Taste circuits in hypothalamus

East Tennessee State University, Johnson City TN

Investigators

Abstract

DESCRIPTION (provided by applicant): Obesity results from a sustained imbalance between energy intake and energy expenditure. This widespread health problem increases the risk of cardiovascular disease, type 2 diabetes, and certain types of cancers. It has been suggested that overdriven brain reward circuitry, hyperstimulated by high food palatability, may underlie the growing prevalence of this condition. The hypothalamus plays a central role in energy balance. The lateral hypothalamus (LH) is believed to participate in circuits that signal and/or respond to food palatability and its reinforcing effects. It is known that in rodents, gustatory afferents from the brainstem reach the LH directly, but very little is known about how taste modulates LH circuits. Although the primate gustatory system does not have such direct input to the LH, many of the mechanisms underlying palatability and food reward circuitry are undoubtedly comparable. Because the rodent is the major model system currently in use for exploring brain systems of energy balance and obesity, it is very important to understand how direct taste input regulates these circuits in rats. We have data showing that stimulation of one of the peripheral taste nerves activates neurons in the LH that contain a feeding-stimulating peptide (i.e., orexin) but not neurons in the same region containing a different feeding-stimulating peptide (MCH). This suggests that the orexin neuron system is selectively responsive to gustatory input, and compared to the MCH system, is more important in circuits involving palatability. Our proposed experiments will determine if all taste nerves produce these same effects on different LH neuron populations, if anatomical connections with gustatory axons in the LH are limited to orexin neurons only, and if the two different peptide systems in the LH demonstrate differential degrees of descending modulatory input to the gustatory region giving rise to the taste input to the LH. The results of these studies will further our understanding of how the taste of food influences the brain's complex, interacting circuitry controlling eating, body weight and energy expenditure.