The vagus nerve (VN) serves as a major communication pathway between the brain and peripheral organs. The left and right VN exhibit asymmetric structures and are considered to sense diverse peripheral organ states. However, it remains unknown how coordinately the left and right VN generate physiological spike activity. Here, we performed simultaneous electrophysiological recordings of left and right cervical VN spike patterns in rats. During non-movement periods, ongoing spike activity in both VNs was predominantly organized into burst events. The occurrence timing of burst events was partially synchronized between the left and right VN, whereas individual spike timing within burst events showed no pronounced synchronization. Under anesthetized conditions, VN spike activity was not strongly entrained to oscillatory gastric or intestinal motility on a cycle-by-cycle basis but pharmacological enhancement of gastrointestinal activity was sufficient to induce bilaterally synchronized burst events in a pattern closely resembling that observed under freely moving conditions. During VN burst events in non-movement periods, prefrontal cortical local field potential power across the wide frequency range was substantially modulated, suggesting a functional link between vagal afferent activity and higher-order brain dynamics. Taken together, these findings advance our insight into VN-mediated brain–body interactions.
Gliomas are increasingly recognized as network diseases in which aberrant interactions between tumor cells, neurons, and immune populations drive hyperexcitability, seizures, cognitive dysfunction, and disease progression. Simultaneously, advances in structural biology and nucleic acid engineering have revealed DNA to be a dynamic molecular architecture capable of sensing, regulating, and modulating cellular states. In this review, we examine how noncanonical DNA structures and functional nucleic acids including Z-DNA, G-quadruplexes, cruciform structures, aptamers, and DNA origami systems, shape neural regulation and glioma associated circuit pathology. We discuss how activity dependent DNA conformational transitions influence transcriptional programs controlling neurotransmission, ion channel expression, synaptic signaling, metabolism, and inflammatory pathways in glioma cells and peritumoral neural networks. Z-DNA formation appears linked to rapid transcriptional activation and enhancer dynamics, whereas G-quadruplex rich regulatory regions modulate genes associated with excitatory signaling, cellular proliferation, and tumor progression. Cruciform DNA structures additionally interface with genome stability and DNA repair, creating mechanistic entry points for therapeutic intervention. Beyond endogenous DNA architectures, we highlight the emergence of aptamer based diagnostics and therapeutics capable of detecting neurotransmitters, cytokines, and metabolites associated with glioma induced network dysfunction. DNA origami platforms further enable programmable multivalent delivery systems for targeted transport of small molecules, oligonucleotides, CRISPR machinery, and ion-channel modulators across the neurovascular unit and tumor microenvironment. We also explore closed-loop neuromodulatory strategies in which electrophysiological signatures guide state dependent therapeutic actuation through nucleic acid based sensing and delivery systems. Finally, we discuss key translational considerations, including blood brain barrier delivery, nuclease stability, immunogenicity, biodistribution, manufacturing reproducibility, and integration with existing neuro-oncology and anti-seizure therapies. By bridging molecular origami, electrophysiology, and neurotechnology, this review proposes a framework for precision neuromedicine in glioma and broader neurological disease, where programmable nucleic acid architectures are coupled to the dynamic circuit states that drive pathology.
Valence, a hedonic value assigned to sensory stimuli that determines subsequent behaviors, is a fundamental organizing principle of affective states and emotional behaviors. Valence influences physiological processes across multiple organ systems — effects that may be mediated in part by the serotonergic (5-HT) system, which itself has widespread distribution throughout the body. The brain serotonergic system projects to the amygdala and its extended structure, the bed nucleus of the stria terminalis (BNST), regions heavily implicated in valence encoding. Despite their anatomical and functional connectivity, the amygdala and BNST express distinct 5-HT receptor subtypes, receive heterogeneous 5-HT projections, and process valence differently. The current study examines the significance of 5-HT projections in the computation of valence in the CeA and BNST. Here, multi-site in vivo electrophysiology was combined with anterograde chemogenetic modulation of 5-HT terminals in either the BNST or the CeA, while recording from both regions during valence presentation tasks where mice were exposed to the odorants of saline (neutral), opposite-sex urine (positive), and trimethylthiazoline (TMT, negative valence) in a counterbalanced manner. Neural responses were then compared across the neutral, appetitive, and aversive stimuli. Our results showed dorsal raphe 5-HT activation in the BNST supported valence coding in the CeA and BNST during stimulus presentation. During the post-stimulus phase, this modulation engaged only CeA-supported valence coding. Conversely, the inhibition of 5-HT terminals in the BNST supported local valence coding. Dorsal raphe 5-HT activation in the CeA enhanced valence coding in both the CeA and BNST only after stimulus offset. However, its suppression in the CeA enhanced valence coding in both the CeA and BNST during and after stimulus presentation. Taken together, our results showed that dorsal raphe serotonergic modulation creates a phasic response pattern in the CeA/BNST circuit by moderating response timing relative to stimulus valence.
Interoception, the sensing and interpretation of internal bodily signals, is increasingly invoked to explain heterogeneity in autism, yet empirical findings remain inconsistent. A major reason is methodological: the field remains cardio-centric and relies heavily on heartbeat counting tasks and trait questionnaires, which are vulnerable to cognitive strategies, attention, expectancy effects, and confounds such as alexithymia and anxiety. Autism research further indicates that interoception is multidimensional (accuracy, sensibility, metacognitive awareness) and developmentally dynamic, with evidence for dissociations across components and compensation across the lifespan. We argue that progress requires reframing interoception as an inference problem: the brain estimates hidden physiological states from noisy sensory evidence under context-dependent precision weighting (predictive processing/active inference). Building on this framework, we propose a participatory, multimodal research program for autism that integrates (i) lived experience as hypothesis-shaping data, (ii) virtual reality (VR) as an experimental testbed to manipulate embodiment, sensory load, agency cues, and feedback, and (iii) computational physiological modelling to estimate latent cardiovascular–respiratory and autonomic-control parameters, which could subsequently constrain separately specified models of perceptual inference.
Cortical modules are thought to provide anatomical frameworks for local microcircuits. However, the mechanisms regulating the morphological organization of these modules during development remain poorly understood. In the rat granular retrosplenial cortex, layer 1 contains prominent dendritic bundle-centered modules formed by the apical dendrites of layer 2 neurons and aligned with specific afferent inputs. I investigated the molecular mechanisms regulating the architecture of these dendritic bundles, focusing on TrkC, a high-affinity receptor for neurotrophin-3. Reanalysis of developmental gene expression data showed that neurotrophin-3 was transiently enriched in layer 2 before dendritic bundle formation, whereas TrkC expression was maintained at above-average levels and became modestly elevated after bundle formation. Pathway analysis further suggested developmental changes in neurotrophin pathways. To examine whether perturbation of TrkC-related signaling affects dendritic bundle architecture, I overexpressed a truncated TrkC construct lacking the intracellular tyrosine kinase domain in layer 2 neurons via in utero electroporation. Overexpression of this construct expanded dendritic bundle territories in upper layer 1. Sparse single-cell labeling revealed that this bundle-level phenotype was accompanied by increased branching of the apical dendrites of individual layer 2 neurons. These findings suggest that TrkC-related signaling may regulate the morphology of dendritic bundles by restricting excessive branching of apical dendrites during development. Thus, regulation of dendritic branching may contribute to the refinement of the distinctive dendritic bundle architecture of the granular retrosplenial cortex.
