The long-term objective of this research is to gain an understanding of the cellular mechanisms by which neurons in the auditory cortex (ACx) process spectrally complex information. The hypothesis to be tested is that individual ACx neurons receive converging, largely subthreshold, inputs subserving most of the audible spectrum, and that synaptic integration produces optimal responses to complex stimuli. The proposed underlying neural architecture involves thalamocortical projections to ACx layer 3/4 mediating characteristic frequency (CF) and near-CF responses, and intracortical projections outside of layer 4 mediating spectrally-distant nonCF responses. The precise synaptic architecture dictates that optimal synaptic integration occurs in response to specific, predictable, spectrotemporally complex stimuli.
Three Specific Aims utilize in vivo intracellular recordings and a newly developed in vitro auditory thalamocortical preparation: 1) Determine if subthreshold receptive fields are much broader than spike-based receptive fields, using in vivo intracellular recordings in ACx. 2) Determine if thalamic stimulation in vitro activates ACx layer 3/4 followed by excitation in upper and lower layers of adjacent ACx. In parallel in vivo experiments, determine if CF stimuli activate synapses in layer 3/4 whereas spectrally-distant nonCF stimuli activate synapses outside of layer 4. 3) Determine in vitro how converging synaptic potentials are optimally integrated, and then determine in vivo if similar integration underlies optimal responses to complex stimuli. An understanding of these mechanisms will enhance treatments for conditions such as partial ACx lesions or cochlear implants, by guiding the design of stimuli to activate ACx optimally. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002967-08
Application #
6845737
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Luethke, Lynn E
Project Start
1996-09-30
Project End
2008-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
8
Fiscal Year
2005
Total Cost
$186,530
Indirect Cost
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Intskirveli, Irakli; Metherate, Raju (2012) Nicotinic neuromodulation in auditory cortex requires MAPK activation in thalamocortical and intracortical circuits. J Neurophysiol 107:2782-93
Kawai, Hideki D; Kang, Ho-An; Metherate, Raju (2011) Heightened nicotinic regulation of auditory cortex during adolescence. J Neurosci 31:14367-77
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Kaur, S; Rose, H J; Lazar, R et al. (2005) Spectral integration in primary auditory cortex: laminar processing of afferent input, in vivo and in vitro. Neuroscience 134:1033-45
Rose, Heather J; Metherate, Raju (2005) Auditory thalamocortical transmission is reliable and temporally precise. J Neurophysiol 94:2019-30