The C-fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c-fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c-fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c-fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c-fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c-fos as well as in the amount of c-fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c-fos expression encompassed both SON and PVN neurons. We conclude that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.
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