Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Single-Unit Activity in the Medial Prefrontal Cortex during Immediate and Delayed Extinction of Fear in Rats

Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit

Macrophage-Stimulated Cardiac Fibroblast Production of IL-6 Is Essential for TGF β/Smad Activation and Cardiac Fibrosis Induced by Angiotensin II

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL-6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of α-SMA and collagen I in fibroblasts. Moreover, TGF-β1 expression and phosphorylation of TGF-β downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-β1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-β1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis

Au Sujet des Approches Symboliques des Équations Intégro-Différentielles

International audienceRecent progress in computer algebra has opened new opportunities for the parameter estimation problem in nonlinear control theory, by means of integro-differential input-output equations. This paper recalls the origin of integro-differential equations. It presents new opportunities in nonlinear control theory. Finally, it reviews related recent theoretical approaches on integro-differential algebras, illustrating what an integro-differential elimination method might be and what benefits the parameter estimation problem would gain from it.Un résultat récent en calcul formel a ouvert de nouvelles opportunités pour l'estimation de paramètres en théorie du contrôle non linéaire, via des équations entrée-sortie intégro-différentielles. Ce chapitre rappelle les origines des équations intégro-différentielles. Il présente de nouvelles opportunités en théorie du contrôle non linéaire. Finalement, il passe en revue des approches théoriques récentes sur les algèbres intégro-différentielles, illustrant ce qu'une méthode d'élimination intégro-différentielle pourrait être et les bénéfices que le problème de l'estimation de paramètres pourrait en tirer

Perceived threat predicts the neural sequelae of combat stress

Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amygdala is a key brain region involved in threat detection and fear regulation, and previous animal studies have suggested that stress sensitizes amygdala responsivity and reduces its regulation by the prefrontal cortex. In this study, we used a prospective design to investigate the consequences of severe stress in soldiers before and after deployment to a combat zone. We found that combat stress increased amygdala and insula reactivity to biologically salient stimuli across the group of combat-exposed individuals. In contrast, its influence on amygdala coupling with the insula and dorsal anterior cingulate cortex was dependent on perceived threat, rather than actual exposure, suggesting that threat appraisal affects interoceptive awareness and amygdala regulation. Our results demonstrate that combat stress has sustained consequences on neural responsivity, and suggest a key role for the appraisal of threat on an amygdala-centered neural network in the aftermath of severe stress

Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung

10.1371/journal.pone.0024019PLoS ONE68

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio