Shigeyuki Kuwada - US grants

The goal of this research is to study the neural mechanisms underlying binaural signal processing in the cat inferior colliculus. The proposal addresses three issues: 1) the mechanism by which high frequency neurons utilize interaural time cues; 2) the relationship between synaptic organization and binaural processing; and 3) the role of descending cortical inputs on binaural response properties. The high frequency studies may provide the neural basis for the observation that human listeners can lateralize complex high frequency signals on the basis of interaural time cues; a finding that has necessitated modification of the classic view that the low and high frequency system use separate localization cues: interaural time and interaural intesity cues, respectively. The purpose of the synaptic organization studies is to determine the neural mechanisms responsible for binaural interactions, and the related ultrastructural components. The rationale of examining cortical influences is the finding that afferents from the ipsilateral auditory cortex project to a specific and division substantial subdivision of the inferior colliculus, viz. the dorsal cortex. Since descending cortical and ascending lemniscal inputs are mixed in this subdivision, the binaural interactions may be different from that in the central nucleus; a division of the inferior colliculus that only receives lemniscal input. To resolve the above issues, we will employ extra and intracellular recordings, acoustical and electrical stimulation, and light and electron microscopic analysis.

The goal is to understand the mechanisms that neurons use to process ongoing interaural time differences (ITD's) in the auditory pathway. The ITD between the signals at the two ears is used for the localization of low-frequency sounds on the azimuth. With earphones, humans can lateralize ITD's that are much smaller than those suggested by responses of neurons in the superior olivary complex (SOC). However, our data in the inferior colliculus (IC) and medial geniculate body (MGB) of the unanesthetized rabbit indicate that this discrepancy is reduced at levels above the SOC. The range of ITD sensitivity of IC neurons is about 50% of that we estimate for neurons in the medial superior olive (MSO); in the MGB the range is about 30% of that in the IC. If we view the range of ITD sensitivity as an estimate of the neuron's spatial receptive field on the azimuth, then, it appears that one consequence of ITD processing in the binaural pathway is to reduce receptive field size. We will test this hypothesis, by making unit recordings from the MSO and lateral superior olive (LSO) of the unanesthetized rabbit so their receptive field estimates may be compared to our data in the IC and MGB. These stuides also would provide the first opportunity to examine ITD processing, free from anesthetic effects, at the primary sites of binaural interaction. We will also test the hypothesis that in the MGB, inhibitory mechanisms are involved in the reduction of receptive field size. There is strong evidence that inhibitory mechanisms play a role in ITD processing by MGB neurons. We will assess directly the role of inhibitory events in ITD processing by recording intracellularly from MGB neurons in the unanesthetized rabbit. Finally, we will test the hypothesis that segregated ITD regions in the MGB received distinct patterns of input from the midbrain. We propose, through unit recordings, to map the distribution of ITD regions in the MGB. These studies should elucidate the differences in ITD processing between subdivisions of the MGB. We will then inject retrograde tracers into these regions. The anatomical studies should clarify whether ITD processing in the MGB involves particular cell types and whether they involve converging or parallel pathways.

The goal is to understand the mechanisms that neurons use to process ongoing interaural time differences (ITD's) in the auditory pathway. The ITD between the signals at the two ears is used for the localization of low-frequency sounds on the azimuth. With earphones, humans can lateralize ITD's that are much smaller than those suggested by responses of neurons in the superior olivary complex (SOC). However, our data in the inferior colliculus (IC) and medial geniculate body (MGB) of the unanesthetized rabbit indicate that this discrepancy is reduced at levels above the SOC. The range of ITD sensitivity of IC neurons is about 50% of that we estimate for neurons in the medial superior olive (MSO); in the MGB the range is about 30% of that in the IC. If we view the range of ITD sensitivity as an estimate of the neuron's spatial receptive field on the azimuth, then, it appears that one consequence of ITD processing in the binaural pathway is to reduce receptive field size. We will test this hypothesis, by making unit recordings from the MSO and lateral superior olive (LSO) of the unanesthetized rabbit so their receptive field estimates may be compared to our data in the IC and MGB. These stuides also would provide the first opportunity to examine ITD processing, free from anesthetic effects, at the primary sites of binaural interaction. We will also test the hypothesis that in the MGB, inhibitory mechanisms are involved in the reduction of receptive field size. There is strong evidence that inhibitory mechanisms play a role in ITD processing by MGB neurons. We will assess directly the role of inhibitory events in ITD processing by recording intracellularly from MGB neurons in the unanesthetized rabbit. Finally, we will test the hypothesis that segregated ITD regions in the MGB received distinct patterns of input from the midbrain. We propose, through unit recordings, to map the distribution of ITD regions in the MGB. These studies should elucidate the differences in ITD processing between subdivisions of the MGB. We will then inject retrograde tracers into these regions. The anatomical studies should clarify whether ITD processing in the MGB involves particular cell types and whether they involve converging or parallel pathways.

