Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior.

Granule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of positive versus negative changes in activity. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and the average sign of response. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks under-represented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning

Cerebellar Motor Learning: When Is Cortical Plasticity Not Enough?

Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo–ocular reflex (VOR) have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This “cortex-first” learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed “brainstem-first” mechanism that operates when ocular tracking mechanisms are effective. These results (i) describe a process whereby information originally learnt in one area of the brain (cerebellar cortex) can be transferred and expressed in another (brainstem), and (ii) indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay

Traditional and Non-Traditional Inputs to the Vestibular System

One of the primary functions of the vestibular system is to provide stabilizing reflexes to the eye, head, and body. These reflexes are often coordinated with inputs from the visual and proprioceptive systems. More recently, research has shown that other, non-traditional, stimuli also affect the vestibular system, though the scope of this research has been limited. This thesis explores the effect of both traditional and non-traditional inputs on the vestibular system by characterizing their influence compensatory movements. We begin by looking at the influence of the vestibular periphery and efference copy on compensatory eye movements (Chapter 2). While each of these has been described individually (as the vestibular-ocular reflex (VOR) and pre-programmed eye movements (PPEM) respectively), there is currently controversy in the field regarding 1) to what extent PPEM influence gaze stabilization in healthy animals, and 2) how these two inputs interact with each other. We propose a model of gaze stability in which VOR and PPEM work cooperatively, and compare model predictions to our data as well as data others have reported. We found that our model accurately predicted eye movements for all behavioral contexts tested. In Chapter 3, we describe the effect of single high-intensity noise exposure on the vestibular system. Currently, controversy surrounds whether, and to what extent, noise damages the semi-circular canals. We characterized changes to both ocular and head stability to better answer this question and found that after noise exposure there was loss of both ocular and head stability. However, the exact nature of this deficit was not as expected and the influence of cervical pathways after vestibular lesion is discussed. Finally, in Chapter 4, we examine the effect of galvanic vestibular stimulation (GVS) and optokinetic stimulation on standing posture. We propose a model of postural stability inspired by the velocity storage model of ocular stability. While others have proposed more complex models that make similar predictions, those predictions have not been explicitly tested and, further, it’s not clear if the added complexity is necessary. We found that, while simple, our model could correctly predict subjects’ responses to both stimuli, suggesting that the body interprets and uses sensory information for postural stability in a manner similar to that for ocular stability. Taken together these findings demonstrate that the influence of non-traditional inputs and pathways to vestibular system is substantial and should be considered both in laboratory and clinical settings. Specifically, we showed in Chapter 2 that PPEM are not merely an enhanced or adapted VOR, but part of a unique gaze stabilization system that merits independent consideration. In Chapter 3, we showed that a single noise exposure can cause significant functional damage to the vestibular system, suggesting that patients with noise-induced hearing loss should be tested for vestibular loss as well. Finally, in Chapter 4, we showed that GVS can be integrated like natural vestibular stimulation but only if it is properly conditioned first. This is of particular importance for vestibular prosthetic design, which uses GVS to substitute for lost vestibular input.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143914/1/hastepha_1.pd

Microgravity vestibular investigations (10-IML-1)

Our perception of how we are oriented in space is dependent on the interaction of virtually every sensory system. For example, to move about in our environment we integrate inputs in our brain from visual, haptic (kinesthetic, proprioceptive, and cutaneous), auditory systems, and labyrinths. In addition to this multimodal system for orientation, our expectations about the direction and speed of our chosen movement are also important. Changes in our environment and the way we interact with the new stimuli will result in a different interpretation by the nervous system of the incoming sensory information. We will adapt to the change in appropriate ways. Because our orientation system is adaptable and complex, it is often difficult to trace a response or change in behavior to any one source of information in this synergistic orientation system. However, with a carefully designed investigation, it is possible to measure signals at the appropriate level of response (both electrophysiological and perceptual) and determine the effect that stimulus rearrangement has on our sense of orientation. The environment of orbital flight represents the stimulus arrangement that is our immediate concern. The Microgravity Vestibular Investigations (MVI) represent a group of experiments designed to investigate the effects of orbital flight and a return to Earth on our orientation system

Space medicine research publications: 1983-1984

A list of publications supported by the Space Medicine Program, Office of Space Science and Applications is given. Included are publications entered into the Life Sciences Bibliographic Database by The George Washington University as of October 1, 1984

Gaze stabilization in the rabbit : three-dimensional organization and cholinergic floccular control

Whereas a large body of knowledge is available on the rabbit's optokinetic responses about a vertical axis, only fragmentary data have been obtained about horizontal-axis optokinetic responses. With emerging knowledge on the spatial organization of the three dimensional visual messages in the flocculus there is a need for a detailed description of three-dimensional optokinetic responses. We conducted a behavioral study of three-dimensional eye movements, elicited by optokinetic stimulation about horizontal axes, which will be presented in Chapter 2 of this thesis. Chapter 3 descnbes the positive modulatory effects of floccular injection of the cholinergic agonist carbachol and the AChE inhibitor eserine on the OKR and the VOR. A possible mechanism for the positive action of carbachol is proposed in Chapter 4, in the context of a synergistic action between injections of carbachol and the ,8-noradrenergic agonist isoproterenol. Specification of the receptor type involved in the action of carbachol is attempted in Chapter 5. The effects of bilateral and unilateral injections of carbachol on optokinetic nystagmus and afternystagmus are presented in Chapters 6 and 7, whereas Chapter 8 descnbes the effect of bilateral injection of carbachol on vestibular, post-rotatory nystagmus

