Rapid activation, desensitization, and resensitization of synaptic channels of crayfish muscle after glutamate pulses

Completely desensitizing excitatory channels were activated in outside-out patches of crayfish muscle membrane by applying glutamate pulses with switching times of approximately 0.2 ms for concentration changes. Channels were almost completely activated with 10 mM glutamate. Maximum activation was reached within 0.4 ms with greater than or equal to 1 mM glutamate. Channel open probability decayed with a time constant of desensitization of 2 ms with 10 mM glutamate and more rapidly at lower glutamate concentrations. The rate of beginnings of bursts (average number of beginnings of bursts per time bin) decayed even faster but approximately in proportion to the glutamate concentration. The dose-response curve for the channel open probability and for the rate of bursts had a maximum double-logarithmic slope of 5.1 and 4.2, respectively. Channels desensitized completely without opening at very low or slowly rising glutamate concentrations. Desensitization thus originates from a closed channel state. Resensitization was tested by pairs of completely desensitizing glutamate pulses. Sensitivity to the second pulse returned rapidly at pulse intervals between 1 and 2 ms and was almost complete with an interval of 3 ms. Schemes of channel activation by up to five glutamate binding steps, with desensitization by glutamate binding from closed states, are discussed. At high agonist concentrations bursts are predominantly terminated by desensitization. Quantal currents are generated by pulses of greater than 1 mM glutamate, and their decay is determined by the duration of presence of glutamate and possibly by desensitization

Explicit Logic Circuits Predict Local Properties of the Neocortex's Physiology and Anatomy

Background: Two previous articles proposed an explicit model of how the brain processes information by its organization of synaptic connections. The family of logic circuits was shown to generate neural correlates of complex psychophysical phenomena in different sensory systems. Methodology/Principal Findings: Here it is shown that the most cost-effective architectures for these networks produce correlates of electrophysiological brain phenomena and predict major aspects of the anatomical structure and physiological organization of the neocortex. The logic circuits are markedly efficient in several respects and provide the foundation for all of the brain’s combinational processing of information. Conclusions/Significance: At the local level, these networks account for much of the physical structure of the neocortex as well its organization of synaptic connections. Electronic implementations of the logic circuits may be more efficient than current electronic logic arrays in generating both Boolean and fuzzy logic

A Nonparametric Partially Identified Estimator for Equivalence Scales

Methods for estimating equivalence scales usually rely on rather strong identifying assumptions. This paper considers a partially identified estimator for equivalence scales derived from the potential outcomes framework and using nonparametric methods for estimation, which requires only mild assumptions. Instead of point estimates, the method yields only lower and upper bounds of equivalence scales. Results of an analysis using German expenditure data show that the range implied by these bounds is rather wide, but can be reduced using additional covariates.Methoden zur Ermittlung von Äquivalenzskalen gehen in aller Regel von relativ starken Annahmen aus. In der vorliegenden Arbeit wird ein partiell identifizierter Schätzer für Äquivalenzskalen vorgestellt, der auf dem Potential Outcomes Ansatz basiert und nur vergleichsweise schwache Annahmen benötigt. Anstelle eines Punktschätzers liefert das Verfahren nur Unter- und Obergrenzen für Äquivalenzskalen. Eine Anwendung auf Daten der Einkommens- und Verbrauchsstichprobe zeigt, dass die durch Unter- und Obergrenze gegebenen Intervalle oftmals sehr breit sind. Die Breite der Intervalle kann reduziert werden, wenn zusätzliche Variablen bei der Schätzung herangezogen werden

A framework for a European network for a systematic environmental impact assessment of genetically modified organisms (GMO)

