Peptides that signal hunger – a new role in memory and social behaviors

Abstract

Neuroactive peptides and their receptors in neurons are a large group of molecules essential for central nervous system homeostasis. They participate in the control of basic functions, such as regulation of the cardiovascular system and gastrointestinal tract, and in higher function, such as cognition and social behavior. In this work we provide an overview of common features of these signaling molecules, their receptors and explore how they regulate two important behaviors: memory and social behaviors. We describe the role of the constitutive activity of the ghrelin receptor on learning and memory and explore a mechanism for its effect on neuronal transmission. Through pharmacologic manipulation, we observed that the ligand-independent activity of the ghrelin receptor regulates the surface and synaptic expression of AMPA receptors on neurons. This effect is exerted through the regulation of AMPA receptor mobility and phosphorylation state. On another section of the work, we describe alterations to the prefrontal cortex in a model of early life stress. We find that social subordinate behavior is induced by stress and explore the mechanism leading to this behavioral alteration. We find increased inhibition in pyramidal neurons of the prefrontal cortex in subordinate animals accompanied by increased expression of the Y1 receptor for neuropeptide Y. Using whole-cell patch-clamp recordings, we observed a reversion of the increased inhibition in the prefrontal cortex of subordinate animals when using an NPY Y1 antagonist. In addition to its well-known role in feeding behavior, our observations suggest that the neuropeptide Y signaling plays a role in the processing of social behaviors in the mammalian brains. This work illustrates the versatility of neuroactive peptides in the regulation of animal behavior. We provide potential avenues for the development of treatments for diseases associated with cognitive deficits and dysfunctional subordinate behavior.