scholarly journals Stress-induced changes in the activity of parvocellular neurosecretory cells in the paraventricular nucleus of the hypothalamus

2019 ◽  
Vol 73 ◽  
pp. 217-224
Author(s):  
Magdalena Kusek ◽  
Izabela Ciurej ◽  
Krzysztof Tokarski

This paper summarizes a series of studies aimed at characterizing the effects of stress-related changes in synaptic inputs to the hypothalamic paraventricular nucleus (PVN). This structure generates an integrated physiological stress response by activating the hypothalamus-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine neurons of the PVN play a key role in this process. They receive extensive excitatory and inhibitory innervation conveying information about interoceptive and exteroceptive stressful stimuli from a variety of sources within the brain. These synaptic inputs modulate the activity of PVN neurons, which regulates the amount of CRH released into the portal circulation of the anterior pituitary. It has been demonstrated that with either single or repeated stress sessions, the efficacy of excitatory and inhibitory synapses on parvocellular neuroendocrine neurons changes considerably, which may be related to repeated stress-induced sensitization of the HPA axis. The nature of these changes depends on the type of stress and its duration. Changes in synaptic inputs and the excitability of parvocellular neuroendocrine neurons are thought to be responsible for dysfunctions of the HPA axis observed in affective disorders. Assessing how this controlling function of PVN neurons is modulated in response to stress is crucial to our understanding of the pathophysiology of affective disorders.

2021 ◽  
Vol 12 ◽  
Author(s):  
Kevin Gley ◽  
Frieder Hadlich ◽  
Nares Trakooljul ◽  
Fiete Haack ◽  
Eduard Murani ◽  
...  

The molecular basis of porcine coping behavior (CB) relies on a sophisticated interplay of genetic and epigenetic features. Deep sequencing technologies allowed the identification of a plethora of new regulatory small non-coding RNA (sncRNA). We characterized mRNA and sncRNA profiles of central parts of the physiological stress response system including amygdala, hippocampus, hypothalamus and adrenal gland using systems biology for integration. Therefore, ten each of high- (HR) and low- (LR) reactive pigs (n = 20) carrying a CB associated haplotype in a prominent QTL-region on SSC12 were selected for mRNA and sncRNA expression profiling. The molecular markers related to the LR group included ATP1B2, MPDU1, miR-19b-5p, let-7g-5p, and 5′-tiRNALeu in the adrenal gland, miR-194a-5p, miR-125a-5p, miR-7-1-5p, and miR-107-5p in the hippocampus and CBL and PVRL1 in the hypothalamus. Interestingly, amygdalae of the LR group showed 5′-tiRNA and 5′-tRF (5′-tRFLys, 5′-tiRNALys, 5′-tiRNACys, and 5′-tiRNAGln) enrichment. Contrarily, molecular markers associated with the HR group encompassed miR-26b-5p, tRNAArg, tRNAGlyiF in the adrenal gland, IGF1 and APOD in the amygdala and PBX1, TOB1, and C18orf1 in the hippocampus and miR-24 in the hypothalamus. In addition, hypothalami of the HR group were characterized by 3′-tiRNA enrichment (3′-tiRNAGln, 3′-tiRNAAsn, 3′-tiRNAVal, 3′-tRFPro, 3′-tiRNACys, and 3′-tiRNAAla) and 3′-tRFs enrichment (3′-tRFAsn, 3′-tRFGlu, and 3′-tRFVal). These evidence suggest that tRNA-derived fragments and their cleavage activity are a specific marker for coping behavior. Data integration revealed new bio-signatures of important molecular interactions on a multi-transcript level in HPA axis and limbic system of pigs carrying a CB-associated haplotype.


2021 ◽  
Author(s):  
Nadya Povysheva ◽  
Huiyuan Zheng ◽  
Linda Rinaman

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.


