Impact of synaptic localization and subunit composition of ionotropic glutamate receptors on synaptic function: modeling and simulation studies.

Ionotropic NMDA and AMPA glutamate receptors (iGluRs) play important roles in synaptic function under physiological and pathological conditions. iGluRs sub-synaptic localization and subunit composition are dynamically regulated by activity-dependent insertion and internalization. However, understanding the impact on synaptic transmission of changes in composition and localization of iGluRs is difficult to address experimentally. To address this question, we developed a detailed computational model of glutamatergic synapses, including spine and dendritic compartments, elementary models of subtypes of NMDA and AMPA receptors, glial glutamate transporters, intracellular calcium and a calcium-dependent signaling cascade underlying the development of long-term potentiation (LTP). These synapses were distributed on a neuron model and numerical simulations were performed to assess the impact of changes in composition and localization (synaptic vs extrasynaptic) of iGluRs on synaptic transmission and plasticity following various patterns of presynaptic stimulation. In addition, the effects of various pharmacological compounds targeting NMDARs or AMPARs were determined. Our results showed that changes in NMDAR localization have a greater impact on synaptic plasticity than changes in AMPARs. Moreover, the results suggest that modulators of AMPA and NMDA receptors have differential effects on restoring synaptic plasticity under different experimental situations mimicking various human diseases.

Impact of synaptic localization and subunit composition of ionotropic glutamate receptors on synaptic function: modeling and simulation studies.

Ionotropic NMDA and AMPA glutamate receptors (iGluRs) play important roles in synaptic function under physiological and pathological conditions. iGluRs sub-synaptic localization and subunit composition are dynamically regulated by activity-dependent insertion and internalization. However, understanding the impact on synaptic transmission of changes in composition and localization of iGluRs is difficult to address experimentally. To address this question, we developed a detailed computational model of glutamatergic synapses, including spine and dendritic compartments, elementary models of subtypes of NMDA and AMPA receptors, glial glutamate transporters, intracellular calcium and a calcium-dependent signaling cascade underlying the development of long-term potentiation (LTP). These synapses were distributed on a neuron model and numerical simulations were performed to assess the impact of changes in composition and localization (synaptic vs extrasynaptic) of iGluRs on synaptic transmission and plasticity following various patterns of presynaptic stimulation. In addition, the effects of various pharmacological compounds targeting NMDARs or AMPARs were determined. Our results showed that changes in NMDAR localization have a greater impact on synaptic plasticity than changes in AMPARs. Moreover, the results suggest that modulators of AMPA and NMDA receptors have differential effects on restoring synaptic plasticity under different experimental situations mimicking various human diseases.

Modeling neuron-glia interactions: from parametric model to neuromorphic hardware.

Recent experimental evidence suggests that glial cells are more than just supporting cells to neurons - they play an active role in signal transmission in the brain. We herein propose to investigate the importance of these mechanisms and model neuron-glia interactions at synapses using three approaches: A parametric model that takes into account the underlying mechanisms of the physiological system, a non-parametric model that extracts its input-output properties, and an ultra-low power, fast processing, neuromorphic hardware model. We use the EONS (Elementary Objects of the Nervous System) platform, a highly elaborate synaptic modeling platform to investigate the influence of astrocytic glutamate transporters on postsynaptic responses in the detailed micro-environment of a tri-partite synapse. The simulation results obtained using EONS are then used to build a non-parametric model that captures the essential features of glutamate dynamics. The structure of the non-parametric model we use is specifically designed for efficient hardware implementation using ultra-low power subthreshold CMOS building blocks. The utilization of the approach described allows us to build large-scale models of neuron/glial interaction and consequently provide useful insights on glial modulation during normal and pathological neural function.

Characteristics and use as spin trapping agent of a beta-phosphorylated nitroso compound, DEPNP.

2-(Diethylphosphonate)-nitrosopropane (DEPNP), prepared by oxidation of the corresponding aminophosphonate, was found to essentially exist as monomer in both water and organic solvents. The mechanisms of its degradation under 80 degrees C heating or visible light exposure were studied by EPR spectroscopy: its decomposition gave rise to paramagnetic by-products, which have been identified as DEPNP/.C(CH(3) )(2) [P(O)(OC(2) H(5) )(2) ] and DEPNP/.P(O)(OC(2) H(5) )(2) spin adducts. Despite this drawback, DEPNP was successfully used as spin trapping agents to scavenge various carbon - and phosphorus-centred free radicals both in aqueous and organic media, giving rise to intense EPR spectra characteristic of the species trapped.

[Calcified lipogranuloma after gomenoleo oil injection: "paraffinoma" 60 years later]. / Lipogranulome calcifié après injection d'huile goménolée: un "paraffinome" 60 ans après.

The authors describe one case of calcified lipogranuloma observed in the forearm tissues of a 67 year old patient. This lesion seems to be due to a long term treatment by S.C injection of gomenoleo oil 60 years before. The analysis by high performance liquid chromatography of fat parts of the lesion identified the original olive oil (excipient).