Temporal dissociation of the feedback effects of dendritically co-released peptides on rhythmogenesis in vasopressin cells

doi:10.1016/j.neuroscience.2003.11.038

Neuroscience

Volume 124, Issue 1, 2004, Pages 105-111

https://doi.org/10.1016/j.neuroscience.2003.11.038 Get rights and content

Abstract

Vasopressin neurones fire action potentials in a rhythmic ‘phasic’ pattern, characterised by alternating periods of activity and silence. Vasopressin and dynorphin are co-packaged in neurosecretory vesicles that are exocytosed from vasopressin cell dendrites and terminals and both have been implicated in the generation of phasic activity patterning through autoregulatory mechanisms. Here, identified supraoptic nucleus vasopressin cells exhibiting spontaneous phasic activity were recorded from urethane-anaesthetised rats administered the V₁ vasopressin receptor antagonist, OPC 21268, or the κ-opioid receptor antagonist, nor-binaltorphimine. OPC 21268 elevated firing rate throughout each burst whereas nor-binaltorphimine excitation emerged over the course of each burst, indicating a progressive activation of κ-opioid receptor mechanisms during bursts. To determine whether changes in post-spike excitability could account for these effects, we plotted the probability of action potential firing with time after the preceding action potential (hazard function) and found that, similarly to firing rate, this too was elevated by OPC 21268 throughout each burst whilst the excitatory effects of nor-binaltorphimine progressively increased over the course of each burst. Thus, the temporal organisation of the feedback effects of these co-released peptides is different, with vasopressin effectively causing an immediate reduction in overall excitability whilst dynorphin causes a progressive decrease in post-spike excitability over the course of each burst.

Section snippets

Experimental procedures

All procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act, 1986 and associated guidelines. All efforts were made to minimize the number of animals used and their suffering.

Results

Extracellular single unit recordings were made from 15 cells, each from a different rat, for >60 min; all cells recorded displayed spontaneous phasic activity, typical of vasopressin cells. Under control conditions, the mean (±S.E.M.) burst duration and intra-burst firing rate of the 15 cells were 56.3±10.5 s and 6.7±0.4 spikes s⁻¹, respectively. A total of 289 phasic bursts were analysed. Seven phasic cells were challenged with microdialysis application of the V₁ receptor antagonist, OPC 21268

Discussion

Here, we show that endogenous vasopressin release restrains spike firing throughout bursts, whilst endogenous κ-opioid inhibition emerges as bursts progress since the V₁ receptor antagonist, OPC 21268, increases firing rate from the onset of, and throughout, bursts whilst the κ-opioid receptor antagonist, BNI, has no effect on activity at the beginning of bursts but causes a progressive increase in firing rate over the course of bursts. The inferred actions of vasopressin seem to be generally

Acknowledgements

Supported by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council and the Medical Research Council.

References (29)

C.H. Brown et al.
Opioid modulation of magnocellular neurosecretory cell activity
Neurosci Res
(2000)
J.P. Burbach et al.
Properties of aminopeptidase activity involved in the conversion of vasopressin by rat brain membranes
Peptides
(1993)
K. Inenaga et al.
Kappa-selective agonists decrease postsynaptic potentials and calcium components of action potentials in the supraoptic nucleus of rat hypothalamus in vitro
Neuroscience
(1994)
G. Leng et al.
Physiological pathways regulating the activity of magnocellular neurosecretory cells
Prog Neurobiol
(1999)
W.T. Mason et al.
Ionic currents in cultured supraoptic neuronsActions of peptides and transmitters
Brain Res Bull
(1988)
D.V. Pow et al.
Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis
Neuroscience
(1989)
P. Richard et al.
Rhythmic activities of hypothalamic magnocellular neuronsAutocontrol mechanisms
Biol Cell
(1997)
S.J. Shuster et al.
The kappa opioid receptor and dynorphin co-localize in vasopressin magnocellular neurosecretory neurons in guinea-pig hypothalamus
Neuroscience
(2000)
R.D. Andrew et al.
Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism
Science
(1983)
R.J. Bicknell
Optimizing release from peptide hormone secretory nerve terminals
J Exp Biol
(1988)

R.J. Bicknell et al.

