Adrian A. Perachio - US grants

The purpose of the proposed research is to investigate the relationships between morphological and physiological characteristics of vestibular nuclei and primary afferent neurons. Electrophysiological studies will be conducted on decerebrated gerbils to examine the responses of neurons in the major vestibular nuclei and selected accessory nuclei to time-varying linear head acceleration and to angular acceleration about the vertical head axis. Linear force will be applied in the form of sinusoidal translational head acceleration at single fundamental frequencies ranging, from 0.2 to 5.0 Hz, along the cardinal horizontal and vertical head axes. This study will provide data related to mechanisms for convergence of input from semicircular canals and otolith organ receptors onto single neurons of the vestibular nuclei. In addition, measures of the relationship between the stimulus vector and the nature of the neuronal response will be used to test hypotheses concerning the functional organization of the central otolith related system. Two sets of anatomical experiments will be conducted. Vestibular nuclei neurons that exhibit responses to linear head acceleration will be injected intracellularly with horseradish peroxidase (HRP) to label the cell bodies and their processes. Physiological characteristics and morphological features will be compared. In double labeling experiments, physiologically identified otolith-related afferents will be intra-axonally injected with HRP; concurrently, ipsilateral vestibular nuclei neurons that respond both monosynaptically to electrical stimulation of the labyrinth and to linear forces will be labeled intracellularly with a fluorescent dye, e.g. Lucifer Yellow or Texas Red. This will provide direct anatomical identification of second order neurons and both physiological and anatomical description of their primary vestibular input from otolith related afferents.

The purpose of the proposed research is to examine the role of specific visual pathways in the recovery of vestibulo-ocular and vestibular neuronal responsiveness following unilateral labyrinth lesions. We will test hypotheses concerning the influence of different inputs to the brainstem and cerebellum that may provide visual signals that promote the development of and are necessary for the maintenance of vestibular compensation. Neurons in the vestibular nuclear complex and prepositus nucleus will be assessed for their responses to linear and angular head acceleration, for visual sensitivity and for oculomotor-related activity, in trained primates, prior to and during recovery from unilateral labyrinthectomy. Those data will be compared with that obtained from additional animals in which hemilabyrinthecomy is preceded by lesions of one of two structures involved in the transmission of signals relayed from visual motion processing areas in the cortex. We hypothesize that lesions of the nucleus of the optic tract, which are known to impair optokinetic responses, will also result in deficits in the recovery of vestibulo-ocular responses to horizontal head acceleration. We will evaluate, in additional animals, another pathway that has been implicated in the early component of optokinetic and smooth pursuit eye movements, the dorsal lateral pontine nucleus, which provides visual inputs to a portion of the vestibulo- cerebellum. Vestibulo-ocular, optokinetic and vestibular neuronal responses will be assessed. The findings of the proposed studies combined with our previous results on the response characteristic of neurons in each visual pathway will provide insights as to the type of visual stimuli that are implicated in the development and maintenance of vestibular compensation. This would in turn suggest strategies for new therapies that could be used in the rehabilitation of patients following labyrinthine injury.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Animal models of human disease, especially those focusing on the human genome, have become increasingly important in all areas of biomedical research and development of these models is a specific strategic research objective of the UTMB. The Animal Research Resource Center (ARC) is experiencing a dramatic increase in usage, due primarily to the exponential growth in investigator demand for genetically engineered animals. This application requests support to renovate space for the existing TAF. As part of this renovation, the TAF will be moved from the Medical Research Building (MRB; Building 59) to Building 18, allowing expansion of animal space from 693 to 3,745 sq. ft. to meet current research needs. Renovation of the TAF on the UTMB campus will accomplish three specific aims: 1) expand the space available for production and housing of transgenic, knockout, and rederived mice within a pathogen-free environment; 2) renovate and expand existing laboratory space (procedure room, microinjection laboratory, etc.,) and animal housing to accommodate specialized equipment and expanded holding facilities; and 3) acquire additional specialized laboratory equipment for holding and generating transgenic stocks. These aims will result in more effective work-flow in the laboratory, and increased specialized services of the facility. This expansion and renovation will assist National Institutes of Health (NIH)-supported researchers at UTMB in expediting and enhancing their research. The generation of transgenic, knockout, and rederived mice can be completed in a timely and cost-effective fashion because investigators will not have to wait for equipment or personnel availability. The proposed expansion of laboratory space, expansion of animal holding space and acquisition of new, efficient caging systems will result in a 540 percent larger area in which to carry out transgenic services. This TAF space renovation, and the accompanying equipment purchase, is an important step toward UTMB's goal of strengthening and enhancing the Institution's ability to conduct genomics research. [unreadable] [unreadable]