MATHEMATICAL EXPLORATION OF PULSATILITY IN CULTURED GONADOTROPIN-RELEASING-HORMONE NEURONS

Pulsatile gonadotropin-releasing hormone (GnRH) release has been demon strated in cultures of an immortalized line of GnRH expressing neurons (GT1 cells) in experiments by four different research groups. Pulsati le release is known to play a crucial role in GnRH-mediated signaling in vivo, and thus deserves theoretical and quantitative consideration, especially as GT1 cells are presumably genetically homogeneous. Here we have modeled idealized GT1 cells with a differential equation/logic based modeling program, Stella II. We have created a network of 'neur ons', with randomized (within the same preset limits for each neuron) thresholds, number and weight of connections to other neurons, and bui ld-up of signal; as well as continuous decay of stored signal. Surpris ingly, we found that with this minimal set of assumptions, without any sort of predefined pacemaking cells, it is possible to create pulsati lity similar to that observed in the laboratory. A variety of differen t parameter sets was found to produce these pulses. Network behaviors similar to those of GT1 cells depended on the degree of interconnectio n between neurons and their functioning within a critical range of net work excitability. These findings allow for a clearer consideration of the critical elements of such networks as well as experimental predic tions regarding the production of pulsatile behavior.