According to previous studies on rat models of chronic hyperammonemia and HE34, 35, 42, the deficit in hippocampal LTP is associated with an altered function of the NMDAR-nitric oxide (NO)- cGMP- protein kinase G (PKG)- cGMP-degrading phosphodiesterase (PDE5) pathway, which is involved in LTP induction and maintenance, and with the dysfunction of Ca2+−calmodulin-dependent proteinkinase II (CaMKII) leading to impaired phosphorylation and trafficking of the GluA1 subunit of AMPAR. The gene discussed is PDE5A; the disease is Hyperammonemia.