The role of NPY in learning and memory.

High levels of NPY expression in brain regions important for learning and memory together with its neuromodulatory and neurotrophic effects suggest a regulatory role for NPY in memory processes. Therefore it is not surprising that an increasing number of studies have provided evidence for NPY acting as a modulator of neuroplasticity, neurotransmission, and memory. Here these results are presented in relation to the types of memory affected by NPY and its receptors. NPY can exert both inhibitory and stimulatory effects on memory, depending on memory type and phase, dose applied, brain region, and NPY receptor subtypes. Thus NPY act as a resilience factor by impairing associative implicit memory after stressful and aversive events, as evident in models of fear conditioning, presumably via Y1 receptors in the amygdala and prefrontal cortex. In addition, NPY impairs acquisition but enhances consolidation and retention in models depending on spatial and discriminative types of associative explicit memory, presumably involving Y2 receptor-mediated regulations of hippocampal excitatory transmission. Moreover, spatial memory training leads to increased hippocampal NPY gene expression that together with Y1 receptor-mediated neurogenesis could constitute necessary steps in consolidation and long-term retention of spatial memory. Altogether, NPY-induced effects on learning and memory seem to be biphasic, anatomically and temporally differential, and in support of a modulatory role of NPY at keeping the system in balance. Obtaining further insight into memory-related effects of NPY could inspire the engineering of new therapeutics targeting diseases where impaired learning and memory are central elements.