Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites

Abstract

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 Ca(2+) 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 Ca(2+) 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.

Oxytocin in survivors of childhood-onset craniopharyngioma

“…It has been described that-in addition to the synthesis in the paraventricular and supraoptic nuclei of the hypothalamus-lesser amounts of oxytocin are generated in the bed nucleus of the striaterminalis, medial preoptic area, and lateral amygdala, depending on the species [21]. The release of oxytocin in humans is known not to happen exclusively via axonal secretion in the posterior pituitary but also from the dendrites (opposed to the axons) for intracerebral release [22][23][24]. By discrete grading and comparisons of CP patients with grade 1 hypothalamic surgical damage (damage exclusively to the anterior hypothalamic structures) and grade 2 (damage of anterior and posterior hypothalamic regions), we found that patients with grade 1 damage only to the anterior hypothalamus had a lower oxytocin level before breakfast compared to patients with grade 2 damage and to patients without any hypothalamic damage.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Magnocellular neurons of the hypothalamic paraventricular nucleus (PVN) and the supraoptic nucleus , the primary sources of OT synthesis, project to the posterior pituitary, where OT is stored in large secretory vesicles, so-called large dense-core vesicles . In response to calcium influx as well as intracellular calcium release from the endoplasmic reticulum, OT is released into systemic circulation (Meyer-Lindenberg et al, 2011) from axonal terminals within the neurohypophysis (Ludwig and Leng, 2006; Ludwig et al, 2002). The most prominent peripheral OT effects via the classical hypothalamic-neurohypophyseal pathway are the induction of parturition through increased contractibility of the uterine smooth muscles and milk ejection from the mammary gland in response to suckling stimuli in lactating females (Lee et al, 2009).…”

Somatodendritic dopamine release: recent mechanistic insights

“…Another factor to consider is that somatodendritic DA release may require a very rapid elevation in [Ca 2þ ] i close to the releasing organelle to trigger release, whereas slower global increases in [Ca 2þ ] i could act to enhance priming, for example, as seen for the release of oxytocin from the dendrites of hypothalamic neurons [126]. Whether, the differential expression of RyRs near the plasma membrane versus cytoplasmic IP 3 Rs reflect these different functions remains an open question.…”

“…A strong candidate for such amplification is Ca 2þ -induced Ca 2þ release from intracellular ER stores [25,126,127]. Neuronal ER forms a continuous network extending from the soma to axons and presynaptic release sites, as well as to dendrites and dendritic spines [128].…”