ZIP, or Zeta inhibitory peptide, is a cell permeable pseudo-substrate inhibitor of protein kinase Mi (PKMi), a constitutively active, atypical PKC isozyme involved in LTP maintenance. ZIP selectively blocks PKMi induced synaptic potentiation in hippocampal slices in vitro and is widely used to investigate memory in a variety of learning tasks, including spatial sensitization, pain sensitization, fear-associated memories, conditioned taste aversion and development of locomotor sensitization in rodents. However, LTP and LTM are unaffected in both constitutive and conditional PKMi knock-out mice, yet both are still impaired by ZIP application, suggesting another mechanism of action which may involve ionotropic glutamate AMPA receptors (AMPARs).
