1996 — 1999 |
Hackett, Troy A. |
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. |
Organization of Auditory Cortex
The mammalian auditory cortex is comprised of several areas which can be distinguished on the basis of anatomical and physiological differences. The major objectives of the proposed research is to determine in greater detail the anatomical and physiological substrates which underly information processing in the auditory cortex of higher primates. Specific goals include: (1) description of the cortical, callosal, and thalamic connections of the three auditory cortical regions (core, belt, parabelt) and their respective subdivisions; (2) derivation of tonotopic/functional maps of each region and subdivision based on multi- unit responses to pure tone, bandpass noise bursts, and species-specific vocalizations; and (3) formulation of a basic theory of information processing within and between each auditory region. Microelectrode mapping, neuroanatomical tracing of connections, architectonic analysis, and standard histochemical staining methods will be used in combination to determine the borders between fields. Parallel experiments will be conducted in New World (owl) monkeys for technical advantages, and Old World (macaque) monkeys for their closer phylogenetic relationship to humans. The underlying premise is that the auditory system includes an array of control areas that are modularly organized and hierarchically interconnected, with parallel and serial components. The proposed studies will provide a better understanding of the anatomical and physiological substrates on which the processing and distribution of auditory information are based. This work will also serve as a framework for subsequent research on adult plasticity and recovery from peripheral or central auditory impairments.
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2000 — 2005 |
Hackett, Troy A. |
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. R55Activity Code Description: Undocumented code - click on the grant title for more information. |
Functional Organization of the Auditory Cortex
We have proposed that the primate auditory cortex includes a core region of three primary-like areas, surrounded by a belt region containing seven or eight areas, and a parabelt region that has at least two subdivisions. Each region represents a successive level of processing, and subdivisions within each region are activated by parallel inputs. Some aspects of the proposed organization are well-established, while others are not. Thus, one goal is to evaluate and extend the current theory by examining functional organization in the medial belt region, which occupies an intermediate position between the auditory core and insular/parietal cortex, and has not been studied in detail. Characterization of the anatomical and physiological properties of the medial belt fields is important for a more complete understanding of auditory cortical organization, and also in the establishment of the relationship between auditory and somatic sensory systems in cortex. In these experiments, multiunit recordings will be used to guide tracer injections and determine the frequency response area of neuronal clusters within these fields. Through analysis of connections, architecture, and physiology we will evaluate and extend proposals of the organization of medial belt fields, and determine their relationship to auditory-related cortical and subcortical areas. Thus, although the focus of these studies will be on the medial belt region, the experimental design involves analysis at all levels of auditory processing in the cortex, thalamus, and midbrain. A related issue concerns the extent to which the basic principles of auditory cortical organization in monkeys can be generalized to humans. As a second aim, we will compare architectonic features of auditory cortex in non-human primates and humans. Analyses of cytoarchitecture, myeloarchitecture, and the distribution of acetylcholinesterase, cytochrome oxidase, parvalbumin, calbindin, SMI-32, and CAT-301 will be combined to characterize and compare the architecture of core, belt, and parabelt fields in the auditory cortex of monkeys, apes, and humans. We expect to find similarities across species, but important differences may exist that relate to functional specializations. As more is learned concerning the basic functional organization of auditory cortex, it becomes possible to study the effects of pathology on cortical organization and the capacity for recovery.
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2007 — 2011 |
Hackett, Troy A. |
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. |
Functional Organization of Auditory Cortex
DESCRIPTION (provided by applicant): The long-term goal of this research program is a comprehensive description of human auditory cortex organization. What are its structural components and what are their functions? How do these elements work together to produce the perceptual experience of hearing? Underlying current conceptions is a regional (modular) system of organization formed by an interconnected group of cortical areas, but the number of areas involved and their connections are unknown for humans. A testable working model of human auditory cortex has not been developed, even though such models are fundamental to studies of auditory cortex in other species. To establish this model, detailed neuroanatomical analyses will be used to reveal the underlying structures that comprise this part of the brain. Efforts will focus on the planum temporale in the superior temporal lobe, which is thought to be an important region for integrating the neural codes required to perceive and interpret sound. Although often treated as a single area, the planum temporale appears to contain several areas that are anatomically and physiologically distinct. Temporal lobes will be obtained postmortem and processed for marker proteins of neurons, axons, neurofilaments, and key enzymes. Areas will be profiled and compared on the basis several measurements (surface area, cortical thickness, neuron density, optical density). The research will be guided and grounded by comparative studies of other primates, which continue to provide an invaluable foundation for studies of auditory cortex in humans. In addition, parallel studies in monkeys will focus on the connections and neuron response properties in the posterior temporal lobe that correspond to the human planum temporale. The relevance of this research applies broadly to patient populations in which the temporal lobe is involved, and directly supports related areas of research involving both normal and clinical populations. These include: 1) Noninvasive methods to study auditory activity in the human brain (e.g., functional imaging);2) Neurosurgical planning and assessment of function associated with surgery, injury, or related pathology (e.g., cerebrovascular accidents, tumors);3) Evaluation of cortical function in clinical populations in which auditory processing or memory is affected (e.g., Alzheimer's, schizophrenia, autism, dyslexia, epilepsy, language delay, hearing impairment, and aging);and 4) Maturational and genomic studies of auditory cortex in normal and clinical populations.
