Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses

Functional maturation of afferent synaptic connections to inner hair cells (IHCs) 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 (Pit1dw) 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 IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs 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 Pit1dw IHCs 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. In the hypothyroid Snell dwarf mouse (Pit1dw), we show that a lack of thyroid hormone (TH) caused defective afferent synaptic pruning and delayed calcium channel clustering in the cochlea. We also saw afferent terminal damage and reduced levels of the glial glutamate transporter, GLAST. We restored normal pruning with TH supplementation from postnatal day 3 (P3) to P8, establishing the critical window for TH action on this process. TH is required for both afferent synapse pruning and maintenance.