Figure 1.

Relationship between electrical activity, intracellular calcium, and secretion in gonadotropin-releasing hormone (GnRH) neurons in mice. GnRH neurons can be divided into two main functional segments: cell body/proximal process, mainly in the preoptic area (POA), and distal process/nerve terminals, in the mediobasal hypothalamus. First row: blue light, flashed in the POA, electrically activates GnRH neurons expressing channelrhodopsin in vivo. The functional read-out reflecting GnRH secretion is the luteinizing hormone (LH) increase (blue trace) in the systemic circulation evoked by the gonadotrophs. The gray trace shows a spontaneously occurring LH pulse, much smaller. Second row: electrical stimulation of GnRH fibers activates GnRH neurons expressing genetically encoded calcium sensor GCaMP3 in vitro and evokes a calcium rise in the nerve terminals. Note the stimulus-restricted calcium increase. Third row: spontaneous action currents at the cell body evoke simultaneous rises in [Ca²⁺]_i. Note: the difference between the frequency of spontaneous events (10 s, every 30 s) and the frequency of spontaneously occurring LH pulses [every 21 min in ovariectomized mice (124)]. Fourth row: Kisspeptin, locally applied at the cell body, binds to its cognate receptor, GPR54, and evokes a long-lasting calcium rise and train of action potentials (APs). Fifth row: Kisspeptin, locally applied at the nerve terminals, evokes a long-lasting calcium rise (>60 min) in GnRH neurons expressing genetically encoded calcium sensor GCaMP6s but no APs are required. Sixth row: Kisspeptin, locally applied at the nerve terminals, evokes secretion (~1 min). Figures adapted with permission of the authors [row 1 (88); row 2–5 (115); row 6 (141)].