Hypoxia, Leptin and Hippocampal Neurons Firing Figure 11. Leptin opposes to the depressive action of hypoxia through BK channels. A. Representative MEAs showing hippocampal spontaneous activity monitored for 90 seconds in normoxia and for 90 seconds after hypoxia+leptin treatment (light grey area). B. Representative MEAs showing hippocampal spontaneous activity monitored for 90 seconds in normoxia and for 90 seconds after hypoxia+leptin+paxilline treatment (light grey area). The hypoxic-induced inhibition of the firing rate is restored when leptin is applied together with paxilline. doi:10.1371/journal.pone.0041530.g011 Galan et al. [39], and it is independent of changes in the firing rate. Thus we provide here a functional evaluation of spontaneous firing impairment in hippocampal primary cultures, following chronic hypoxia, by means of the MEA technology. This issue is not deeply explored in literature, since only few reports show the effect of hypoxia on neuronal activity using the microelectrode array technique [40,12]. Leptin Counteracts the Hypoxia-induced Inhibition of Firing Frequency through BK Channels Activation In the last few years an increasing number of reports has pointed out the pivotal role of leptin signalling in learning, memory and neuroprotection, as its receptor is found to be expressed also in extra-hypothalamic regions such as the hippocampus [41,42]. The discovery of leptin’s action in cognition and neuronal survival triggered a strong interest on the possible correlation between leptin levels and neurodegenerative disorders, like the Alzheimer disease (AD). Recent works have indentified PLoS ONE | www.plosone.org 15 July 2012 | Volume 7 | Issue 7 | e41530