2001 — 2003 |
Burger, R. Michael |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Role of Inhibition in the Auditory Brainstem @ University of Washington
The project will investigate the role of inhabitation in acoustic processing in the mature and developing brainstem auditory system of the domestic chicken. This stay involves a three-pronged approach that constitute the specific aims: 1) to asses the influence of GABAergic input on both pre and postsynaptic elements in thee nucleus in the nucleus magnocellularis; 2) to asses the relative contribution of the primary excitatory and inhibitory inputs to processing of neurons in the superior olivary nucleus; 3) to describe and investigate influences on the efficacy and temporal characteristics of inhibitory inputs to nucleus magnocellularis and nucleus laminar is during development. Aim 1 will be addressed in vivo using multibarrel electrodes which allow for the pharmacological analysis of the contribution of various GABA receptor electrodes which allow for the pharmacological analysis of the contribution of various GABA receptor subtypes which are differently expressed in pre and postsynaptic terminals in nucleus magnocellularis. Aims 2 and 3 will autolysin in vitro preparation that will allow for the experimental segregation of inputs to brainstem nuclei and provide access to the biophysical properties of the neurons. These studies will contribute to a more complete understanding of acoustic processing in vertebrate nervous systems. Furthmore, developmental studies may reveal factors that could play a role in recovery of function in deaf patients. Understanding developmental influences on synaptic properties may contribute to the development of appropriate therapies for patients deprived of acoustic stimulation early in life.
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0.97 |
2009 — 2013 |
Burger, R. Michael |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Efferent Inhibitory Mechanisms in Binaural Processing
DESCRIPTION (provided by applicant): The proposed study investigates an efferent inhibitory circuit of the central auditory system. In both birds and mammals, the neural centers involved in sound localization receive inhibitory efferents from higher order nuclei. In birds, inhibitory feedback to the cochlear nuclei and binaural NL arise from a distinct pair of nuclei residing just ventral to the second and third order nuclei. This elegantly arranged system in birds provides a unique opportunity to gain a mechanistic and holistic understanding of the role of inhibitory efferents in a functionally well defined circuit of the auditory system. The long term goal of the study is to further our understanding of the contribution of efferent feedback to sound localization. The specific aims are: 1) Evaluation of the contributions of efferent inhibition to response properties in the avian cochlear nucleus;2) Evaluation of response properties and classification of SON neuron populations;3) Determine the role of the commissural connection of the SONs. The models that will be tested in this proposal involve the role of this inhibitory circuit for equalizing afferent inputs for binaural computations. The requirement for this equalization process has been proposed in models of binaural function that date to the 1970s, but the presence of such a system has not been demonstrated. The findings of the proposed studies could have direct implications for a number of hearing disorders, in particular, profoundly deaf patients whose treatment includes bilateral auditory prostheses. Binaural hearing provides advantages for detecting moving signals, signals in noise such as speech, and sound location compared to monaural conditions. These studies will enhance understanding of the central mechanisms of binaural processing, and this information may contribute to refinements of treatment strategies for the hearing impaired and in particular, bilaterally treated cochlear implant recipients. This proposal will investigate central mechanisms of binaural hearing. Binaural hearing is crucial for listeners to discriminate signals in noise as well as the location of sound sources. Development of modern auditory prosthetic devices relies on an understanding of auditory brain function. The proposed experiments will focus on revealing principles of binaural computations in the auditory system.
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1.009 |
2018 |
Burger, R. Michael |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Cholinergic Modulation of Auditory Processing in Sound Localization Circuitry
Project Summary: Nicotinic acetylcholine receptors underlie widespread modulatory processes throughout the brain including the auditory pathway. Acetylcholine release is driven both by behavioral state and in response to specific stimuli. For example, activation of nicotinic receptors is a key mechanism of prepulse inhibition, a physiological manifestation of sensory gating in the auditory system. These processes are deficient in schizophrenic patients, a patient population with a high tendency to self-medicate with nicotine. Therapeutic interventions that reverse auditory processing deficiencies in these patients directly or indirectly target nicotinic receptors. Previous investigation of cholinergic modulation in the auditory system has focused on the auditory cortex, but also to a lesser extent in the cochlear nucleus. However, the same cholinergic pathways that project to the cortex also provide input to lower auditory centers in the brainstem. The superior olivary complex is a major component of the auditory pathway and includes the medial nucleus of the trapezoid body (MNTB) and its postsynaptic target the medial superior olive (MSO). Both nuclei process sounds with extreme temporal precision, a computational process essential to detection of signals in noise, speech sounds and sound localization. Indeed, the MSO is the first sight of binaural integration in the auditory pathway, and performs the fundamental sound localization computations. MNTB and MSO express markers suggesting a prominent role for cholinergic modulation of these processes. However, cholinergic inputs have never been investigated in these regions, leaving a critical gap in our understanding of SOC function. The central hypothesis of this proposal is that cholinergic input exerts an acoustically driven modulation of the excitatory afferent terminals in the SOC and their postsynaptic targets in the MNTB and MSO. The primary objective of this research proposal is to build a mechanistic understanding of cholinergic modulation in MNTB and MSO, and to reveal its role in shaping responses to acoustic input. This objective will be achieved by pursuing three Specific Aims: 1) Determine the mechanisms of cholinergic modulation of presynaptic inputs to MSO and MNTB neurons; 2) Investigate the functional consequence of AChR expression by principal neurons in MNTB and MSO; 3) Reveal the specific computational contribution of acoustically driven cholinergic modulation of MNTB and MSO neurons. These aims constitute a novel and innovative approach to understanding fundamental computations in the temporal processing pathway. The data derived from these studies will provide substantial insight into a very poorly understood but potentially important neural feedback system in the auditory pathway. The specific investigation of temporal processing neurons will reveal mechanisms that may enhance our understanding of how such temporal precision is achieved in the sound localization pathway.
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1.009 |