title: Hearing loss raises excitability in the auditory cortex.
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.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA. kotak@cns.nyu.edu
authors.forename: Vibhakar C
authors.initials: VC
authors.lastname: Kotak
authors.forename: Sho
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Fanyee Anja
authors.initials: FA
authors.lastname: Lee
authors.forename: Omkar
authors.initials: O
authors.lastname: Karthikeyan
authors.forename: Chiye
authors.initials: C
authors.lastname: Aoki
authors.forename: Dan H
authors.initials: DH
authors.lastname: Sanes
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000166:cytology / Q000503:physiopathology*; D002452:Cell Count / Q000379:methods; D017626:Cochlear Nucleus / Q000503:physiopathology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005849:Gerbillinae; D034381:Hearing Loss / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D016253:Microscopy, Immunoelectron / Q000379:methods; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C013411:biocytin; D008239:Lysine