Vasopressin (VP) and oxytocin (OT) are essential for maintaining normal water balance, blood pressure, salt excretion and reproductive processes. An understanding of the basic function of the neurons synthesizing these hormones is paramount to understanding secretory regulation. Supraoptic OT and VP neurons are similar in many regards, yet certain morphological and electrophysiological characteristics differ and are dynamically influenced by the secretory state of the animal. Such differences may underlie differences in stimulus-secretion coupling between OT and VP.
The specific aims of the project are to determine: 1) the time course, reversibility and hormone-dependence of shrinkage (OT neurons), dendritic expansion (VP neurons), and electrophysiological changes observed duration lactation; 2) whether dendritic Ca++ transients resulting from back-propagating spikes are enhanced in OT, and diminished in VP neurons during lactation; 3) whether the arborization patterns of OT and VP axons differ, and whether arborization changes with lactation; and 4) whether OT and VP axons differ in the frequency-dependence of spike propagation, spike broadening, and axonal Ca++ transients, whether differences are correlated with morphology, and whether these properties are modulated by lactation. Investigations of the time course of dendritic architectural and electrophysiological properties during gestation, lactation and weaning will determine whether these properties are correlated with the altered neuronal activity of the neurons, or whether these changes are induced by the ovarian hormone secretion pattern characterizing gestation. Ca++-dependent processes are important to somatodendritic function, including local hormone release and the control of Ca++-dependent currents regulating firing patterns. The efficiency of back-propagating spikes to increase dendritic [Ca++]i will be examined for both cell types, as will the modulation of this increase by feedback from locally released hormone. Investigation of lactating rats will determine whether the relationship between spike activity, dendritic (Ca++]i, and local hormone release is state-dependent. Similarly, axonal geometry will be quantified and compared to the spike-propagating ability of the terminal arbor in neural lobe slices. Ca++ imaging will be used to determine whether frequency-dependent facilitation of [Ca++]i and hormone release differ between OT and VP terminals, whether they relate to differences in spike-broadening, spike propagation, and axonal morphology, and whether they vary as a function of lactation.
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