Aquaporin-4 (AQP4) is a water-selective transport protein expressed in glial cells throughout the nervous system. The protein is the main water channel in the neuropil, and it has different isoforms that play several physiological roles ranging from astrocyte volume regulation to neuronal activity modulation. AQP4 isoforms are expressed in the supporting cells of the olfactory epithelium (OE) and astrocytes of the olfactory bulb (OB). Interestingly, a mouse lacking all APQ4 isoforms has been shown to have olfactory deficits. Hence, we wondered whether we could dissect the physiological role of two AQP4 isoforms, namely AQP4M23 and AQP4ex, in the olfactory system. We performed electro-olfactogram recordings founding that odorant responses are reduced in mice lacking the isoforms AQP4ex or AQP4M23 compared to wild type, indicating that they are involved in odorant detection. Both isoforms are also expressed in the OB. By analyzing the expression of the immediate early gene c-Fos, we evaluated the neuronal activity in the glomerular layer in response to a novel environmental odorant stimulus such as amyl acetate and compared it with a neutral, odorless stimulus. We found a decrease in the number of c-Fos positive cells in AQP4M23-KO compared to wild type only after the exposure to the neutral stimulus, suggesting that the astrocytic expression of AQP4M23 contributes to setting the basal levels of neuronal activation in the glomerular layer.
Altogether, these results establish that AQP4 isoforms have a critical role in odorant-evoked responses acting via a glial-like cell type: the supporting cells of the OE. Moreover, AQP4M23 could be involved in modulating neuronal activity in the OB, providing a foundation for future work investigating the precise physiological function of the water channel in the olfactory system.