43 research outputs found

    Identification of a Circadian Clock-Controlled Neural Pathway in the Rabbit Retina

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    Background: Although the circadian clock in the mammalian retina regulates many physiological processes in the retina, it is not known whether and how the clock controls the neuronal pathways involved in visual processing. Methodology/Principal Findings: By recording the light responses of rabbit axonless (A-type) horizontal cells under darkadapted conditions in both the day and night, we found that rod input to these cells was substantially increased at night under control conditions and following selective blockade of dopamine D2, but not D1, receptors during the day, so that the horizontal cells responded to very dim light at night but not in the day. Using neurobiotin tracer labeling, we also found that the extent of tracer coupling between rabbit rods and cones was more extensive during the night, compared to the day, and more extensive in the day following D 2 receptor blockade. Because A-type horizontal cells make synaptic contact exclusively with cones, these observations indicate that the circadian clock in the mammalian retina substantially increases rod input to A-type horizontal cells at night by enhancing rod-cone coupling. Moreover, the clock-induced increase in D2 receptor activation during the day decreases rod-cone coupling so that rod input to A-type horizontal cells is minimal. Conclusions/Significance: Considered together, these results identify the rod-cone gap junction as a key site in mammals through which the retinal clock, using dopamine activation of D2 receptors, controls signal flow in the day and night fro

    The effect of two β-alanine dosing strategies on 30-minute rowing performance: a randomized, controlled trial

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    Background: β-alanine (βA) supplementation has been shown to increase intramuscular carnosine content and subsequent high-intensity performance in events lasting <4 minutes, which may be dependent on total, as opposed to daily, dose. The ergogenic effect of βA has also been demonstrated for 2000-m rowing performance prompting interest in whether βA may be beneficial for sustained aerobic exercise. This study therefore investigated the effect of two βA dosing strategies on 30-minute rowing and subsequent sprint performance. Methods: Following University Ethics approval, twenty-seven healthy, male rowers (age: 24±2 years; body-height: 1.81±0.02m; body-mass: 82.3±2.5kg; body-fat: 14.2±1.0%) were randomised in a double-blind manner to 4 weeks of: i) βA (2.4 g·d-1, βA1); ii) matched total βA (4.8g on alternate days, βA2); or iii) cornflour placebo (2.4 g·d-1, PL). Participants completed a laboratory 30-minute rowing time-trial, followed by 3x30s maximal sprint efforts at days 0, 14 and 28 (T1-T3). Total distance (m), average power (W), relative average power (W·kg-1), cardio-respiratory measures and perceived exertion were assessed for each 10-minute split. Blood lactate ([La-]b mmol·L-1) was monitored pre-post time-trial and following maximal sprint efforts. A 3-way repeated measures ANOVA was employed for main analyses, with Bonferonni post-hoc assessment (P≤0.05). Results: Total 30-minute time-trial distance significantly increased from T1-T3 within βA1 only (7397±195m to 7580±171m, P=0.002, ƞp2 = 0.196), including absolute average power (194.8±18.3W to 204.2±15.5W, P=0.04, ƞp2=0.115) and relative average power output (2.28±0.15W·kg-1 to 2.41±0.12W·kg-1, P=0.031, ƞp2= 0.122). These findings were potentially explained by within-group significance for the same variables for the first 10 minute split (P≤0.01), and for distance covered (P=0.01) in the second 10-minute split. However, no condition x time interactions were observed. No significant effects were found for sprint variables (P>0.05) with comparable values at T3 for mean distance (βA1: 163.9±3.8m; βA2: 161.2±3.5m; PL: 162.7±3.6m), average power (βA1: 352.7±14.5W; βA2: 342.2±13.5W; PL: 348.2±13.9W) and lactate (βA1: 10.0±0.9mmol·L-1; βA2: 9.2±1.1mmol·L-1; PL: 8.7±0.9mmol·L-1). Conclusions: Whilst daily βA may confer individual benefits, these results demonstrate limited impact of βA (irrespective of dosing strategy) on 30-minute rowing or subsequent sprint performance. Further investigation of βA dosage > 2.4 g·d-1 and/or chronic intervention periods (>4-8 weeks) may be warranted based on within-group observations

    Functional expression of the murine connexin 36 gene coding for a neuron-specific gap junctional protein

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    The mouse connexin 36 (Cx36) gene was mapped on chromosome 2 and an identical transcriptional start site was determined in brain and retina on exon I. Rabbit polyclonal antibodies to the presumptive cytoplasmic loop of the Cx36 protein recognized in immunohistochemical analyses Cx36 expression in the retina, olfactory bulb, hippocampus, inferior olive and cerebellum. In olivary neurons strong punctate labeling at dendritic cell contacts and weaker labeling in the cytoplasm of dendrites were shown by immuno electron microscopy. After expression of mouse Cx36 cDNA in human HeLa cells, neurobiotin transfer was increased 1.8-fold and electrical conductance at least 15-fold compared to untransfected HeLa cells. No Lucifer Yellow transfer was detected in either untransfected or Cx36 transfected HeLa cells. Single Cx36 channels in transfected HeLa cells showed a unitary conductance of 14.3 ± 0.8 pS. The sensitivity of Cx36 channels to transjunctional voltage was low in both HeLa-Cx36 cells and Xenopus oocytes expressing mouse Cx36. No increased transfer of neurobiotin was detected in heterotypic gap junctions formed by Cx36 and 9 other connexins expressed in HeLa cells. Our results suggest that Cx36 channels function as electrical synapses for transmission of electrical and metabolic signals between neurons in the central nervous system
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