Prandial increase of leptin in the brain activates spatial learning and memory

Leptin is well known to be involved in the control of feeding, thermogenesis, reproduction and neuroendocrine functions through its actions on the rodents hypothalamic receptors. Leptin facilitated the presynaptic transmitter release and postsynaptic sensitivity to the transmitters in the hippocampal CA1 neurons. Thus long-term potentiation (LTP) and the phosphorylation of Ca(2+)/calmodulin protein kinase II (CaMKII) were facilitated in the CA1 neurons. Therefore behavioral performance related to spatial learning and memory was improved by leptin in vivo applications. We also investigated LTP and spatial learning and memory function in two leptin receptor-deficient rodents, Zucker fatty rats and db/db mice. The CA1 region of both strains showed impairments of LTP and leptin application did not improve these impairments. These strains showed lower basal levels of CaMKII activity in the CA1 region than the respective controls, and the levels did not respond to a brief tetanic stimulation. These strains also showed impaired spatial learning and memory. The present studies suggest that leptin signaling in the brain may have important implications for cognitive function.