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Thyroid hormone is required for pruning, functioning and long‐term maintenance of afferent inner hair cell synapses
Author(s) -
Sundaresan Srividya,
Kong JeeHyun,
Fang Qing,
Salles Felipe T.,
Wangsawihardja Felix,
Ricci Anthony J.,
Mustapha Mirna
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13081
Subject(s) - synaptic pruning , hair cell , neuroscience , glutamate receptor , afferent , biology , cochlea , endocrinology , medicine , receptor , microglia , inflammation
Functional maturation of afferent synaptic connections to inner hair cells ( IHC s) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone ( TH )‐critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse ( Pit1 dw ) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHC s of Pit1 dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1 dw IHC s by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1 dw IHC s by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1 dw IHC s showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST . Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long‐term homeostatic maintenance of afferent synapses.