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<title>bioRxiv Subject Collection: Neuroscience</title>
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This feed contains articles for bioRxiv Subject Collection "Neuroscience"
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<title>bioRxiv</title>
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<link>https://www.biorxiv.org</link>
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<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.730254v1?rss=1">
<title>
<![CDATA[
Spatiotemporal Patterns and Structural Substrates of Individual Functional Variability in Youth 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.730254v1?rss=1
</link>
<description><![CDATA[
Youth is a period of emerging individuality and extensive neural remodeling, yet how functional brain individuality is organized across development remains unclear. Prior work has often conflated variability in functional topography and connectivity, highlighting the need to examine them separately to better understand how functional individuality relates to brain structure and cognition. Here we used individualized functional parcellation in a large multimodal developmental cohort to separately quantify variability in individualized functional parcellation (vIFP) and variability in functional connectivity (vFC). Both forms of variability followed the sensorimotor-association axis and were greatest in the association cortex. vIFP increased significantly with age, whereas vFC showed regionally specific maturation without a significant whole-brain increase. Both trajectories showed a common mid-adolescent inflection at 14-16 years, marking a window of accelerated functional individualization. Despite shared spatial and temporal organization, vIFP and vFC showed dissociable links to structure and cognition. vIFP was more strongly coupled to structural variability, whereas vFC was more strongly associated with cognitive variability. These findings reveal convergent and divergent developmental principles of topographic and connectional functional variability, highlighting their complementary roles in structural constraints and cognitive specialization.
]]></description>
<dc:creator><![CDATA[ Yang, Z., Dong, X., Zeng, D., Chu, L., He, Y., Zhang, J., Li, Q., Zhang, Y., Sun, L., Wang, X., Li, S. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.730254</dc:identifier>
<dc:title><![CDATA[Spatiotemporal Patterns and Structural Substrates of Individual Functional Variability in Youth]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732149v1?rss=1">
<title>
<![CDATA[
Retinal cell mosaics in the valproate-induced rat model of autism spectrum disorder 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732149v1?rss=1
</link>
<description><![CDATA[
Valproic acid (VPA) is a widely used antiepileptic drug that also increases the risk of neurodevelopmental disorders in the offspring of exposed mothers. Prenatal exposure to VPA is a widely used rodent model of autism spectrum disorder (ASD). Anatomical, functional and molecular alterations in the retinas of various ASD model animals have been described in the literature, but the impact on the neural composition of the retina remains unclear. We examined whether and how the density and spatial regularity of selected retinal neurons are altered in the VPA induced model of ASD. Whole-mount retinas of 2-month-old VPA-treated and control animals were immunolabeled for S-cones, horizontal cells, AII amacrine cells, and parvalbumin-positive wide-field amacrines (PV-wfACs), and the positions of labelled cells mapped in various regions of interest (n = 39 for treated, n = 32 for control animals) across the retinas. Multivariate analysis of variance revealed a significant overall effect of VPA on cell densities (p = 6.1x10-7, 2 = 0.43), driven mainly by reduced AII amacrine density, while horizontal cells showed a modest reduction and S-cones were unaffected. After adjusting for retinal location, analysis of covariance indicated a 7% decrease in AII cells and a 15% increase in PV-wfACs. Regularity indices calculated from nearest neighbor distances or Voronoi-domain areas of cell mosaics were largely unchanged. These findings suggest that prenatal VPA exposure selectively alters inhibitory inner retinal circuitry in the rat ASD model at the time of cell differentiation, but self-organizing mechanisms responsible for spatial order are not affected.
]]></description>
<dc:creator><![CDATA[ Telkes, I., Fusz, K., Janosi, T. Z., Kobor, P., ElZafarany, A., Sari, Z., Laszlo, K., Buzas, P. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732149</dc:identifier>
<dc:title><![CDATA[Retinal cell mosaics in the valproate-induced rat model of autism spectrum disorder]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.17.733040v1?rss=1">
<title>
<![CDATA[
Human striatal population state dynamics 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.17.733040v1?rss=1
</link>
<description><![CDATA[
Animal models reveal that striatal projection neurons (SPNs) fluctuate between discrete electrophysiological states with distinct levels of cortical interaction. These dynamics and their behavioral relevance remain uncharacterized in humans. Leveraging neurobiologically informed modeling of over 3 billion voxel-frame-wise striatal coactivation profiles with cortex in functional magnetic resonance imaging (fMRI), we identified population-level striatal states in humans resembling canonical SPN states that reorganized systematically with task demands, arousal and behavior. A background of low- and moderate-coactivation "down-like" and "up-like" striatal rest states with high transition reciprocity modulated task reaction times and reward reactivity. Meanwhile, sparse, disproportionately high-magnitude "bursts" of striatal coactivation with cortex, which emerged preferentially from the up-like rest state and whose cortical input composition varied with task context, tracked task engagement and arousal level. Findings bring a critical feature of corticostriatal neurobiology into systems-level view in humans and reveal a subthreshold state architecture whose balance encodes behaviorally relevant information.
]]></description>
<dc:creator><![CDATA[ Korponay, C., stein, e. a., Ross, T. J., Janes, A. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.17.733040</dc:identifier>
<dc:title><![CDATA[Human striatal population state dynamics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.18.732834v1?rss=1">
<title>
<![CDATA[
Distinct cortical patches for syntactic and semantic composition in the human brain 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.18.732834v1?rss=1
</link>
<description><![CDATA[
Although the brain areas for language processing are well delimited, whether lexical-semantic and syntactic processes are spatially segregated remains debated. To clarify this issue, we conducted two experiments using 7-Tesla functional MRI in 20 participants performing: a functional localizer involving reading sequences of words of increasing linguistic complexity; and a presentation of short, semantically impoverished three-word mini-sentences, flashed in a single glance (e.g., "he does it"), whose grammaticality and syntactic complexity was manipulated through syntactic movement. Our results reveal two functionally dissociable sets of cortical patches within the language system: one sensitive to syntactic structure even in the absence of meaning, and the other involved in semantic composition. This dual-network architecture was consistently observed in the majority of participants, although its precise anatomical localization varied. The two types of voxels coexisted even within a given brain region of the Glasser atlas. Results were confirmed using subject-specific analyses and region-by-condition interactions, as voxels in those two systems displayed markedly different responses to mini-sentences. Thus, high-resolution functional imaging reveals a division of labor between syntactic and semantic composition within the classical language network.
