Yale researchers demonstrate the crucial role of a membrane lipid called phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5)P2) in the communication of information between synapses in the brain, according to a study published this week in Nature.
"This study is the first to show that lowering the levels of this lipid in nerve terminals affects the efficiency of neurotransmission," said senior author, Pietro De Camilli, Eugene Higgins Professor of Cell Biology and a Howard Hughes Medical Institute investigator.
De Camilli's laboratory has extensively studied the mechanism underlying cycling of synaptic vesicles, the small sacs containing neurotransmitters that exchange information between neurons. Synaptic vesicles release their contents at junctions between nerve terminals by fusing with the plasma membrane where they rapidly re-internalize, reload with neurotransmitter, and are reused.
The researchers genetically engineered laboratory mice lacking the enzyme PIPK1-gamma at the synapse. This enzyme plays a major role in the synthesis of PtdIns(4,5)P2, a member of a class of lipids called phosphoinositides. The mice born without PIPK1-gamma were apparently normal, but they were unable to feed and died quickly. Studies of their nervous system revealed lower levels of PtdIns(4,5)P2 and a partial impairment both of the process of fusion of synaptic vesicles as well as of their recycling.