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2013 — 2014 |
Hackett, Troy A. |
K18Activity Code Description: Undocumented code - click on the grant title for more information. |
Gene Expression During Postnatal Development of the Central Auditory Pathway
DESCRIPTION (provided by applicant): A comprehensive understanding of the genetic and environmental factors that govern pre- and postnatal development of the auditory system is essential for conceiving of and improving existing therapeutic approaches that address impaired auditory function in clinical populations. Since their influence varies between individuals and by etiology, these factors combine to shape auditory processing in different ways. As a tool for revealing the underlying structure of the auditory system, and how it develops and changes with experience, studies of gene expression are indispensable. Some of these genes govern general metabolic and regulatory functions common to all central nervous system structures. Others are linked to specific processes, such as cell communication, motility, fate and differentiation. Moreover, their expression varies by age, between regions of the brain, and with sensory experience. To date, comprehensive gene expression profiles have not been generated for most structures in the central auditory pathway, and none are complete for any species at any age. The scientific aims of this proposal address this need in a novel study designed to document changes in gene and protein expression in the mouse at key stages of postnatal development to maturity. The PI is an established auditory neuroscientist whose research program combines neuroanatomical and neurophysiological methods to link structure and function in auditory and multisensory circuits in the brain. In terms of career development, the purpose of this proposal is to expand and enrich the scope of this research program by equipping the PI with the tools of molecular biology. Under the supervision of an expert mentor, the PI will be trained to characterize gene expression in selected brain areas, and then follow up by localizing transcripts to those brain structures at the mRNA and protein levels. Retooling in this manner will enable the PI to plan and conduct studies that are informed by the transcriptome profile of specific brain regions. Compared to existing strategies, the whole genome expression profiling approach is more comprehensive in scope and more effectively bridges structure and function. The scientific and career development goals of this K18 proposal will be achieved in the context of a study that combines DNA microarray analysis, in situ hybridization, and immunohistochemistry to: (1) identify genes that are differentially expressed in auditory cortex, medial geniculate, and inferior colliculus during postnatal development; and (2) localize the transcripts of selected genes to their expression within the cells, divisions, and laminae of each structure. These efforts will generate the first catalog of gene expression in the mouse central auditory pathway at key stages of postnatal development, while adding an important new dimension to studies of brain structure and function by the PI. Overall, this proposal advances efforts to characterize key neurobiological processes associated with communication disorders, such as hearing loss, autism, and stroke.
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2016 — 2020 |
Hackett, Troy A. |
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. |
Identification of Cellular Phenotypes in the Auditory Forebrain @ Vanderbilt University Medical Center
? DESCRIPTION (provided by applicant): In central auditory systems research, the basic layout and wiring diagrams of major brain areas in the most widely used model species have been generated. Neuroanatomical efforts are now primarily focused on the characterization of specific circuits. An important and rudimentary component in that process is to (1) identify the functionally-distinct cellular phenotypes that comprise each brain region; and (2) determine their precise locations in the pathway. The tools to acquire these data are now available. In this proposal, we have used the transcriptome (mRNA sequencing database) of the auditory forebrain to identify 72 (of 140) neurotransmitter receptor genes that are significantly expressed in the primary auditory cortex and medial geniculate body. Using multiplexed fluorescence in situ hybridization assays, each of those genes will be localized to each of 5 major cell types (neurons: glutamatergic, GABAergic)(glia: astrocytes, oligodendrocytes, microglia). Analyses of the co-expression patterns will permit us to identify and localize distinct neuronal and glial phenotypes in the each brain region based on their gene expression profiles. These data will expand understanding of the mechanisms that govern neurotransmission and plasticity at the cellular level, and permit greater specificity in the targeting of functionally-distinct cell typesfor neurophysiological study. More generally, the sequencing- guided approach adds a new dimension to studies of brain structure and function, and provides an expanded foundation for ongoing efforts to characterize the neurobiological mechanisms associated with communication disorders of all types. A comprehensive understanding of the molecular mechanisms that govern function in the auditory system is essential for conceiving of and improving existing therapeutic approaches that address impaired auditory function in clinical populations (hearing loss, autism, aging and stroke).
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