AgRP neurons control structure and function of the medial prefrontal cortex.

Abstract

Hypothalamic agouti-related peptide and neuropeptide Y-expressing (AgRP) neurons have a critical role in both feeding and non-feeding behaviors of newborn, adolescent, and adult mice, suggesting their broad modulatory impact on brain functions. Here we show that constitutive impairment of AgRP neurons or their peripubertal chemogenetic inhibition resulted in both a numerical and functional reduction of neurons in the medial prefrontal cortex (mPFC) of mice. These changes were accompanied by alteration of oscillatory network activity in mPFC, impaired sensorimotor gating, and altered ambulatory behavior that could be reversed by the administration of clozapine, a non-selective dopamine receptor antagonist. Theobserved AgRP effects are transduced to mPFC in part via dopaminergic neurons in the ventral tegmental area and may also be conveyedby medial thalamic neurons. Our results unmasked a previously unsuspected role for hypothalamic AgRP neurons in control ofneuronal pathways that regulate higher-order brain functions during development and in adulthood.