Nicotinic acetylcholine receptor subunit α7 knockout mice exhibit degraded auditory temporal processing.

Abstract

The CHRNA7 gene that encodes α7 subunit of the nicotinic acetylcholine receptor (α7 nAChR) has been associated with some autism spectrum disorders and other neurodevelopmental conditions characterized, in part, by auditory and language impairment. These conditions may include auditory processing disorders that represent impaired timing of neural activity, often accompanied by problems understanding speech. Here, we measure timing properties of sound-evoked activity via the auditory brainstem response (ABR) of α7 nAChR knockout mice of both sexes and wild type colony controls. We find a significant timing delay in evoked ABR signals that represents midbrain activity in knockouts. We also examine spike-timing properties of neurons in the inferior colliculus, a midbrain nucleus that exhibits high levels of α7 nAChR during development. We find delays of evoked responses along with degraded spiking precision in knockout animals. We find similar timing deficits in responses of neurons in the superior paraolivary nucleus and ventral nucleus of the lateral lemniscus, which are brainstem nuclei thought to shape temporal precision in the midbrain. In addition, we find that other measures of temporal acuity including forward masking and gap detection are impaired for knockout animals. We conclude that altered temporal processing at the level of the brainstem in α7 nAChR-deficient mice may contribute to degraded spike-timing in the midbrain, which may underlie the observed timing delay in the ABR signals. Our findings are consistent with a role for the α7 nAChR in types of neurodevelopmental and auditory processing disorders and we identify potential neural targets for intervention.