Hamilton E. Farris - US grants

DESCRIPTION (provided by applicant): That vertebrates produce otoacoustic emissions and detect sounds near Brownian motion amplitudes suggests that the auditory system contains an active amplifier and filter. This project examines how hair cells contribute to this active process by measuring the relationship of mechanical tuning and amplification in the hair bundles of auditory hair cells to the overall spectral tuning in the end organ. Using patch clamp recordings and photometric measures of hair bundle movement, proposed research will test whether hair bundles tune mechano-electric transduction, amplify their mechanical response at certain frequencies and receive feedback from the electrical filter of hair cells' basolateral membrane. The test preparation will be the hair cells of the turtle auditory papilla, which are known to contain hair bundles that oscillate near the characteristic frequency of the cells. Although this project should be of interest to a broad audience in auditory neuroscience, particular interest should come from those studying active processing in mammals, where hair bundles potentially play a role in the tuning of outer hair cell motility.

DESCRIPTION (provided by applicant): Mechanoelectric transduction (MET) in auditory hair cells employs multiple Ca2+ dependent processes that regulate activation, adaptation and the steady-state properties of the channel. These processes may be mediated either directly at the MET channel, as with Ca2+ block of the pore, or indirectly through accessory structures, such as myosin and its regulation of slow adaptation. Separately quantifying these processes is complicated by the fact that most are not only sensitive to both mechanical perturbation and Ca2+ but also exhibit interdependence: changes in the properties of one process elicit changes in another. For example, because adaptation is sensitive to stimulus rise time, alterations in activation kinetics are predicted to change adaptation. Thus, devising means to alter these processes independently is needed to better quantify their role in MET. The experiments are designed to circumvent these issues by using flash photolysis to regulate intracellular Ca2+ independently from mechanical stimulation. Understanding how Ca2+ regulates activation and adaptation has taken on more significance, as tonotopic variance in these processes suggests their kinetics are important in establishing a bandpass filter that may play a role in the tuning required for outer hair cell motility and the active process.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims (summary): Disorders that disrupt attention (e.g., dyslexia, ADHD) prevent proper stimulus sorting. This may be particularly detrimental to speech processing, due in part to: disrupted working memory, the acoustic characteristics of speech and the fact that sounds from multiple sources are combined as a single complex upon reaching a receiver. Thus, the long-range goals of this project are to understand 1) how an acoustic complex is deconstructed into its components so that sounds may be identified, grouped and assigned to their correct sources;and, 2) how such sorting and grouping is modulated by attention. There is presently no neuronal definition of attention in general and to speech in particular, as model systems rarely exhibit the processing shown by humans for speech. The proposed research tests the overall hypotheses that for speech-like sounds auditory groups are formed through comparisons between multiple cues and that the pre-cortical neural units responsible for such processing can be modulated by dopaminergic input to produce different grouping decisions. This research uses an animal model in which speech-like sounds are behaviorally relevant, there is a robust bioassasy for attention, and the brain is readily accessible through electrophysiological and molecular-marking techniques.

Consistent with our institution?s continued support of competitive students from underrepresented/underserved, and/or disadvantaged backgrounds, we are seeking to increase diversity in the neurosciences by the implement a sustainable undergraduate pre-biomedical sciences enrichment platform to strengthen our pipeline. The proposed ?Inspiring Diversity to Explore the Mind in the 21st Century: The NIHNDS/LSUHSC-NO, Undergraduate Diversity in Neuroscience Research Experiences? Program is a one (1) year, non-residential/commutator undergraduate summer academic enrichment program, which will provide students from partnered-institutions the opportunity to perform research and experience graduate education under the egis of neurosciences. The implementation of our undergraduate academic enrichment program will continue to incorporate the resources of the LSUHSC- NO institution, advancing the and conduct of a robust, evidence-based enrichment program, based on the development of core competencies, such as critical thinking and reasoning, interpersonal and intrapersonal skills, and science competencies, which are essential tools for aspiring biomedical professions candidates. These items, along with mentorship and empowerment, will allow our scholars to navigate successfully the admissions pathway into health professions education. Our target student population will focus on Louisiana residents who are rising sophomores and junior undergraduate students, who are interested in biomedical careers in the neurosciences and who are attending local/partnered-institutions, Through well-established partnerships, we will continue to leverage partnerships with our LSU Main Campus, regional historically black colleges/universities; predominantly minority serving institutions (including, but not limited to Xavier University of Louisiana, Dillard University, and Southern University of New Orleans) as well as regional institutions such as, the University of New Orleans, and Tulane University for program recruitment. Our programmatic strategy is to select 6 student scholars, yearly, who are rising sophomores and juniors. Our core curriculum will provide career development activities in the neurosciences, inclusive of the integration of leadership and professionalism, as well as separate laboratory experiences, critical thinking and reading skills, and skills? preparation for professional schools? entrance examination, the GRE. We will address fundamental principles of critical thinking & reasoning, medical ethics, cultural competence, and professionalism. Program enrichment workshops will provide: 1) scholars with awareness of career path options in the neurosciences, such as our PhD program, as well as our dual-degree track of MD/PhD programs; 2) facilitation of mentoring relationships with biomedical/health professions faculty, students, and neuroscience researchers; 3) advising on Pre-admissions biomedical professions admissions tools ? Professional curriculum vitae (CV)/resume? development and approaches to admissions interviews.