R. Bruce Masterton - US grants

Despite a wide array of fundamental data concerning the dorsal cochlear nucleus and despite the prevalence of acoustic gliomas and meningiomas involving it, little or nothing is yet known either about its contribution to hearing or the deficits in hearing that accompany its damage as a result of injury or disease. This project includes a series of tissue-level ablation-behavior experiments on the dorsal cochlear nucleus of the cat. Cats with and without ablation of the dorsal cochlear nucleus will be tested on a variety of auditory psychophysical tasks. The psychophysical tests themselves are derived from the cytoarchitecture, the intrinsic and extrinsic afferent and efferent connections, and the electrophysiological and neurochemical characteristics of the dorsal cochlear nucleus and its constituent neural elements. Because the dorsal cochlear nucleus takes on somewhat different forms in different orders of mammals and these differences form the basis of some of the behavioral tests included, a complete inquiry must eventually make use of several carefully selected species of mammals. However, only cats will be used in the present series of exploratory experiments because of the vastly greater body of knowledge that is already available on their auditory system.

The research entails anatomical, biochemical, and ablation-behavior analyses of neocortex in primitive mammals. The long term objective is to discover the contribution of sensory, association, and motor cortex to the neurological and psychological adjustment of man to his environment. The specific aims include the assessment of the structure and function of major areas of neocortex in a number of primitive mammals, including opossum, mouse opossums, armadillos, hedgehogs, tree shrews, and bushbabies, specifically selected to allow inferences to the extinct animals in mankind's ancestral lineage. The methods include anatomical tract-tracing techniques to determine the changes in the location, extent, and connections of sensory and motor areas, receptor-binding techniques to determine changes in the biochemical characteristics of the same areas, and ablation techniques combined with rigorous behavioral testing to determine the changes in the contributions of these areas. In this manner the evolutionary development of Primate neocortex is traced from its most primitive mammalian form to its current form in an attempt to understand the contributions of its many parts. Since surgical ablation duplicates the type of brain damage that often results from stroke, the inquiry also can be expected to yield information about the fragmentation of man's psychological capacities as a result of cerebrovascular accidents.

The proposed research entails anatomical, biochemical, and ablation- behavior analyses of neocortex in neurologically primitive mammals. The long term objective is to discover the contribution of sensory, association, and motor cortex to the neurological and psychological adjustment of man and animals to their environment. The specific aims include the assessment of the structure and function of major areas of neocortex in a number of neurologically generalized mammals (including opossums, armadillos, rabbits, rats, hedgehogs, tree shrews, lemurs, and bushbabies) specifically selected for their sequential common ancestry with Primates, in order to allow inferences to the neurological and psychological condition of the extinct animals in the Primate ancestral lineage. The methods include anatomical tract-tracing techniques to determine the changes in the location, extent, and connections of sensory and motor areas, receptor-binding and immunohistochemical techniques to determine changes in the biochemical characteristics of that same areas, and ablation-behavior techniques to determine the changes in the behavioral contributions of the areas. In this manner the evolutionary development of Primate neocortex is traced from its most primitive mammalian form to its current form in an attempt to understand the contributions of its many parts.

The proposed research entails anatomical, biochemical, and ablation- behavior analyses of neocortex in neurologically primitive mammals. The long term objective is to discover the contribution of sensory, association, and motor cortex to the neurological and psychological adjustment of man and animals to their environment. The specific aims include the assessment of the structure and function of major areas of neocortex in a number of neurologically generalized mammals (including opossums, armadillos, rabbits, rats, hedgehogs, tree shrews, lemurs, and bushbabies) specifically selected for their sequential common ancestry with Primates, in order to allow inferences to the neurological and psychological condition of the extinct animals in the Primate ancestral lineage. The methods include anatomical tract-tracing techniques to determine the changes in the location, extent, and connections of sensory and motor areas, receptor-binding and immunohistochemical techniques to determine changes in the biochemical characteristics of that same areas, and ablation-behavior techniques to determine the changes in the behavioral contributions of the areas. In this manner the evolutionary development of Primate neocortex is traced from its most primitive mammalian form to its current form in an attempt to understand the contributions of its many parts.