]]></description>
<dc:creator><![CDATA[ Dighiero-Becht, T., Friedmann, N., Rizzi, L., Pallier, C., Dehaene, S. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.18.732834</dc:identifier>
<dc:title><![CDATA[Distinct cortical patches for syntactic and semantic composition in the human brain]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.17.732971v1?rss=1">
<title>
<![CDATA[
Early life Oxytocin treatment Attenuates Seizure Susceptibility in Male, but not Female, Fmr1-KO Mice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.17.732971v1?rss=1
</link>
<description><![CDATA[
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, and is frequently accompanied by seizures. Early-life treatment with the hormone oxytocin (OXT) improves social behavior and cognitive function in rodent models of autism with intellectual disability, including FXS, but potential OXT treatment effects on seizure susceptibility have not been evaluated. Here we tested, in both sexes, if intranasal OXT (iOXT) or saline (iSAL) during the second postnatal week reduces audiogenic seizures (AGS) in the Fmr1-Knockout (KO) mouse model of FXS. OXT given daily from postnatal day (P) 7 to P13 significantly reduced the incidence and severity of AGS and the latency to seize in adult male Fmr1-KOs. Female KOs exhibited less severe seizures that were unaffected by treatment. Wild type mice did not exhibit AGS independent of treatment. To test if antiepileptic effects of iOXT are age-dependent, a separate cohort received iOXT daily from P30 to P36. Male KOs receiving later treatments exhibited robust seizures that were comparable between OXT- and SAL-treatment groups, suggesting that OXTs enduring antiepileptic effects are confined to early postnatal treatments. Tests of acute OXT effects in adulthood demonstrated an attenuation of male Fmr1-KO AGS at testing 30-60 min and 1 day post-treatment but these effects were not evident 15 days later. These findings reveal marked sex differences in the propensity for audiogenic seizures in Fmr1-KO mice and demonstrate that early-life OXT treatment mitigates seizure susceptibility in males FXS model mice.
]]></description>
<dc:creator><![CDATA[ Chavez, J., Lauterborn, J. M., Lynch, G., Gall, C. M. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.17.732971</dc:identifier>
<dc:title><![CDATA[Early life Oxytocin treatment Attenuates Seizure Susceptibility in Male, but not Female, Fmr1-KO Mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.731945v1?rss=1">
<title>
<![CDATA[
The lysosomal cation channel TRPML1 regulates the oligodendrocyte cytoskeleton 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.731945v1?rss=1
</link>
<description><![CDATA[
Differentiating oligodendrocytes undergo dramatic morphologic alterations to transition from progenitors to mature oligodendrocytes that synthesize myelin, the lipid-rich membrane coating axons which strengthens saltatory conduction and provides metabolic support. Actin dynamics, which are often regulated by membrane bound nucleators associated with organelles, underpin the morphologic shifts in oligodendrocyte maturation; however, the origin of such regulation during oligodendrocyte differentiation remains unknown. Here, we demonstrate that the lysosomal non-selective cation channel, transient potential mucolipin 1 (TRPML1), is a critical regulator of oligodendrocyte morphology during differentiation and initial myelination. Lysosomes move into oligodendrocyte processes during differentiation. While manipulation of TRPML1 did not change the expression of oligodendrocyte lineage markers, activation of TRPML1 resulted in altered oligodendrocyte morphology and an increase in actin filament content driven by the small GTPase Rac1 and subsequent disinhibition of PAK1 via phosphorylation. Actin associated changes in morphology are accompanied by the presence of lysosomal-derived calcium transients in nascent oligodendrocyte processes, potentially revealing a link between localized calcium signaling and actin polymerization. Lastly, adolescent mice (Mcoln1-/- ), in which TRPML1 had been deleted, had significantly impaired myelination and decreased numbers of mature oligodendrocyte, which was associated with a reduction in staining for the phosphorylated form of the actin regulator, PAK1, in the motor cortex and corpus callosum as evidence of decreased TRPML1/Rac1/PAK1 signaling. Together, our work reveals lysosomal TRPML1 activity as a central regulator of oligodendrocyte morphology independent of myelin protein expression and may provide mechanistic insight into the distinct but coordinated pathways that lead to oligodendrocyte differentiation and how lysosomal dysfunction impacts these processes in diseased states.
]]></description>
<dc:creator><![CDATA[ Festa, L. K., Fandino Pachon, N., Anderson, R. N., Chen, S. J., Grinspan, J. B., Jordan-Sciutto, K. L. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.731945</dc:identifier>
<dc:title><![CDATA[The lysosomal cation channel TRPML1 regulates the oligodendrocyte cytoskeleton]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.17.732833v1?rss=1">
<title>
<![CDATA[
A hippocampal neuroimaging signature of neurovascular insulin signalling links metabolism to mood 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.17.732833v1?rss=1
</link>
<description><![CDATA[
Depression is a leading cause of global disability and is increasingly linked to systemic metabolic dysfunctions, including insulin resistance. However, the biological pathways connecting metabolic state to affective symptoms are unresolved. A growing body of evidence indicates that insulin, beyond its role in systemic glucose homeostasis, supports brain metabolism, synaptic function and cognition, yet its contribution to mood regulation remains unclear. Here, we identify a human hippocampal metabolic signature associated with glycaemic variation in individuals with depression. Using multimodal neuroimaging, we show that hippocampal concentrations of GABA and lactate correlate with HbA1c and with mood severity, while functional connectivity between the hippocampus and the default mode network tracks affective symptoms independently of adiposity. To causally probe these relationships, we generated a mouse model of hippocampus-specific insulin receptor depletion. Unexpectedly, reducing insulin signalling at the blood brain barrier enhanced neuronal metabolism and attenuated anxiety-like behaviour. Notably, hippocampal lactate and GABA levels similarly tracked anxiety-related behaviour in mice, mirroring their association with symptom severity in humans. Together, these findings identify a conserved neurometabolic signature linking hippocampal insulin signalling to affective state, and reveal that brain insulin resistance exerts context- and cell-type-specific effects on behaviour. This work establishes a mechanistic basis for brain insulin resistance in depression and highlights the hippocampus as a critical hub for metabolic modulation of mood.
