Electrical Advantages of Dendritic Spines

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations.This work was supported by National Institutes of Health grant R01 MH83806 (ATG), the National Health and Medical Research Council of Australia (GJS), and NIH grants NS11613 and DC00086 (NTC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Recent Developments in NEURON

Abstract. We describe four recent additions to NEURON's suite of graphical tools that make it easier for users to create and manage models: an enhancement to the Channel Builder that facilitates the specification and efficient simulation of stochastic channel models; an enhancement to the Cell Builder that enables the convenient specification of spatially non-uniform properties in anatomically complex cells; the Model Viewer, which presents a browsable and quickly understood summary of the properties of models of individual cells and networks; and the Import3D tool, which simplifies conversion of detailed morphometric data into computational models of neurons

Evaluation of the Effectiveness of Treatments to Remove Per- and Polyfluoroalkyl Substances from Water—Are We Using the Right Approach? Proposal of a Paradigm Shift from “Chemical Only” towards an Integrated Bio-Chemical Assessment

Per- and polyfluoroalkyl substances (PFASs) have been under intense investigation by the scientific community due to their persistence in the environment and potentially hazardous effects on living organisms. In order to tackle the presence of these compounds in water, to date, the research has been strongly focused on the evaluation of the effectiveness of different types of technologies. Considering the extreme complexity of the matter of PFASs and our relatively low knowledge in this topic, the following question arises: is the “chemical only” approach that is followed for evaluating the effectiveness of technologies for PFAS removal from water reliable enough? In this work, some limitations of the present approach are discussed, highlighting the reasons why it cannot be considered a reliable tool to correctly estimate the effectiveness of technology when referring to emerging compounds such as PFASs. Bioassays can play a key role in moving towards an integrated bio-chemical evaluation (chemical analysis and ecotoxicological evaluation), which is strongly encouraged. This represents the only way to completely characterize a water matrix and fully evaluate the impact of technologies when dealing with micropollutants in water, such as PFASs. Future research should focus on defining an optimal battery of bioassays that specifically fit to best represent changes in water quality in terms of short- and long-term impacts on living organisms

Establishment of the Coast Range ophiolite microbial observatory (CROMO): Drilling objectives and preliminary outcomes

Abstract. This project aimed to establish a subsurface microbial observatory in ultramafic rocks, by drilling into an actively serpentinizing peridotite body, characterizing cored rocks, and outfitting the boreholes for a program of long-term observation and experimentation to resolve the serpentinite-hosted subsurface biosphere. We completed drilling in August 2011, drilling two boreholes with core recovery and possibility for down-hole experimentation, and six smaller-diameter monitoring wells arrayed around the two primary holes, in the Coast Range ophiolite (CRO) locality in the UC-Davis McLaughlin Natural Reserve, Lower Lake, CA. Every effort was made during drilling to keep the cores and wells as free of drilling-induced contamination as possible: clean, purified water was used as drilling fluid, fluorescent microbead tracers were suspended in that water for quantification of drilling fluid penetration into the cores, and high resolution next generation sequencing approaches were used to characterize the microbial populations in the drill fluids and core materials. In December 2011, we completed installation of well pumps (slow flow bladder pumps) in the monitoring wells, and have deployed a set of in situ incubation experiments in the two uncased boreholes. Preliminary findings illustrate natural variability in actively serpentinizing strata, and confirm distinct groundwater flow regimes and microbial ecosystems in (a) shallow, surface-impacted soil water horizons and (b) deeper, ultramafic bedrock-sourced formation fluids

Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study

The integrative properties of cortical pyramidal dendrites are essential to the neural basis of cognitive function, but the impact of amyloid beta protein (aβ) on these properties in early Alzheimer's is poorly understood. In animal models, electrophysiological studies of proximal dendrites have shown that aβ induces hyperexcitability by blocking A-type K+ currents (IA), disrupting signal integration. The present study uses a computational approach to analyze the hyperexcitability induced in distal dendrites beyond the experimental recording sites. The results show that back-propagating action potentials in the dendrites induce hyperexcitability and excessive calcium concentrations not only in the main apical trunk of pyramidal cell dendrites, but also in their oblique dendrites. Evidence is provided that these thin branches are particularly sensitive to local reductions in IA. The results suggest the hypothesis that the oblique branches may be most vulnerable to disruptions of IA by early exposure to aβ, and point the way to further experimental analysis of these actions as factors in the neural basis of the early decline of cognitive function in Alzheimer's

Simulation of networks of spiking neurons: A review of tools and strategies

We review different aspects of the simulation of spiking neural networks. We start by reviewing the different types of simulation strategies and algorithms that are currently implemented. We next review the precision of those simulation strategies, in particular in cases where plasticity depends on the exact timing of the spikes. We overview different simulators and simulation environments presently available (restricted to those freely available, open source and documented). For each simulation tool, its advantages and pitfalls are reviewed, with an aim to allow the reader to identify which simulator is appropriate for a given task. Finally, we provide a series of benchmark simulations of different types of networks of spiking neurons, including Hodgkin-Huxley type, integrate-and-fire models, interacting with current-based or conductance-based synapses, using clock-driven or event-driven integration strategies. The same set of models are implemented on the different simulators, and the codes are made available. The ultimate goal of this review is to provide a resource to facilitate identifying the appropriate integration strategy and simulation tool to use for a given modeling problem related to spiking neural networks.Comment: 49 pages, 24 figures, 1 table; review article, Journal of Computational Neuroscience, in press (2007