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High-probability grants
According to our matching algorithm, Jeffrey Garrett Mellott is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2012 — 2014 |
Mellott, Jeffrey Garrett |
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. |
Cholinergic Inputs to Excitatory and Inhibitory Midbrain Auditory Circuits @ Northeast Ohio Medical University
DESCRIPTION (provided by applicant): The auditory system comprises ascending pathways that transmit information from the ear to higher levels for perception, and descending pathways that can modify how that information is processed at each auditory nucleus. Descending projections from auditory cortex to the inferior colliculus of the midbrain play a role in a wide range of auditory functions, including selective attention, plasticity and learning, and understanding speech in noisy environments. Recent progress indicates that cholinergic cells (neurons that use acetylcholine as a neurotransmitter) play an important role in many of these functions. Many of the cholinergic effects are mediated through interactions with GABAergic cells (neurons that use GABA as a neurotransmitter) in the inferior colliculus, but further understanding has been hindered by questions regarding the underlying neural circuitry. The present proposal focuses on possible connections between the cholinergic and descending systems to a recently discovered GABAergic pathway from cells of the inferior colliculus to the medial subdivision of the medial geniculate body. One aim is to identify the locations of these cells across the functional subdivisions of the inferior colliculus cells. The second and third aim determine whether these cells receive cholinergic or auditory cortical inputs. The study will be conducted in guinea pigs, a well-researched model for many aspects of auditory function. The experiments will use multilabeling anatomical techniques, including fluorescent neuronal tracers for labeling specific circuit elements and immunochemical techniques for identifying the neurotransmitters associated with those elements. Coordinated studies with both light and electron microscopes will allow for the direct identification of synapses, a necessary step for identifying neuronal circuits. The results will provide an important step in characterizing excitatory and inhibitory midbrain circuits and their relationships to ascending and descending auditory pathways as well as their relationships to the cholinergic system. This may have important implications for normal function as well as dysfunction (such as presbycusis or tinnitus) associated with aging or injury and for the evolving design and use of cochlear implants and brainstem implants. From a training perspective, the proposed experiments cover a broad range of sensitive anatomical techniques, including a variety of multi-labeling methods and strategies for the effective combination of light and electron microscopy. This anatomical training is designed to expand and diversify the applicant's prior limited training in neuroanatomical techniques. The ability to combine and analyze multiple anatomical approaches will greatly expand the range of research questions that he will be able to address in the future. PUBLIC HEALTH RELEVANCE: Descending auditory pathways and the pathways that use acetylcholine as a neurotransmitter play critical roles in functions such as selective attention an adaptation to changing sensory inputs. Identifying the associated circuits and improving their functions is an important goal in persons with hearing loss, tinnitus, cochlear implants or various disorders such as autism or schizophrenia. The present proposal will answer important questions about the circuitry that underlies these functions.
|
1.009 |
2020 — 2021 |
Mellott, Jeffrey Garrett |
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. |
Age-Related Gabaergic Loss in the Central Auditory Circuits @ Northeast Ohio Medical University
Project Summary Our long-term goal is to understand the relationship between peripheral and central changes in the auditory system during age-related hearing loss (ARHL). GABA, an inhibitory neurotransmitter critical for precise temporal processing, is downregulated in the central auditory system during aging. This loss of GABA has been best documented in the inferior colliculus (IC), an auditory nucleus that gives rise to ascending circuits that carry temporally precise signals to the auditory cortex for perception and descending circuits that play a pivotal role in the temporal processing of interpreting speech from noise. Recent studies hypothesize that the downregulation of GABA is a homeostatic response to ?re-up? the gain in central neurons as the cochlear input is diminished. However, our understanding of GABAergic function in the aging IC is inadequate due to the lack of information about the relationship of GABA loss to increasing hearing deficits, about which specific IC circuits lose GABA, and how those circuits respond during aging. Our central hypothesis is that age-related GABAergic downregulation in the IC occurs prior to the onset of auditory processing deficits and in two stages: an initial loss of GABA prior to age-related auditory processing deficits that is associated with descending IC circuits, and a subsequent loss associated with the ascending IC circuits. The objective of this proposal is to determine where in the IC age-related changes of GABA occur and if so, do these changes occur before the onset of auditory processing deficits. The experiments will combine data from gap detection using the prepulse inhibition of the acoustic startle, envelope following responses, auditory brainstem responses, immunochemistry and immunoelectron microscopy-intersectional viral tracing to determine age-related GABAergic changes in the IC that occur before hearing deficits. Examining the relationship between the loss of GABAergic cells, boutons and synapses in the aging IC before the onset of hearing deficits is the focus of Aim 1. Aim 2 will determine if specific IC circuits lose GABAergic input with age and if so, when those losses occur relative to each other. Aim 3 will identify when inhibitory and excitatory IC circuits change their GABAA receptor subunit composition to compensate for the declining levels of GABAergic input during ARHL. Data generated from these three Aims will move the field forward by establishing precise points in time when age-related changes in specific circuits of the central auditory system occur in relation to hearing loss. The results will provide essential information for designing and interpreting future experiments with viral tracing, physiology and behavior to investigate GABAergic function in the aging auditory system.
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1.009 |