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

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. The observed AgRP effects are transduced to mPFC in part via dopaminergic neurons in the ventral tegmental area and may also be conveyed by medial thalamic neurons. Our results unmasked a previously unsuspected role for hypothalamic AgRP neurons in control of neuronal pathways that regulate higher-order brain functions during development and in adulthood.

Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding.

The essential role of the brain in maintaining energy homeostasis has motivated the drive to define the neural circuitry that integrates external and internal stimuli to enact appropriate and consequential metabolic and behavioral responses. The hypothalamus has received significant attention in this regard given its ability to influence feeding behavior, yet organisms rely on a much broader diversity and distribution of neuronal networks to regulate both energy intake and expenditure. Because energy balance is a fundamental determinant of survival and success of an organism, it is not surprising that emerging data connect circuits controlling feeding and energy balance with higher brain functions and degenerative processes. In this review, we will highlight both classically defined and emerging aspects of brain control of energy homeostasis.