Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo

Most excitatory synapses terminate on dendritic spines. Spines vary in size, and their volumes are proportional to the area of the postsynaptic density (PSD) and synaptic strength. PSD-95 is an abundant multi-domain postsynaptic scaffolding protein that clusters glutamate receptors and organizes the associated signaling complexes. PSD-95 is thought to determine the size and strength of synapses. Although spines and their synapses can persist for months in vivo, PSD-95 and other PSD proteins have shorter half-lives in vitro, on the order of hours. To probe the mechanisms underlying synapse stability, we measured the dynamics of synaptic PSD-95 clusters in vivo. Using two-photon microscopy, we imaged PSD-95 tagged with GFP in layer 2/3 dendrites in the developing (postnatal day 10–21) barrel cortex. A subset of PSD-95 clusters was stable for days. Using two-photon photoactivation of PSD-95 tagged with photoactivatable GFP (paGFP), we measured the time over which PSD-95 molecules were retained in individual spines. Synaptic PSD-95 turned over rapidly (median retention times τ (r) ~ 22–63 min from P10–P21) and exchanged with PSD-95 in neighboring spines by diffusion. PSDs therefore share a dynamic pool of PSD-95. Large PSDs in large spines captured more diffusing PSD-95 and also retained PSD-95 longer than small PSDs. Changes in the sizes of individual PSDs over days were associated with concomitant changes in PSD-95 retention times. Furthermore, retention times increased with developmental age (τ (r) ~ 100 min at postnatal day 70) and decreased dramatically following sensory deprivation. Our data suggest that individual PSDs compete for PSD-95 and that the kinetic interactions between PSD molecules and PSDs are tuned to regulate PSD size

Treating Survivors of Torture and Refugee Trauma: A Preliminary Case Series Using Qigong and T'ai Chi

Objectives: This paper seeks to explore the potential value of qigong and t'ai chi practice as a therapeutic intervention to aid in the treatment of survivors of torture and refugee trauma. Design: The common effects of torture and refugee trauma are surveyed with a focus on post-traumatic stress disorder. An alternative theoretical framework for conceptualizing and healing trauma is presented. Evidence is reviewed from the scientific literature that describes how qigong and t'ai chi have been used in studies of the general population to alleviate symptoms that are also expressed in torture survivors. Observations are presented from a combined, simplified qigong and t'ai chi intervention with a convenience sample of four refugee survivors of torture. Results: Preliminary observations from four cases and a review of the literature support the potential efficacy of incorporating qigong and t'ai chi into the treatment of survivors of torture and refugee trauma. Conclusions: The incorporation of qigong and t'ai chi into the treatment of torture survivors, within a new framework for healing trauma, merits further investigation

Factors influencing the bioaccumulation of persistent organic pollutants in food webs of the Scheldt estuary

Concentrations of several persistent organic pollutants (POPs: PCBs, PBDEs, OCPs) in aquatic species from the Scheldt estuary were related with factors (body size, lipids, trophic position), possibly influencing their bioaccumulation. Stable nitrogen isotope ratios (δ15N) were used as a measure for trophic position. A decreasing trend in POP levels towards the sea was observed. For POP concentrations in sediments, this trend could be attributed to a dilution effect from mixing with seawater. However, concentrations in biota more downstream were higher than expected after taking into account the dilution effect, possibly due to differences in bioavailability. Tissue concentrations were correlated with the lipid content in biota, but not with body size. Biomagnification was only significant for some PCB congeners and p,p'-DDE at the most marine sampling location (Terneuzen, L1) and for p,p'-DDD and BDE 100 at the second sampling location (Bath, L2). A significant decreasing relationship was found for ɣ-HCH concentrations with increasing δ15N at Terneuzen. For Antwerpen (L3), no significant relationships were detected. TMFs ranged from 0.64 for ɣ-HCH up to 1.60 for PCB 194. These results suggest that biomagnification was more important in the marine part of the estuary, although the presence of multiple carbon sources at the freshwater side might have led to an underestimation of the influence of trophic position

Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model

R6/The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington's disease cognitive impairments