Biology subjects

Zanos, T.

Publications and source records attributed to Zanos, T..

4 recordsLinked to original sources

bioRxiv2026

A standardized, surgically relevant map of organ-spesific branch emergence in the human vagus nerve

IntroductionVagus nerve stimulation modulates airway, cardiac, pulmonary, and gastrointestinal functions through respective organ-specific branches. Knowledge of where along the nerve vagal branches emerge may support alternative surgical placement of stimulation devices to activate targeted functions while avoiding off-target effects. However, no quantified map of the emergence of vagal branches and their relationship to surgically relevant anatomical landmarks exists in humans. MethodsFifty-eight vagus nerves (29 left, 29 right) from 29 embalmed donor bodies (15 females) were dissected from the jugular foramen through the thoracic cavity. Branches were traced to end organs and allocated to one of seven groups (sympathetic, muscular, vascular, cardiac, pulmonary, esophageal, or multiple targets) and several sub-groups. Distances between branch emergence and jugular foramen (JF) were normalized to three anatomical landmarks: carotid bifurcation, laryngeal prominence, and superior border of clavicle. ResultsEmergence of branches follows a proximal-to-distal order (median [IQR] distance from JF): sympathetic (3.9 cm [3.0-6.6]), muscular (6.2 [3.4-17.0]), vascular (9.6 [5.5-15.1]), cardiac (20.1 [16.9-22.5]), pulmonary (25.0 [22.8-27.6]), and esophageal (26.5 [24.3-29.1]). Branches emerge into two embryological domains separated at the clavicle: pharyngeal arch branches cluster proximally (7.3 cm [3.9-14.0]) and primitive mediastinum branches cluster distally (24.2 cm [20.9-27.1]), with sympathetic, muscular, and vascular sub-groups occupying distinct zones within the proximal domain. The longest branch-free intervals are all left-sided, occurring around the laryngeal prominence (3.0 cm [1.8-5.7]), the superior border of the clavicle (2.7 cm [1.3- 5.2]), and the carotid bifurcation (2.2 cm [0.9-5.7]). Several "target" branches are maximally separated from "off-target" branches at specific distances: sympathetic vs. cervical/ muscular/ vascular at 6/8 cm (L/R), cardiac vs. carotid sinus at 14/10 cm, and recurrent laryngeal vs. other muscular at 18/13 cm. Minimal differences are found between male and female donors. ConclusionThis study describes a quantified, landmark-registered map of cervical and thoracic vagal branch emergence and provides an anatomical reference that may help guide more selective device design and placement.

neuroscience↗

bioRxiv2025

Longitudinal Characterization of Compound Action Potentials in Chronic Vagus Nerve Recordings in Mice

The vagus nerve (VN) mediates bidirectional communication between the body and brain to maintain physiological homeostasis; likewise, alterations in ongoing vagal signaling may be indicators of disease and/or contribute to disease pathogenesis. Even though extensively documented in acute experiments, ongoing vagal activity has not been characterized longitudinally, over days or weeks, in mice, a preferred preclinical model. In addition, even though many VN recordings in mice occur during anesthesia, the effects of anesthesia on vagal signaling are unknown. This study uses a chronic implant mouse model to record vagal activity in anesthetized and awake, behaving animals for an average of 10 weeks and up to 6 months. Individual compound action potentials (CAPs) are tracked across multiple days by quantifying comparisons in features, including firing rates, waveform shape, inter-CAP interval histograms, and phase-locking to cardiac and respiratory signals while demonstrating long-term electrode-nerve interface viability and stable signal-to-noise ratios. Additionally, cytokine challenge experiments produced detectable CAP responses up to 3 months after electrode implantation. Lastly, awake recordings incorporated video analysis to identify and remove motion artifacts to preserve and extract neural and cardiac recordings during behavior. Results reveal diverse CAP populations with diverse physiological coupling and firing rates modulated by anesthesia. This work highlights the potential of chronic VN recordings to assess long-term changes in vagal activity in health and disease, with implications in discovery of autonomic markers of disease and closed-loop VNS stimulation strategies.

neuroscience↗

bioRxiv2022

Organ- and function-specific organization and bioelectronic modulation of vagus fascicles and fibers

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Vagus nerve stimulation (VNS) therapies activate fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. Transverse and longitudinal arrangement of fibers according to functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using microcomputed tomography, we found that, in swine, fascicles are arranged in 2 overlapping axes, with sensory and motor fascicles separated cephalad and merging caudad, and larynx-, heart- and lung-specific fascicles separated caudad and progressively merging cephalad. Using immunohistochemistry, we found that the distribution of single fibers is highly nonuniform: myelinated afferents and efferents occupy separate fascicles, unmyelinated efferents co-localize with myelinated afferents, and small unmyelinated afferents are widely distributed. Using a multi-contact cuff electrode, we delivered fascicular cervical VNS in anesthetized and awake swine. Compound action potentials, from distinct fiber types, and organ responses, including laryngeal muscle, cough, breathing, heart rate and blood pressure responses are elicited in a radially asymmetric manner, with consistent angular separations. These results indicate that vagal fibers are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

neuroscience↗

bioRxiv2021

A Fully Implantable Wireless Bidirectional Neuromodulation System for Mice

Novel research in the field of bioelectronic medicine requires systems that pair high-performance neurostimulation and bio-signal acquisition hardware with advanced software signal processing and control algorithms. Although mice are the most commonly used animal in medical research, the size, weight, and power requirements of such systems either preclude their use or impose significant constraints on experimental design. Here, we describe a fully-implantable neuromodulation system suitable for use in mice, measuring 2.2 cm3 and weighing 2.8 g. A bidirectional wireless interface allows simultaneous readout of multiple physiological signals and complete control over stimulation parameters, and a wirelessly rechargeable battery provides a lifetime of up to 5 days on a single charge. The device was successfully implanted (N=12) and a functional neural interface (capable of inducing acute bradycardia) is demonstrated with functional lifetimes exceeding to three weeks. The design utilizes only commercially-available components and 3D-printed packaging, with the goal of accelerating discovery and translation of future bioelectronic therapeutics.

bioengineering↗