RT Journal Article SR Electronic T1 Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons JF bioRxiv FD Cold Spring Harbor Laboratory SP 282731 DO 10.1101/282731 A1 Joseph D. Zak A1 Julien Grimaud A1 Rong-Chang Li A1 Chih-Chun Lin A1 Venkatesh N. Murthy YR 2018 UL http://biorxiv.org/content/early/2018/03/29/282731.abstract AB The calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in ORNs, a hypothesis supported by previous studies in dissociated neurons from Ano2−/− mice. Paradoxically, despite a reduction in transduction currents in Ano2−/− ORNs, their spike output for odor stimuli may be higher. We examined the role of Ano2 in ORNs in their native environment in freely breathing mice by imaging activity in ORN axons as they arrive in the olfactory bulb glomeruli. Odor-evoked responses in ORN axons of Ano2−/− mice were consistently larger for a variety of odorants and concentrations. In an open arena, Ano2−/− mice took longer to approach a localized odor source than wild-type mice, revealing clear olfactory behavioral deficits. Our studies provide the first in vivo evidence toward an alternative role for Ano2 in the olfactory transduction cascade, where it may serve as a feedback mechanism to clamp ORN spike output.