Brain circuits governing thermoregulation in a thyroid hormone dependent manner

Project Description:

Thyroid hormone is a major factor in the maintenance of body temperature. It is involved in almost every aspect, including obligatory and facultative thermogenesis (Silva 2005 Physiol Rev) as well as heat dissipation over the surface (Warner et al. 2015 PNAS). Recently, the concept emerged that thyroid hormone also acts centrally to modulate body temperature (Lopez et al. 2010 Nat Med). Our own data show that in addition to these acute actions, the hormone is also important during the development of neurons involved in the regulation of BAT thermogenesis or vardiovascular functions (Harder et al. 2018 JNE; Mittag et al. 2013 JCI). The project now aims to study the role of thyroid hormone during brain development, both pre- and postnatally, for the development of thypothalamic parvalbumin neurons (that regulate cardivascular functions) and zona incerta dopaminergic neurons (that control BAT function, Shi et al. 2013 Cell Met). 


Research Aims:

• Neuroanatomical characterization of hypothalamic parvalbumin and zona incerta dopaminergic neurons with regard to the developmental window of thyroid hormone dependency receptor repertoire and connectivity
• Funcational characterization of hypothalamic parvalbumin and zona incerta dopaminergic neurons with regard to their role in BAT thermogenesis and peripheral heat conservation
• Specific modulation of thyroid hormone signaling during different periods of neuronal development to alter the neuronal number of hypothalamic parvalbumin and zona incerta dopaminergic neurons