Electrophysiology direct central nervous system

The development of in vitro brain slice and isolated neuron techniques has greatly facilitated detailed studies of the electrophysiology of a wide range of neuronal types in the adult and neonatal vertebrate central nervous system (CNS). Particularly advantageous are the greater mechanical stability that these preparations provide over in vivo models and the control allowed over the composition of the extracellular environment. In addition, the development of the patch-clamp technique has opened up the possibility of direct access to the intracellular environment via internal patch pipet solutions. In combination, these approaches have enabled detailed investigations of neuronal membrane properties, the cellular actions of neurotransmitters, and synaptic mechanisms. 

An intermediate-duration oral MRL of 0.0007 mg/kg/day was derived for methyl parathion based on the observation of electrophysiological effects in the central and peripheral nervous systems of male rats exposed to methyl parathion through gavage administration of 0.22 mg/kg/day to the dams on days 5-15 of gestation and days 2-28 of lactation, followed by direct administration of the same dose to the male pups for 8 weeks. More marked effects occurred at the two higher doses, 0.44 and 0.88 mg/kg/day. The effects were dose-related, and were statistically significant at all three dose levels. The MRL was derived by dividing the LOAEL from this study (0.22 mg/kg/day) by an uncertainty factor of 300 (3 for a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). 

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