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Tau aggregate replication occurs at the pre-synapse of cultured human neurons and increases with application of TNFa

Tau aggregation at synapses is a key process driving Alzheimer's disease but the mechanism(s) that cause this have not been established. We used a model system of forward-programming induced glutamatergic neurons (iNeurons) with three independent cell lines treated with TNFa. Using aggregate-specific SIMOA, STED microscopy, and SynPull to detect nanoscopic tau aggregates in bulk samples and at individual synapses, we found that TNFa-driven tau aggregation occurs preferentially at the...

bioRxiv 7d ago

Hybrid-plasticity Photonic Synapses Enabling Hardware-Level Neural Reuse

arXiv:2605.25712v2 Announce Type: replace Abstract: Biological intelligence is distinguished by neural reuse, the capacity to preserve established learning memory while repurposing it for new tasks and dynamic environments. Bringing this capability to photonic hardware requires hybrid plasticity, namely the coexistence of long-term synaptic plasticity for persistent weight storage and short-term synaptic plasticity for rapid, reversible adaptation within a single synaptic element; however,...

arXiv Physics 7d ago

Synapse: Federated Tool Routing via Typed Compendium Artifacts

arXiv:2602.00911v2 Announce Type: replace Abstract: The unit of collaboration in federated learning determines what guarantees are even expressible. Flat units like weights, prompts, raw examples, carry no type signature on which privacy, conflict resolution, or cross-model transfer can dispatch as well-defined operations. We propose typed federated artifacts: schema validated objects whose declared field structure makes per field differential privacy, schema aware merging, and cross...

arXiv CS 5d ago

Spontaneous neurotransmitter release is regulated by Unc-5

The spontaneous quantal release of single vesicles of neurotransmitter in the absence of an action potential is a universal feature of all neuronal chemical synapses. These miniature events have long been thought to be stochastic and unregulated, leading to measurement of their frequency as a widely employed estimate of the number of synaptic connections within neuronal networks. Here we show using high resolution live imaging of Drosophila adult glutamatergic synapses that the spontaneous...

bioRxiv 5d ago

Patient-Derived Air-Liquid Interface Forebrain Organoids Reveal Functional Synaptic Deficits in Schizophrenia

Schizophrenia (SCZ) is a severe and debilitating neurodevelopmental disorder with lifelong impact on everyday life. Disruptions in synapse functions play a key role in its complex and poorly understood etiological and pathological mechanisms. Here, we investigated both the molecular composition and the spontaneous and stimulated functional properties of synapses in neural organoids from SCZ individuals.

bioRxiv 7d ago

I Like To Move It -- Computation Instead of Data in the Brain

arXiv:2509.26193v2 Announce Type: replace Abstract: The detailed functioning of the human brain remains incompletely understood. Large-scale brain simulations complement experimental research but face substantial computational challenges: the human brain comprises approximately $10^{11}$ neurons connected by $10^{14}$ synapses, collectively forming the connectome. Empirical evidence indicates that modifications of the connectome -- specifically the formation and elimination of synapses,...

arXiv CS 7d ago

A prognostic human brain network for diffuse midline glioma

Abstract Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses.

Nature 18h ago

A Na⁺-PINK1 signaling axis couples mitochondrial fission to structural remodeling during synaptic depression

Mitochondrial density in dendrites adapts to the number of synaptic inputs to adequately sustain local ATP and Ca2+ buffering for neuronal signaling. During long-term depression (LTD), synapse elimination is accompanied by activation of caspase-3 through sublethal mitochondria-derived apoptotic signals, driving neurotransmitter receptor internalization and spine shrinking. However, the upstream signals that link synaptic activity to mitochondrial remodeling remain unknown.

bioRxiv 10d ago

The Dark Regulome: Disentangling Predictability from Regulation in Genomic Foundation Models

Announce Type: new Abstract: High-grade gliomas integrate into neural circuits through functional synapses with neurons, raising the question of which noncoding elements shape synaptogenic gene expression in tumor cells. The regulatory program written across the dark genome, what we call the $\textit{dark regulome}$, is the natural substrate to probe, and sequence foundation models offer a zero-shot route through in-silico mutagenesis (ISM); yet likelihood-based scoring is tautologically...

arXiv CS 2d ago

Neural birth time and somatosensory circuit assembly are linked by Robo3 regulation of dendrite morphology

Neural circuit wiring requires a remarkable level of precision, as thousands of neurons generate millions of synapses in distinct configurations. While neural circuits are known to be shaped by both neural birth timing and multiple classes of guidance molecules, the relationship between the two and how they coordinate circuit assembly has yet to be evaluated. Leveraging the well-defined stem cell lineages of the Drosophila embryonic nerve cord, we investigate how Roundabout (Robo) guidance...

bioRxiv 10d ago