Gonadotropin releasing hormone (GnRH) neurons form the final common pathway for integration of signals regulating sexual reproduction. The pulsatile release of GnRH controls secretion of gonadotropins from the anterior pituitary which subsequently regulate function of the gonads. The peptide content of single GnRH neurons together with levels of GnRH during pulses suggest coordinated or synchronized activity of GnRH neurons during hormone secretion. The mechanisms that coordinate activity of single GnRH neurons are largely unknown. Moreover, there are relatively few approaches for the study of synchronized electrical activity in GnRH neurons particularly in hypothalamic slices. The present proposal will develop methodologies to permit simultaneous recordings from GnRH neurons in hypothalamic slices and then use this approach for hypothesis-testing.
Specific Aim 1 optimizes dual, long-term recordings using the loose-cell attached configuration in current-clamp (to directly detect action potentials) and tests the hypothesis that synchronized firing of GnRH neurons occurs in hemisagittal slices.
Specific Aim 2 uses this recording strategy to test the hypothesis that synaptic transmission controls synchronized firing. Lack of coordination or so-called desynchronization of GnRH neuronal activity has been invoked to account for a variety of reproductive states. These include the low levels of GnRH secretion prior to puberty, elevated levels of GnRH at the time of the preovulatory surge and inhibition of GnRH pulses by estradiol negative feedback. The methodologies in the present proposal will permit systematic study of synchronized firing in GnRH neurons in hypothalamic slices. This will allow us to determine whether desynchronization of firing is a viable mechanism for changes in GnRH secretion during normal reproduction and in reproductive pathologies. ? ?
| Gay, Vernon L; Hemond, Peter J; Schmidt, Deena et al. (2012) Hormone secretion in transgenic rats and electrophysiological activity in their gonadotropin releasing-hormone neurons. Am J Physiol Endocrinol Metab 303:E243-52 |
