Tristan P. Wallis1 and Frédéric A. Meunier1,2 1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, St Lucia 4067, Queensland, Australia 2School of Biomedical Sciences, The University of Queensland, St Lucia 4067, Queensland, Australia Correspondence: f.meunieruq.edu.au

The synapse is the communication unit of the brain, linking billions of neurons through trillions of synaptic connections. The lipid landscape of the synaptic membrane underpins neurotransmitter release through the exocytic fusion of neurotransmitter-containing vesicles, endocytic recycling of these synaptic vesicles, and the postsynaptic response following binding of the neurotransmitter to specialized receptors. How the connected brain can learn and acquire memories through synaptic plasticity is unresolved. Phospholipases, and especially the phospholipase A1 isoform DDHD2, have recently been shown to play a critical role in memory acquisition through the generation of saturated free fatty acids such as myristic and palmitic acids. This emerging synaptic plasticity pathway suggests that phospholipases cannot only respond to synaptic activity by altering the phospholipid landscape but also contribute to the establishment of long-term memories in our brain.