Somatostatin type-2 receptor activation inhibits glutamate release and prevents status epilepticus.

Newer therapies are needed for the treatment of status epilepticus (SE) refractory to benzodiazepines. Enhanced glutamatergic neurotransmission leads to SE, and AMPA receptors are modified during SE. Reducing glutamate release during SE is a potential approach to terminate SE. The neuropeptide somatostatin (SST) is proposed to diminish presynaptic glutamate release by activating SST type-2 receptors (SST2R). SST exerts an anticonvulsant action in some experimental models of seizures. Here, we investigated the mechanism of action of SST on excitatory synaptic transmission at the Schaffer collateral-CA1 synapses and the ability of SST to treat SE in rats using patch-clamp electrophysiology and video-EEG monitoring of seizures. SST reduced action potential-dependent EPSCs (sEPSCs) at Schaffer collateral-CA1 synapses at concentrations up to 1µM; higher concentrations had no effect or increased the sEPSC frequency. SST also prevented paired-pulse facilitation of evoked EPSCs and did not alter action-potential-independent miniature EPSCs (mEPSCs). The effect of SST on EPSCs was inhibited by the SST2R antagonist cyanamid-154806 and was mimicked by the SST2R agonists, octreotide and lanreotide. Both SST and octreotide reduced the firing rate of CA1 pyramidal neurons. Intraventricular administration of SST, within a range of doses, either prevented or attenuated pilocarpine-induced SE or delayed the median time to the first grade 5 seizure by 11min. Similarly, octreotide or lanreotide prevented or attenuated SE in more than 65% of animals. Compared to the pilocarpine model, octreotide was highly potent in preventing or attenuating continuous hippocampal stimulation-induced SE in all animals within 60min of SE onset. Our results demonstrate that SST, through the activation of SST2Rs, diminishes presynaptic glutamate release and attenuates SE.

Receptor trafficking hypothesis revisited: plasticity of AMPA receptors during established status epilepticus.

Status epilepticus (SE) is associated with a dynamic plasticity of postsynaptic neurotransmitter receptors. The plasticity of AMPA receptor (AMPAR)-mediated glutamatergic transmission during established SE (ESE), after development of benzodiazepine resistance, was evaluated. There was increased frequency and inward rectification of AMPAR-mediated excitatory postsynaptic currents at Schaffer collateral - CA1 pyramidal neuron synapses during ESE. Surface expression of the GluA1 subunit increased, and this was a consequence of N-methyl-d-aspartate receptor activation. Further, diminishing glutamate release by activation of somatostatin receptors prevented SE. These studies suggest that AMPAR-mediated glutamatergic transmission is strengthened during ESE.

OpenAlea: a visual programming and component-based software platform for plant modelling.

The development of functional-structural plant models requires an increasing amount of computer modelling. All these models are developed by different teams in various contexts and with different goals. Efficient and flexible computational frameworks are required to augment the interaction between these models, their reusability, and the possibility to compare them on identical datasets. In this paper, we present an open-source platform, OpenAlea, that provides a user-friendly environment for modellers, and advanced deployment methods. OpenAlea allows researchers to build models using a visual programming interface and provides a set of tools and models dedicated to plant modelling. Models and algorithms are embedded in OpenAlea 'components' with well defined input and output interfaces that can be easily interconnected to form more complex models and define more macroscopic components. The system architecture is based on the use of a general purpose, high-level, object-oriented script language, Python, widely used in other scientific areas. We present a brief rationale that underlies the architectural design of this system and we illustrate the use of the platform to assemble several heterogeneous model components and to rapidly prototype a complex modelling scenario.