2020 ◽  
Vol 32 (5) ◽  
pp. 1888-1898
Author(s):  
Melissa J. Hagan ◽  
Danielle S. Roubinov ◽  
W. Thomas Boyce ◽  
Nicole R. Bush

AbstractThere is emerging evidence that the development of problematic aggression in childhood may be associated with specific physiological stress response patterns, with both biological overactivation and underactivation implicated. This study tested associations between sex-specific patterns of stress responses across the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis and peer nominations of aggression among 271 kindergarten children (Mean age = 5.32 years; 52% Female; 44% White). Upon entry to kindergarten, children participated in a multidomain standardized stress paradigm. Changes in pre-ejection period (PEP) and salivary cortisol were assessed. On a separate day, children provided peer ratings of physical and relational aggression in a standardized interview. As expected, there was a significant three-way interaction between PEP, cortisol reactivity, and sex, but only for physical aggression. Among boys, cortisol reactivity was positively associated with physical aggression only for those with higher SNS reactivity. Findings suggest that for boys, asymmetrical and symmetrical HPA/SNS reactivity may be associated with lower and higher risk for peer-directed physical aggression, respectively. Understanding the complex associations between multisystem physiology, child sex and peer-directed aggression in early childhood may offer insight into individual differences underlying the emergence of behavioral dysregulation in early peer contexts.


2021 ◽  
Vol 239 ◽  
pp. 105940
Author(s):  
Laura Simões Andrade ◽  
Domingos Garrone-Neto ◽  
Manuela Alves Nobre Sales ◽  
Luciana Rodrigues de Souza-Bastos ◽  
Ursulla Pereira Souza ◽  
...  

Author(s):  
Alexander S. Häusl ◽  
Lea M. Brix ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Juan-Pablo Lopez ◽  
...  

AbstractDisturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of Fkbp5 in Sim1+ neurons dampens the acute stress response and increases GR sensitivity. In contrast, Fkbp5 overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of Fkbp5 expression in full Fkbp5 KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of Fkbp5 in the PVN and showed that Fkbp5 expression is specifically upregulated in Crh+ neurons after stress. Finally, Crh-specific Fkbp5 overexpression alters Crh neuron activity, but only partially recapitulates the PVN-specific Fkbp5 overexpression phenotype. Together, the data establish the central and cell-type-specific importance of Fkbp5 in the PVN in shaping HPA axis regulation and the acute stress response.


2020 ◽  
Author(s):  
Yang-Sun Hwang ◽  
Catherine Maclachlan ◽  
Jérôme Blanc ◽  
Anaëlle Dubois ◽  
Carl C H Petersen ◽  
...  

Abstract Synapses are the fundamental elements of the brain’s complicated neural networks. Although the ultrastructure of synapses has been extensively studied, the difference in how synaptic inputs are organized onto distinct neuronal types is not yet fully understood. Here, we examined the cell-type-specific ultrastructure of proximal processes from the soma of parvalbumin-positive (PV+) and somatostatin-positive (SST+) GABAergic neurons in comparison with a pyramidal neuron in the mouse primary visual cortex (V1), using serial block-face scanning electron microscopy. Interestingly, each type of neuron organizes excitatory and inhibitory synapses in a unique way. First, we found that a subset of SST+ neurons are spiny, having spines on both soma and dendrites. Each of those spines has a highly complicated structure that has up to eight synaptic inputs. Next, the PV+ and SST+ neurons receive more robust excitatory inputs to their perisoma than does the pyramidal neuron. Notably, excitatory synapses on GABAergic neurons were often multiple-synapse boutons, making another synapse on distal dendrites. On the other hand, inhibitory synapses near the soma were often single-targeting multiple boutons. Collectively, our data demonstrate that synaptic inputs near the soma are differentially organized across cell types and form a network that balances inhibition and excitation in the V1.


2009 ◽  
Vol 73 (4) ◽  
pp. 609-614 ◽  
Author(s):  
Remington J. Moll ◽  
Joshua J. Millspaugh ◽  
Jeff Beringer ◽  
Joel Sartwell ◽  
Rami J. Woods ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document