Lifelong Reductions of PKM[zeta] in Ventral Hippocampus of Nonhuman Primates Exposed to Early-Life Adversity Due to Unpredictable Maternal Care

Protein kinase M[zeta] (PKM[zeta]) maintains long-term potentiation (LTP) and long-term memory through persistent increases in kinase expression. Early-life adversity is a precursor to adult mood and anxiety disorders, in part, through persistent disruption of emotional memory throughout life. Here we subjected 10- to 16-wk-old male bonnet macaques to adversity by a maternal variable-foraging demand paradigm. We then examined PKM[zeta] expression in their ventral hippocampi as 7- to 12-yr-old adults. Quantitative immunohistochemistry reveals decreased PKM[zeta] in dentate gyrus, CA1, and subiculum of subjects who had experienced early-life adversity due to the unpredictability of maternal care. Adult animals with persistent decrements of PKM[zeta] in ventral hippocampus express timid rather than confrontational responses to a human intruder. Persistent down-regulation of PKM[zeta] in the ventral hippocampus might reduce the capacity for emotional memory maintenance and contribute to the long-lasting emotional effects of early-life adversity.