The assessment of the impacts of growing genetically modified (GM) crops remains a major political and scientific challenge in Europe. Concerns have been raised by the evidence of adverse and unexpected environmental effects and differing opinions on the outcomes of environmental risk assessments (ERA). The current regulatory system is hampered by insufficiently developed methods for GM crop safety testing and introduction studies. Improvement to the regulatory system needs to address the lack of well designed GM crop monitoring frameworks, professional and financial conflicts of interest within the ERA research and testing community, weaknesses in consideration of stakeholder interests and specific regional conditions, and the lack of comprehensive assessments that address the environmental and socio economic risk assessment interface. To address these challenges, we propose a European Network for systematic GMO impact assessment (ENSyGMO) with the aim directly to enhance ERA and post-market environmental monitoring (PMEM) of GM crops, to harmonize and ultimately secure the long-term socio-political impact of the ERA process and the PMEM in the EU. These goals would be achieved with a multi-dimensional and multi-sector approach to GM crop impact assessment, targeting the variability and complexity of the EU agro-environment and the relationship with relevant socio-economic factors. Specifically, we propose to develop and apply methodologies for both indicator and field site selection for GM crop ERA and PMEM, embedded in an EU-wide typology of agro-environments. These methodologies should be applied in a pan-European field testing network using GM crops. The design of the field experiments and the sampling methodology at these field sites should follow specific hypotheses on GM crop effects and use state-of-the art sampling, statistics and modelling approaches. To address public concerns and create confidence in the ENSyGMO results, actors with relevant specialist knowledge from various sectors should be involved

The regional and global significance of nitrogen removal in lakes and reservoirs

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 93 (2009): 143-157, doi:10.1007/s10533-008-9272-x.Human activities have greatly increased the transport of biologically available N through watersheds to potentially sensitive coastal ecosystems. Lentic water bodies (lakes and reservoirs) have the potential to act as important sinks for this reactive N as it is transported across the landscape because they offer ideal conditions for N burial in sediments or permanent loss via denitrification. However, the patterns and controls on lentic N removal have not been explored in great detail at large regional to global scales. In this paper we describe, evaluate, and apply a new, spatially explicit, annual-scale, global model of lentic N removal called NiRReLa (Nitrogen Retention in Reservoirs and Lakes). The NiRReLa model incorporates small lakes and reservoirs than have been included in previous global analyses, and also allows for separate treatment and analysis of reservoirs and natural lakes. Model runs for the mid-1990s indicate that lentic systems are indeed important sinks for N and are conservatively estimated to remove 19.7 Tg N yr-1 from watersheds globally. Small lakes (< 50 km2) were critical in the analysis, retaining almost half (9.3 Tg N yr-1) of the global total. In model runs, capacity of lakes and reservoirs to remove watershed N varied substantially (0-100%) both as a function of climate and the density of lentic systems. Although reservoirs occupy just 6% of the global lentic surface area, we estimate they retain approximately 33% of the total N removed by lentic systems, due to a combination of higher drainage ratios (catchment surface area : lake or reservoir surface area), higher apparent settling velocities for N, and greater N loading rates in reservoirs than in lakes. Finally, a sensitivity analysis of NiRReLa suggests that, on-average, N removal within lentic systems will respond more strongly to changes in land use and N loading than to changes in climate at the global scale.The NSF26 Research Coordination Network on denitrification for support for collaboration (award number DEB0443439 to S.P. Seitzinger and E.A. Davidson). This project was also supported by grants to J.A. Harrison from California Sea Grant (award number RSF8) and from the U.S. Geological Survey 104b program and R. Maranger (FQRNT Strategic Professor)

Beitrag zum Problem der heterosynaptischen Facilitation in Aplysia californica

1. Heterosynaptic facilitation (H.S.F.) of single neurons in the central nervous system of Aplysia can be repeated virtually indefinitely, provided sufficient time is allowed for recovery between the trials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47439/1/424_2004_Article_BF00362956.pd

Effects of maintained depolarization of presynaptic neurons on inhibitory transmission in lobster neuropil

1. Intracellular microeleotrode recordings were obtained from somata of the pre- and postsynaptic neurons of each of four neuron pairs in the stomatogastric ganglion of Panulirus argus . The microelectrodes were incorporated into a bridge circuit, permitting simultaneous recording and current passing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47114/1/359_2004_Article_BF00617544.pd

The time course of transmitter release in mouse motor nerve terminals is differentially affected by activation of muscarinic M1 or M2 receptors.