Reversible fatigue of stimulus-secretion coupling in the rat neurohypophysis

J Physiol

(1984)

C.H. Brown et al.

Kappa-opioid receptor activation inhibits post-spike depolarizing after-potentials in rat supraoptic nucleus neurones in vitro

J Neuroendocrinol

(1999)

C.H. Brown et al.

In vivo modulation of post-spike excitability in vasopressin cells by kappa-opioid receptor activation

J Neuroendocrinol

(2000)

C.H. Brown et al.

Kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo

J Neurosci

(1998)

Cited by (39)

Vasopressin (AVP)
2016, The Curated Reference Collection in Neuroscience and Biobehavioral Psychology
Neuropeptide Transmission in Brain Circuits
2012, Neuron
Citation Excerpt :
Another role for opposing peptide signaling would be in feedback regulation of release of peptides from the same or neighboring release sites. In vasopressin neurosecretory cells, dynorphin is coreleased with vasopressin locally by the somatodendritic complex and serves a key role in feedback inhibition of vasopressin cells (Brown and Bourque, 2004; Brown et al., 2004), in part by inhibition of plateau potentials required for spike bursts. In most brain regions, vasopressin acts via a Gq receptor to excite neurons (Raggenbass, 2008).
Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G protein-coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation.
G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei - serpentine gateways to neuroendocrine homeostasis
2012, Frontiers in Neuroendocrinology
Citation Excerpt :
Dendritic peptides may also regulate local blood flow [5] and have local (e.g., OT is anxiolytic via the PVN OT receptor [333]) and distant effects on behavior [204]. Examples of GPCRs that modulate neuropeptide release, typically performed in studies measuring VP and/or OT release from large magnocellular cells, rather than CRF release from the smaller pPVN neurons, include the α1-adrenoceptors (inhibit intra-PVN hypoxia-induced CRF release [50]), apelin APJ (increases firing rate of VP neurons and VP dendritic release [327]), histamine H1/2 (increases dendritic release of OT via stimulating noradrenaline release [18]), melanocortin MC4 (increases Ca2+ in OT neurons; stimulation of dendritic, and inhibition of terminal OT release [204,276]), κ opioid (locally released dynorphin inhibits VP neurons and is essential for expression of VP neuron phasic activity; inhibits VP terminal release [34,36]), VIP/PACAP (stimulates somatodendritic and terminal VP release [208,289]), VP V1A (acting on autoreceptors to excite and inhibit quiescent and phasic VP neurons, respectively [35,203,204]), and OT (stimulates dendritic OT release via OT receptor; inhibits OT neurons by increasing endocannabionoid inhibition of glutamate release [204]) receptors. The release of neurohypophysial hormones from posterior pituitary nerve terminals, and CRF and other pPVN products from the median eminence into the anterior pituitary portal circulation is often reflected by increased circulating levels of VP and OT, ACTH (due to the action of CRF, VP and other ACTH secretagogues) and CORT, and thyroid hormones, and in changes in water homeostasis (principally brought about by altered VP secretion) (Supplementary Table 9 gives some examples).
G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in the mammalian genome. They are activated by a multitude of different ligands that elicit rapid intracellular responses to regulate cell function. Unsurprisingly, a large proportion of therapeutic agents target these receptors. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus are important mediators in homeostatic control. Many modulators of PVN/SON activity, including neurotransmitters and hormones act via GPCRs – in fact over 100 non-chemosensory GPCRs have been detected in either the PVN or SON. This review provides a comprehensive summary of the expression of GPCRs within the PVN/SON, including data from recent transcriptomic studies that potentially expand the repertoire of GPCRs that may have functional roles in these hypothalamic nuclei. We also present some aspects of the regulation and known roles of GPCRs in PVN/SON, which are likely complemented by the activity of ‘orphan’ GPCRs.
Multi-factorial somato-dendritic regulation of phasic spike discharge in vasopressin neurons
2008, Progress in Brain Research
Citation Excerpt :
