Hearing loss can perturb speech and language acquisition and ultimately compromise cognitive performance. The core hypothesis of this proposal is that sensorineural (SNHL) or conductive hearing loss (CHL) disrupts the balance between excitatory and inhibitory conductances, and severely limits the ability of primary auditory (Al) cortex neurons to encode acoustic cues. Deafness will be surgically induced before hearing onset in gerbils, and the properties of Al pyramidal neurons will be examined using whole-cell recording techniques in a thalamocortical brain slice preparation. The research plan will address four major issues: (1) Does hearing loss influence intrinsic properties in Al? Changes in Al neuron electrical characteristics will be examined, including electrotonic and firing properties, and key inward and outward currents. (2) Does hearing loss influence excitatory synapses in Al? Changes in thalamus-evoked excitatory postsynaptic currents (EPSCs) will be investigated, including their amplitude and kinetics. Pre- or postsynaptic involvement will be assessed with focal delivery of agonists, mEPSC analyses, and EPSC failure rates. (3) Does hearing loss influence inhibitory synapses in Al? Changes in intracortically-evoked inhibitory postsynaptic potentials (IPSPs) will be studied, including the pharmacology of GABAa and GABAb receptor mediated components. Pre- or postsynaptic involvement will be assessed with focal delivery of GABA agonists, and miniature IPSCs. (4) Does hearing loss affect cortical processing? Changes in temporal processing will be explored by stimulating thalamic afferents with trains of rectangular or sinusoidal current pulses while recording EPSPs in Al. Synaptic integration will be assessed by timing intracortical inhibition with current- or thalamus- evoked action potentials. Together, the results are significant for understanding at a cellular level how auditory processing is influenced by mild to severe deafness, and how we might compensate for these deficits.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC006864-05S1
Application #
7763535
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2005-04-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
5
Fiscal Year
2009
Total Cost
$135,623
Indirect Cost
Name
New York University
Department
Neurology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Sanes, Dan H; Kotak, Vibhakar C (2011) Developmental plasticity of auditory cortical inhibitory synapses. Hear Res 279:140-8
Takesian, Anne E; Kotak, Vibhakar C; Sanes, Dan H (2010) Presynaptic GABA(B) receptors regulate experience-dependent development of inhibitory short-term plasticity. J Neurosci 30:2716-27
Jercog, Pablo E; Svirskis, Gytis; Kotak, Vibhakar C et al. (2010) Asymmetric excitatory synaptic dynamics underlie interaural time difference processing in the auditory system. PLoS Biol 8:e1000406
Xu, Han; Kotak, Vibhakar C; Sanes, Dan H (2010) Normal hearing is required for the emergence of long-lasting inhibitory potentiation in cortex. J Neurosci 30:331-41
Sanes, Dan H; Bao, Shaowen (2009) Tuning up the developing auditory CNS. Curr Opin Neurobiol 19:188-99
Takesian, Anne E; Kotak, Vibhakar C; Sanes, Dan H (2009) Developmental hearing loss disrupts synaptic inhibition: implications for auditory processing. Future Neurol 4:331-349
Gai, Yan; Doiron, Brent; Kotak, Vibhakar et al. (2009) Noise-gated encoding of slow inputs by auditory brain stem neurons with a low-threshold K+ current. J Neurophysiol 102:3447-60
Miko, Ilona J; Sanes, Dan H (2009) Transient gain adjustment in the inferior colliculus is serotonin- and calcium-dependent. Hear Res 251:39-50
Sarro, Emma C; Kotak, Vibhakar C; Sanes, Dan H et al. (2008) Hearing loss alters the subcellular distribution of presynaptic GAD and postsynaptic GABAA receptors in the auditory cortex. Cereb Cortex 18:2855-67
Kotak, Vibhakar C; Takesian, Anne E; Sanes, Dan H (2008) Hearing loss prevents the maturation of GABAergic transmission in the auditory cortex. Cereb Cortex 18:2098-108

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