M-type channels selectively control bursting in rat dopaminergic neurons

Midbrain dopaminergic neurons in the substantia nigra, pars compacta and ventral tegmental area are critically important in many physiological functions. These neurons exhibit firing patterns that include tonic slow pacemaking, irregular firing and bursting, and the amount of dopamine that is present in the synaptic cleft is much increased during bursting. The mechanisms responsible for the switch between these spiking patterns remain unclear. Using both in-vivo recordings combined with microiontophoretic or intraperitoneal drug applications and in-vitro experiments, we have found that M-type channels, which are present in midbrain dopaminergic cells, modulate the firing during bursting without affecting the background low-frequency pacemaker firing. Thus, a selective blocker of these channels, 10,10-bis(4-pyridinylmethyl)-9(10H)- anthracenone dihydrochloride, specifically potentiated burst firing. Computer modeling of the dopamine neuron confirmed the possibility of a differential influence of M-type channels on excitability during various firing patterns. Therefore, these channels may provide a novel target for the treatment of dopamine-related diseases, including Parkinson's disease and drug addiction. Moreover, our results demonstrate that the influence of M-type channels on the excitability of these slow pacemaker neurons is conditional upon their firing pattern. © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Structural analysis of plate-type fuel assemblies and development of a non-destructive method to assess their integrity

This work is concerned with the structural behaviour and the integrity of parallel plate-type nuclear fuel assemblies. A plate-type assembly consists of several thin plates mounted in a box-like structure and is subjected to a coolant flow that can result in a considerable drag force. A finite element model of an assembly is presented to study the sensitivity of the natural frequencies to the stiffness of the plates' junctions. It is shown that the shift in the natural frequencies of the torsional modes can be used to check the global integrity of the fuel assembly while the local natural frequencies of the inner plates can be used to estimate the maximum drag force they can resist. Finally a non-destructive method is developed to assess the resistance of the inner plates to bear an applied load. Extensive computational and experimental results are presented to prove the applicability of the method presented. © 2013 Elsevier B.V. All rights reserved.