]]></description>
<dc:creator><![CDATA[ Cherix, A., Godlewska, B., Lazari, A., Zhao, S., Dugan, G., Tachrount, M., Greco, M., Smart, S., Clarke, W. T., Bannerman, D., Stagg, C. J., Husain, M., Cowen, P. J., Lerch, J. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.17.732833</dc:identifier>
<dc:title><![CDATA[A hippocampal neuroimaging signature of neurovascular insulin signalling links metabolism to mood]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.15.732482v1?rss=1">
<title>
<![CDATA[
Parallel basal ganglia and frontal cortical outputs differentially encode context-dependent evaluation and categorical commitment during choice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.15.732482v1?rss=1
</link>
<description><![CDATA[
Adaptive choice requires transforming the evaluation of available options into commitment to a specific action but understanding how this transformation is implemented across neural circuits remains a central challenge. Here we recorded well-isolated neurons in the substantia nigra pars reticulata (SNr) and frontal eye field (FEF), which send parallel projections to the superior colliculus for driving the eye movement choice, while monkeys performed a sequential-offer choice task designed to partially dissociate scene-defined ordinal rank from the categorical commitment. Before target onset, SNr displayed stronger scene-related modulation than FEF. During target evaluation, SNr activity showed ordered modulation across behavioral outcomes dominated by ordinal rank, whereas FEF activity categorically separated acceptance from rejection and strongly encoded target direction. Behavioral model decomposition revealed that ordinal rank alone best explained SNr activity, outperforming both reward magnitude and even a composite acceptability measure that incorporated rank together with reward, scene context, and waiting cost, whereas FEF activity was best explained by categorical commitment. This dissociation was consistent across multivariable modeling, single-neuron response patterns, and all three monkeys. Together, these findings support a division of labor in which context-dependent evaluation and categorical commitment are distributed across parallel basal ganglia and frontal cortical output pathways to efficiently guide voluntary choices.
]]></description>
<dc:creator><![CDATA[ Yoshida, A., Krauzlis, R., Hikosaka, O. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.15.732482</dc:identifier>
<dc:title><![CDATA[Parallel basal ganglia and frontal cortical outputs differentially encode context-dependent evaluation and categorical commitment during choice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.18.733090v1?rss=1">
<title>
<![CDATA[
Acute hypercapnic stress modulates innate and learned defensive behavior 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.18.733090v1?rss=1
</link>
<description><![CDATA[
Survival depends on avoiding threats, a process shaped by experience and internal states. Notably, acute stress can induce analgesia, yet the neural mechanisms by which stress alters aversive value coding remain unclear. Using Drosophila, we show that prior noxious experience induces intensity-dependent analgesia and triggers the release of CO2, a known stress signal. Surprisingly, this effect is mediated by tracheal dendrite (td) neurons in the respiratory system rather than classic olfactory pathways. We then demonstrated that activation of td neurons induces analgesia, whereas their inhibition suppresses it and restores normal nocifensive and learned behavior. Finally, high CO2 exposure decreases dopaminergic neuron responses to electric shocks, thereby impairing aversive memory formation. Together, we propose that under hypercapnic (high CO2) stress, td neurons modulate nociceptive computation and aversive value coding in the brain to facilitate appropriate innate and learned behavioral responses.
]]></description>
<dc:creator><![CDATA[ Merabet, N., Guiraud, C., Zuefle, P., Vieu, M., Zirah, C., Truong, A.-K., Martelli, C., Perisse, E. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.18.733090</dc:identifier>
<dc:title><![CDATA[Acute hypercapnic stress modulates innate and learned defensive behavior]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.731709v1?rss=1">
<title>
<![CDATA[
Striatal activity maintains a short-term action-outcome memory to guide future choice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.731709v1?rss=1
</link>
<description><![CDATA[
Adaptive behavior requires animals to use the outcomes of recent actions (action-outcomes) to guide future decisions. While the striatum is critical for decision-making, it is currently unclear how it is involved in the storage and retrieval of short-term associative memories. Here, we implemented a head-fixed memory-guided decision-making task in which mice use the outcome of a previous choice to determine whether to repeat or switch their next action. We show that dopamine fluctuations in the ventrolateral striatum are modulated by reward receipt or omission and recent outcome history, while the activity of direct and indirect pathway striatal projection neurons encodes recent action-outcome associations and predicts future switch/repeat choices. Closed-loop optogenetic activation and inhibition of direct and indirect pathway neurons during either the action-outcome association period or the delay preceding the next choice bidirectionally biased future actions away from those favored by reward history. Together, these findings suggest that striatal activity maintains a short-term action-outcome associative memory that links completed actions to future motor plans during adaptive decision-making.
]]></description>
<dc:creator><![CDATA[ Girasole, A. E., Mandelbaum, G., Murray, L. C., Beron, C. C., Albanese, M. A., Zhang, R. Y., van den Boom, B. J. G., Alvarado, R. N., Hochbaum, D. R., Haynes, T. M., Bobillo, M. D., Wang, W., Sabatini, B. L. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.731709</dc:identifier>
<dc:title><![CDATA[Striatal activity maintains a short-term action-outcome memory to guide future choice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732743v1?rss=1">
<title>
<![CDATA[
PTEN Subcellular Localization Dictates Function 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732743v1?rss=1
</link>
<description><![CDATA[
Mutations in phosphatase and tensin homolog (PTEN) drive unregulated activation of the phosphatidylinositol-3-kinase (PI3K) pathway, resulting in neuronal hypertrophy, and are strongly associated with autism spectrum disorder (ASD). Several PTEN mutations alter subcellular localization, yet how localization governs PTEN function in developing neurons remains unclear. Although PTEN has been reported broadly distributed throughout neurons, here, live imaging of HaloTagged PTEN reveals dynamically regulated localization, suggesting spatial control of its signaling. We then used retroviral-mediated genetic manipulation to delete endogenous Pten in developing hippocampal neurons while simultaneously expressing PTEN fused to defined localization motifs, allowing us to directly test how subcellular targeting regulates neuronal morphology. Loss of Pten produces neurons characterized by enlarged somata, more elaborate dendritic arbors, and increased spine density, length, and head area. Nuclear-excluded PTEN fully rescued these phenotypes, whereas targeting PTEN to filopodia via fusion to the FBAR domain of srGAP3 or to the postsynaptic density via Homer1C corrected or corrected all morphological abnormalities in PTEN-deficient neurons and simplified dendritic arborization compared to wild-type. In contrast, nuclear-localized PTEN produced only partial rescue, normalizing soma size and spine head area but not dendritic complexity or spine density. These findings indicate that PTEN acts locally to restrain growth and structural connectivity, whereas regulation of spine head size can be mediated by PTEN both inside and outside the nucleus, potentially through transcriptional or splicing-dependent mechanisms. Together, our results identify subcellular localization as a critical determinant of PTEN function and reveal spatially distinct mechanisms through which PTEN sculpts neuronal development.
