title: Hearing loss prevents the maturation of GABAergic transmission in the auditory cortex.
abstract: 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 alpha1- and beta2/3 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 GABA(A) receptor subunits are coregulated by hearing.
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA. kotak@cns.nyu.edu
authors.forename: Vibhakar C
authors.initials: VC
authors.lastname: Kotak
authors.forename: Anne E
authors.initials: AE
authors.lastname: Takesian
authors.forename: Dan H
authors.initials: DH
authors.lastname: Sanes
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D001306:Auditory Pathways / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D003714:Denervation; D005829:Geniculate Bodies / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D005849:Gerbillinae; D006319:Hearing Loss, Sensorineural / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid