Regulation of hypothalamic corticotropin‐releasing hormone neurone excitability by oxytocin

Jamieson, Bradley B.; Nair, Betina B.; Iremonger, Karl J.

doi:10.1111/jne.12532

Cited by 47 publications

(23 citation statements)

References 53 publications

(130 reference statements)

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“…By contrast to our expectations, we were unable to produce reliable tonic inhibition of PVN CRH neurones using bath application of either oxytocin or TGOT at concentrations between 20 and 600 nmol L −1 in either control or salt‐loaded animals. In that respect, our results are consistent with another recent study reporting that bath application of 1 µmol L −1 oxytocin had no direct effect on PVN CRH neurones . To reduce the possibility that bath application was leading to rapid receptor desensitisation and/or internalisation, we attempted to directly activate PVN CRH neurones by locally applying OT via a picospritzer.…”

Section: Discussionsupporting

confidence: 91%

“…In that respect, our results are consistent with another recent study reporting that bath application of 1 µmol L −1 oxytocin had no direct effect on PVN CRH neurones. 38 To reduce the possibility that bath application was leading to rapid receptor desensitisation and/or internalisation, [39][40][41][42] we attempted to directly activate PVN CRH neurones by locally applying OT via a picospritzer. These experiments also failed to produce a clear or reliable immediate response to oxytocin application; however, we did note a small yet statistically significant increase in current density over time when oxytocin was applied in this manner (1 second 5-Hz train of 10-msec puffs delivered every 30 seconds, with 1 µmol L −1 oxytocin in the pipette).…”

Section: Discussionmentioning

confidence: 99%

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Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

Pati

Harden

Sheng

et al. 2020

J Neuroendocrinology

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Significant prior evidence indicates that centrally acting oxytocin robustly modulates stress responsiveness and anxiety‐like behaviour, although the neural mechanisms behind these effects are not entirely understood. A plausible neural basis for oxytocin‐mediated stress reduction is via inhibition of corticotrophin‐releasing hormone (CRH) neurones in the paraventricular nucleus of the hypothalamus (PVN) that regulate activation of the hypothalamic‐pituitary‐adrenal axis. Previously, we have shown that, following s.c. injection of 2.0 mol L−1 NaCl, oxytocin synthesising neurones are activated in the rat PVN, an oxytocin receptor (Oxtr)‐dependent inhibitory tone develops on a subset of parvocellular neurones and stress‐mediated increases in plasma corticosterone levels are blunted. In the present study, we utilised transgenic male CRH‐reporter mice to selectively target PVN CRH neurones for whole‐cell recordings. These experiments reveal that acute salt loading produces tonic inhibition of PVN CRH neurones through a mechanism that is largely independent of synaptic activity. Further studies reveal that a subset of CRH neurones within the PVN synthesise mRNA for Oxtr(s). Salt induced Oxtr‐dependent inhibitory tone was eliminated in individual PVN CRH neurones filled with GDP‐β‐S. Additional electrophysiological studies suggest that reduced excitability of PVN CRH neurones in salt‐loaded animals is associated with increased activation of inwardly rectifying potassium channels. Nevertheless, substantial effort to recapitulate the core effects of salt loading by activating Oxtr(s) with an exogenous agonist produced mixed results. Collectively, these results enhance our understanding of how oxytocin receptor‐mediated signalling modulates the function of CRH neurones in the PVN.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

Pati

Harden

Sheng

et al. 2020

J Neuroendocrinology

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“…Microinjection of oxytocin into the hypothalamic paraventricular nucleus has been reported to reduce stress responses of anxiety-related behaviours and the hypothalamic-adrenal axis, whereas that of an oxytocin antagonist impairs the social buffering actions on behavioural and neuroendocrine responses in female prairie voles. 93 These findings suggest that oxytocin suppresses the activity of hypothalamic CRH neurones also by suppressing excitatory synaptic transmission onto CRH neurones presynaptically. Pharmacological blockade of the GABA A receptor has been reported to block the actions of oxytocin in prairie voles.…”

