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Cerebral Cortex Advance Access published online on April 9, 2008

Cerebral Cortex, doi:10.1093/cercor/bhn044
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Hearing Loss Alters the Subcellular Distribution of Presynaptic GAD and Postsynaptic GABAA Receptors in the Auditory Cortex

Emma C. Sarro1, Vibhakar C. Kotak1, Dan H. Sanes1,2 and Chiye Aoki1,2

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

Address correspondence to Chiye Aoki, PhD. Center for Neural Science, New York University, 4 Washington Place, Rm. 809, New York, NY 10003, USA. Email: ca3{at}nyu.edu.

We have shown previously that auditory experience regulates the maturation of excitatory synapses in the auditory cortex (ACx). In this study, we used electron microscopic immunocytochemistry to determine whether the heightened excitability of the ACx following neonatal sensorineural hearing loss (SNHL) also involves pre- or postsynaptic alterations of GABAergic synapses. SNHL was induced in gerbils just prior to the onset of hearing (postnatal day 10). At P17, the gamma-aminobutyri acid type A (GABAA) receptor's β2/3-subunit (GABAAβ2/3) clusters residing at plasma membranes in layers 2/3 of ACx was reduced significantly in size (P < 0.05) and number (P < 0.005), whereas the overall number of immunoreactive puncta (intracellular + plasmalemmal) remained unchanged. The reduction of GABAAβ2/3 was observed along perikaryal plasma membranes of excitatory neurons but not of GABAergic interneurons. This cell-specific change can contribute to the enhanced excitability of SNHL ACx. Presynaptically, GABAergic axon terminals were significantly larger but less numerous and contained 47% greater density of glutamic acid decarboxylase immunoreactivity (P < 0.05). This suggests that GABA synthesis may be upregulated by a retrograde signal arising from lowered levels of postsynaptic GABAAR. Thus, both, the pre- and postsynaptic sides of inhibitory synapses that form upon pyramidal neurons of the ACx are regulated by neonatal auditory experience.

Key Words: β2/3 subunits • deafness • development • electron microscopy • immunocytochemistry


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