Synaptic removal of diacylglycerol by DGKζ and PSD‐95 regulates dendritic spine maintenance

Diacylglycerol (DAG) is an important lipid signalling molecule that exerts an effect on various effector proteins including protein kinase C. A main mechanism for DAG removal is to convert it to phosphatidic acid (PA) by DAG kinases (DGKs). However, it is not well understood how DGKs are targeted to specific subcellular sites and tightly regulates DAG levels. The neuronal synapse is a prominent site of DAG production. Here, we show that DGKζ is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD‐95. Overexpression of DGKζ in cultured neurons increases the number of dendritic spines, which receive the majority of excitatory synaptic inputs, in a manner requiring its catalytic activity and PSD‐95 binding. Conversely, DGKζ knockdown reduces spine density. Mice deficient in DGKζ expression show reduced spine density and excitatory synaptic transmission. Time‐lapse imaging indicates that DGKζ is required for spine maintenance but not formation. We propose that PSD‐95 targets DGKζ to synaptic DAG‐producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.     

A Compartmental Model for Activity-Dependent Dendritic Spine Branching

Dendritic spines are small, mushroom-like protrusions from the arbor of a neuron in the central nervous system. Interdependent changes in the morphology, biochemistry, and activity of spines have been associated with learning and memory. Moreover, post-mortem cortices from patients with Alzheimer’s or Parkinson’s disease exhibit biochemical and physical alterations within their dendritic arbors and a reduction in the number of dendritic spines. For over a decade, experimentalists have observed perforations in postsynaptic densities on dendritic spines after induction of long-term potentiation, a sustained enhancement of response to a brief electrical or chemical stimulus, associated with learning and memory. In more recent work, some suggest that activity-dependent intraspine calcium may regulate the surface area of the spine head, and reorganization of postsynaptic densities on the surface. In this paper, we develop a model of a dendritic spine with the ability to partition its transmission and receptor zones, as well as the entire spine head. Simulations are initially performed with fixed parameters for morphology to study electrical properties and identify parameters that increase efficacy of the synaptic connection. Equations are then introduced to incorporate calcium as a second messenger in regulating continuous changes in morphology. In the model, activity affects compartmental calcium, which regulates spine head morphology. Conversely, spine head morphology affects the level of local activity, whether the spines are modeled with passive membrane properties, or excitable membrane using Hodgkin–Huxley kinetics. Results indicate that merely separating the postsynaptic receptors on the surface of the spine may add to the diversity of circuitry, but does not change the efficacy of the synapse. However, when the surface area of the spine is a dynamic variable, efficacy of the synapse may vary continuously over time.     

Reliability of a new virtual reality test to measure cervicocephalic kinaesthesia

The aim of this study was to investigate the cervicocephalic kinaesthesia of healthy subjects for gender and age effects and its reliability in a new virtual reality test procedure. 57 healthy subjects (30 male, 27 females; 18-64 years) were immersed into a virtual 3D scene via a headmounted display, which generated specific head movements. The joint repositioning error was determined in a static and dynamic test at the times T0, T1 (T0 + 10 minutes) and T2 (T0 + 24 hours). The intrasession reliability (T0-T1) and the intersession reliability (T0-T2) were analysed. In both tests no gender- or age-specific effects were found. In the overall group the means of the static test were 6.2°-6.9° and of the dynamic test were 4.5°-4.9°. The intratest difference in the static test was -0.16° and the intertest difference was 0.47°. The intratest difference in the dynamic test was 0.42° and the intertest difference was 0.37°. The static and dynamic test was reproducible in healthy subjects, with minor deviations, irrespective of gender and age. The smaller interindividual differences in the dynamic test could be beneficial in the comparison of healthy individuals and individuals with cervical spine disorders.     

青海湖裸鲤生长特征的研究

对2002年5月—2003年7月采自青海湖的1174尾青海湖裸鲤样本年龄进行了耳石鉴定,并依据年龄推算了生长率。青海湖裸鲤体长与体重的关系为:W=0.000174×L2.4990(♀)、W=0.0000402×L2.7538(♂),雌、雄个体生长差异显著。其体长Von Bertalanffy生长方程为:Lt=551.9301(1-e-0.0711(t 0.3044))(♀),Lt=682.8688(1-e-0.0530(t 0.4240))(♂);体重Von Bertalanffy生长方程为:Wt=1237.3431(1-e-0.0711(t 0.3044))2.4990(♀),Wt=2567.3242×(1-e-0.0530(t 0.4240))2.7538(♂)。其雌、雄生长拐点分别为12.57龄和18.67龄。     

Climate change alters the reproductive phenology and investment of a lacustrine fish,the three‐spine stickleback

