scholarly journals Functional Interplay of Type-2 Corticotrophin Releasing Factor and Dopamine Receptors in the Basolateral Amygdala-Medial Prefrontal Cortex Circuitry

Author(s):  
H E Yarur ◽  
J Zegers ◽  
I Vega-Quiroga ◽  
J Novoa ◽  
F Ciruela ◽  
...  

Abstract Background Basolateral amygdala (BLA) excitatory projections to medial prefrontal cortex (PFC) play a key role controlling stress behavior, pain, and fear. Indeed, stressful events block synaptic plasticity at the BLA-PFC circuit. The stress responses involve the action of corticotrophin releasing factor (CRF) through type 1 and type 2 CRF receptors (CRF1 and CRF2). Interestingly, it has been described that dopamine receptor 1 (D1R) and CRF peptide have a modulatory role of BLA-PFC transmission. However, the participation of CRF1 and CRF2 receptors in BLA-PFC synaptic transmission still is unclear. Methods We used in vivo microdialysis to determine dopamine and glutamate (GLU) extracellular levels in PFC after BLA stimulation. Immunofluorescence anatomical studies in rat PFC synaptosomes devoid of postsynaptic elements were performed to determine the presence of D1R and CRF2 receptors in synaptical nerve endings. Results Here, we provide direct evidence of the opposite role that CRF receptors exert over dopamine extracellular levels in the PFC. We also show that D1R colocalizes with CRF2 receptors in PFC nerve terminals. Intra-PFC infusion of antisauvagine-30, a CRF2 receptor antagonist, increased PFC GLU extracellular levels induced by BLA activation. Interestingly, the increase in GLU release observed in the presence of antisauvagine-30 was significantly reduced by incubation with SCH23390, a D1R antagonist. Conclusion PFC CRF2 receptor unmasks D1R effect over glutamatergic transmission of the BLA-PFC circuit. Overall, CRF2 receptor emerges as a new modulator of BLA to PFC glutamatergic transmission, thus playing a potential role in emotional disorders.

2020 ◽  
Author(s):  
Jessica A. Cooper ◽  
Makiah R. Nuutinen ◽  
Victoria M. Lawlor ◽  
Brittany A. M. DeVries ◽  
Elyssa M. Barrick ◽  
...  

ABSTRACTStress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.


2019 ◽  
Vol 116 (9) ◽  
pp. 3799-3804 ◽  
Author(s):  
Tingting Sun ◽  
Zihua Song ◽  
Yanghua Tian ◽  
Wenbo Tian ◽  
Chunyan Zhu ◽  
...  

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.


Animals ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 358 ◽  
Author(s):  
Angelo Peli ◽  
Annamaria Grandis ◽  
Marco Tassinari ◽  
Paolo Famigli Bergamini ◽  
Claudio Tagliavia ◽  
...  

Calves reared for the production of white veal are subjected to stressful events due to the type of liquid diet they receive. Stress responses are mediated by three main stress-responsive cerebral regions: the prefrontal cortex, the paraventricular nucleus of the hypothalamus, and the nucleus of the solitary tract of the brainstem. In the present study, we have investigated the effects of different diets on these brain regions of ruminants using immunohistochemical methods. In this study, 15 calves were used and kept in group housing systems of five calves each. They were fed with three different diets: a control diet, a milk diet, and a weaned diet. Brain sections were immunostained to evaluate the distribution of neuronal nitric oxide synthase and myelin oligodendrocyte glycoprotein immunoreactivity in the prefrontal cortex; the expression of oxytocin in the paraventricular nucleus; and the presence of c-Fos in the A2 group of the nucleus of the solitary tract. The main results obtained indicate that in weaned diet group the oxytocin activity is lower than in control diet and milk diet groups. In addition, weaning appears to stimulate myelination in the prefrontal cortex. In summary, this study supports the importance of maintaining a nutritional lifestyle similar to that occurring in natural conditions.


2017 ◽  
Vol 42 (13) ◽  
pp. 2537-2544 ◽  
Author(s):  
Thomas F Giustino ◽  
Jocelyn R Seemann ◽  
Gillian M Acca ◽  
Travis D Goode ◽  
Paul J Fitzgerald ◽  
...  

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