Hearing loss alters the subcellular distribution of presynaptic GAD and postsynaptic GABAA receptors in the auditory cortex

Emma C. Sarro, Vibhakar C. Kotak, Dan Sanes, Chiye Aoki

Research output: Contribution to journalArticle

Abstract

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 GABA Aβ2/3 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.

Original languageEnglish (US)
Pages (from-to)2855-2867
Number of pages13
JournalCerebral Cortex
Volume18
Issue number12
DOIs
StatePublished - Dec 2008

Fingerprint

Auditory Cortex
Hearing Loss
Sensorineural Hearing Loss
Acids
Synapses
gamma-Aminobutyric Acid
Cell Membrane
GABAergic Neurons
Glutamate Decarboxylase
Gerbillinae
Pyramidal Cells
Presynaptic Terminals
Interneurons
varespladib methyl
Hearing
Immunohistochemistry
Electrons

Keywords

  • β2/3 subunits
  • Deafness
  • Development
  • Electron microscopy
  • Immunocytochemistry

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Hearing loss alters the subcellular distribution of presynaptic GAD and postsynaptic GABAA receptors in the auditory cortex. / Sarro, Emma C.; Kotak, Vibhakar C.; Sanes, Dan; Aoki, Chiye.

In: Cerebral Cortex, Vol. 18, No. 12, 12.2008, p. 2855-2867.

Research output: Contribution to journalArticle

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