scholarly journals Glucagon-like peptide 1 receptor-mediated stimulation of a GABAergic projection from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus

2021 ◽  
Author(s):  
Nadya Povysheva ◽  
Huiyuan Zheng ◽  
Linda Rinaman
Keyword(s):  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Brain Slices ◽  
Gabaergic Neurons ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Synaptic Inputs ◽  
Bath Application ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We previously reported that GABAergic neurons within the ventral anterior lateral bed nucleus of the stria terminalis (alBST) express glucagon-like peptide 1 receptor (GLP1R) in rats, and that virally-mediated <knock-down> of GLP1R expression in the alBST prolongs the hypothalamic-pituitary-adrenal axis response to acute stress. Given other evidence that a GABAergic projection pathway from ventral alBST serves to limit stress-induced activation of the HPA axis, we hypothesized that GLP1 signaling promotes activation of GABAergic ventral alBST neurons that project directly to the paraventricular nucleus of the hypothalamus (PVN). After PVN microinjection of fluorescent retrograde tracer followed by preparation of ex vivo rat brain slices, whole-cell patch clamp recordings were made in identified PVN-projecting neurons within the ventral alBST. Bath application of Exendin-4 (a specific GLP1R agonist) indirectly depolarized PVN-projecting neurons in the ventral alBST and adjacent hypothalamic parastrial nucleus (PS) via circuit-mediated effects that increased excitatory synaptic inputs and decreased inhibitory synaptic inputs to the PVN-projecting neurons; these effects were occluded by prior bath application of a GLP1R antagonist. Additional retrograde tracing experiments combined with in situ hybridization confirmed that PVN-projecting neurons within the ventral alBST/PS are GABAergic, and do not express GLP1R mRNA. Conversely, GLP1 mRNA is expressed by a subset of GABAergic neurons within the oval subnucleus of the dorsal alBST that project into the ventral alBST. Our novel findings reveal a potential GLP1R-mediated mechanism through which the alBST exerts inhibitory control over the endocrine HPA axis.

scholarly journals The Anteroventral Bed Nucleus of the Stria Terminalis Differentially Regulates Hypothalamic-Pituitary-Adrenocortical Axis Responses to Acute and Chronic Stress

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 818-826 ◽  
Author(s):  
Dennis C. Choi ◽  
Nathan K. Evanson ◽  
Amy R. Furay ◽  
Yvonne M. Ulrich-Lai ◽  
Michelle M. Ostrander ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Restraint Stress ◽  
Body Weight Gain ◽  
Stria Terminalis ◽  
Thymic Involution ◽  
Bed Nucleus ◽  
Acute And Chronic Stress

The anteroventral region of the bed nucleus of the stria terminalis (BST) stimulates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress. However, the role of the anterior BST nuclei in chronic drive of the HPA axis has yet to be established. Therefore, this study tests the role of the anteroventral BST in physiological responses to chronic drive, using a chronic variable stress (CVS) model. Male Sprague-Dawley rats received either bilateral ibotenate lesions, targeting the anteroventral BST, or vehicle injection into the same region. Half of the lesion and control rats were exposed to a 14-d CVS paradigm consisting of twice-daily exposure to unpredictable, alternating stressors. The remaining rats were nonhandled control animals that remained in home cages. On the morning after the end of CVS exposure, all rats were exposed to a novel restraint stress challenge. CVS induced attenuated body weight gain, adrenal hypertrophy, thymic involution, and enhanced CRH mRNA in hypophysiotrophic neurons of the hypothalamic paraventricular nucleus, none of which were affected by anteroventral BST lesions. In the absence of CVS, lesions attenuated the plasma corticosterone and paraventricular nucleus c-fos mRNA responses to the acute restraint stress. In contrast, lesions of the anteroventral BST elevated plasma ACTH and corticosterone responses to novel restraint in the rats previously exposed to CVS. These data suggest that the anterior BST plays very different roles in integrating acute stimulation and chronic drive of the HPA axis, perhaps mediated by chronic stress-induced recruitment of distinct BST cell groups or functional reorganization of stress-integrative circuits.

scholarly journals Orexin depolarizes rat hypothalamic paraventricular nucleus neurons

2001 ◽  
Vol 281 (4) ◽  
pp. R1114-R1118 ◽  
Author(s):  
Tetsuro Shirasaka ◽  
Satoshi Miyahara ◽  
Takato Kunitake ◽  
Qing-Hua Jin ◽  
Kazuo Kato ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Brain Slices ◽  
Hypothalamic Paraventricular Nucleus ◽  
Dependent Manner ◽  
Patch Clamp Recording ◽  
Concentration Dependent Manner ◽  
Whole Cell Patch Clamp ◽  
Orexin Receptors ◽  
Bath Application

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01–1.0 μM) depolarized 80.8% of type 1 ( n = 26) and 79.2% of type 2 neurons tested ( n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 μM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd2+(1 mM) to artificial cerebrospinal fluid containing TTX (1 μM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.

scholarly journals Hypothalamic supraoptic but not paraventricular nucleus is involved in cardiovascular responses to carbachol microinjected into the bed nucleus of stria terminalis of unanesthetized rats

2011 ◽  
Vol 1393 ◽  
pp. 31-43 ◽  
Author(s):  
Fernando H.F. Alves ◽  
Carlos C. Crestani ◽  
Cristiane Busnardo ◽  
José Antunes-Rodrigues ◽  
Felipe V. Gomes ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Cardiovascular Responses ◽  
Stria Terminalis ◽  
Bed Nucleus

scholarly journals Differential effects of static and dynamic inputs on neuronal excitability

2015 ◽  
Vol 113 (1) ◽  
pp. 232-243 ◽  
Author(s):  
Attila Szücs ◽  
Ramon Huerta
Keyword(s):  
Neuronal Excitability ◽  
Computational Study ◽  
Ionic Currents ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Synaptic Inputs ◽  
Cation Current ◽  
Excitability Of Neurons ◽  
Inwardly Rectifying ◽  
Activity Dependent

The intrinsic excitability of neurons is known to be dynamically regulated by activity-dependent plasticity and homeostatic mechanisms. Such processes are commonly analyzed in the context of input-output functions that describe how neurons fire in response to constant levels of current. However, it is not well understood how changes of excitability as observed under static inputs translate to the function of the same neurons in their natural synaptic environment. Here we performed a computational study and hybrid experiments on rat bed nucleus of stria terminalis neurons to compare the two scenarios. The inward rectifying Kir current ( IKir) and the hyperpolarization-activated cation current ( Ih) were found to be considerably more effective in regulating the firing under synaptic inputs than under static stimuli. This prediction was experimentally confirmed by dynamic-clamp insertion of a synthetic inwardly rectifying Kir current into the biological neurons. At the same time, ionic currents that activate with depolarization were more effective regulating the firing under static inputs. When two intrinsic currents are concurrently altered such as those under homeostatic regulation, the effects in firing responses under static vs. dynamic inputs can be even more contrasting. Our results show that plastic or homeostatic changes of intrinsic membrane currents can shape the current step responses of neurons and their firing under synaptic inputs in a differential manner.

Sign in / Sign up

Export Citation Format

Share Document