A Cell-Permeable Phospholipase Cγ1-Binding Peptide Transduces Neurons and Impairs Long-Term Spatial Memory

Growth factor-mediated signaling has emerged as an essential component ofmemory formation. In this study, we used a phospholipase C gamma 1(PLCγ1) binding, cell-penetrating peptide to sequester PLCγ1 awayfrom its target, the phosphotyrosine residues within the activated growthfactor receptor. Peptides appear to transduce neurons but not astrocytes oroligodendrocytes. The presence of the peptides in the hippocampus duringtraining in the Morris water maze significantly impaired long-term memory, butnot memory acquisition. These results, along with previous studies onextracellular signal-regulated kinase (ERK) and phosphoinositide-3 kinase(PI3K), implicate all three key growth factor receptor-activated intracellularsignaling pathways in memory storage.