The Rønnekleiv Research group is investigating the function and regulation of gonadotropin releasing hormone (GnRH) neurons and upstream neuronal circuits that are essential for both reproduction and energy metabolism. Our current work uses transgenic mouse models to study the mechanism by which 17β-estradiol, neurotransmitters and metabolic factors regulate GnRH neurons and kisspeptin neurons, which are immediately upstream of GnRH neurons. We are combining whole-cell patch recording with molecular biology to explore membrane properties, intracellular signaling and gene expression changes in individual hypothalamic neurons. We have recently discovered that both GnRH neurons and kisspeptin neurons express T-type calcium channels, which are particularly important for burst firing and neuropeptide release. In both cell-types estradiol augments the T-current as well as modulates a number of other ion channels important for burst firing. To date, kisspeptin neurons provide the most potent excitatory drive to GnRH neurons and it is known that patients with deletion in its cognate receptor (GPR 54) exhibit hypothalamic hypogonadism. Finally, we have initiated studies to explore these hypothalamic neuronal circuits involved in reproduction and other homeostatic functions using optogenetics. The development of this technique in combination whole-cell recording and single cell RT-PCR allow us to establish the correlation between neuronal firing properties, transmitter release and animal behavior.