A population of hypothalamic thermosensitive neurons regulating cardiovascular functions

Abstract

Thyroid hormone is known for its profound direct effects on cardiovascular function and metabolism; however, recent studies demonstrated that the hormone also regulates these systems indirectly through the autonomic nervous system. While some of the mechanisms underlying the hormone's central effects on metabolism have been identified, its actions in the central cardiovascular control have remained enigmatic. Here we describe a novel population of neurons in the hypothalamus that require thyroid hormone receptor signaling for their development. Stereotaxic ablation of these cells in the mouse using a conditionally neurotoxic virus results in hypertension and temperature dependent tachycardia, indicating a role in the central autonomic control of blood pressure and heart rate. Moreover, the neurons exhibit intrinsic temperature sensitivity in patch clamping experiments, thus providing a new connection between cardiovascular function and core temperature. Taken together, we have discovered a previously uncharacterized hypothalamic cell population potentially important for understanding hypertension, and identified developmental hypothyroidism as a novel epigenetic risk factor for cardiovascular disorders.