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).
The purpose of this research is to identify functionally-distinct cell types in auditory areas of the brain based on the expression of genes involved in the transmission of signals. This information will be used to better understand the function of those cells in individuals with normal hearing, and determine how those normal functions are altered by hearing loss, tinnitus, and other communication disorders (autism, aging, stroke). Application of these data to clinical populations will permit improved targeting of the genes and cell types that contribute to pathology, and thereby optimize the effectiveness of therapeutic intervention.
| Hackett, Troy A (2018) Adenosine A1 Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain. Anat Rec (Hoboken) 301:1882-1905 |
| Balaram, P; Hackett, T A; Polley, D B (2018) Synergistic Transcriptional Changes in AMPA and GABAA Receptor Genes Support Compensatory Plasticity Following Unilateral Hearing Loss. Neuroscience : |
| Sottile, Sarah Y; Hackett, Troy A; Cai, Rui et al. (2017) Presynaptic Neuronal Nicotinic Receptors Differentially Shape Select Inputs to Auditory Thalamus and Are Negatively Impacted by Aging. J Neurosci 37:11377-11389 |
| Blundon, Jay A; Roy, Noah C; Teubner, Brett J W et al. (2017) Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling. Science 356:1352-1356 |
