Activity-dependent regulation of vesicular glutamate and GABA transporters: a means to scale quantal size

The functional balance of glutamatergic and GABAergic signaling in neuronal cortical circuits is under homeostatic control. That is, prolonged alterations of global network activity leads to opposite changes in quantal amplitude at glutamatergic and GABAergic synapses. Such scaling of excitatory and inhibitory transmission within cortical circuits serves to restore and maintain a constant spontaneous firing rate of pyramidal neurons. Our recent work shows that this includes alterations in the levels of expression of vesicular glutamate (VGLUT1 and VGLUT2) and GABA (VIAAT) transporters. Other vesicle markers, such as synaptophysin or synapsin, are not regulated in this way. Endogenous regulation at the level of mRNA and synaptic protein controls the number of transporters per vesicle and hence, the level of vesicle filling with transmitter. Bidirectional and opposite activity-dependent regulation of VGLUT1 and VIAAT expression would serve to adjust the balance of glutamate and GABA release and therefore the level of postsynaptic receptor saturation. In some excitatory neurons and synapses, co-expression of VGLUT1 and VGLUT2 occurs. Bidirectional and opposite changes in the levels of two excitatory vesicular transporters would enable individual neocortical neurons to scale up or scale down the level of vesicular glutamate storage, and thus, the amount available for release at individual synapses. Regulated vesicular transmitter storage and release via selective changes in the level of expression of vesicular glutamate and GABA transporters indicates that homeostatic plasticity of synaptic strength at cortical synapses includes presynaptic elements.     

Gene regulation by homeobox transcription factor Prox1 in murine hepatoblasts

Protein kinase C (PKC) is a signalling enzyme critically involved in many aspects of synaptic plasticity. In cyprinid retinae, the PKC alpha isoform is localized in a subpopulation of depolarizing bipolar cells that show adaptation-related morphological changes of their axon terminals. We have studied the subcellular localization of phosphorylated PKC alpha (pPKC alpha) in retinae under various conditions by immunohistochemistry with a phosphospecific antibody. In dark-adapted retinae, pPKC alpha immunoreactivity is weak in the cytoplasm of synaptic terminals, labelling being predominantly associated with the membrane compartment. In light-adapted cells, immunoreactivity is diffusely distributed throughout the terminal. Western blot analysis has revealed a reduction of pPKC alpha immunoreactivity in cytosolic fractions of homogenized dark-adapted retinae compared with light-adapted retinae. Pharmacological experiments with the isoform-specific PKC blocker Goe6976 have shown that inhibition of the enzyme influences immunolabelling for pPKC alpha, mimicking the effects of light on the subcellular distribution of immunoreactivity. Our findings suggest that the state of adaptation modifies the subcellular localization of a signalling molecule (PKC alpha) at the ribbon-type synaptic complex. We propose that changes in the subcellular distribution of PKC alpha immunoreactivity might be one component regulating the strength of the signal transfer of the bipolar cell terminal. Uwe D. Behrens and Johannes Borde contributed equally to this work. This research was supported by an SFB-430 grant.     

Land use impacts on freshwater regulation, erosion regulation, and water purification: a spatial approach for a global scale level

Purpose

Rarely considered in environmental assessment methods, potential land use impacts on a series of ecosystem services must be accounted for in widely used decision-making tools such as life cycle assessment (LCA). The main goal of this study is to provide an operational life cycle impact assessment characterization method that addresses land use impacts at a global scale by developing spatially differentiated characterization factors (CFs) and assessing the extent of their spatial variability using different regionalization levels.

Methods

The proposed method follows the recommendations of previous work and falls within the framework and principles for land use impact assessment established by the United Nations Environment Programme/Society of Environmental Toxicology and Chemistry Life Cycle Initiative. Based on the spatial approach suggested by Saad et al. (Int J Life Cycle Assess 16: 198–211, 2011), the intended impact pathways that are modeled pertain to impacts on ecosystem services damage potential and focus on three major ecosystem services: (1) erosion regulation potential, (2) freshwater regulation potential, and (3) water purification potential. Spatially-differentiated CFs were calculated for each biogeographic region of all three regionalization scale (Holdridge life regions, Holdridge life zones, and terrestrial biomes) along with a nonspatial world average level. In addition, seven land use types were assessed considering both land occupation and land transformation interventions.

Results and discussion

A comprehensive analysis of the results indicates that, when compared to all resolution schemes, the world generic averaged CF can deviate for various ecosystem types. In the case of groundwater recharge potential impacts, this range varied up to factors of 7, 4.7, and 3 when using the Holdridge life zones, the Holdridge regions, and the terrestrial biomes regionalization levels, respectively. This validates the importance of introducing a regionalized assessment and highlights how a finer scale increases the level of detail and consequently the discriminating power across several biogeographic regions, which could not have been captured using a coarser scale. In practice, the implementation of such regionalized CFs suggests that an LCA practitioner must identify the ecosystem in which land occupation or transformation activities occur in addition to the traditional inventory data required—namely, the land use activity and the inventory flow.

Conclusions

The variability of CFs across all three regionalization levels provides an indication of the uncertainty linked to nonspatial CFs. Among other assumptions and value choices made throughout the study, the use of ecological borders over political boundaries was deemed more relevant to the interpretation of environmental issues related to specific functional ecosystem behaviors.