La transmission glutamatergique cortico-accumbens (régulation et plasticité pré-synaptique)

Le noyau accumbens est souvent considéré comme une interface des systèmes moteurs et limbiques. Les neurones moyens épineux de ce noyau reçoivent une afférentation glutamatergique dense dont ils dépendent pour la genèse de potentiels d'action. Bien qu'un nombre croissant d'études impliquant l'activité du noyau accumbens dans les processus attentionnels, motivationnels ou les processus de récompense, les conditions physiologiques de régulation des afférences glutamatergiques sur les neurones efférents de ce noyau restent mal connues. Les autorécepteurs et le patron temporel d'activité afférent sont des acteurs essentiels de la régulation synaptique glutamatergique. L'étude de la transmission synaptique glutamatermique cortico-accumbens, par la technique du patch-clamp sur tranches aigues de cerveau de souris, nous a permis de mettre en évidence de nouveaux phénomènes de régulation de ces afférences : (1) les récepteurs kaïnate localisés au niveau présynaptique sur les afférences corticales modulent négativement la transmission glutamatergique, (2) l'augmentation tonique de l'activité de décharge synaptique facilite ou déprime la transmission glutamatergique dépendamment de la probabilité de libération initiale de la synapse, (3) l'activation des afférences corticales par des décharges en bouffées induit une augmentation cumulative de la transmission glutamatergique résultant d'une augmentation de la fiabilité de la propagation axonale des potentiels d'action, et (4) la stimulation prolongée (2 min) à 14 Hz des afférences corticales induit une potentialisation à long terme induite par l'activation de récepteurs ionotropiques du glutamate. L'ensemble de ces résultats met en évidence des phénomènes originaux permettant une régulation fine des entrées exitatrices corticales sur les neurones efférents du noyau accumbens.The nucleus accumbens forms the ventral part of the striatum. It has been proposed to serve as an interface between the limbic system and the motor system. Medium spiny neurons of the nucleus accumbens, that depend on excitatory afferents to generate action potentials, receive a dense glutamatergic innervation from the prefrontal cortex and form various limbic structures, including the hippocampal formation, the basolateral amygdala and the thalamus. Despite growing evidence that the nucleus accumbens is involved in important brain functions such as motivation, attention or reward, physiological regulation of the glutamatergic input in medium spiny neurons is still largely unknown. The efficacy of excitatory glutamatergic synaptic transmission is highly dependent on the activation of presynaptic autoreceptors and on the temporal pattern of activity of afferents. Using patch-clamp whole-cell recordings in acute slices of the mouse nucleus accumbens, we have highlighted new forms of synaptic modulation of the cortico-accumbens pathway : (1) functional presynaptic kainate receptors on cortical afferrents fibers inhibited glutamatergic synaptic transmission, (2) increase in tonic frequency stimulation of the cortical input to the nucleus accumbens induced a presynaptic facilitation or depression of the synaptic transmission depending on the initial release probability, (3) burst stimulation of cortical afferent fibers lead to a cumulative increase of the glutamatergic synaptic input through presynaptic increase in axonal reliability of action potentials propagation, and (4) sustained stimulation (14 Hz, 2 min) of cortical afferent fibers, induced long-term potentiation of glutamatergic synaptic transmission through presynaptic mechanisms and activation of ionotropic glutamate receptors. These results demonstrtate new original phenomenons that modulate cortico-accumbens glutamatergic synaptic strength in nucleus accumbens efferent neurons.BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala

NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo–LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico–LA synapses. Here, we show that presynaptic cortico–LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α−/−), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico–LA synaptic transmission in RIM1α−/− mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico–LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling

L-type voltage-dependent Ca2+ channels mediate expression of presynaptic LTP in amygdala

International audienc

Optical coherence tomography to guide percutaneous coronary intervention of the left main coronary artery: the LEMON study

International audienceBackground: Intravascular ultrasound (IVUS)-guided PCI improves the prognosis of left main stem (LMS) PCI and is currently recommended by international guidelines. Although OCT resolution is greater than that of IVUS, this tool is not yet recommended in LMS angioplasty due to the absence of data.Aims: This pilot study aimed to analyse the feasibility, safety and impact of OCT-guided LMS PCI.Methods: This prospective, multicentre trial investigated whether patients might benefit from OCT-guided PCI for mid/distal LMS according to a pre-specified protocol. The primary endpoint was procedural success defined as follows: residual angiographic stenosis <50% + TIMI 3 flow in all branches + adequate OCT stent expansion (LEMON criteria).Results: Seventy patients were included in the final analysis (median age: 72 [64-81] years, 73% male). The OCT pre-specified protocol was applied in all patients. The primary endpoint was achieved in 86% of subjects. Adequate stent expansion was observed in 86%, significant edge dissection in 30% and residual significant strut malapposition in 24% of the cases. OCT guidance modified the operators’ strategy in 26% of the patients. The rate of one-year survival free from major adverse clinical events was 98.6% (97.2-100).Conclusions: This pilot study is the first to report the feasibility and performance of OCT-guided LMS PCI according to a pre-specified protocol

Publisher Note: Circumbinary, not transitional: On the spiral arms, cavity, shadows, fast radial flows, streamers and horseshoe in the HD142527 disc

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Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI

International audienceBackground - Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited. Objectives - The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period. Methods - TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers. Results - A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased. Conclusions - The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828)