First Author | Chang HHV | Year | 2021 |
Journal | Front Cell Neurosci | Volume | 15 |
Pages | 799752 | PubMed ID | 35095424 |
Mgi Jnum | J:319722 | Mgi Id | MGI:6864756 |
Doi | 10.3389/fncel.2021.799752 | Citation | Chang HHV, et al. (2021) Loss of alpha-9 Nicotinic Acetylcholine Receptor Subunit Predominantly Results in Impaired Postural Stability Rather Than Gaze Stability. Front Cell Neurosci 15:799752 |
abstractText | The functional role of the mammalian efferent vestibular system (EVS) is not fully understood. One proposal is that the mammalian EVS plays a role in the long-term calibration of central vestibular pathways, for example during development. Here to test this possibility, we studied vestibular function in mice lacking a functional alpha9 subunit of the nicotinic acetylcholine receptor (nAChR) gene family, which mediates efferent activation of the vestibular periphery. We focused on an alpha9 (-/-) model with a deletion in exons 1 and 2. First, we quantified gaze stability by testing vestibulo-ocular reflex (VOR, 0.2-3 Hz) responses of both alpha9 (-/-) mouse models in dark and light conditions. VOR gains and phases were comparable for both alpha9 (-/-) mutants and wild-type controls. Second, we confirmed the lack of an effect from the alpha9 (-/-) mutation on central visuo-motor pathways/eye movement pathways via analyses of the optokinetic reflex (OKR) and quick phases of the VOR. We found no differences between alpha9 (-/-) mutants and wild-type controls. Third and finally, we investigated postural abilities during instrumented rotarod and balance beam tasks. Head movements were quantified using a 6D microelectromechanical systems (MEMS) module fixed to the mouse's head. Compared to wild-type controls, we found head movements were strikingly altered in alpha9 (-/-) mice, most notably in the pitch axis. We confirmed these later results in another alpha9 (-/-) model, with a deletion in the exon 4 region. Overall, we conclude that the absence of the alpha9 subunit of nAChRs predominately results in an impairment of posture rather than gaze. |