STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER–plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites

Adoption of intercropping among smallholder rubber farmers in Xishuangbanna, China

While the expansion of rubber plantations in the mountainous areas of Southern China has contributed to poverty reduction among the indigenous ethnic groups, the concerns about the associated negatives on ecosystems and sustainable development of livelihoods is rising. One of the measures suggested to reduce environmental and economic risks is rubber intercropping. This study uses cross-section data of some 600 rubber farmers in Xishuangbanna, as a basis to develop four empirical models in order to analyse adoption of intercropping at farm and at plot level. Our study shows that only a small proportion of rubber farmers have adopted intercropping, with tea being the most frequently adopted intercrop. However, we also find that intercropping is an important source of income for the household in the lower income category. Intercropping adoption is affected by ethnicity, household wealth and family labour. The choice of intercrops depends on the nature of rubber plots, the age of rubber trees and geography. This study contributes to a better understanding of the transformation path from rubber monoculture to more diversified, rubber-based agroforestry systems and thus can provide important information for agricultural extension services charged with the promotion of sustainable rubber-based livelihood systems in the Mekong area.German Federal Ministry of Education and Research; FKZ [01LL0919A]; National Natural Science Foundation of China [71333013]SCI(E)SSCIARTICLE3223-2371

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review

Item does not contain fulltextPedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. (c) 2017 International Parkinson and Movement Disorder Society

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology

Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Background: Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson’s Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity./nResults: We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson’s Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson’s Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms./nConclusions: The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.MLK and TJVH are funded by the TrygFonden Charitable Foundation. TZA is funded by the Medical Research Council, the Norman Collisson Foundation/nand the Charles Wolfson Charitable Trust. ALG is supported by the NIHR Biomedical Research Centre, Oxford. GD and JC were supported by the ERC Advanced/nGrant: DYSTRUCTURE (n. 295129), by the Spanish Research Project SAF2010-16085 and by the CONSOLIDER-INGENIO 2010 Programme CSD2007-00012, the FP7-/nICT BrainScales and by the Brain Network Recovery Group through the James S. McDonnell Foundation