Hearing loss raises excitability in the auditory cortex

Vibhakar C. Kotak, Sho Fujisawa, Fanyee Anja Lee, Omkar Karthikeyan, Chiye Aoki, Dan Sanes

Research output: Contribution to journalArticle

Abstract

Developmental hearing impairments compromise sound discrimination, speech acquisition, and cognitive function; however, the adjustments of functional properties in the primary auditory cortex (A1) remain unknown. We induced sensorineural hearing loss (SNHL) in developing gerbils and then reared the animals for several days. The intrinsic membrane and synaptic properties of layer 2/3 pyramidal neurons were subsequently examined in a thalamocortical brain slice preparation with whole-cell recordings and electron microscopic immunocytochemistry. SNHL neurons displayed a depolarized resting membrane potential, an increased input resistance, and a higher incidence of sustained firing. They also exhibited significantly larger thalamocortically and intracortically evoked excitatory synaptic responses, including a greater susceptibility to the NMDA receptor antagonist AP-5 and the NR2B subunit antagonist ifenprodil. This correlated with an increase in NR2B labeling of asymmetric synapses, as visualized ultrastructurally. Furthermore, decreased frequency and increased amplitude of miniature EPSCs (mEPSCs) in SNHL neurons suggest that a decline in presynaptic release properties is compensated by an increased excitatory response. To verify that the increased thalamocortical excitation was elicited by putative monosynaptic connections, minimum amplitude ventral medial geniculate nucleus-evoked EPSCs were recorded. These minimum-evoked responses were of larger amplitude, and the NMDAergic currents were also larger and longer in SNHL neurons. These findings were supported by significantly longer AP-5-sensitive durations and larger amplitudes of mEPSCs. Last, the amplitudes of intracortically evoked monosynaptic and polysynaptic GABAergic inhibitory synaptic responses were significantly smaller in SNHL neurons. These alterations in cellular properties after deafness reflect an attempt by A1 to sustain an operative level of cortical excitability that may involve homeostatic mechanisms.

Original languageEnglish (US)
Pages (from-to)3908-3918
Number of pages11
JournalJournal of Neuroscience
Volume25
Issue number15
DOIs
StatePublished - Apr 13 2005

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Auditory Cortex
Sensorineural Hearing Loss
Hearing Loss
Neurons
Geniculate Bodies
Social Adjustment
Synaptic Membranes
Speech Perception
Phonetics
Gerbillinae
Pyramidal Cells
Deafness
Patch-Clamp Techniques
N-Methyl-D-Aspartate Receptors
Membrane Potentials
Synapses
Cognition
Immunohistochemistry
Electrons
Incidence

Keywords

  • Disuse
  • GABA
  • Homeostasis
  • mEPSC
  • NMDA receptor
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hearing loss raises excitability in the auditory cortex. / Kotak, Vibhakar C.; Fujisawa, Sho; Lee, Fanyee Anja; Karthikeyan, Omkar; Aoki, Chiye; Sanes, Dan.

In: Journal of Neuroscience, Vol. 25, No. 15, 13.04.2005, p. 3908-3918.

Research output: Contribution to journalArticle

Kotak, Vibhakar C. ; Fujisawa, Sho ; Lee, Fanyee Anja ; Karthikeyan, Omkar ; Aoki, Chiye ; Sanes, Dan. / Hearing loss raises excitability in the auditory cortex. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 15. pp. 3908-3918.
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