Evidence for a reference frame transformation of vestibular contributions to voluntary reaching movements

Les estimations des mouvements de soi provenant des signaux vestibulaires contribuent à la planification et l’exécution des mouvements volontaires du bras lorsque le corps se déplace. Cependant, comme les senseurs vestibulaires sont fixés à la tête alors que le bras est fixé au corps, les signaux vestibulaires doivent être transformés d’un système de référence centré sur la tête à un système centré sur le corps pour pouvoir contribuer de façon appropriée au contrôle moteur du bras. Le but premier de ce travail était d’étudier l’évidence d’une telle transformation. La stimulation galvanique vestibulaire (SGV) a été utilisée pour activer les afférences vestibulaires et simuler une rotation autour d’un axe naso-occipital fixe pendant que des sujets humains faisaient des mouvements du bras dans le plan horizontal, avec la tête dans différentes orientations. Une transformation des signaux vestibulaires implique que la SVG devrait simuler une rotation autour d’un axe horizontal lorsque la tête est droite et autour d’un axe vertical lorsque la tête est en flexion antérieure. La SGV devrait ainsi perturber les mouvements du bras en fonction de l’orientation de la tête. Nos résultats démontrent que les signaux vestibulaires contribuant aux mouvements d’atteinte sont effectivement transformés en un système de référence centrée sur le corps. Le deuxième but de ce travail était d’explorer les mécanismes utilisant ces signaux vestibulaires transformés. En comparant les effets de la SGV appliquée avant ou pendant les mouvements d’atteinte nous avons montré que les signaux vestibulaires transformés contribuent à des mécanismes de compensation distincts durant la planification des mouvements d’atteinte comparativement à l’exécution.Vestibular signals provide self-motion estimates that contribute to the planning and execution of voluntary reaching movements during body motion. However, because the vestibular sensors are fixed in the head whereas the arm is fixed to the trunk vestibular signals must be transformed from a head-centered to a body-centered reference frame to contribute appropriately to limb motor control. The first goal of the current work was to investigate the evidence for such a transformation. To do so we used galvanic vestibular stimulation (GVS) to selectively activate vestibular afferents and simulate rotation about a fixed roughly naso-occipital axis as human subjects performed reaching movements with the head in different orientations. If vestibular signals that contribute to reaching are transformed to body-centered coordinates, then with the head upright GVS should simulate mainly tilt about an earth-horizontal axis (roll), whereas with the head pitched forward the same stimulus should simulate rotation about an earth-vertical axis (yaw). We therefore predicted that GVS should perturb horizontal-plane reach trajectories in a head-orientation dependent manner. Our results demonstrate that vestibular signals which contribute to reaching are indeed transformed to a body-centered reference frame. The second goal of this work was to explore the mechanisms that use these transformed vestibular signals. By comparing the effect of GVS applied during versus prior to reaching we also provide evidence that transformed vestibular signals contribute to distinct compensation mechanisms for body motion during reach planning versus execution

Eye movements in the wild : Oculomotor control, gaze behavior & frames of reference

Understanding the brain's capacity to encode complex visual information from a scene and to transform it into a coherent perception of 3D space and into well-coordinated motor commands are among the outstanding questions in the study of integrative brain function. Eye movement methodologies have allowed us to begin addressing these questions in increasingly naturalistic tasks, where eye and body movements are ubiquitous and, therefore, the applicability of most traditional neuroscience methods restricted. This review explores foundational issues in (1) how oculomotor and motor control in lab experiments extrapolates into more complex settings and (2) how real-world gaze behavior in turn decomposes into more elementary eye movement patterns. We review the received typology of oculomotor patterns in laboratory tasks, and how they map onto naturalistic gaze behavior (or not). We discuss the multiple coordinate systems needed to represent visual gaze strategies, how the choice of reference frame affects the description of eye movements, and the related but conceptually distinct issue of coordinate transformations between internal representations within the brain.Peer reviewe

A Model of Blood Pressure, Heart Rate, and Vaso-Vagal Responses Produced by Vestibulo-Sympathetic Activation

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation of an input related to Desired BP, feedback from the states, and an input from the vestibular system into one of the feedback loops. This nonlinear function was structured to best simulate the shapes of systoles and diastoles, the relationship between BP and Heart Rate (HR) as well as the amplitude modulations of BP and Pulse Pressure. Increases in threshold in one of the feedback loops produced lower frequencies of HR, but generated large pulse pressures to maintain orthostasis, without generating a VasoVagal Response (VVR). Pulse pressures were considerably smaller in the anesthetized rats than during the simulations, but simulated pulse pressures were lowered by including saturation in the feedback loop. Stochastic changes in threshold maintained the compensatory Baroreflex Sensitivity. Sudden decreases in Desired BP elicited non-compensatory VVRs with smaller pulse pressures, consistent with experimental data. The model suggests that the Vestibular Sympathetic Reflex (VSR) modulates BP and HR of an oscillating system by manipulating parameters of the baroreflex feedback and the signals that maintain the oscillations. It also shows that a VVR is generated when the vestibular input triggers a marked reduction in Desired BP