TY - JOUR
T1 - A unique “Angiotensin-Sensitive” neuronal population coordinates neuroendocrine, cardiovascular, and behavioral responses to stress
AU - de Kloet, Annette D.
AU - Wang, Lei
AU - Pitra, Soledad
AU - Hiller, Helmut
AU - Smith, Justin A.
AU - Tan, Yalun
AU - Nguyen, Dani
AU - Cahill, Karlena M.
AU - Sumners, Colin
AU - Stern, Javier Eduardo
AU - Krause, Eric G.
N1 - Funding Information:
This work was supported by the following grants: National Institutes of Health (NIH) HL122494 (E.G.K.), NIH HL125805(A.D.d.K.), NIH HL033610(C.S.), NIH HL112225(J.E.S.). We thank David J. Pioquinto and Jacob A. Ludin for their technical assistance.
Publisher Copyright:
© 2017 the authors.
PY - 2017/3/29
Y1 - 2017/3/29
N2 - Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses. Initial studies use neuroanatomical techniques to reveal that angiotensin type-1a receptors are localized predominantly to the parvocellular neurosecretory neurons of the paraventricular nucleus of the hypothalamus. These neurons are almost exclusively glutamatergic and send dense projections totheexterior portionof themedianeminence. Furthermore, theseneurons largelyexpress corticotrophin-releasinghormoneor thyrotropin-releasing hormone and do not express arginine vasopressin or oxytocin. Functionally, optogenetic stimulation of these neurons promotes the activation of the hypothalamic-pituitary–adrenal and hypothalamic-pituitary–thyroid axes, as well as a rise in systolic blood pressure. When these neurons are optogenetically inhibited, the activity of these neuroendocrine axes are suppressed and anxiety-like behavior in the elevated plus maze is dampened. Collectively, these studies implicate this neuronal population in the integration and coordination of the physiological responses to stress and may therefore serve as a potential target for therapeutic intervention for stress-related pathology.
AB - Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses. Initial studies use neuroanatomical techniques to reveal that angiotensin type-1a receptors are localized predominantly to the parvocellular neurosecretory neurons of the paraventricular nucleus of the hypothalamus. These neurons are almost exclusively glutamatergic and send dense projections totheexterior portionof themedianeminence. Furthermore, theseneurons largelyexpress corticotrophin-releasinghormoneor thyrotropin-releasing hormone and do not express arginine vasopressin or oxytocin. Functionally, optogenetic stimulation of these neurons promotes the activation of the hypothalamic-pituitary–adrenal and hypothalamic-pituitary–thyroid axes, as well as a rise in systolic blood pressure. When these neurons are optogenetically inhibited, the activity of these neuroendocrine axes are suppressed and anxiety-like behavior in the elevated plus maze is dampened. Collectively, these studies implicate this neuronal population in the integration and coordination of the physiological responses to stress and may therefore serve as a potential target for therapeutic intervention for stress-related pathology.
KW - Anxiety
KW - Cardiovascular
KW - Depression
KW - Glucocorticoids
KW - Hypertension
KW - Thyroid
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U2 - 10.1523/JNEUROSCI.3674-16.2017
DO - 10.1523/JNEUROSCI.3674-16.2017
M3 - Article
C2 - 28219987
AN - SCOPUS:85016476844
SN - 0270-6474
VL - 37
SP - 3478
EP - 3490
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 13
ER -