Conservative nature of oestradiol signalling pathways in the brain lobes of Octopus vulgaris involved in reproduction, learning and motor coordination.

Oestradiol plays in the mammalian brain crucial roles by modulating reproductive behaviour, neural plasticity and pain perception. The cephalopod Octopus vulgaris is considered, along with its relatives, the most behaviourally advanced invertebrate, although the neurophysiological basis of its behaviours including pain perception remain largely unknown. In the present study, using a combination of molecular and imaging techniques, we found that oestradiol up-regulated the Octopus vulgaris GnRH (Oct-GnRH) and Octopus vulgaris oestrogen receptor (Oct-ER) mRNA levels in the olfactory lobes, in turn Oct-ER mRNA was regulated by N-methyl-D-asparate (NMDA) in lobes involved in learning and motor coordination. Fluorescence Resonance Energy Transfer (FRET) analysis revealed that oestradiol binds Oct-ER causing conformational modifications and nuclear translocation consistent with the classical genomic mechanism of oestrogen receptor. Moreover oestradiol triggered a calcium influx and CREB (cyclic AMP response element binding protein) phosphorylation via membrane receptors, providing evidence for a rapid non-genomic action of oestradiol in Octopus vulgaris. In this paper we demonstrate, for the first time, the physiological role of oestradiol in the brain lobes of Octopus vulgaris involved in reproduction, learning and motor coordination.