The Ca2+-activated Cl− channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons

Abstract

TMEM16B is expressed in olfactory sensory neurons, but previous attempts to establish a physiological role in olfaction have been unsuccessful. Pietra et al. find that genetic ablation of TMEM16B results in defects in the olfactory behavior of mice and the cellular physiology of olfactory sensory neurons.

The long tale of the calcium activated Cl−channels in olfactory transduction

“…Modified from Pietra et al 2016 originally published in the Journal of General Physiology with permission. 87 the glomeruli. This model, though, has been questioned and requires further studies, [108][109][110] but the idea of having an OR-dependent regulation of the expression of guidance molecules involved in OB targeting and glomerular formation seems to hold because of the mosaic pattern of expression of such molecules in the OB (i.e., Nrp1).…”

“…The number of glomeruli in the OB onto which I7-expressing OSNs converge almost doubled in the TMEM16B KO mice. 87 As the expression of I7 ORs confers to OSNs a high rate of spontaneous firing, I7-expressing OSNs are more sensitive to the reduction of the firing rate as is the case in the TMEM16B KO, while OSNs expressing other more silent ORs might not be affected. 87,81 Indeed, this might be the case in the 2 other ORs, M72 and P2, for which glomerular targeting has also been studied in TMEM16B KO mice, which appeared to target normally to the OB.…”

“…87 As the expression of I7 ORs confers to OSNs a high rate of spontaneous firing, I7-expressing OSNs are more sensitive to the reduction of the firing rate as is the case in the TMEM16B KO, while OSNs expressing other more silent ORs might not be affected. 87,81 Indeed, this might be the case in the 2 other ORs, M72 and P2, for which glomerular targeting has also been studied in TMEM16B KO mice, which appeared to target normally to the OB. 81 Thus, TMEM16B could play an important role to enable correct glomerular targeting, and the role of spontaneous firing in targeting needs to be carefully reconsidered.…”

“…In addition, both TMEM16B and native CaCCs are similarly blocked by niflumic acid (Fig. 3G-I 87 re-examined the question from a slightly different perspective, starting with a na€ ıve behavioral task, the "finding the buried food test" which, unlike the Go/NoGo task, does not involve any animal training and pre-learning. Indeed, from the perspective of the mouse, the Go/NoGo task is an artificial operant conditioning experiment for which the mouse has to be extensively trained and be exposed to the same odorant repeatedly.…”

“…Modified from Pietra et al 2016 originally published in the Journal of General Physiology with permission. 87 Usually, APs in OSNs are generated at the very onset of an odorant response and by the end of the rising phase of the transduction current, their spike amplitude has collapsed into the noise of the recording. This is most likely due to the progressive and ultimately complete inactivation of voltage-gated Na C channels during strong and sustained depolarization.…”