The long-term goal of our investigations is to understand the functional role of certain neuronal subtypes in the processing of sound in the cortex. Understanding this circuitry is likely to have an impact on the diagnosis and treatment of clinically important cortical neuropathologies, including autism, schizophrenia, tinnitus and epilepsy. Our central hypothesis is that a certain subtype of inhibitory neuron plays an important role in determining how other cortical neurons respond to sound. To achieve our goals, we propose to monitor and perturb the activity of these neurons.
In aim 1, we will study this circuit in vitro, substituting electrical for auditory stimulation.
In aims 2 and 3 we will study this circuit in vivo, presenting simple sounds and monitoring the responses they elicit in single neurons, and looking at their role in an auditory behavior. If successful, our studies will provide the link between molecular, circuit and functional aspects of sound processing in the auditory system, and will facilitate the development of treatments for psychiatric and neurological diseases. This proposal will test the function of a particular class of cortical neurons implicated in the etiology of clinically important neuropathologies, including autism, schizophrenia, tinnitus and epilepsy. If successful, our studies will lead to improved strategies for diagnosing and treating these and related disorders.

Public Health Relevance

This proposal will test the function of a particular class of cortical neurons implicated in the etiology of clinically important neuropathologies, including autism, schizophrenia, tinnitus and epilepsy. If successful, our studies will lead to improved strategies for diagnosing and treating these and related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005415-08
Application #
7894589
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2002-04-01
Project End
2013-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
8
Fiscal Year
2010
Total Cost
$366,053
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
Znamenskiy, Petr; Zador, Anthony M (2013) Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination. Nature 497:482-5
Hromadka, Tomas; Zador, Anthony M; DeWeese, Michael R (2013) Up states are rare in awake auditory cortex. J Neurophysiol 109:1989-95
Xiong, Qiaojie; Oviedo, Hysell V; Trotman, Lloyd C et al. (2012) PTEN regulation of local and long-range connections in mouse auditory cortex. J Neurosci 32:1643-52
Yang, Yang; Zador, Anthony M (2012) Differences in sensitivity to neural timing among cortical areas. J Neurosci 32:15142-7
Jaramillo, Santiago; Zador, Anthony M (2011) The auditory cortex mediates the perceptual effects of acoustic temporal expectation. Nat Neurosci 14:246-51
Oviedo, Hysell V; Bureau, Ingrid; Svoboda, Karel et al. (2010) The functional asymmetry of auditory cortex is reflected in the organization of local cortical circuits. Nat Neurosci 13:1413-20
Bledsoe Jr, Sanford C; Koehler, Seth; Tucci, Debara L et al. (2009) Ventral cochlear nucleus responses to contralateral sound are mediated by commissural and olivocochlear pathways. J Neurophysiol 102:886-900
Otazu, Gonzalo H; Tai, Lung-Hao; Yang, Yang et al. (2009) Engaging in an auditory task suppresses responses in auditory cortex. Nat Neurosci 12:646-54
Hromádka, Tomás; Zador, Anthony M (2009) Representations in auditory cortex. Curr Opin Neurobiol 19:430-3
Hromadka, Tomas; Zador, Anthony M (2007) Toward the mechanisms of auditory attention. Hear Res 229:180-5

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