]]></description>
<dc:creator><![CDATA[ Desmet, N. M., Griffin, C. F., Seo, H., OuYang, A., Tir, P., Prina, M. L., Wang, W., Li, M., Luikart, B. W. ]]></dc:creator>
<dc:date>2026-06-18</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732743</dc:identifier>
<dc:title><![CDATA[PTEN Subcellular Localization Dictates Function]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732142v1?rss=1">
<title>
<![CDATA[
Parallel processing of orthogonal manifolds enables zero-shot composition in recurrent networks 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732142v1?rss=1
</link>
<description><![CDATA[
Animals flexibly combine learned behaviors into novel actions without practicing their combinations, yet the computational mechanisms that enable independently acquired computations to be expressed in parallel remain unclear. Here we show that feedback geometry during learning determines whether recurrent dynamics can be recombined through zero-shot parallel composition. Using recurrent networks trained by a local predictive plasticity rule, we found that distinct feedback vectors embed independently learned computations in separable dynamical subspaces, allowing novel input combinations to co-activate these components and generate composite outputs without joint training. In contrast, aligned feedback vectors, as well as networks trained by backpropagation through time, exhibited accurate single-task performance but failed to support parallel composition, demonstrating that task acquisition and future reusability are dissociable properties of learning. A combined input evoked a single composite population trajectory, whose projections onto feedback-shaped task subspaces recovered the independently learned component dynamics. The same principle reproduced additive reach-posture geometry observed in motor cortex and generalized to higher-dimensional movement primitives. These results identify feedback geometry as a computational principle by which learning systems structure recurrent dynamics for future compositional reuse.
]]></description>
<dc:creator><![CDATA[ Osako, Y., Arango, A., Asabuki, T. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732142</dc:identifier>
<dc:title><![CDATA[Parallel processing of orthogonal manifolds enables zero-shot composition in recurrent networks]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732053v1?rss=1">
<title>
<![CDATA[
Uncovering Sex Differences in the Drosophila Ventral Nerve Cord Through Connectome Alignment 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732053v1?rss=1
</link>
<description><![CDATA[
There are now multiple Drosophila connectomes available, comprising both its brain and spinal cord - comparing these connectomes requires first classifying neurons into cell types. Existing approaches for cell typing typically require extensive manual curation. Here we present a new method that automatically aligns connectomes via network topology alone. Using two complete male ventral nerve cord (VNC) connectomes as references, we assign cell types to ~13,000 neurons intrinsic to the female VNC, and automatically identify sex-specific and sexually dimorphic cell types. We not only provide a comprehensive census of cell types across male and female nerve cords, but we uncover connectivity differences that underlie differences in function. We focus on circuits underlying song production in males and oviposition behaviors in females, and investigate the counterparts of these circuits across sexes. Our automated methods and analyses provide insights into sex differences in circuits that connect the brain and body, and pave the way for comparative connectomics at scale.
]]></description>
<dc:creator><![CDATA[ Matsliah, A., Salmon, C. K., Bates, A. S., Yang, H. H., Lee, D. D., Saul, L. K., Silverman, B., Gager, J., Yu, S.-C., Willie, K. P., Burke, A. T., Willie, R., Bland, D., Sorek, M., David, C., Sterling, A. R., The BANC-FlyWire Consortium,, Lee, W.-C. A., Seung, H. S., Murthy, M. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732053</dc:identifier>
<dc:title><![CDATA[Uncovering Sex Differences in the Drosophila Ventral Nerve Cord Through Connectome Alignment]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.729168v1?rss=1">
<title>
<![CDATA[
A Structural Principle for Macroscopic Neural Dynamics Correlations 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.729168v1?rss=1
</link>
<description><![CDATA[
A central question in neuroscience is how the brain's structural connectivity gives rise to its emergent, correlated dynamics. These large-scale dynamical correlations underlie functional networks that support cognitive functions. Here, we identify coupling correlation, the similarity between the input connectivity profiles of brain regions, as a key structural determinant of macroscopic neural dynamical correlation. Using dynamical mean-field theory (DMFT) and numerical simulations of random neural network models, we demonstrate that coupling correlation quantitatively governs dynamical correlation. The functional form of this structure-function mapping is dictated by the eigenvalue spectrum of the coupling correlation matrix: networks with bulk eigenspectra exhibit an exact linear relationship, whereas biologically plausible long-tailed spectra yield an approximately linear mapping except when the magnitude of coupling correlation approaches unity. Particularly, a long-tailed spectrum is necessary to reproduce the appropriate magnitude and size-invariance of coupling correlations observed in empirical data, thereby sustaining non-vanishing dynamical correlations that may support brain function in large systems. The theoretical prediction of approximate linearity is consistently validated using empirical datasets that include both structural coupling and neural dynamics in humans, mice, and Drosophila. Together, these results provide a mechanistic and quantitative framework linking macroscopic brain network structure to emergent neural dynamics, an essential step toward a theory of structure-function relationship in the brain.
]]></description>
<dc:creator><![CDATA[ Wu, Q., Wen, Q., Liu, C. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.729168</dc:identifier>
<dc:title><![CDATA[A Structural Principle for Macroscopic Neural Dynamics Correlations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.13.732103v1?rss=1">
<title>
<![CDATA[
Ventricular Expansion Couples Hyperosmotic Stress to Thirst 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.13.732103v1?rss=1
</link>
<description><![CDATA[
Thirst is thought to arise from osmotic signals detected by circumventricular organs, yet how hyperosmotic stress activates mechanosensitive channels remains unclear because cell shrinkage should reduce membrane tension. Here we identify a brain-scale mechanical signal that couples systemic osmotic stress to drinking. In mice, hypertonic saline rapidly increased serum and cerebrospinal fluid osmolality, expanded the lateral ventricles, and promoted water intake. Relieving or blocking ventricular deformation attenuated drinking without eliminating osmotic gradients. Hyperosmotic challenge also produced localized deformation of periventricular cells, where spatial transcriptomics revealed candidate mechanosensitive channels, including Tmem63b and Piezo1. Thus, ventricular expansion provides a mechanical component of osmotic thirst, uncovering an osmo-mechanical layer of interoceptive regulation.
]]></description>
<dc:creator><![CDATA[ Zhu, T., Jiang, C., Yang, J., Zheng, H., Lin, X., He, W., Zhang, L., Chen, Z., Shi, Y. S., Ren, H., Qiu, Z. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.13.732103</dc:identifier>
<dc:title><![CDATA[Ventricular Expansion Couples Hyperosmotic Stress to Thirst]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732113v1?rss=1">
<title>
<![CDATA[
Reactivating a schizophrenia risk gene-enriched prefrontal ensemble suppresses decision noise 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732113v1?rss=1
</link>
<description><![CDATA[
Schizophrenia genetics and single-cell transcriptomics implicate prefrontal excitatory neurons and synaptic programs, but how these vulnerabilities alter circuit dynamics, behavior, and pharmacological targetability remains unclear. We identify a clozapine-responsive prefrontal ensemble enriched for schizophrenia risk genes that stabilizes value-guided choice. NMDA receptor hypofunction increased value-independent decision noise and weakened the ensemble's pre-choice transient, while clozapine rescued both. Chemogenetic inhibition of the ensemble increased decision noise, demonstrating causality. By integrating receptor affinities with mouse and human single-cell transcriptomes, we designed a rational multi-receptor antagonist cocktail that reactivated the ensemble and rescued decision noise without increasing NREM sleep time or NREM delta power, in contrast to clozapine. These findings link schizophrenia genetics to cortical ensemble dynamics and establish ensemble-targeted pharmacology as a strategy for ameliorating pathological computations.
