James C. Saunders - US grants

Children with specific oral language and reading problems have language processing difficulties which produce delays in their language development and in bringing language knowledge to conscious awareness. The long range goal of the research proposed is to develop age appropriate treatment procedures which will help these children to reduce or overcome their language processing difficulties. the specific aims of the research are 1) to examine the development of the abilities of children with known specific oral or written language impairment to process varying aspects of language (phonology, lexicon, semantax and discourses), and the relations between patterns of development and oral language and reading performance and 2) to examine under which alterations in processing conditions these abilities can be improved during which periods of development. The changes in processing conditions that will be examined are a) provision of encoding strategies as the linguistic information is presented b) provision of retrieval cues as the material is recalled and c) changes in the amount of information to be processed. Forty children with specific language impairment and an equal number with reading problems in two age groups of (6 to 7 years and 9 to 10 years) will be followed for a three year period. Ten children in each group will be seen every nine months and the relation between these children's development of language processing abilities, as assessed by an experimental language processing battery, and their oral and written language performance on standard tests at the beginning and end of the study will be determined. Thirty children in each age group will be seen every eight to nine months and given the language processing tasks on the experimental battery under the altered conditions described above. The effects of these different conditions on language processing on the battery at different times in development and on standard tests of oral language and written language performance at the end of three years will be determined.

This proposal is concerned with the micromechanical properties of the sensory hair bundles. The author believes that most of our knowledge about hair bundle behavior is derived from stimuli that produce a static, low frequency or pulse displacement of the hairs. Data from these sources have advanced our understanding of hair micromechanics a great deal. However, the cochlear hair cell is designed to respond at high frequencies, and a physiology based on these stimuli may bias the picture of hair bundle and hair cell behavior. A microwaterjet has been developed which is capable of delivering a non-contact stimulus over a relatively wide bandwidth. Similarly, imaging technology, using stroboscopic illumination or photodiode detection has been developed, and this permits either direct visual observation of high frequency hair bundle motion, or examination of an electrical analogue of that motion. In vitro studies of hair cells on the chick basilar papilla are proposed in which hair bundle behavior is examined in relation to the stimulus waveshape, hair bundle stiffness, differential hair movements, and hair bundle resonance. In addition, the pathophysiology of hair behavior is studied following overstimulation. Hair bundle micromechanics are correlated with the receptor potential of the hair cell, and with the structural morphology of the bundle. Finally, new technological developments will be explored to improve and expand the measurement system. These include the development of reflected light microscopy to image inaccessible hair cells, the implementation of vital dye methods to study Ca++ flux in hair cells during stimulation, and isolated cochlear preparation for the gerbil, and micromechanical studies on isolated hair cells. The investigations presented in this proposal offer a new way of looking at hair cell micromechanics and I am confident that important observations, which expand our appreciation of the transduction process, will emerge.

DESCRIPTION: (provided by applicant) The research in this proposal examines the effects of acoustic overstimulation at the ?top and bottom" of the hair cell, and at the "output" from the hair cell. The top of the hair cell is where acoustic information is transduced via hair bundle movements and the gating of mechanosensitive transduction channels. Various machinery at the bottom of the cell culminates in the release of neurotransmitter. The net effect of these hair cell actions is the production of discharge activity in the cochlear nerve. Tools are now available to dissect the processes in each of these cellular compartments and examine their contribution to the loss and recovery of chick auditory function after exposure to damaging levels of sound. Whole-cell patch clamping of tall hair cells measures transduction currents during in vitro water-jet stimulation. Measures of membrane current and capacitance describe tall hair cell calcium currents and exocytotic processes. The profile shape of the tall hair cell stereocilia staircase, and tip-link morphology, are also evaluated. In vivo recordings of cochlear nerve activity gauge hair cell output. Tracer-dye labeling of cochlear nerves identifies tall hair cell location on the sensory surface. These methods are applied in control and sound damaged ears. Aims are proposed that test hypotheses concerning the susceptibility to, and consequence of, acoustic overstimulation on the tall hair cell and cochlear nerve. The first two aims dissect the effects of overstimulation on the cellular mechanism of transduction and exocytosis. The remaining two compliment the in vitro investigations and explore related in vivo phenomena in cochlear nerve activity. The objective of the research is to develop an integrated picture of peripheral pathophysiology in the hair cell and cochlear nerve. The hypotheses examined are: 1. The tall hair cell transduction process is damaged by overstimulation, and tall hair cell susceptibility to damage is related to the profile shape of the sensory hair bundle; 2. Overstimulation disrupts calcium influx, the kinetics of exocytosis, and the size of the releasable pool of vesicles; 3. Neural adaptation in chick cochlear nerve units changes as a consequence of exposure to intense sound, and; 4. Cochlear nerve abnormal rate-intensity functions two-weeks post exposure originate from tall hair cells adjacent to the "patch" lesion.

[unreadable] DESCRIPTION (provided by applicant): An interdisciplinary Research-Training Program is proposed that focuses on "The Neurobiology of Otorhinolaryngology" (TNO). The Program prepares exceptional students for academic research careers in the Hearing, Vestibular, and Chemo Sensory Sciences. The Program provides research training to Medical Students, Graduate Students, Postdoctoral Fellows, and Physician Scientist Research Fellows. Research opportunities are offered in development, cochlear function, neural signal processing, human and animal psychophysics, animal communication, middle-ear function, olfaction and taste, neuroengineering, and vestibular function. The 24 training faculty come from the Departments of Otorhinolaryngology, Biology, Psychology, Neuroscience, Bioengineering, Neurology, Psychiatry, Pathology, and Clinical Studies. Faculty membership is governed by expertise in Program areas, a commitment to student training, and funding to supplement trainee support. An Executive Committee oversees program activities, appoints students to the Program, and monitors trainee progress. Graduate Students are drawn from the Neuroscience, Bioengineering, Biology or Cell and Molecular Biology Graduate Groups, while Medical Students are recruited from the School of Medicine. The M.D. and Ph.D. Postdoctoral Fellows are "recruited nationally. The Program provides three years of Graduate Student support during the dissertation years. Medical Students are supported for one full year of research. Two or three years of support are provided for Ph.D. Postdoctoral Fellows. Physician Scientist Postdoctoral Fellows are supported for two years of research. All Trainees participate in seminars on the ethical conduct of research, scientific seminars, journal clubs, and the annual TNO Retreat. They are provided instruction in the process of preparing publications, posters, and grants. The concept of a "Meeting Place" is utilized to foster faculty/trainee interactions by broadening the trainees' appreciation of research strategies in the TNO disciplines, by providing historical perspectives on the field, and in developing an understanding of the pathophysiological basis for hearing, vestibular, and smell and taste disorders. The "Meeting Place" provides an opportunity to refine trainees' instructional and teaching skills. Research is conducted under the supervision of one of the trainers. We are requesting four predoctoral, three postdoctoral positions per year. [unreadable] [unreadable]