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The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and developmental regulation. Although interesting findings emerged, showing that different subunits are specifically regulated during development, or that excitatory and inhibitory neuronal networks exhibit various electrical connectivity patterns, gap junctions did not receive much further interest. Originally, it was believed that gap junctions represent simple passageways for electrical and biochemical coordination early in development. Today, we know that gap junction connectivity is tightly regulated, following independent developmental patterns for excitatory and inhibitory networks. Electrical connections are important for many specific functions of neurons, and are, for example, required for the development of neuronal stimulus tuning in the visual system. Here, we integrate the available data on neuronal connectivity and gap junction properties, as well as the most recent findings concerning the functional implications of electrical connections in the developing thalamus and neocortex.

AimsAldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis.Methods and resultsC57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR.ConclusionObesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications

Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.

Aims Endothelial activation, macrophage infiltration, and foam cell formation are pivotal steps in atherogenesis. Our aim in this study was to analyse the role of SIRT1, a class III deacetylase with important metabolic functions, in plaque macrophages and atherogenesis. Methods and results Using partial SIRT1 deletion in atherosclerotic mice, we demonstrate that SIRT1 protects against atherosclerosis by reducing macrophage foam cell formation. Peritoneal macrophages from heterozygous SIRT1 mice accumulate more oxidized low-density lipoprotein (oxLDL), thereby promoting foam cell formation. Bone marrow-restricted SIRT1 deletion confirmed that SIRT1 function in macrophages is sufficient to decrease atherogenesis. Moreover, we show that SIRT1 reduces the uptake of oxLDL by diminishing the expression of lectin-like oxLDL receptor-1 (Lox-1) via suppression of the NF-kappaB signalling pathway. Conclusion Our findings demonstrate protective effects of SIRT1 in atherogenesis and suggest pharmacological SIRT1 activation as a novel anti-atherosclerotic strategy by reducing macrophage foam cell formation.

Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized. Thus, we have investigated the endothelial effects of decreased endogenous SIRT1 in hypercholesterolemic ApoE-/- mice. We observed no difference in endothelial relaxation and eNOS (Ser1177) phosphorylation between 20-week old male atherosclerotic ApoE-/- SIRT1+/- and ApoE-/- SIRT1+/+ mice. However, SIRT1 prevented endothelial superoxide production, inhibited NF-kappaB signaling, and diminished expression of adhesion molecules. Treatment of young hypercholesterolemic ApoE-/- SIRT1+/- mice with lipopolysaccharide to boost NF-kappaB signaling led to a more pronounced endothelial expression of ICAM-1 and VCAM-1 as compared to ApoE-/- SIRT1+/+ mice. In conclusion, endogenous SIRT1 diminishes endothelial activation in ApoE-/- mice, but does not affect endothelium-dependent vasodilatation.

