects, including the devastating rice pest, the brown planthopper (BPH) Nilaparvata lugens. Here, we show that the neuropeptide corazonin (CRZ) and its receptor (CrzR) are critical for the PMR in female BPHs. Peptide injection, RNAi knockdown, and CRISPR/Cas9 mutagenesis confirm that intact CRZ signaling reduces re-mating frequency and increases ovulation in mated BPH females. The CrzR is highly expressed in the female reproductive tract, and CrzR knockdown phenocopies CRZ diminishment. Importantly, female CRZ/CrzR signaling is required for male seminal factors, such as the peptide maccessin, to induce the PMR; with disrupted CrzR signaling, injection of seminal fluid or maccessin fails to reduce female receptivity. Notably, CRZ is not produced in male accessory glands (MAGs) of BPHs and thus not transferred during copulation. We furthermore demonstrate that also in D. melanogaster disrupted CRZ signaling increases female re-mating and reduces oviposition, while CRZ injection suppresses virgin receptivity and increases oviposition. Finally, we detected no CRZ in the MAG of D. melanogaster, supporting its role as an endogenous signal in the female PMR also in this species. In summary, our findings reveal a conserved role of endogenous CRZ signaling in regulating the female PMR and demonstrate that female CRZ signaling and male-derived signals cooperate to induce post-mating transitions in BPHs and D. melanogaster. CRZ is a paralog of the peptide gonadotropin-releasing hormone, known to regulate reproduction in vertebrates, including humans, suggesting evolutionary conservation of an ancient function.

Cross-modal interaction of human alpha activity does not reflect inhibition of early sensory processing in a frequency-tagging study using EEG and MEG

marion.brickwedde@charite.de (Ali Mazaheri) — Mon, 11 May 2026 00:00:00 +0000

Selective attention involves prioritising relevant sensory input while suppressing irrelevant stimuli. It has been proposed that oscillatory alpha-band activity (~10 Hz) aids this process by functionally inhibiting early sensory regions. However, recent studies have challenged this notion. Our EEG and MEG studies aimed to investigate whether human alpha oscillations serve as a 'gatekeeper' for downstream signal transmission. We first observed these effects in an EEG study and then replicated them using MEG, which allowed us to localise the sources. We employed a cross-modal paradigm where visual cues indicated whether upcoming targets required visual or auditory discrimination. To assess inhibition, we utilised frequency-tagging, simultaneously flickering the fixation cross at 36 Hz and playing amplitude-modulated white noise at 40 Hz during the cue-to-target interval. Consistent with prior research, we observed an increase in posterior alpha activity following cues signalling auditory targets. However, remarkably, both visual and auditory frequency-tagged responses amplified in anticipation of auditory targets, correlating with alpha activity amplitude. Our findings suggest that when attention shifts to auditory processing, the visual stream remains responsive and is not hindered by occipital alpha activity. This implies that alpha modulation does not solely regulate 'gain control' in early visual areas but rather orchestrates signal transmission to later stages of the processing stream.

Regime shift detection and neurocomputational substrates for under and overreactions to change

raccoon65.y@nycu.edu.tw (George Wu) — Mon, 11 May 2026 00:00:00 +0000

The world constantly changes, with the underlying state of the world shifting from one regime to another. The ability to detect a regime shift, such as the onset of a pandemic or the end of a recession, significantly impacts individual decisions, as well as governmental policies. However, determining whether a regime has changed is usually not obvious, as signals are noisy and reflective of the volatility of the environment. We designed an fMRI paradigm that examines a stylized regime-shift detection task. Human participants showed systematic overreaction and underreaction: Overreaction was most commonly seen when signals were noisy, but when environments were stable and change is possible but unlikely. By contrast, underreaction was observed when signals were precise but when environments were unstable and hence change was more likely. These behavioral signatures are consistent with the system-neglect computational hypothesis, which posits that sensitivity or lack thereof to system parameters (noise and volatility) is central to these behavioral biases. Guided by this computational framework, we found that individual subjects’ sensitivity to system parameters was represented by two distinct brain networks. Whereas a frontoparietal network selectively represented individuals’ sensitivity to signal noise but not environment volatility, the ventromedial prefrontal cortex (vmPFC) showed the opposite pattern. Further, these two networks were involved in different aspects of regime-shift computations: while vmPFC correlated with subjects’ beliefs about change, the frontoparietal network represented the strength of evidence in favor of regime shifts. Together, these results suggest that regime-shift detection recruits belief-updating and evidence-evaluation networks and that under- and overreactions arise from how sensitive these networks are to the system parameters.

