Biology subjects

Lunsford, E. T.

Publications and source records attributed to Lunsford, E. T..

6 recordsLinked to original sources

bioRxiv2026

Noradrenaline prolongs the state of motor arrest via cerebrospinal fluid signaling

Neuromodulators can mediate whole-body physiological changes, however how signaling from relatively small populations of neurons produces widespread and sustained effects remains incompletely understood. Here, we demonstrate that sustained noradrenergic activation induces prolonged motor arrest accompanied by postural collapse, bradycardia, and emetic responses. Motor suppression arises from inhibition of brainstem commands to the spinal cord rather than motoneuron silencing. Noradrenaline induces a glial calcium wave that propagates throughout the central nervous system. This wave most prominently persists at the brainstem-spinal cord boundary and ventricular midline. At this location, ependymal radial glia express Adra1a receptors on cilia contacting cerebrospinal fluid (CSF). Ventricular noradrenaline injections recapitulated the glial wave and motor arrest, while CSF administration of an Adra1 antagonist shortened motor arrest. Altogether, noradrenaline sustains motor arrest by signaling through the CSF via ciliary Adra1a receptors on ependymal radial glia showing that cerebrospinal fluid as a critical transmission route for persistence of behavioral states. HighlightsO_LINoradrenergic surges coordinate a whole-body response with motor arrest, postural disruptions, bradycardia, and emesis-like reflexes C_LIO_LIMotor arrest results from silencing of brainstem motor commands to the spinal cord C_LIO_LINoradrenaline-induced glial calcium waves last longest at the obex/ventricular midline where cilia of CSF-contacting glial cells bear Adra1 receptors C_LIO_LINoradrenergic signaling in the CSF is necessary and sufficient for motor arrest to persist C_LI

neuroscience↗

bioRxiv2025

Whole-body central processing of lateral line inputs encodes flow direction relative to the center-of-mass

From shifting visual scenes to tactile deformations and fluid motion, animals must interpret patterns of sensory flow around their body to construct stable internal models and produce adaptive behavior. Understanding of how such transformations are encoded within the brain remains incomplete. To tackle this question, we leverage the lateral line of larval zebrafish as a tractable sensory system sensitive to fluid motion that is used to steer navigation, feed, and avoid predators. By presenting stimuli of either direction to neuromasts along the body, we used high-resolution calcium imaging to map hindbrain responses. Unexpectedly, our findings challenge the notion that central lateral line processing lacks topographic structure by revealing a simple yet powerful principle centered on a egocentric spatial framework: the direction and location of local flow motions are encoded in reference to the animals center-of-mass. This simple representation enables the brain to register complex flow patterns and provides a robust basis for subsequent behavioral action selection. MON neurons that encode flow toward the center-of-mass broadly project to form bilateral connections onto reticulospinal neurons that coordinate forward locomotion while MON neurons that encode flow away from the center-of-mass displayed a more selective and unilateral projection profile to command neurons for turns. Our discovery represents a shift from purely somatotopic encoding toward an integrative representation of axial position and directionality combined, revealing a novel principle of encoding spatio-directional cues in the hindbrain. This study advances our understanding of how complex mechanosensory inputs select appropriate motor outputs via simple egocentric neural maps in the hindbrain. Significance StatementSpatial and directional cues are essential to select appropriate actions in response to changes in the environment. How information from broadly distributed mechanosensors across the entire body occurs in the brain enables motor selection remains elusive. By directionally stimulating each and virtually all neuromasts distributed along the lateral line of larval zebrafish, our study uncovers that spatial and directional inputs from each flow sensors is encoded in the medial octavolateralis nuclei relative to the animals center-of-mass in order to subsequently recruit reticulospinal neurons driving forward and turn bouts. These results establish a new framework for understanding how broadly distributed inputs get integrated to recruit motor command neurons responsible for producing diverse behaviors.