Hintergrund: Das Ziel einer Strabismusoperation ist die Sehachsenausrichtung, die Beseitigung von Diplopie, eine Beidäugigkeit zu entwickeln bzw. wieder herzustellen und das beidäugige Blickfeld zu erweitern. Bei Erwachsenen mit Strabismus und mittel- bis hochgradiger Amblyopie (Sehschärfe < 0,4) jedoch wird die Starbismusoperation manchmal als kosmetischer Eingriff betrachtet. Methode: Diese retropektive Studie analysierte die funktionellen Veränderungen (mögliche Verbesserungen und potentielle Risiken) einer Starbimusoperation bei 36 Erwachsenen mit Strabismus und mittel- bis hochgradiger Amblyopie. Von 20 der 36 Patienten wurden nach mindestens 1 Jahr bzw. höchstens 5 Jahren ( Durchschnittlich 3,55 Jahren) weitere Befunde erhoben um die Stabilität der postoperativen Sehachsenausrichtung zu ermittlen. Diese wurden gebeten einen Fragebogen auszufüllen, der die subjektiven und psychosozialen Veränderungen erhebt. Ergebnisse: Eine Sehachsenausrichtung und eine Entwicklung der Beidäugigkeit konnte in Abhängigkeit von der Schielform und der Sehschärfe für diese Patienten erreicht werden. Auch im Verlauf blieben die Winkel überwiegend konstant. Jedoch trat Diplopie gehäuft auf. Eine subjektive Veränderung wurde beim Selbstwertgefühl und im gesellschaftlichen Leben bemerkt., Background: The goal of the treatment of strabismus is to align the visual axes to eliminate diplopia, produce or restore binocular vision and to expand the binocular visual field. For adults with strabismus and with moderate to high grade amblyopia (visual acuity < 0, 4) strabismus surgery has sometimes been regarded as “cosmetic”. Methods: A retrospective analysis of 36 adults with strabismus and with moderate to high grade amblyopia has been conducted to examine the functional changes (possible benefits and potential risk) of surgical treatment. 20 of 36 patients have been examined 1 year to five years ( average 3, 55 years) after the operation to asses the stability of the alignment of the optical axes. The patients completed a self- reporting repertory grid to appraise the psychosocial and subjective changes. Results: An alignment of the optical axes and the development of binocularity have been observed depending on the type of strabismus and the amount of acuteness of vision reached by the patients. Subsequently, the alignment of the optical axes remained constant. Binocular diplopia occurred cumulatively. A subjective change in self-esteem and in social life is noticeable.

Hintergrund: Das Ziel einer Strabismusoperation ist die Sehachsenausrichtung, die Beseitigung von Diplopie, eine Beidäugigkeit zu entwickeln bzw. wieder herzustellen und das beidäugige Blickfeld zu erweitern. Bei Erwachsenen mit Strabismus und mittel- bis hochgradiger Amblyopie (Sehschärfe < 0,4) jedoch wird die Starbismusoperation manchmal als kosmetischer Eingriff betrachtet. Methode: Diese retropektive Studie analysierte die funktionellen Veränderungen (mögliche Verbesserungen und potentielle Risiken) einer Starbimusoperation bei 36 Erwachsenen mit Strabismus und mittel- bis hochgradiger Amblyopie. Von 20 der 36 Patienten wurden nach mindestens 1 Jahr bzw. höchstens 5 Jahren ( Durchschnittlich 3,55 Jahren) weitere Befunde erhoben um die Stabilität der postoperativen Sehachsenausrichtung zu ermittlen. Diese wurden gebeten einen Fragebogen auszufüllen, der die subjektiven und psychosozialen Veränderungen erhebt. Ergebnisse: Eine Sehachsenausrichtung und eine Entwicklung der Beidäugigkeit konnte in Abhängigkeit von der Schielform und der Sehschärfe für diese Patienten erreicht werden. Auch im Verlauf blieben die Winkel überwiegend konstant. Jedoch trat Diplopie gehäuft auf. Eine subjektive Veränderung wurde beim Selbstwertgefühl und im gesellschaftlichen Leben bemerkt., Background: The goal of the treatment of strabismus is to align the visual axes to eliminate diplopia, produce or restore binocular vision and to expand the binocular visual field. For adults with strabismus and with moderate to high grade amblyopia (visual acuity < 0, 4) strabismus surgery has sometimes been regarded as “cosmetic”. Methods: A retrospective analysis of 36 adults with strabismus and with moderate to high grade amblyopia has been conducted to examine the functional changes (possible benefits and potential risk) of surgical treatment. 20 of 36 patients have been examined 1 year to five years ( average 3, 55 years) after the operation to asses the stability of the alignment of the optical axes. The patients completed a self- reporting repertory grid to appraise the psychosocial and subjective changes. Results: An alignment of the optical axes and the development of binocularity have been observed depending on the type of strabismus and the amount of acuteness of vision reached by the patients. Subsequently, the alignment of the optical axes remained constant. Binocular diplopia occurred cumulatively. A subjective change in self-esteem and in social life is noticeable.