Dendritic Peptide Release Mediates Interpopulation Crosstalk between Neurosecretory and Preautonomic Networks

Abstract

SUMMARY Although communication between neurons is considered a function of the synapse, neurons also release neurotransmitter from their dendrites. We found that dendritic transmitter release coordinates activity across distinct neuronal populations to generate integrative homeostatic responses. We show that activity-dependent vasopressin release from hypothalamic neuroendocrine neurons in the paraventricular nucleus stimulates neighboring (~100 μm soma-to-soma) presympathetic neurons, resulting in a sympathoexcitatory population response. This interpopulation crosstalk was engaged by an NMDA-mediated increase in dendritic Ca2+, influenced by vasopressin’s ability to diffuse in the extracellular space, and involved activation of CAN channels at the target neurons. Furthermore, we demonstrate that this interpopulation crosstalk plays a pivotal role in the generation of a systemic, polymodal neurohumoral response to a hyperosmotic challenge. Because dendritic release is emerging as a widespread process, our results suggest that a similar mechanism could mediate interpopulation crosstalk in other brain systems, particularly those involved in generating complex behaviors.

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

“…Furthermore, Badoer et al (2003) showed that glutamatergic inputs into the PVN play an important role in the renal nerve response to elevations in osmolality. More recently, Son et al (2013) have demonstrated that an acute osmotic challenge increased RSNA, which was attenuated by the antagonism of V1a receptors within the PVN, supporting the concept that local, dendritic release of vasopressin is another relevant signal regulating sympathoexcitatory outflow from the PVN.…”

“…Furthermore, Badoer et al (2003) showed that glutamatergic inputs into the PVN play an important role in the renal nerve response to elevations in osmolality. More recently, Son et al (2013) have demonstrated that an acute osmotic challenge increased RSNA, which was attenuated by the antagonism of V1a receptors within the PVN, supporting the concept that local, dendritic release of vasopressin is another relevant signal regulating sympathoexcitatory outflow from the PVN.In the last decades, adenosine triphosphate (ATP) has been recognized as an important neurotransmitter involved in many physiological and pathological mechanisms, besides its wellknown role as an intracellular energy source. ATP actions as a neurotransmitter are mediated via P2 receptor activation, which are divided into two classes: P2Y and P2X.…”

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

“…Also, we have shown that during exposure of rats to air-jet stress, selective blockade of central VP receptors do not affect the response of the hypothalamo-pituitary axis as judged by the concentration of blood corticosterone (Stojičić et al, 2008), suggesting that VP released into the portal circulation during air-jet stress does not modulate ACTH release into the blood stream. Nonetheless, physiological stimuli know to increase VP release into the blood stream, such as hyperosmotic challenge, have been reported to increase intranuclear release of VP (Son et al, 2013) and that its role is to coordinate the optimal firing rate of the whole population of magnocellular neurons (Gouzènes et al, 1998), and also to activate pre-sympathetic neurons in the parvocellular division of PVN. This inter-neural cross-talk has been shown to involve V1aRs in PVN (Son et al, 2013), supporting the present findings.…”

“…Nonetheless, physiological stimuli know to increase VP release into the blood stream, such as hyperosmotic challenge, have been reported to increase intranuclear release of VP (Son et al, 2013) and that its role is to coordinate the optimal firing rate of the whole population of magnocellular neurons (Gouzènes et al, 1998), and also to activate pre-sympathetic neurons in the parvocellular division of PVN. This inter-neural cross-talk has been shown to involve V1aRs in PVN (Son et al, 2013), supporting the present findings.…”

“…Although VP containing neurons in PVN that participate in neuroendocrine and autonomic cardiovascular control are anatomically segregated, they act in concert in response to physiological challenges requiring a multimodal homeostatic response. This neuronal coordination, at least for hyperosmotic challenges, has been shown to involve intranuclear, somato-dendritic release of VP and activation of V1a receptors on somata and dendrites of presympathetic neurons of the PVN (Stern, 2001;Son et al, 2013;Stern, 2015).…”