The major efferent tracts of the cochlear nucleus (the ventral, intermediate and dorsal acoustic stria) impose a three-way subdivision on the central auditory system as it ascends through the hindbrain. A good deal is already known about the functional role of the ventral system: it is necessary for the discrimination of most of the usual dimensions of normal hearing; that is, for normal thresholds for noises and tones, for discriminating frequency and amplitude of tones, for detecting sounds in noisy environments and for determining the azimuth of a sound source. However, the role of the dorsal system (i.e., dorsal cochlea nucleus or DCN and dorsal acoustic stria or DAS) is unknown. Despite a vast collection of cellular- and molecular-level knowledge about DCN itself, little or nothing is yet known about its contribution to hearing for the deficits in hearing that might accompany its damage as a result of injury or disease. This proposal includes a series of tissue-level ablation-behavior experiments directed at the functional anatomy of the dorsal acoustic system--beginning at DCN's output over the DAS. Animals with and without section of the dorsal (and intermediate) acoustic stria along with appropriate control cases will be tested on two discriminations of sound-source elevation--tasks derived specifically from the only function of the dorsal system yet discovered.

The proposed research entails anatomical, biochemical, and ablation- behavior analyses of neocortex in neurologically primitive mammals. The long term objective is to discover the contribution of sensory, association, and motor cortex to the neurological and psychological adjustment of man and animals to their environment. The specific aims include the assessment of the structure and function of major areas of neocortex in a number of neurologically generalized mammals (including opossums, armadillos, rabbits, rats, hedgehogs, tree shrews, lemurs, and bushbabies) specifically selected for their sequential common ancestry with Primates, in order to allow inferences to the neurological and psychological condition of the extinct animals in the Primate ancestral lineage. The methods include anatomical tract-tracing techniques to determine the changes in the location, extent, and connections of sensory and motor areas, receptor-binding and immunohistochemical techniques to determine changes in the biochemical characteristics of that same areas, and ablation-behavior techniques to determine the changes in the behavioral contributions of the areas. In this manner the evolutionary development of Primate neocortex is traced from its most primitive mammalian form to its current form in an attempt to understand the contributions of its many parts.

The overall goal of the project is to define and understand the central neural circuits of pinna movement control. This system has important advantages for the study of sensorimotor systems including accessibility, availability of a good neuro-anatomical data base, and a means for quantifying movement data. Insofar as it can be considered a prototype of other motor control systems, understanding the pinna control system has relevance to humans who suffer from motor disorders. The strategy of the research employs two methodologies; 1) the application of the ablation- behavior technique in which specific neural structures or pathways are selectively interrupted and the effects both on stimulus-elicited and spontaneous pinna movements are measured; and 2) the application of neuroanatomic tract-tracing and functional labeling methods guided by the outcomes of the ablation studies to uncover additional pathways and nuclei which might contribute to pinna movements. Four specific goals are to be achieved; 1) establish the functional role of known ascending and descending components of the sound-pinna control circuit; 2) anatomically define the critical components of the system; 3) characterize the system's response to the spatial components of acoustic stimuli; and 4) develop a neural circuit model based on the results of anatomical and functional studies. In the behavioral studies, the horizontal position of the pinnae and head are electronically derived (from small coils of fine wire temporarily pasted to their posterior surfaces) both during spontaneous activity and in response to specific acoustic stimuli in awake, lightly restrained cats before and after selective ablation of selected neural sites. In the anatomic studies, conventional orthograde and retrograde tract- tracing methods are used to identify each source of inputs to the motor nuclei controlling the pinna. In addition, 2-DG labeling methods are used to identify the array of sites activated by electrical stimulation of area known or suspected to be part of the relevant circuits.