Metaplastic contribution of neuropeptide Y receptors to spatial memory acquisition

Neuropeptide Y (NPY) is highly abundant in the brain and is released as a co-transmitter with plasticity-related neurotransmitters such as glutamate, GABA and noradrenaline. Functionally, its release is associated with appetite, anxiety, and stress regulation. NPY acting on Y2 receptors (Y₂R), facilitates fear extinction, suggesting a role in associative memory. Here, we explored to what extent NPY action at Y₂R contributes to hippocampus-dependent spatial memory and found that dorsal intrahippocampal receptor antagonism improved spatial reference memory acquired in a water maze in rats, without affecting anxiety levels, or spontaneous motor activity. Water maze training resulted in an increase of Y₂R, but not Y₁R expression in the hippocampus. By contrast, in the prefrontal cortex there was a decrease in Y₂R, and an increase of Y₁R expression. Our results indicate that neuropeptide Y₂R are significantly involved in hippocampus-dependent spatial memory and that receptor expression is dynamically regulated by this learning experience. Effects are consistent with a metaplastic contribution of NPY receptors to cumulative spatial learning.