DESCRIPTION (provided by applicant): Localizing a sound in 3-dimensional space requires the processing of azimuth, elevation, and distance. Although considerable attention has been focused on the neural processing of azimuthal and elevational cues, our knowledge of the neural processing of distance is almost non-existent. Psychophysical and modeling studies show distance perception in reverberant environments is based on the ratio of reverberant to direct sound energy. This ratio changes with distance because the direct energy decreases at 6 dB per for doubling of distance, but reverberant energy remains about constant with distance. Another cue for distance are the increases in interaural level difference with decreasing distance. Another potential cue is the systematic decrease in high frequency energy with increasing distance. To investigate the neural processing of sound distance, we will use virtual sounds made from ear canal recordings to sounds emanating from different distances and azimuths that are made in our state-of-the-art anechoic and reverberant chambers. In human listeners, such virtual sounds produce auditory images that are appropriately externalized and localized. We will use this virtual technology because, in comparison to making neural recordings in the real sound field, it allows the dissection and modification of auditory cues and also offers far greater efficiency and flexibility in sampling spatial locations. It also permits switching back and forth from the anechoic to reverberant environment, while recording from a neuron. We will explore distance processing in both anechoic and reverberant environments because the acoustics are quite different and both of these environments, to one degree or another, are normally experienced by humans and other animals. Our aim is to determine the neural coding of sound source distance in anechoic and reverberant environment in neurons of the inferior colliculus in the unanesthetized rabbit. Specifically, we will examine the effect of neural interactions between distance and azimuth, distance and acoustic environment, and azimuth and acoustic environment. The results may be helpful in designing hearing aids, cochlear implants, and robotic devices to incorporate all 3 dimensions of spatial hearing.

DESCRIPTION (provided by applicant): Our goal is to attract and train postdoctoral candidates who seek training in multiple areas of auditory research. The research of our Program Faculty covers a broad spectrum of approaches, i.e., psychophysics, anatomy, physiology, molecular biology, and clinical applications. All of the members of the Program Faculty have extramural funding and state-of-the-art laboratories. We are a long-standing, cohesive, and productive group with a history of individual and cooperative success that is necessary for a training grant to be optimal in terms of both its potential and actual outcomes. The training grant will support three postdoctoral fellows at any one time. The trainees will possess a Ph.D. or M.D. with a strong potential for a research career in auditory neuroscience. The basic goal of the training program is to develop scientists with broad training in auditory neuroscience, a deep awareness and appreciation of many additional aspects of the field, and a love for learning, experimentation and teaching. We view our candidates as intellectual members of a team, budding junior colleagues and not simply workers accomplishing the next step on a grant application. Each postdoctoral trainee will be offered a maximum of three years of support with the understanding that this support depends on satisfactory progress. We anticipate that this is an appropriate training period, but it may need to be tailored to the trainee?s background. For instance, a trainee who needs to strengthen his background through courses and lab experience might require more than three years of support, while a trainee with a strong auditory background or past postdoctoral experience may require less than three years. If more than three years of support is required, then the trainee will submit an individual NRSA (F32) to support their training beyond our three-year maximum. We are a flexible group and the best interests of the trainee will be foremost in determining the optimal period of support. We are excited about our own work and also the work of our colleagues. We respect the contributions that can be made by psychophysicists, electrophysiologists, molecular biologists and anatomists and know that progress on fundamental issues requires the cooperation and integration of outstanding researchers with diverse areas of expertise. A postdoctoral trainee in this milieu cannot help but flourish to become a productive and creative investigator in his own right.