]]></description>
<dc:creator><![CDATA[ Iino, Y., Narita, H., Shimizu, C., Shi, S. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732113</dc:identifier>
<dc:title><![CDATA[Reactivating a schizophrenia risk gene-enriched prefrontal ensemble suppresses decision noise]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.12.731896v1?rss=1">
<title>
<![CDATA[
Characterizing the Effects of Chronic Cannabis Vapour Exposure and Withdrawal on Cannabinoid Triad, Somatic Signs and Behavioural Network Reorganization Adult Male Rats 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.12.731896v1?rss=1
</link>
<description><![CDATA[
Rationale: Cannabis withdrawal contributes to relapse in individuals with cannabis use disorder, yet preclinical studies have largely focused on withdrawal induced by injected cannabinoids rather than inhaled cannabis, which remains the most common route in humans. The behavioural effects of chronic exposure to vapourized cannabis flower and resulting withdrawal after cessation of exposure remain poorly characterized. Objectives: To determine the behavioural effects of chronic vapourized high-THC cannabis flower exposure on cannabinoid tetrad, somatic withdrawal and behavioural transition networks in rats following both chronic vapour exposure and administration of the cannabinoid receptor 1 (CB1) receptor antagonist SR141716A (rimonabant). Methods: Two studies were conducted using adult male Sprague Dawley rats. The first study (N = 16) exposed rats to either air or vapourized high-THC cannabis flower three times a day for seven days using a Volcano vapourizer, followed by intraperitoneal administration of the CB1 antagonist SR141716A (3 mg/kg). The second study (N = 24) included two air controls and two cannabis groups, with one of each receiving either saline or SR141716A. Behavioural assessments included triad measurements to confirm the cannabis effect, along with withdrawal assessment via a sucrose preference test and somatic signs 30 minutes following rimonabant administration. Results: Repeated cannabis vapour exposure produced reduced locomotor activity, hypothermia, and increased tail-flick latency. Rimonabant administration precipitated withdrawal characterized by increased total withdrawal scores and somatic signs, including blinking, body shakes/tremors, and grooming-related behaviours. Behavioural network analyses revealed substantial reorganization of behavioural transition structure during both chronic cannabis exposure and withdrawal. Chronic cannabis exposure was associated with reduced network modularity, a condensed behavioural repertoire, and altered behavioural centrality measures. At the same time, precipitated withdrawal further increased the influence of exploratory behaviours, particularly sniffing, and reduced the network prominence of locomotor-associated behaviours, such as walking, beyond that detected using conventional behavioural measures alone. Conclusion: Chronic exposure to vapourized cannabis flower followed by CB1 receptor antagonism produces reliable withdrawal symptoms in rats. Behavioural network analyses further reveal that cannabis exposure and withdrawal are both associated with widespread reorganization of behavioural dynamics, suggesting that withdrawal alters not only individual behaviours but also the structure of behavioural transitions. These findings establish a translational model of cannabis withdrawal using inhaled cannabis flower vapour and identify behavioural network analysis as a sensitive approach for characterizing withdrawal-related behavioural states.
]]></description>
<dc:creator><![CDATA[ Albeely, A. M., Kayir, H., Quansah Amissah, R., Zali, B., Karahan, S., Smith, J., Ibrahim, A. A., Hassan, A., Hussein, S., Frie, J. A., Khokhar, J. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.12.731896</dc:identifier>
<dc:title><![CDATA[Characterizing the Effects of Chronic Cannabis Vapour Exposure and Withdrawal on Cannabinoid Triad, Somatic Signs and Behavioural Network Reorganization Adult Male Rats]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.13.732042v1?rss=1">
<title>
<![CDATA[
Pupil responses reveal temporally distinct signatures of value updating and decision strategy 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.13.732042v1?rss=1
</link>
<description><![CDATA[
Adaptive decision making depends on dopaminergic and noradrenergic systems supporting value learning and exploratory decision strategies, respectively, yet their contributions remain difficult to dissociate noninvasively. Here, we investigated whether pupil dynamics provide dissociable readouts of computational processes underlying value-based decision making across sensory modalities, potentially reflecting distinct neuromodulatory processes. Human participants performed a dynamic foraging task in which they chose between auditory, visual, or audio-visual options based on their estimated value, alongside a control task where choices were instructed. Behavior in the value-based task was well captured by a probabilistic choice model, revealing adaptive integration of reward history and a balance between exploration and exploitation. Pupil responses revealed temporally distinct computational signatures of decision strategy and value updating. Reaction time was associated with sustained pupil dilation throughout the decision process, whereas value differences between chosen and unchosen options selectively modulated pupil responses during stimulus evaluation and following feedback. These findings are consistent with computational processes linked to noradrenergic regulation of exploration-exploitation behavior and dopaminergic value updating, respectively. Both effects were significantly stronger during value-based than instructed decisions, indicating enhanced engagement of these computational processes when choices depended on learned reward values. Importantly, these effects were largely modality-independent, indicating a domain-general encoding of computational variables. Together, these findings identify pupil dynamics as a temporally sensitive and non-invasive marker of distinct computational stages underlying adaptive decision making and establish a framework for linking pupillometry to neuromodulatory theories of value learning and uncertainty processing.
]]></description>
<dc:creator><![CDATA[ Dang, S., Pooresmaeili, A. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.13.732042</dc:identifier>
<dc:title><![CDATA[Pupil responses reveal temporally distinct signatures of value updating and decision strategy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.12.732007v1?rss=1">
<title>
<![CDATA[
Incorporation of single-neuron projectome-based connectivity motifs enhances the cortex-specific performance of artificial neural networks 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.12.732007v1?rss=1
</link>
<description><![CDATA[
The organizational principles of natural neural networks could inspire the new architecture design of artificial neural networks (ANNs). Analysis of single-neuron connectomes of mouse brains revealed distinct profiles of three-node connectivity motifs in various cortical areas and hippocampal formation. A connectome-informed neural network algorithm ("CINA") was developed to incorporate natural connectivity motifs into ANN algorithms represented by recurrent neural network (RNN) and transformer-based large language model (LLM). We found that incorporation of the average profile of cortical motifs improved the RNN's performance in noise-resistant categorization and motor learning benchmark tasks, as compared with RNNs with random connectivity. Notably, incorporating cortex-specific motifs further elevated the RNN's performance in tasks related to the cortical function, and this effect was enhanced by artificially increasing the bias in the motif profile. Similar experimental results were verified on an LLM using Motif-Transformer for natural language question answering and brain-signal decoding tasks. Graph-theoretic analyses showed that incorporating natural motifs drove the emergence of modular and small-world properties in ANNs. Together, we demonstrated not only connectome-inspired optimization of ANN architecture but also functional significance of specific motif profiles in various cortices.
