Activation of PPG neurons following acute stressors differentially involves hindbrain serotonin in male rats

Leon, Rosa M.; Borner, Tito; Stein, Lauren M.; Urrutia, Norma A.; Jonghe, Bart C. De; Schmidt, Heath D.; Hayes, Matthew R.

doi:10.1016/j.neuropharm.2021.108477

Cited by 8 publications

(9 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study reported that hindbrain 5-HT contributes to stress-induced activation of GLP1 neurons in rats (Leon et al, 2021). Here we show that NTS-projecting PVN neurons are another necessary source of input for the ability of restraint stress to activate GLP1/PPG and other cNTS neurons in male wildtype mice.…”

Section: Discussionmentioning

confidence: 99%

“…The caudal part of the nucleus of the solitary tract (cNTS) is particularly well-positioned to integrate such signals (Holt, 2021; Maniscalco & Rinaman, 2017, 2018). Neurons within the cNTS are sensitive to both interoceptive and psychogenic stressors (Maniscalco & Rinaman, 2017), presumably mediated by their receipt of interoceptive sensory input from the spinal cord and vagal afferents along with descending input from brainstem regions, the cerebral cortex, limbic system, and hypothalamic nuclei, including the paraventricular nucleus of the hypothalamus (PVN) (Holt, Pomeranz, et al, 2019; Leon et al, 2021; Rinaman & Rothe, 2002; van der Kooy et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence suggests that rather than driving meal-induced satiation under normal physiological conditions, PPG neurons are more strongly engaged by stressful conditions that inhibit food intake. PPG neurons are activated by a variety of acute stressors in both rats and mice (Leon et al, 2021;Maniscalco et al, 2015;Rinaman, 1999;Terrill et al, 2019), and GLP1 acts centrally to generate stressor-like physiological responses that include activation of the HPA axis (Gil-Lozano et al, 2010;Kinzig et al, 2003) and increased heart rate (Barragán et al, 1999;Holt et al, 2020). Additional evidence indicates that PPG neurons are necessary for stress-induced hypophagia in mice (Holt, Richards, et al, 2019), that stress-induced hypophagia is significantly reduced in rats after central blockade of GLP1 receptors (Maniscalco et al, 2015;Zheng et al, 2019), and that central endogenous GLP1 elicits anxiety-like behaviours in rats (Kinzig et al, 2003;López-Ferreras et al, 2020;Maniscalco et al, 2015;Zheng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of stress-related behaviour by hypothalamic engagement of preproglucagon neurons in the nucleus of the solitary tract

Holt

Valderrama

Polanco

et al. 2022

Preprint

View full text Add to dashboard Cite

Stress-induced behaviours are driven by complex neural circuits and some neuronal populations concurrently modulate diverse behavioural and physiological responses to stress. Glucagon-like peptide-1 (GLP1)-producing preproglucagon (PPG) neurons within the lower brainstem caudal nucleus of the solitary tract (cNTS) are particularly sensitive to stressful stimuli and are implicated in multiple physiological and behavioural responses to interoceptive and psychogenic threats. However, the afferent inputs driving stress-induced activation of PPG neurons are largely unknown, and the role of PPG neurons in anxiety-like behaviour is controversial. Through chemogenetic manipulations we reveal that cNTS PPG neurons have the ability to moderately increase anxiety-like behaviours in mice in a sex-dependent manner. Using an intersectional approach, we show that a corticotropin-releasing hormone (CRH)-rich input from the paraventricular nucleus of the hypothalamus (PVN) drives activation of both the cNTS as a whole and PPG neurons in particular in response to acute stress. Finally, we demonstrate that NTS-projecting PVN neurons are necessary for the ability of acute stress to suppress food intake. Our findings reveal sex differences in behavioural responses to PPG neural activation and highlight a hypothalamic-brainstem pathway in stress-induced hypophagia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of stress-related behaviour by hypothalamic engagement of preproglucagon neurons in the nucleus of the solitary tract

Holt

Valderrama

Polanco

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…A recent study by Leon et al (2021) confirmed that multiple types of stressors (interoceptive and psychogenic) activate GLP1 neurons in rats and that this activation is mediated in part, by 5hydroxytryptamine (5-HT) receptor signalling. Intriguingly, the authors identified the raphe magnus as a potential driver of stress-induced activation of GLP1 neurons and also confirmed our previous finding that GLP1 neurons receive monosynaptic input from the raphe magnus (Holt et al, 2019a).…”

Section: 2mentioning

confidence: 92%

“…Interestingly, different types of stressors were differentially dependent on 5-HT signalling for GLP1 neuron activation. Although LiCl-induced activation of GLP1 neurons was abolished after blockade of 5-HT signalling, restraint stress-induced activation was only attenuated, suggesting that multiple pathways contribute to psychogenic stress-induced activation of these neurons (Leon et al, 2021).…”

Section: 2mentioning

confidence: 99%

Mind affects matter: Hindbrain GLP1 neurons link stress, physiology and behaviour

Holt

2021

Experimental Physiology

View full text Add to dashboard Cite

The brain responds rapidly to stressful stimuli by increasing sympathetic outflow, activating the hypothalamic-pituitary-adrenal axis and eliciting avoidance behaviours to limit risks to safety. Stress responses are adaptive and essential but can become maladaptive when the stress is chronic, causing autonomic imbalance, hypothalamicpituitary-adrenal axis hyper-reactivity and a state of hypervigilance. Ultimately, this contributes to the development of cardiovascular disease and affective disorders, including major depression and anxiety. Stress responses are often thought to be driven mainly by forebrain areas; however, the brainstem nucleus of the solitary tract (NTS) is ideally located to control both autonomic outflow and behaviour in response to stress. Here, I review the preclinical evidence that the NTS and its resident glucagon-like peptide-1 (GLP1)-expressing neurons are prominent mediators of stress responses. This Lecture introduces the reader to the idea of good and bad stress and outlines the types of stress that engage the NTS and GLP1 neurons. I describe in particular detail the recent studies by myself and others aimed at mapping sources of synaptic inputs to GLP1 neurons and consider the implications for our understanding of the role of GLP1 neurons in stress. This is followed by a discussion of the contribution of brain GLP1 and GLP1 neurons to behavioural and physiological stress responses.The evidence reviewed highlights a potentially prominent role for GLP1 neurons in the response of the brain to acute stress and reveals important unanswered questions regarding their role in chronic stress. K E Y W O R D Sglucagon-like peptide-1, hypothalamic-pituitary-adrenal axis, nucleus of the solitary tract, preproglucagon, stress INTRODUCTION AND SCOPE OF REVIEWThe brain continuously monitors the health and function of the body and responds rapidly to potential threats by eliciting changes in physiology and behaviour (Holt & Trapp, 2016;Ulrich-Lai & Herman, 2009). These processes are driven by corticolimbic, hypothalamic and brainstem circuits, with the caudal nucleus of the solitary tract

show abstract

High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice

Bales

Centanni²,

Luchsinger³

et al. 2022

Molecular Metabolism

View full text Add to dashboard Cite

Activation of PPG neurons following acute stressors differentially involves hindbrain serotonin in male rats

Cited by 8 publications

References 94 publications

Modulation of stress-related behaviour by hypothalamic engagement of preproglucagon neurons in the nucleus of the solitary tract

Modulation of stress-related behaviour by hypothalamic engagement of preproglucagon neurons in the nucleus of the solitary tract

Mind affects matter: Hindbrain GLP1 neurons link stress, physiology and behaviour

High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice

Contact Info

Product

Resources

About