Mike Ludwig

Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites

Information in neurons flows from synapses, through the dendrites and cell body (soma), and, finally, along the axon as spikes of electrical activity that will ultimately release neurotransmitters from the nerve terminals. However, the dendrites of many neurons also have a secretory role, transmitting information back to afferent nerve terminals. In some central nervous system neurons, spikes that originate at the soma can travel along dendrites as well as axons, and may thus elicit secretion from both compartments. Here, we show that in hypothalamic oxytocin neurons, agents that mobilize intracellular Ca2+ induce oxytocin release from dendrites without increasing the electrical activity of the cell body, and without inducing secretion from the nerve terminals. Conversely, electrical activity in the cell bodies can cause the secretion of oxytocin from nerve terminals with little or no release from the dendrites. Finally, mobilization of intracellular Ca2+ can also prime the releasable pool of oxytocin in the dendrites. This priming action makes dendritic oxytocin available for release in response to subsequent spike activity. Priming persists for a prolonged period, changing the nature of interactions between oxytocin neurons and their neighbours.

Vasopressin from hypothalamic magnocellular neurons has opposite actions at the adenohypophysis and in the supraoptic nucleus on ACTH secretion

Magnocellular vasopressinergic and oxytocinergic neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei comprise the hypothalamic–neurohypophysial system, which is crucially involved in the regulation of body fluid and electrolyte homeostasis. However, still controversial is to what extent the same system influences the secretion of adrenocorticotropic hormone (ACTH) from the adenohypophysis. Therefore, we selectively stimulated magnocellular neurons of the SON of conscious male Wistar rats via retrodialysis. As expected, dialysis of the SON with hypertonic medium increased both the release of vasopressin within the SON and the secretion of vasopressin and oxytocin into the systemic blood circulation. This activation of the hypothalamic–neurohypophysial system was accompanied by a fivefold increase in plasma ACTH concentration. This effect was observed only if the tip of the microdialysis probe was within the SON. Intravenous infusion of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly attenuated the effects of local osmotic stimulation of the SON on ACTH secretion. In contrast, administration of the same antagonist directly into the SON significantly enhanced the osmotically stimulated secretion of ACTH and corticosterone, primarily by delaying the restoration of the hormone secretion to prestimulation levels. We conclude from these findings that vasopressin from the hypothalamic–neurohypophysial system participates in the regulation of the hormonal stress response in a counterbalanced manner at the level of the SON and the adenohypophysis.