]]></description>
<dc:creator><![CDATA[ Sun, Y., Yao, W., Zhang, J., Song, W., Zhao, X., Hao, C., Chen, X., Zeng, S., Jia, S., Yang, Y., Chen, X., Xiao, X., Poo, M.-m., Sun, Y., Xu, B., Zhang, T. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.12.732007</dc:identifier>
<dc:title><![CDATA[Incorporation of single-neuron projectome-based connectivity motifs enhances the cortex-specific performance of artificial neural networks]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.731818v1?rss=1">
<title>
<![CDATA[
Single-cell, single-shot stimulation reveals heterogeneous network recruitment not explained by standard functional properties. 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.731818v1?rss=1
</link>
<description><![CDATA[
Understanding how minimal perturbations influence cortical network dynamics remains a central challenge in neural engineering. While single-cell stimulation has been shown to affect population activity, the resulting variability is often treated as noise rather than an informative feature of network behavior. Here, we investigated how single-cell stimulation reflects heterogeneous modulation of neuronal recruitment and the extent to which these effects can be explained by the functional state of the stimulated cell. For this, we combined single-cell optogenetic stimulation with wide-field calcium imaging in cortical cultures. In each network, a single stimulation event was induced, and subsequent alterations in stimulus-coupled recruitment, synchrony, and pairwise correlations were quantified. Additionally, we evaluated whether the baseline functional state of the stimulated neurons, including their event activity levels and Pearson correlation structures, were linked to the observed network responses. Single cell stimulation induced effects were transient, and the network dynamics recovered over a few seconds within the responder population. Importantly, Our findings demonstrate that the observed direction and magnitude of recruitment changes were not significantly explained by the functional state of the stimulated neurons, indicating that these parameters do not capture the determinants of perturbation-induced network responses. This highlights a possibilities in the future approaches for characterizing network responsiveness and suggests that additional unobserved features govern the response of microcircuits to localized inputs.
]]></description>
<dc:creator><![CDATA[ Roy, S., Maybeck, V., Offenhaeusser, A. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.731818</dc:identifier>
<dc:title><![CDATA[Single-cell, single-shot stimulation reveals heterogeneous network recruitment not explained by standard functional properties.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.12.731966v1?rss=1">
<title>
<![CDATA[
Cocaine-Enriched Oral Streptococcus parasanguinis Promotes Neuroimmune Dysfunction and Memory Impairment 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.12.731966v1?rss=1
</link>
<description><![CDATA[
Chronic cocaine use is associated with neuroinflammation and cognitive dysfunction, but the underlying mechanisms remain unclear. We previously identified oral enrichment of Streptococcus parasanguinis (SP) and other species in individuals with cocaine use disorder (CUD), and here demonstrate that cocaine selectively enhanced SP growth in vitro. To investigate causality, antibiotic-pretreated wild-type C57BL/6 mice received chronic oral inoculation of SP, S. salivarius, Neisseria flavescens, or vehicle. SP-treated mice exhibited spatial memory impairment, increased brain IL-1{beta}, and non-region-specific microglial activation, without detectable bacterial translocation into the brain. While amyloid-associated signaling changes were observed across all bacterial treatment groups, only SP induced cognitive deficits and neuroinflammation. Untargeted metabolomics identified distinct SP-associated oral-to-brain metabolite signatures, including cysteine S-sulfate (CSS) and altered histamine-associated metabolites. CSS and histamine induced neuroinflammatory and amyloid-associated responses in vitro. Together, these findings identify a cocaine-associated oral pathobiont that promotes neuroinflammation and neurodegeneration, suggesting a novel oral microbiome-brain axis in CUD.
]]></description>
<dc:creator><![CDATA[ Johnson, D., Salman, T., Noorani, A. A., Benowitz, B., He, Y., Sundararaj, K. P., Shelley, H., Luo, Z., Wan, Z., Fitting, S., Penrod-Martin, R., Jiang, W. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.12.731966</dc:identifier>
<dc:title><![CDATA[Cocaine-Enriched Oral Streptococcus parasanguinis Promotes Neuroimmune Dysfunction and Memory Impairment]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732179v1?rss=1">
<title>
<![CDATA[
Mitochondrial Complex I Modulator Restores Network Resilience in Advanced Alzheimer's Disease Through Metabolic Reprogramming 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732179v1?rss=1
</link>
<description><![CDATA[
Mitochondrial dysfunction and lipid dysregulation are among the earliest abnormalities in Alzheimers disease (AD), yet their mechanistic interplay and therapeutic potential remain poorly understood. Here, we investigated whether restoration of mitochondrial function can reverse metabolic dysfunction and promote resilience in advanced-stage AD. Female APP/PS1 mice were treated with the brain-penetrant mitochondrial complex I (mtCI) modulator CP2 beginning at 19 months of age, when pathology and cognitive deficits were well established. To define the metabolic mechanisms underlying therapeutic response, we developed iMiceBrain, the first brain-specific genome-scale metabolic model of the mouse brain, and integrated transcriptomics, targeted metabolomics, lipidomics, and metabolic network analyses. CP2 treatment broadly reprogrammed AD-associated molecular signatures and restored pathways involved in mitochondrial function, glucose utilization, lipid metabolism, synaptic activity, and cellular stress responses. Metabolic modeling identified enhanced mitochondrial substrate flexibility, activation of fatty acid utilization, restoration of pyruvate dehydrogenase flux, and normalization of cholesterol metabolism as key features of the therapeutic response. Lipidomic analyses further demonstrated correction of disease-associated alterations in cholesteryl esters, phospholipids, and sphingolipids. Together, these findings demonstrate that mild mtCI modulation restores metabolic resilience by coordinating mitochondrial and lipid metabolism, establishing it as a disease-modifying therapeutic strategy for AD.