Adult-neurogenesis allows for representational stability and flexibility in early olfactory system

Krishnan_Padmanabhan@urmc.rochester.edu (Krishnan Padmanabhan) — Mon, 11 May 2026 00:00:00 +0000

In the olfactory system, adult-neurogenesis results in the continuous reorganization of synaptic connections and network architecture throughout the animal’s life. This poses a critical challenge: How does the olfactory system maintain stable representations of odors amidst this ongoing circuit instability? Utilizing a detailed spiking network model of early olfactory circuits, we uncovered dual roles for adult-neurogenesis: one that both supports representational stability to faithfully encode odor information, and also one that facilitates plasticity to allow for learning and adaptation. In the main olfactory bulb, adult-neurogenesis affects neural codes in individual mitral and tufted cells but preserves odor representations at the neuronal population level. By contrast, in the olfactory piriform cortex (PCx), both individual cell responses and overall population dynamics undergo progressive changes due to adult-neurogenesis. This leads to representational drift, a gradual alteration in stimulus-evoked activity patterns. Both processes are dynamic and depend on experience such that repeated exposure to specific odors reduces the drift due to adult-neurogenesis; thus, when the odor environment is stable over the course of adult-neurogenesis, it is spike-timing-dependent plasticity that leads representations to remain stable in the PCx; when those olfactory environments change, adult-neurogenesis allows cortical representations to track environmental change. Whereas perceptual stability and plasticity due to learning are often thought of as two distinct, often contradictory processes in neuronal coding, we find that adult-neurogenesis serves as a shared mechanism for both. In this regard, the quixotic presence of adult-neurogenesis in the mammalian olfactory bulb that has been the focus of considerable investigation in chemosensory neuroscience may be the mechanistic underpinning behind an array of complex computations.

Neural representation of time across complementary reference frames

xuya@cbs.mpg.de (Léo Dutriaux) — Fri, 08 May 2026 00:00:00 +0000

Humans conceptualize time in terms of space, allowing flexible time construals from various perspectives. We can travel internally through a timeline to remember the past and imagine the future (i.e., mental time travel) or watch from an external standpoint to have a panoramic view of history (i.e., mental time watching). However, the neural mechanisms that support these flexible temporal construals remain unclear. To investigate this, we asked participants to learn a fictional religious ritual of 15 events. During fMRI scanning, they were guided to consider the event series from either an internal or external perspective in different tasks. Behavioral results confirmed the success of our manipulation, showing the expected symbolic distance effect in the internal-perspective task and the reverse effect in the external-perspective task. We found that the activation level in the posterior parietal cortex correlated positively with sequential distance in the external-perspective task but negatively in the internal-perspective task. In contrast, the activation level in the anterior hippocampus positively correlated with sequential distance regardless of the observer’s perspectives. These results suggest that the hippocampus stores the memory of the event sequences allocentrically in a perspective-agnostic manner. Conversely, the posterior parietal cortex retrieves event sequences egocentrically from the optimal perspective for the current task context. Such complementary allocentric and egocentric representations support both the stability of memory storage and the flexibility of time construals.

Prolonged oscillating preoptic area kisspeptin neuron activity underlies the preovulatory luteinizing hormone surge in mice

aeh36@cam.ac.uk (Allan Edward Herbison) — Thu, 07 May 2026 00:00:00 +0000

The population of kisspeptin neurons located in the rostral periventricular area of the third ventricle (RP3V) is thought to have a key role in generating the GnRH surge that triggers ovulation. Using a modified GCaMP fibre photometry procedure, we have been able to record the in vivo population activity of RP3V^KISS neurons across the estrous cycle of female mice. A marked increase in GCaMP activity was detected beginning on the afternoon of proestrus that lasted in total for 13±1 hr. This was comprised of slow baseline oscillations with a period of 91±4 min associated with high-frequency rapid transients. Very little oscillating baseline or transient activity was detected at other stages of the estrous cycle. Concurrent blood sampling showed that the peak of the LH surge occurred 3.5±1.1 hr after the first baseline RP3V^KISS neuron baseline oscillation on the afternoon of proestrus. The time of onset of RP3V^KISS neuron oscillations varied between mice and across subsequent proestrous stages in the same mice. To assess the impact of estradiol on RP3V^KISS neuron activity, mice were ovariectomized and given an incremental estradiol replacement regimen. Minimal patterned GCaMP activity was found in OVX mice, and this was not changed acutely by any of the estradiol treatments. However, on the afternoon of the expected LH surge, the same oscillating baseline activity with associated transients occurred for 7.1±0.5 hr. These observations reveal an unexpected prolonged oscillatory pattern of RP3V^KISS neuron activity that is dependent on estrogen and underlies the preovulatory LH surge as well as potentially other facets of reproductive behavior.