High‐latitude lakes are particularly sensitive to the effects of global climate change, demonstrating earlier ice breakup, longer ice‐free seasons, and increased water temperatures. Such physical changes have implications for diverse life‐history traits in taxa across entire lake food webs. Here, we use a five‐decade time series from an Alaskan lake to explore effects of climate change on growth and reproduction of a widely distributed lacustrine fish, the three‐spine stickleback (Gasterosteus aculeatus). We used multivariate autoregressive state‐space (MARSS) models to describe trends in the mean length for multiple size classes and to explore the influence of physical (date of ice breakup, surface water temperature) and biological (density of con‐ and heterospecifics) factors. As predicted, mean size of age 1 and older fish at the end of the growing season increased across years with earlier ice breakup and warmer temperatures. In contrast, mean size of age 0 fish decreased over time. Overall, lower fish density and warmer water temperatures were associated with larger size for all cohorts. Earlier ice breakup was associated with larger size for age 1 and older fish but, paradoxically, with smaller size of age 0 fish. To explore this latter result, we used mixing models on age 0 size distributions, which revealed an additional cohort in years with early ice breakup, lowering the mean size of age 0 fish. Moreover, early ice breakup was associated with earlier breeding, evidenced by earlier capture of age 0 fish. Our results suggest that early ice breakup altered both timing and frequency of breeding; three‐spine stickleback spawned earlier and more often in response to earlier ice breakup date. While previous studies have shown the influence of changing conditions in northern lakes on breeding timing and growth, this is the first to document increased breeding frequency, highlighting another pathway by which climate change can alter the ecology of northern lakes.     

Effect of lumbar fasciae on the stability of the lower lumbar spine

The biomechanical effect of tensioning the lumbar fasciae (LF) on the stability of the spine during sagittal plane motion was analysed using a validated finite element model of the normal lumbosacral spine (L4-S1). To apply the tension in the LF along the direction of the fibres, a local coordinate was allocated using dummy rigid beam elements that originated from the spinous process. Up to 10 Nm of flexion and 7.5 Nm of extension moment was applied with and without 20 N of lateral tension in the LF. A follower load of 400 N was additionally applied along the curvature of the spine. To identify how the magnitude of LF tension related to the stability of the spine, the tensioning on the fasciae was increased up to 40 N with an interval of 10 N under 7.5 Nm of flexion/extension moment. A fascial tension of 20 N produced a 59% decrease in angular motion at 2.5 Nm of flexion moment while there was a 12.3% decrease at 10 Nm in the L5-S1 segment. Its decrement was 53 and 9.6% at 2.5 Nm and 10 Nm, respectively, in the L4-L5 segment. Anterior translation was reduced by 12.1 and 39.0% at the L4-L5 and L5-S1 segments under 10 Nm of flexion moment, respectively. The flexion stiffness shows an almost linear increment with the increase in fascial tension. The results of this study showed that the effect of the LF on the stability of the spine is significant.     

A review of methods to assess coactivation in the spine

Coactivation is an important component for understanding the physiological cost of muscular and spinal loads and their associations with spinal pathology and potentially myofascial pain. However, due to the complex and dynamic nature of most activities of daily living, it can be difficult to capture a quantifiable measure of coactivation. Many methods exist to assess coactivation, but most are limited to two-muscle systems, isometric/complex analyses, or dynamic/uniplanar analyses. Hence, a void exists in that coactivation has not been documented or assessed as a multiple-muscle system under realistic complex dynamic loading. Overall, no coactivation index has been capable of assessing coactivation during complex dynamic exertions. The aim of this review is to provide an understanding of the factors that may influence coactivation, document the metrics used to assess coactivity, assess the feasibility of those metrics, and define the necessary variables for a coactivation index that can be used for a variety of tasks. It may also be clinically and practically relevant in the understanding of rehabilitation effectiveness, efficiency during task performance, human-task interactions, and possibly the etiology for a multitude of musculoskeletal conditions.     

ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in?vitro

The ε4 allele of the gene that encodes apolipoprotein E (APOE4) is the greatest genetic risk factor for Alzheimer''s disease (AD), while APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD pathology remains unclear. In vivo, dendritic spine density is lower in APOE4-targeted replacement (APOE-TR) mice compared with APOE2- and APOE3-TR mice. To investigate whether this apoE4-induced decrease in spine density results from alterations in the formation or the loss of dendritic spines, the effects of neuron age and apoE isoform on the total number and subclasses of spines were examined in long-term wild-type neurons co-cultured with glia from APOE2-, APOE3- and APOE4-TR mice. Dendritic spine density and maturation were evaluated by immunocytochemistry via the presence of drebrin (an actin-binding protein) with GluN1 (NMDA receptor subunit) and GluA2 (AMPA receptor subunit) clusters. ApoE isoform effects were analyzed via a method previously established that identifies phases of spine formation (day-in-vitro, DIV10–18), maintenance (DIV18–21) and loss (DIV21–26). In the formation phase, apoE4 delayed total spine formation. During the maintenance phase, the density of GluN1+GluA2 spines did not change with apoE2, while the density of these spines decreased with apoE4 compared to apoE3, primarily due to the loss of GluA2 in spines. During the loss phase, total spine density was lower in neurons with apoE4 compared to apoE3. Thus, apoE4 delays total spine formation and may induce early synaptic dysfunction via impaired regulation of GluA2 in spines.