]]></description>
<dc:creator><![CDATA[ Gabal, E., Nguyen, T. K. O., Kovalenko, T., Gao, H., Rappaport, N., Funk, C. C., Baloni, P., Trushina, E. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732179</dc:identifier>
<dc:title><![CDATA[Mitochondrial Complex I Modulator Restores Network Resilience in Advanced Alzheimer's Disease Through Metabolic Reprogramming]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732595v1?rss=1">
<title>
<![CDATA[
Cell-type-specific cortical feedback coordinates hierarchical credit assignment 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732595v1?rss=1
</link>
<description><![CDATA[
Learning is thought to arise from synaptic modifications embedded in brain-wide circuits, yet how such circuits coordinate plasticity to support complex behaviour is not known. Inspired by deep learning, we propose a theory in which pathway-specific cortical feedback drives dendrite-dependent burst plasticity across cortical hierarchies. We show that this mechanism enables online hierarchical credit assignment and learning of complex image recognition and reward-driven tasks. This theory links credit assignment to cell-type-specific control of dendritic excitation-inhibition balance. In doing so, it provides a unified account of cell-type-specific modulation of synaptic plasticity, learning-dependent changes in interneurons, and neuron-specific dendritic error signals. The theory further predicts that interneurons constrain the dimensionality of error-related feedback, offering a functional rationale for cortex-wide gradients in interneuron density. Taken together, these findings indicate that distinct cortical cell types jointly coordinate learning across hierarchical circuits, connecting synaptic plasticity, circuit-level computation, and behaviour.
]]></description>
<dc:creator><![CDATA[ Greedy, W., Zhu, H. W., Duriez, A., Pemberton, J., McCarthy, P. T., Nejad, K. K., Costa, R. P. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732595</dc:identifier>
<dc:title><![CDATA[Cell-type-specific cortical feedback coordinates hierarchical credit assignment]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732615v1?rss=1">
<title>
<![CDATA[
Competitive Olivocerebellar Input Selection Promotes Resilient Circuit Formation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732615v1?rss=1
</link>
<description><![CDATA[
Many neural circuits undergo competitive input selection, a process in which supernumerary connections compete for innervation territory on target cells. This process can create atypical circuits when functional inputs are favored over compromised ones. Yet, it is often unclear whether such atypical circuits are maladaptive or promote functional resilience. We investigated this using the olivocerebellar climbing fiber circuit, where multiple inputs compete to mono-innervate Purkinje cells. We found that eliminating neurotransmission from ~50% of olivocerebellar neurons reduced climbing fibers' competitiveness during input selection and decreased survival of parental inferior olive neurons. Conversely, functional climbing fibers expanded their innervation territory. Despite these atypical circuits, climbing-fiber-dependent motor control was only minimally affected and social behaviors were fully preserved. These results demonstrate that neurotransmission-dependent competition promotes resilient cerebellar circuits, maintaining complex behaviors even when a large proportion of inputs are developmentally compromised.
]]></description>
<dc:creator><![CDATA[ Coello, J. A., Crane, K. M., Lyon, A. M., Walls, A. E., Pickeral, P. A., Fernandez, J. R., Dao, B. L., Bongiovanni, E. A., Fitzgerald, A. L., van der Heijden, M. E. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732615</dc:identifier>
<dc:title><![CDATA[Competitive Olivocerebellar Input Selection Promotes Resilient Circuit Formation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732120v1?rss=1">
<title>
<![CDATA[
Sleep forms flexible context representations in toddlers 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732120v1?rss=1
</link>
<description><![CDATA[
Sleep consolidates episodic memory through a hippocampus-dependent process in adults. Whether and how sleep supports memory consolidation during early life, when hippocampal function is immature, remains unclear. Here, we examined effects of sleep on the consolidation of spatial context, a core component of episodic memory, in toddlers aged 2-3 years. Toddlers were familiarized with two spatial contexts, followed by a ~90-min nap or an equivalent wake period. Afterwards, with a hide-and-seek game we tested their ability to relocate toys within these contexts. Only after post-familiarization sleep, the toddlers showed significant context memory and formed stronger associations between toys and specific contexts compared to wakefulness. Contextual memory was positively correlated with spindle density and slow oscillation-spindle phase-amplitude coupling during non-rapid eye movement (NonREM) sleep. Despite hippocampal immaturity, the sleeping toddler's brain seems to engage consolidation processes similar to those in adults to form spatial context memory for the flexible use in novel situations.
]]></description>
<dc:creator><![CDATA[ Bastian, L., Kurz, E.-M., Gutjahr, L., Noack, H., Born, J. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732120</dc:identifier>
<dc:title><![CDATA[Sleep forms flexible context representations in toddlers]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732101v1?rss=1">
<title>
<![CDATA[
MacaSurfer: unified surface-volume mapping of the macaque brain across the lifespan 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732101v1?rss=1
</link>
<description><![CDATA[
Macaque brain MRI is central to translational and comparative neuroscience, yet multi-site, longitudinal, and cross-species analyses are hindered by a lack of unified, automated structural processing tools. Existing pipelines, mostly adapted from human neuroimaging or restricted to fragmented steps, fail to provide robust surface-volume representations across heterogeneous acquisitions and developmental stages. Here we introduce MacaSurfer, a fully automated, containerized framework for unified surface-volume mapping of the macaque brain across the lifespan. MacaSurfer features components tailored for macaque anatomy: a tissue segmentation model, a tissue-guided bias-field correction method optimizing structural mapping from T1-weighted images alone, topology-aware surface reconstruction, and surface-aware volumetric registration. Validated on 1,346 imaging sessions from 965 macaques across 39 international sites (spanning 2 weeks to 23 years of age), MacaSurfer demonstrated exceptional anatomical consistency, test-retest precision, and robustness against image degradation. Leveraging MacaSurfer-derived morphometry, we established normative trajectories from 835 macaques, providing a standardized reference for downstream individualized deviation analysis. MacaSurfer is openly available with source code, containers, and pretrained models, offering a reproducible ecosystem to accelerate developmental, translational, and comparative neuroimaging.
