This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Kuehl-Kovarik, M. C. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Kuehl-Kovarik, M. C.

Age Affects Spontaneous Activity and Depolarizing Afterpotentials in Isolated Gonadotropin-Releasing Hormone Neurons

Departments of Biomedical Sciences (Y.W., M.G., H.A.D., D.D.K., M.C.K.-K.) and Biology (J.A.T.), University of Missouri, Columbia, Missouri 65211

Address all correspondence and requests for reprints to: M. Cathleen Kuehl-Kovarik, Department of Biomedical Sciences, E102 Vet Med, 1600 East Rollins, University of Missouri-Columbia, Columbia, Missouri 65211. E-mail: kovarikc{at}missouri.edu.

Neuronal activity underlying the pulsatile secretion of GnRH remains poorly understood, as does the endogenous generation of such activity. It is clear that changes at the level of the hypothalamus are taking place during reproductive aging, yet virtually nothing is known about GnRH neuronal physiology in aging and postreproductive animals. In these studies, we performed cell-attached and whole-cell recordings in GnRH-enhanced green fluorescent protein neurons dissociated from young (3 months), middle-aged (10 months), and old (15–18 months) female mice. All mice were ovariectomized; half were estradiol replaced. Neurons from all ages fired spontaneously, most in a short-burst pattern that is characteristic of GnRH neuronal firing. Membrane characteristics were not affected by age. However, firing frequency was significantly reduced in neurons from old animals, as was spike patterning. The amplitude of the depolarizing afterpotential, evoked by a 200-msec current pulse, was significantly smaller in aged animals. In addition, inward whole-cell currents were reduced in estradiol-treated animals, although they were not significantly affected by age. Because depolarizing afterpotentials have been shown to contribute to prolonged discharges of activity after a very brief excitatory input, a decreased depolarizing afterpotential could lead to attenuated pulses in older animals. In addition, decreases in frequency and pattern generation could lead to improper information coding. Therefore, changes in the GnRH neuron during aging could lead to dysregulated activity, potentially resulting in the attenuated LH pulses observed in the transition to reproductive senescence.