Hence, V1bR mediated activation of PLC might underpin the vasopressin induced excitation of spike discharge in vasopressin neurons (Sabatier et al., 1998). Whilst exogenous vasopressin can excite or inhibit spike discharge in vasopressin neurons, to date only inhibitory actions of endogenous vasopressin have been identified; antagonism of supraoptic nucleus V1aRs prolongs phasic bursts and increases spike discharge by ∼1 Hz during bursts in vivo (Ludwig and Leng, 1997; Brown et al., 2004b). Hence, it appears that vasopressin neurons are continuously exposed to endogenous vasopressin at levels that reflect the average activity of the vasopressin neuron population as whole.
Classically, neuropeptide release occurs from axon terminals to influence post-synaptic neurons. However, it has become increasingly clear that many neurons in the central nervous system also release neuropeptide from their somata and dendrites. This somato-dendritic neuropeptide release can have many functions, amongst which is feedback modulation of activity. In addition, most central neurons also co-express other neurotransmitters/neuromodulators alongside their principal neurotransmitter, yet the function of these co-expressed factors is largely unknown. With regard to the function of somato-dendritic neuropeptide release, hypothalamic vasopressin neurons are amongst the best understood neurons in the central nervous system. Vasopressin neurons co-express a number of other neuropeptides including apelin, dynorphin and galanin as well as the purine, adenosine triphosphate. In addition to factors co-released during exocytosis, vasopressin neurons also generate nitric oxide. Each of these factors has been demonstrated to influence the activity of vasopressin neurons. For at least some of these factors, modulation of the activity of vasopressin neurons is activity dependent; suggesting that autocrine feedback regulation of activity might be an important role for somato-dendritic release of neuromodulators across the central nervous system.
Mechanisms of rhythmogenesis: Insights from hypothalamic vasopressin neurons
2006, Trends in Neurosciences
Many neurons in the CNS, including hypothalamic vasopressin-expressing cells, display rhythmic activity patterning. These vasopressin neurons receive random synaptic input but fire action potentials in alternating periods of activity and silence that each lasts tens of seconds. Recent work demonstrates that vasopressin cell rhythmicity depends on feedback modulation of intrinsic membrane properties and synaptic inputs by peptides released from the dendrites of these neurons. Many other neurons across the CNS release neurotransmitters from their dendrites; therefore, vasopressin cells provide an insight into the potential mechanisms that support neuronal activity patterning across the CNS.
Endogenous opiates and behavior: 2004
2005, Peptides
Citation Excerpt :
The delta antagonists, NTI and naltriben reversibly inhibited 5HT-induced GIRK currents in the DRN that was unaffected by delta agonist administration [1019]. SON VP cells exhibiting spontaneous phasic activity had their firing rates elevated by the VP-1 receptor antagonist, OPC21268, while the kappa antagonist, NBNI produced an emerging excitation over the course of each burst [146]. Inhibition of high-voltage-activated Ca2+ currents in medium-to-small GP cells occurred following DAMGO, DYN and U50488H with the kappa responses blocked by the PKC inhibitor, cehlerythrine.
This paper is the 27th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over 30 years of research. It summarizes papers published during 2004 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.

View all citing articles on Scopus

View full text

Temporal dissociation of the feedback effects of dendritically co-released peptides on rhythmogenesis in vasopressin cells

Abstract

Section snippets

Experimental procedures

Results

Discussion

Acknowledgements

Neurosci Res

Peptides

Neuroscience

Prog Neurobiol

Brain Res Bull

Neuroscience

Biol Cell

Neuroscience

Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism

Science

Optimizing release from peptide hormone secretory nerve terminals

J Exp Biol

Reversible fatigue of stimulus-secretion coupling in the rat neurohypophysis

J Physiol

Kappa-opioid receptor activation inhibits post-spike depolarizing after-potentials in rat supraoptic nucleus neurones in vitro

J Neuroendocrinol

In vivo modulation of post-spike excitability in vasopressin cells by kappa-opioid receptor activation

J Neuroendocrinol

Kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo

J Neurosci