Abstract
With the advent of recent genetic technologies for mice, it is now feasible to investigate the circuit mechanisms of brain functions in an unprecedented manner. Although transgenic mice are commonly used on C57BL/6J (C57) background, hearing research has typically relied on different genetic backgrounds, such as CBA/Ca or CBA due to the genetic defect of C57 mice for early age-related hearing loss. This limits the utilization of available genetic resources for hearing research. Here we report congenic (>F10) Cre-dependent channelrhodopsin2 (ChR2) mice on CBA/Ca background. By crossing this line with Cre-driver mice on C57 background, F1 hybrids restored the hearing deficit of C57 mice. We also found a linear relationship between aging and hearing loss, with progression rates varied depending on genetic backgrounds (3.39 dB/month for C57; 0.82 dB/month for F1 hybrid). We further demonstrate that this approach allows to express ChR2 in a specific type of inhibitory neurons in the auditory cortex and that they can be identified within a simultaneously recorded population of neurons in awake mice. Thus, our Cre-dependent optogenetic transgenic mice on CBA/Ca background are a valuable tool to investigate the circuit mechanisms of hearing across lifespan.
Highlights
To utilize recent genetic technologies in mice for hearing research, we presented Cre-dependent ChR2 mice on CBA/Ca background, Ai32cba/ca mice
We assessed the threshold of auditory evoked responses based on multi-unit activity (MUA) in the auditory cortex (AC)
Our results generally agree with the previous report, which examined the same F1 hybrid using auditory brainstem response (ABR) (Frisina et al, 2011) and are broadly in line with previous observations using ABR in CBA/Ca background (Kane et al, 2012)
Summary
Recent developments in various genetic tools and technologies have revolutionized the investigation of the circuit level mechanisms underlying various behaviors (Yizhar et al, 2011; Deisseroth and Schnitzer, 2013; Wietek et al, 2014; Buzsaki et al, 2015; Rajasethupathy et al, 2016; Roth, 2016; Blackwell and Geffen, 2017; Jun et al, 2017; Gutruf and Rogers, 2018). A growing number of hearing researchers have employed advanced optogenetic technologies developed in C57 mice (Seybold et al, 2015; Nelson and Mooney, 2016; Phillips and Hasenstaub, 2016; Sollini and Chadderton, 2016; Blackwell and Geffen, 2017; Guo et al, 2017; Kato et al, 2017). Comparing auditory functions between C57 mice and other genetic backgrounds, such as, CBA or CBA/Ca (CBA) mice, has been a popular approach to study the aging auditory system. Because of limited availability of transgenic CBA mice, Optogenetic Mice Without Hearing Loss transgenic approaches are not straightforward. Genetically targeting a specific cell-type in both C57 and CBA backgrounds by utilizing available Cre-driver mice is not currently feasible
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