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Cerebral Cortex Advance Access published online on January 24, 2008

Cerebral Cortex, doi:10.1093/cercor/bhm233
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Hearing Loss Prevents the Maturation of GABAergic Transmission in the Auditory Cortex

Vibhakar C. Kotak1, Anne E. Takesian1 and Dan H. Sanes1,2

1 Center for Neural Science, 4 Washington Place, New York University, New York, NY 10003, USA, 2 Department of Biology, 4 Washington Place, New York University, New York, NY 10003, USA

Address correspondence to Vibhakar C. Kotak, Ph.D. Email: kotak{at}cns.nyu.edu

Inhibitory neurotransmission is a critical determinant of neuronal network gain and dynamic range, suggesting that network properties are shaped by activity during development. A previous study demonstrated that sensorineural hearing loss (SNHL) in gerbils leads to smaller inhibitory potentials in L2/3 pyramidal neurons in the thalamorecipient auditory cortex, ACx. Here, we explored the mechanisms that account for proper maturation of {gamma}-amino butyric acid (GABA)ergic transmission. SNHL was induced at postnatal day (P) 10, and whole-cell voltage-clamp recordings were obtained from layer 2/3 pyramidal neurons in thalamocortical slices at P16–19. SNHL led to an increase in the frequency of GABAzine-sensitive (antagonist) spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs), accompanied by diminished amplitudes and longer durations. Consistent with this, the amplitudes of minimum-evoked IPSCs were also reduced while their durations were longer. The {alpha}1- and β2/3 subunit–specific agonists zolpidem and loreclezole increased control but not SNHL sIPSC durations. To test whether SNHL affected the maturation of GABAergic transmission, sIPSCs were recorded at P10. These sIPSCs resembled the long SNHL sIPSCs. Furthermore, zolpidem and loreclezole were ineffective in increasing their durations. Together, these data strongly suggest that the presynaptic release properties and expression of key postsynaptic GABAA receptor subunits are coregulated by hearing.

Key Words: {alpha}1 and β2/3 subunits • auditory cortex • development • GABAA receptor • hearing impairment


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