Canonical neurodevelopmental trajectories of structural and functional manifolds

Alicja.Monaghan@mrc-cbu.cam.ac.uk (Alicja Monaghan) — Wed, 06 May 2026 00:00:00 +0000

Organisational gradients refer to a continuous low-dimensional embedding of brain regions and can quantify core organisational principles of complex systems like the human brain. Mapping how these organisational principles are altered or refined across development and phenotypes is essential to understanding the relationship between brain and behaviour. Taking a developmental approach and leveraging longitudinal and cross-sectional data from two multi-modal neuroimaging datasets, spanning the full neurotypical-neurodivergent continuum, we charted the organisational variability of structural (610 participants, N=390 with one observation, N=163 with two observations and N=57 with three) and functional (512 participants, N=340 with one observation, N=128 with two observations and N=44 with three). Across datasets, despite differing phenotypes, we observe highly similar structural and functional gradients. These gradients, or organisational principles, are highly stable across development, with the exact same ordering across early childhood into mid-adolescence. However, there is substantial developmental change in the strength of embedding within those gradients: by modelling developmental trajectories as non-linear splines, we show that structural and functional gradients are refined across development. Specifically, structural gradients gradually contract in low-dimensional space as networks become more integrated, whilst the functional manifold expands, indexing functional specialisation. The coupling of these structural and functional gradients follows a unimodal-association axis and varies across individuals, with developmental effects concentrated in the more plastic higher-order networks. Importantly, these developmental effects on coupling, in these higher-order networks, are attenuated in the neurodivergent sample. Finally, we mapped structure-function coupling onto dimensions of psychopathology and cognition and demonstrate that dimensions of cognition, such as working memory, are robust predictors of coupling. In summary, across clinical and community samples, we demonstrate consistent principles of structural and functional brain organisation, with progressive structural integration and functional segregation. These gradients are established early in life, refined through development, and their coupling is predicted by working memory.

Continuous flash suppression of neural responses and population orientation coding in macaque V1

tangshm@pku.edu.cn (Cai-Xia Chen) — Wed, 06 May 2026 00:00:00 +0000

Continuous flash suppression (CFS), in which a dynamic masker presented to one eye suppresses awareness of a stimulus in the other eye, is widely used to study visual subconsciousness. Although some studies report preserved high-level processing under CFS, these effects have been increasingly questioned and may partly reflect residual low-level feature processing. A key unresolved issue is how strongly neuronal responses in V1, where inputs from the two eyes first converge, are affected by CFS, and how much the remaining signals can support downstream processing. Here, we used two-photon calcium imaging to record large populations of V1 neurons in awake, fixating macaques while presenting grating stimuli under CFS. CFS strongly suppressed V1 orientation responses in an ocular-dominance-dependent manner, nearly abolishing responses in neurons preferring the masker eye or both eyes, and significantly reducing responses in neurons preferring the grating eye. Modeling analyses further indicated that V1 population activity under CFS may still support coarse orientation classification but not accurate stimulus reconstruction. These results suggest that CFS substantially degrades orientation information in V1. The residual signals may support limited low-level processing but are likely insufficient for downstream higher-level visual and cognitive tasks.

Auditory perception and neural representation of temporal features are altered by age but not by cochlear synaptopathy

georg.klump@uni-oldenburg.de (Christine Köppl) — Tue, 05 May 2026 00:00:00 +0000

Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between the cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.

Are kinocilia motile?

eatock@uchicago.edu (Marina Kabirova) — Tue, 05 May 2026 00:00:00 +0000

Gene expression patterns in the inner ear put an old question about structures called kinocilia back in motion.

Human adherent cortical organoids in a multi-well format

sk2602@cumc.columbia.edu (Femke MS de Vrij) — Tue, 05 May 2026 00:00:00 +0000

In the growing diversity of human induced pluripotent stem cell (iPSC)-derived models of brain development, we present here a novel method that exhibits 3D cortical layer formation in a reproducible topography of minimal dimensions. The resulting adherent cortical organoids (ACOs) develop by self-organization after seeding frontal cortex-patterned iPSC-derived neural progenitor cells in 384-well plates during 8 weeks of differentiation. The organoids have stereotypical dimensions of 3 × 3 × 0.2 mm, contain multiple subtypes of neurons, astrocytes, and oligodendrocyte lineage cells, and are amenable to extended culture for at least 10 months. Longitudinal imaging revealed morphologically mature dendritic spines, axonal myelination, and robust neuronal activity. Moreover, ACOs compare favorably to existing free-floating brain organoid models on the basis of robust reproducibility in obtaining topographically standardized radial cortical structures and circumventing internal necrosis. Adherent human cortical organoids hold considerable potential for high-throughput drug discovery applications, neurotoxicological screening, and mechanistic pathophysiological studies of brain disorders.