Hearing loss alters the subcellular distribution of presynaptic GAD and postsynaptic GABAA receptors in the auditory cortex.
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 (GABA(A)) receptor's beta2/3-subunit (GABA(A)beta2/3) 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(A)beta2/3 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 GABA(A)R. Thus, both, the pre- and postsynaptic sides of inhibitory synapses that form upon pyramidal neurons of the ACx are regulated by neonatal auditory experience.
Sarro
Emma C
EC
Center for Neural Science, New York University, New York, NY 10003, USA.
Kotak
Vibhakar C
VC
Sanes
Dan H
DH
Aoki
Chiye
C
D000818:Animals; D001303:Auditory Cortex / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D005849:Gerbillinae; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D012016:Reference Values; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure
D011963:Receptors, GABA-A; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2