Section: Hypothalamic Paraventricular Nucleusmentioning

confidence: 93%

Role of oxytocin in the control of stress and food intake

Onaka

Takayanagi

2019

J Neuroendocrinology

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Oxytocin neurones in the hypothalamus are activated by stressful stimuli and food intake. The oxytocin receptor is located in various brain regions, including the sensory information‐processing cerebral cortex; the cognitive information‐processing prefrontal cortex; reward‐related regions such as the ventral tegmental areas, nucleus accumbens and raphe nucleus; stress‐related areas such as the amygdala, hippocampus, ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray; homeostasis‐controlling hypothalamus; and the dorsal motor complex controlling intestinal functions. Oxytocin affects behavioural and neuroendocrine stress responses and terminates food intake by acting on the metabolic or nutritional homeostasis system, modulating emotional processing, reducing reward values of food intake, and facilitating sensory and cognitive processing via multiple brain regions. Oxytocin also plays a role in interactive actions between stress and food intake and contributes to adaptive active coping behaviours.

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“…In contrast to the hypothalamus, where OT was shown to regulate CRF neurons’ activity and expression (Nomura et al, 2003; Bulbul et al, 2011; Jurek et al, 2015; Jamieson et al, 2017), and CRF receptors were shown to interact with OT secretion (Bruhn et al, 1986; Arima and Aguilera, 2000; Dabrowska et al, 2011), very little is known about the functional interaction between OT and CRF in the extra-hypothalamic limbic systems critical for the regulation of fear and anxiety-like behavior.…”

Section: Role Of the Bed Nucleus Of The Stria Terminalis (Bnst) In Thmentioning

confidence: 99%

“…However, evidence for direct interaction of OT with the CRF neurons in the BNST has not been yet found, but see (Jurek et al, 2015; Jamieson et al, 2017) for OT-CRF interaction in the PVN. Further, potential mechanism of how OTR in the BNST dl may differentially modulate cued and non-cued fear remains unknown.…”

Section: Role Of the Bed Nucleus Of The Stria Terminalis (Bnst) In Thmentioning

confidence: 99%

Oxytocin facilitates adaptive fear and attenuates anxiety responses in animal models and human studies—potential interaction with the corticotropin-releasing factor (CRF) system in the bed nucleus of the stria terminalis (BNST)

Janeček

Dabrowska

2018

Cell Tissue Res

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Despite its relatively well-understood role as a reproductive and pro-social peptide, oxytocin (OT) tells a more convoluted story in terms of its modulation of fear and anxiety. This nuanced story has been obscured by a great deal of research into the therapeutic applications of exogenous OT, driving more than 400 ongoing clinical trials. Drawing from animal models and human studies, we review the complex evidence concerning OT’s role in fear learning and anxiety, clarifying the existing confusion about modulation of fear versus anxiety. We discuss animal models and human studies demonstrating the prevailing role of OT in strengthening fear memory to a discrete signal or cue, which allows accurate and rapid threat detection that facilitates survival. We also review ostensibly contrasting behavioral studies that nonetheless provide compelling evidence of OT attenuating sustained contextual fear and anxiety-like behavior, arguing that these OT effects on the modulation of fear vs. anxiety are not mutually exclusive. To disambiguate how endogenous OT modulates fear and anxiety, an understudied area compared to exogenous OT, we survey behavioral studies utilizing OT receptor (OTR) antagonists. Based on emerging evidence about the role of OTR in rat dorsolateral bed nucleus of stria terminalis (BNST) and elsewhere, we postulate that OT plays a critical role in facilitating accurate discrimination between stimuli representing threat and safety. Supported by human studies, we demonstrate that OT uniquely facilitates adaptive fear but reduces maladaptive anxiety. Furthermore, we show that the effects of OT are primarily observed in conditions of novelty or elevated stress level. Last, we explore the limited literature on endogenous OT and its interaction with corticotropin-releasing factor (CRF) with a special emphasis on the dorsolateral BNST, which may hold the key to the neurobiology of phasic fear and sustained anxiety.

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Regulation of hypothalamic corticotropin‐releasing hormone neurone excitability by oxytocin

Cited by 47 publications

References 53 publications

Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

Role of oxytocin in the control of stress and food intake

Oxytocin facilitates adaptive fear and attenuates anxiety responses in animal models and human studies—potential interaction with the corticotropin-releasing factor (CRF) system in the bed nucleus of the stria terminalis (BNST)

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