Developmental hearing loss (HL) can induce profound changes to auditory processing and cognitive processes, such as language acquisition. This is because the central nervous system is particularly vulnerable to disruptions of sensory activity during discrete intervals prior to adulthood. These intervals are often referre to as critical periods (CP). Consistent with basic research findings, early remediation of hearing loss in humans is highly correlated with recovery of normal function. This suggests that the critical period concept applies to human hearing loss. The core hypothesis of this proposal is that recovery from hearing loss-induced changes to cortical membrane and synaptic properties depends on the restoration of hearing prior to the closure of one or more critical periods. The key goals of this proposal are to determine the CPs during which mild hearing loss (i.e., bilateral earplugs), or the restoration of normal hearing (i.e., earplug removal) during development will influence cellular properties in auditory cortex. Both the onset of earplug insertion and the time of earplug removal will be varied as a function of postnatal age to explore the timing and termination of auditory CPs. Two key cellular properties that contribute to neuronal excitability will be assessed in the auditory cortex: (1) Membrane and firing properties, and (2) Inhibitory synaptic currents. There are two experimental Aims.
Aim 1 asks whether there is more than one CP during which hearing loss affects cellular properties. To determine whether there are CPs for mild hearing loss, animals will be reared with bilateral earplugs and the age-of-onset for EP insertion will be varied. Whole-cell recordings will be obtained from layer 2/3 pyramidal neurons in thalamocortical brain slices from earplug-reared and age-matched unmanipulated animals. Current-clamp recordings will be used to measure membrane properties and voltage-clamp recordings will be used to measure spontaneous and evoked inhibitory synaptic currents. These measures will reveal whether there are multiple CPs during which specific cortical properties are sensitive to hearing loss.
Aim 2 asks whether there is a critical period during which hearing restoration permits recovery of cellular properties. Therefore, animals will be reared with bilateral EPs and the age of EP removal will be varied throughout development. To evaluate the effects of earplug removal, whole cell recordings will be obtained in animals with restored hearing and age- matched controls. All data collection parameters and analytical approaches will be identical to Aim 1. The experiment will allow me to distinguish whether the critical period for EP insertion and removal occur within the same age window, or whether the critical periods for removal depend on the age of EP insertion. Together, these findings will reveal whether there are discrete critical periods for the maturation of cellular properties, and suggest whether there are optimal periods for remediation of developmental hearing loss.
Hearing loss during critical periods of development can result in pervasive auditory deficits in adulthood. The overall goal of this project is to identify criticl periods during which auditory cortex cellular properties are sensitive to hearing loss, and critica periods during which hearing restoration permits recovery of function.
|Mowery, Todd M; Kotak, Vibhakar C; Sanes, Dan H (2016) The onset of visual experience gates auditory cortex critical periods. Nat Commun 7:10416|
|Kotak, Vibhakar C; Mowery, Todd M; Sanes, Dan H (2015) Characterization of auditory synaptic inputs to gerbil perirhinal cortex. Front Neural Circuits 9:40|
|Mowery, Todd M; Kotak, Vibhakar C; Sanes, Dan H (2015) Transient Hearing Loss Within a Critical Period Causes Persistent Changes to Cellular Properties in Adult Auditory Cortex. Cereb Cortex 25:2083-94|