]]></description>
<dc:creator><![CDATA[ Wei, Y., Wang, H., Wang, Y., Chen, L., Cheng, L., Gao, J., Zhu, Q., Chu, C., Xu, T., Gao, C., Jiang, T., Vanduffel, W., Fan, L. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732101</dc:identifier>
<dc:title><![CDATA[MacaSurfer: unified surface-volume mapping of the macaque brain across the lifespan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.14.732169v1?rss=1">
<title>
<![CDATA[
Early sensory deprivation drives local reorganization of sensory integration within a conserved global hierarchy 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.14.732169v1?rss=1
</link>
<description><![CDATA[
The human brain processes sensory information through a hierarchical system, from primary to higher-level regions, integrating inputs across modalities to support perception and cognition. While early sensory loss triggers widespread neuroplastic changes, its impact on integration across the cortical hierarchy remains unclear. Here, we examined the cortical reorganization of individuals with early blindness and deafness using a sensory integration framework that quantifies how brain regions prioritize different sensory inputs across the hierarchy. We found that early sensory deprivation drives highly localized reorganization adjacent to the deprived primary cortical areas: extrastriate cortex in early blindness and the superior temporal cortex in early deafness. These findings were further corroborated by analysis of the functional gradients, which found reorganization within these sensory regions. Notably, the hierarchy was largely preserved across groups. However, the sensory integration framework uniquely detected reorganization in language-related regions in deaf individuals with knowledge of a visual communication system known as cued speech. The specific differences between early deaf and hearing individuals remained restricted to superior temporal cortex. Together, our findings demonstrate that early sensory deprivation drives targeted reorganization adjacent to the affected primary sensory cortex, while preserving the overall hierarchy of cortical integration.
]]></description>
<dc:creator><![CDATA[ Wei, W., Sarre, A., Abboud, S., Alberti, F., Benn, R. A., Scholz, R., Shevchenko, V., Holmes, A., Klatzmann, U., Vanderwal, T., Jefferies, E., Szwed, M., Collignon, O., Cohen, L., Margulies, D. S. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.14.732169</dc:identifier>
<dc:title><![CDATA[Early sensory deprivation drives local reorganization of sensory integration within a conserved global hierarchy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732587v1?rss=1">
<title>
<![CDATA[
Functional projection of cognitive functions through the human corpus callosum 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732587v1?rss=1
</link>
<description><![CDATA[
Reconciling the anatomical observation that the human brain comprises two asymmetrical halves with the phenomenal unity of the mind is a puzzle that has challenged neuroscientists since the dawn of research in the field. White-matter commissural fibres of the corpus callosum constitute a critical anatomical substrate for the functional resolution of this anatomical duality. However, the extent of the functional involvement of the callosum in different domains of cognition represents, to this day, a mostly uncharted territory. Here we present a probabilistic characterization of callosal involvement in a set of cognitive functions. In particular, we estimated structural callosal connections by means of the Disconnectome approach applied to a reference sample of healthy participants while using the macro-anatomical cortical areas contained in the Harvard-Oxford template as seeds. By multiplying structural connectivity by the involvement of each cortical area in a set of cognitive functions (as derived from Neurosynth meta-analyses), we produced a voxel-wise characterization of the corpus callosum in different functional domains. We were able to highlight greater involvement of posterior callosal regions in vision and episodic memory, greater involvement of more anterior callosal regions in decision making and working memory, with somatosensory and motor functions more related to the central dorsal portion of the callosum.
]]></description>
<dc:creator><![CDATA[ Bonandrini, R., Tettamanti, M., Luzzatti, C. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732587</dc:identifier>
<dc:title><![CDATA[Functional projection of cognitive functions through the human corpus callosum]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732559v1?rss=1">
<title>
<![CDATA[
Directed Human Structural Connectome Reveals Hierarchical Organization and Shapes Large-Scale Brain Dynamics 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732559v1?rss=1
</link>
<description><![CDATA[
The human structural connectome, most commonly derived from diffusionweighted imaging (DWI) and tractography, provides a macroscopic description of whole-brain wiring and serves as the structural foundation of network neuroscience, large-scale brain simulations, and personalized digital brain twins. However, tractography-derived connectomes are fundamentally limited by their inability to distinguish afferent from efferent connections, yielding networks that are undirected and therefore blind to the hierarchical organization imposed by the directionality of anatomical connections. In this study, we introduce a directed human structural connectome (DHSC) by transferring tracer-derived projection patterns from macaque to human using cross-species connectivity blueprints. Topological analysis of the DHSC manifests biological plausibility, a small-world network organization, and a directionality-based hierarchy, which offer the hierarchical organization of human brain networks. In the context of brain dynamics, the introduction of directionality reshapes the propagation and persistence of sensory inputs. DHSC also best captures the empirical spatiotemporal dynamics of stimulus-evoked brain activity. The findings demonstrate that anatomical directionality is a critical determinant of large-scale brain organization and dynamics. This provides evidence that directed connectome may offer potential advantages in large-scale simulations of the human brain. The resulting DHSC, along with all related analyses and data are openly available.
]]></description>
<dc:creator><![CDATA[ Huang, N., Wang, H. E., Triebkorn, P., Gandini Wheeler-Kingshott, C. A. M., Jedyank, M., David, O., Destexhe, A., D'Angelo, E. U., Pedersen, N. P., Jirsa, V. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732559</dc:identifier>
<dc:title><![CDATA[Directed Human Structural Connectome Reveals Hierarchical Organization and Shapes Large-Scale Brain Dynamics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.06.16.732522v1?rss=1">
<title>
<![CDATA[
Single-cell chromatin tracing reveals multimodal molecular programs during memory formation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.06.16.732522v1?rss=1
</link>
<description><![CDATA[
Experience-dependent activity is converted to coordinated molecular programs in neuronal ensembles during memory formation. However, due to the sparsity of the ensembles and the transience of immediate early gene (IEG) expression, it is unclear how IEGs engage downstream secondary response genes (SRGs) to regulate learning-specific neuroplasticity. Here, we generated a single-cell multiomic atlas of aversive learning and developed ChromTRAP, which retrospectively identifies recently activated neuronal ensembles from AP-1 (FOS/JUN)-centred chromatin traces. We integrated transcription, chromatin accessibility, histone modifications, and FOS occupancy across the amygdala, hippocampus, and prefrontal cortex. This revealed regulatory programs of learning-associated genes (LAGs), defined as SRGs preferentially induced by associative learning relative to baseline activity or independent stimulus exposure. These programs followed a brain-region- and cell-type-specific proximal-distal regulatory logic: gene-proximal Polycomb-associated H3K27me3 remodeling and AP-1-bound H3K27ac-marked distal enhancers. LAGs were further associated with enhanced intercellular signaling and MEF-family activity. Our findings establish a single-cell multiomic framework for linking learning experience to layered epigenetic regulation during activity-dependent neuroplasticity.
]]></description>
<dc:creator><![CDATA[ Itoh, K., Khalil, V., Faress, I., Kitazawa, T. ]]></dc:creator>
<dc:date>2026-06-17</dc:date>
<dc:identifier>doi:10.64898/2026.06.16.732522</dc:identifier>
<dc:title><![CDATA[Single-cell chromatin tracing reveals multimodal molecular programs during memory formation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-06-17</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
