Leonard Martin Kitzes - US grants

The long term objectives of this research plan is to define how interactions during post-natal development between pathways within the auditory system determine the structure and function of the auditory system. While it is known that afferent neurons play a critical role in the development and maintenance of targeted cells in the auditory system, the emphasis in this research is the interactions during development between pathways that convey information from each ear. How will pathways conveying information from one ear develop in an animal deprived from birth of sensory information of the other ear? The focus of the present proposal is the localization and definition of the interactions between pathways that occur during the post-natal development of the lower brainstem auditory system. The projections from the cochlear nuclear complex to the component nuclei of the superior olivary complex and nuclei of the lateral lemniscus bilaterally will be examined in control gerbils and in adult gerbils that had been subjected at two days of age to the ablation of one cochlea. These projections will be compared by injecting anterograde tracers into the cochlear nuclear complex on the non-operated side in experimental animals and into one cochlear nucleus of control animals. Secondly, functional differences between the brainstem auditory system of animals that had developed with one or with both cochleas will be studied by analyzing responses of single neurons in those nuclei. Responses to stimulation of the non-operated ear in a neonatally ablated animal will be compared with responses to monaural stimulation in control animals. This research is related to the consequences of perinatal loss of hearing in humans, as often happens, for example, in cases of maternal rubella. Understanding the anatomical and physiological consequences of the neonatal loss of the cochlea in the gerbil shold provide a greater understanding of the clinical situation in humans.

The long term objectives of this research plan is to define how interactions during post-natal development between pathways within the auditory system determine the structure and function of the auditory system. While it is known that afferent neurons play a critical role in the development and maintenance of targeted cells in the auditory system, the emphasis in this research is the interactions during development between pathways that convey information from each ear. How will pathways conveying information from one ear develop in an animal deprived from birth of sensory information of the other ear? The focus of the present proposal is the localization and definition of the interactions between pathways that occur during the post-natal development of the lower brainstem auditory system. The projections from the cochlear nuclear complex to the component nuclei of the superior olivary complex and nuclei of the lateral lemniscus bilaterally will be examined in control gerbils and in adult gerbils that had been subjected at two days of age to the ablation of one cochlea. These projections will be compared by injecting anterograde tracers into the cochlear nuclear complex on the non-operated side in experimental animals and into one cochlear nucleus of control animals. Secondly, functional differences between the brainstem auditory system of animals that had developed with one or with both cochleas will be studied by analyzing responses of single neurons in those nuclei. Responses to stimulation of the non-operated ear in a neonatally ablated animal will be compared with responses to monaural stimulation in control animals. This research is related to the consequences of perinatal loss of hearing in humans, as often happens, for example, in cases of maternal rubella. Understanding the anatomical and physiological consequences of the neonatal loss of the cochlea in the gerbil shold provide a greater understanding of the clinical situation in humans.

The Program Project is focused upon detailed analyses of the structure and function of the primary auditory area of the cerebral cortex. The ultimate goal of the research is to reveal the physiological, anatomical and pharmacological determinants of the processing of monaural and binaural acoustic stimuli in the auditory cortex. The research program consists of five projects, each focused upon a different aspect of cortical function, with project, however, being strongly dependent upon the research conducted in other projects. In addition to sharing the information generated by each of the projects, each depends to a very great extent upon the expertise of each member of the program. 1. The development of auditory cortex will be studied by analyzing the growth of the cortex and its afferent sources in vivo and in vitro and the molecular determinants of its growth. 2. The physiology of auditory cortex will be studied at the level of the single neuron both extracellularly and intracellularly with the goals of understanding the synaptic mechanisms that shape its responses to monaural and binaural acoustic stimuli. 3. The anatomy of auditory cortex will be studied at both the light and electron microscopic levels to understand the intricate architectural features of the cortical circuitry, the afferent sources of this circuitry and the pathways within the cortex that convey information from one area to another. 4 The chemical anatomy of auditory cortex will be studied using the techniques of receptor binding, in situ hybridization, and immunohistochemistry with the goal of defining the chemical interactions between neuron which, ultimately, determine our ability to hear. By revealing the developmental, physiological, anatomical and chemical determinants of auditory cortex function, we should be closer to understand how we hear. Such information is crucial to the clinical treatment of hearing impairment.

biomedical equipment resource; biomedical equipment purchase;

An acoustic stimulus is represented by the activity it evokes in a population of neurons in the auditory system. Differences between stimuli must be represented by differences between the population of units activated by each stimulus and/or between the activity evoked in the population of relevant neurons. Conversely, any change in the identity of the units comprising the population of activated units and any change in the magnitude of their responses should be associated with a change in the quality of the percept evoked by the stimulus. Thus, both the identity and the activity of the units comprising the populations of neurons activated by various stimuli may underlie the ability to distinguish one stimulus from another. The overall goal of the proposed research is to understand the differential coding of stimuli in terms of both the amount and the spatial distribution, i.e., topography, of activity in auditory cortex. In three studies the collective responses of all isolated single units to a fixed set of monaural and binaural stimuli will serve as an estimate of the topographic organization of activity evoked by those stimuli. In all cases stimulus frequency will be fixed. The resulting maps will be examined within a stimulus set, e.g., 40 dB binaural, within a stimulus dimension, e.g., binaural SPL, and across stimulus dimensions, e.g., contralateral vs. binaural. The temporally dynamic nature of these topographic maps will be examined with a forward masking paradigm in which the interval between the masker and the test stimulus is varied. These studies will be conducted along the extent of an isofrequency strip of AI, over an expanse of AI across isofrequency contours, and in the posterior auditory field. Forward masking can cause a response to a test stimulus that would otherwise not occur or reduce or even preclude a response that otherwise would be robust. These effects would contribute to or determine the dynamic behavior of topographic maps in auditory cortex. Consequently, studies are proposed to investigate the changes in sensitivity of single units in AI and the posterior field in a forward masking paradigm. Qualitative pre-dictions are proposed for EE, EI and TWIN cells. The pilot and expected findings of these studies lead to specific predictions that the perceptual localization of a stimulus is not static. The results of these studies are likely to increase our understanding of the clinical impact of strokes and cortical insult resulting in hearing deficits. Perhaps cortical deafness is related to the instability of its topographic maps.