At endplates of mouse diaphragms the effects of activation of presynaptic muscarinic M1 and M2 autoreceptors on the time courses of monoquantal releases have been investigated at 20 degrees C. Quantal excitatory postsynaptic currents (qEPSCs) were elicited and recorded with a perfused macropatch electrode, through which control- and drug-containing solutions were applied to 10 microm phi regions of a neuromuscular junction. M2 receptors were activated with muscarine, while the M1 receptors were blocked by pirenzepine. M2 activation presented a slight, but highly significant augmentation of early releases. Analogously, M1 receptors were activated with muscarine, while M2 receptors were blocked by methoctramine. M1 activation elicited a highly significant small shift of the time course of release towards longer delays. In controls, the number of late releases decayed with a time constant of 0.3 ms. This time constant did not change appreciably when methoctramine or methoctramine + muscarine were applied. However, methoctramine + muscarine reduced the amplitude of qEPSCs and shortened their decay by a partial block of postsynaptic channels. Double blocks with pirenzepine + methoctramine allowed no presynaptic effect of muscarine, showing that the blocker concentrations were sufficient. Neither the addition of methoctramine to pirenzepine, nor the further addition of muscarine changed the time constant of decay of the number of late releases. The results are very similar to that of autoreceptor activations in the glutamatergic crayfish synapse: activation of inhibitory receptors augmented early releases, and that of facilitatory receptors depressed early releases [J. Dudel (2006a) Eur. J. Neurosci., 23, 2695-2700], which may suggest a general presynaptic mechanism

Both d- and l-glutamate induce transporter-mediated presynaptic autoinhibition of transmitter release.

In crayfish motor nerve terminals l-glutamate (Glu) is the excitatory transmitter and low l-Glu concentrations exert autoinhibition by inhibiting release of Glu quanta from the terminals. This autoinhibition has been shown to be mediated by binding and transport of l-Glu by Glu transporters in the presynaptic membrane. Activated transporters open an associated Cl(-) channel and inhibit release [J. Dudel & M. Schramm (2003) Eur. J. Neurosci., 18, 902-910]. The excitatory, glutamatergic synaptic transmission is specific for the l-Glu isomer. However, transporters are non-selective for the stereoisomers. It is shown here that low concentrations (5 micro m) of d- as well as l-Glu inhibit quantal release on average to 55 and 68%, respectively. The power of inhibition varies widely at different terminals but the local sensitivity to d-Glu is seen to be the same as that for l-Glu. l-Glutamate has been reported to reduce the mean amplitude of nerve terminal action currents (excitatory nerve terminal currents) by about 10%, presumably due to the opening of Cl(-) channels. Evidence is given that d-Glu also inhibits this by an average of 10% (P < 0.001), as expected if both l- and d-Glu activate a transporter-associated Cl(-) conductance. The results give further support for this novel mechanism of regulation of synaptic strength

Glutamatergic chloride currents associated to glutamate transport?

Especially in arthropod glutamatergic synaptic systems, microM l-glutamate (Glu) concentrations often elicit Cl- currents, in addition to the excitatory cationic currents that are triggered by much higher Glu concentrations. In crayfish, Ibotenate (Ibo) is a specific agonist of the Glu-ergic Cl- currents. Application of Glu to Glu-transporters opens associated Cl- currents that inhibit quantal release presynaptically and by occupying the transporter prevents removal of released Glu. The latter prolongs the decay of postsynaptic EPSCs. It was tested whether the Ibo-elicited Cl- currents show the same pre- and post-synaptic effects as the transporter elicited ones, suggesting that also this current component arises through transporter activation. Indeed, Ibo applied to single synaptic junctions produced inhibition of quantal release and prolongation of EPSCs, very similar to the effects of Glu. It seems probable, therefore, that at least in crayfish Glu-ergic Cl- currents are generated by activation of transporters. Since generally such transporters are located around Glu-ergic synapses, this is likely to be a general mechanism. The toxin Ivermectin also elicits Cl- currents. However, while Ivermectin inhibits release too, it does not prolong the decay of EPSCs and is probable to activate GABAergic channels