Altered spatial learning, cortical plasticity and hippocampal anatomy in a neurodevelopmental model of schizophrenia-related endophenotypes.

Adult rats exposed to the DNA-methylating agent methylazoxymethanol on embryonic day 17 show a pattern of neurobiological deficits that model some of the neuropathological and behavioral changes observed in schizophrenia. Although it is generally assumed that these changes reflect targeted disruption of embryonic neurogenesis, it is unknown whether these effects generalise to other antimitotic agents administered at different stages of development. In the present study, neurochemical, behavioral and electrophysiological techniques were used to determine whether exposure to the antimitotic agent Ara-C later in development recapitulates some of the changes observed in methylazoxymethanol (MAM)-treated animals and in patients with schizophrenia. Male rats exposed to Ara-C (30 mg/kg/day) at embryonic days 19.5 and 20.5 show reduced cell numbers and heterotopias in hippocampal CA1 and CA2/3 regions, respectively, as well as cell loss in the superficial layers of the pre- and infralimbic cortex. Birth date labeling with bromodeoxyuridine reveals that the cytoarchitectural changes in CA2/3 are a consequence rather that a direct result of disrupted cortical neurogenesis. Ara-C-treated rats possess elevated levels of cortical dopamine and DOPAC (3,4-didyhydroxypheylacetic acid) but no change in norepinephrine or serotonin. Ara-C-treated rats are impaired in their ability to learn the Morris water maze task and showed diminished synaptic plasticity in the hippocampocortical pathway. These data indicate that disruption of neurogenesis at embryonic days 19.5 and 20.5 constitutes a useful model for the comparative study of deficits observed in other gestational models and their relationship to cognitive changes observed in schizophrenia.

Intrashot motional Stark effect calibration technique for lower hybrid current drive experiments.

The spurious drift in pitch angle of order several degrees measured by the motional Stark effect (MSE) diagnostic in the Alcator C-Mod tokamak over the course of an experimental run day has precluded direct utilization of independent absolute calibrations. Recently, the underlying cause of the drift has been identified as thermal stress-induced birefringence in a set of in-vessel lenses. The shot-to-shot drift can be avoided by using MSE to measure only the change in pitch angle between a reference phase and a phase of physical interest within a single plasma discharge. This intrashot calibration technique has been applied to the lower hybrid current drive (LHCD) experiments and the measured current profiles qualitatively demonstrate several predictions of LHCD theory such as an inverse dependence of current drive efficiency on the parallel refractive index and the presence of off-axis current drive.