neuroscience↗

bioRxiv2022

Anion efflux mediates transduction in hair cells of zebrafish lateral line

Hair cells are the principal sensory receptors of the vertebrate auditory system, and transduce sounds with mechanically-gated ion channels that permit cations to flow from the surrounding endolymph into the cells. The lateral line of zebrafish has served as a key model system for understanding hair cell physiology and development, and it has often been speculated that these hair cells employ a similar transduction mechanism. In this study, we demonstrate that the hair cells are exposed to an unregulated external environment with cation concentrations that are too low to support transduction. Instead, our results indicate that hair cell excitation is mediated by a fundamentally different mechanism involving the outward flow of anions.

neuroscience↗

bioRxiv2022

Evolutionary convergence of a neural mechanism in the cavefish lateral line system

Animals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently-derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that regression of the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.

neuroscience↗

bioRxiv2021

Corollary discharge prevents signal distortion and enhances sensing during locomotion

Sensory feedback during movement entails sensing a mix of externally- and self-generated stimuli (respectively, exafference and reafference). In many peripheral sensory systems, a parallel copy of the motor command, a corollary discharge, is thought to eliminate sensory feedback during behaviors. However, reafference has important roles in motor control, because it provides real-time feedback on the animals motions through the environment. In this case, the corollary discharge must be calibrated to enable feedback while avoiding negative consequences like sensor fatigue. The undulatory motions of fishes bodies generate induced flows that are sensed by the lateral line sensory organ, and prior work has shown these reafferent signals contribute to the regulation of swimming kinematics. Corollary discharge to the lateral line reduces the gain for reafference, but cannot eliminate it altogether. We develop a data-driven model integrating swimming biomechanics, hair cell physiology, and corollary discharge to understand how sensory modulation is calibrated during locomotion in larval zebrafish. In the absence of corollary discharge, lateral line afferent units exhibit the highly heterogeneous habituation rates characteristic of hair cell systems, typified by decaying sensitivity and phase distortions with respect to an input stimulus. Activation of the corollary discharge prevents habituation, reduces response heterogeneity, and regulates response phases in a narrow interval around the time of the peak stimulus. This suggests a synergistic interaction between the corollary discharge and the polarization of lateral line sensors, which sharpens sensitivity along their preferred axes. Our integrative model reveals a vital role of corollary discharge for ensuring precise feedback, including proprioception, during undulatory locomotion.

neuroscience↗

bioRxiv2019

Efferent Modulation Of Spontaneous Lateral Line Activity During And After Zebrafish Motor Commands

Accurate sensory processing during movement requires the animal to distinguish between external (exafferent) and self-generated (reafferent) stimuli to maintain sensitivity to biologically relevant cues. The lateral line system in fishes is a mechanosensory organ that experiences reafferent sensory feedback via detection of fluid motion relative to the body generated during behaviors such as swimming. For the first time in larval zebrafish (Danio rerio), we employed simultaneous recordings of lateral line and motor activity to reveal the activity of afferent neurons arising from endogenous feedback from hindbrain efferent neurons during locomotion. Frequency of spontaneous spiking in posterior lateral line afferent neurons decreased during motor activity and was absent for more than half of swimming trials. Targeted photoablation of efferent neurons abolished the afferent inhibition that was correlated to swimming, indicating that inhibitory efferent neurons are necessary for modulating lateral line sensitivity during locomotion. We monitored calcium activity with Tg(elav13:GCaMP6s) fish and found synchronous activity between putative cholinergic efferent neurons and motor neurons. We examined correlates of motor activity to determine which may best predict the attenuation of afferent activity and therefore what components of the motor signal are translated through the corollary discharge. Swim duration was most strongly correlated to the change in afferent spike frequency. Attenuated spike frequency persisted past the end of the fictive swim bout, suggesting that corollary discharge also affects the glide phase of burst and glide locomotion. The duration of the glide in which spike frequency was attenuated increased with swim duration but decreased with motor frequency. Our results detail a neuromodulatory mechanism in larval zebrafish that adaptively filters self-generated flow stimuli during both the active and passive phases of locomotion.

neuroscience↗