Astrocytes constantly adapt their dynamics to support neuronal functions. Such plasticity is mediated by ion and water flux, which rely on the water-selective channel aquaporin-4 (AQP4). AQP4 has different isoforms (M23, M1 and extended) expressed in the glial cells of the olfactory bulb (OB). Although they are implicated in several mechanisms ranging from the regulation of astrocyte morphology to neuronal activity modulation, their role in the OB is still unclear. Hence, we sought to understand the contribution of AQP4 isoforms to the astrocyte’s functionality in the OB. First, we analyzed the astrocyte morphological properties through the 2D and Sholl analysis. We found that the astrocyte branch length and dimensions are reduced in AQP4M23-KO mice, suggesting that the M23 isoform affects the astrocytic structure in the OB. Then, we evaluated the neuronal activity in the glomerular layer (GL) in response to a novel environmental odorant stimulus such as amyl acetate by analyzing the immediate early gene c-Fos expression. We found a decrease in the number of c-Fos positive cells in AQP4M23-KO compared to wild type during the basal neuronal activity and an increase of the activated cells under stimulated conditions, suggesting that M23 contributes to setting the basal levels of neuronal activation in the glomerular layer. Furthermore, compensation mechanisms are implemented to re-establish the odorant-evoked response in the mouse model lacking the M23 isoform.
Altogether, our results establish that AQP4 isoforms have a critical role in modulating neuronal homeostasis, shedding light on the involvement of astrocytes in mediating this process and providing a foundation to dissect the contribution of these cells in controlling neuronal activity in the olfactory bulb.