Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields.

The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network.

Does cigarette smoking modify the association between change in body mass index during young adulthood and risk of coronary mortality during middle-age in men? Twenty-five year follow-up results from the Chicago Western Electric Study

Many persons in the U.S. gain weight during young adulthood, and the prevalence of obesity has been increasing among young adults. Although obesity and physical inactivity are generally recognized as risk factors for coronary heart disease (CHD), the magnitude of their effect on risk may have been seriously underestimated due to failure to adequately handle the problem of cigarette smoking. Since cigarette smoking causes weight loss, physically inactive cigarette smokers may remain relatively lean because they smoke cigarettes. We hypothesize cigarette smoking modifies the association between weight gain during young adulthood and risk of coronary heart disease during middle age, and that the true effect of weight gain during young adulthood on risk of CHD can be assessed only in persons who have not smoked cigarettes. Specifically, we hypothesize that weight gain during young adulthood is positively associated with risk of CHD during middle-age in nonsmokers but that the association is much smaller or absent entirely among cigarette smokers. The purpose of this study was to test this hypothesis. The population for analysis was comprised of 1,934 middle-aged, employed men whose average age at the baseline examination was 48.7 years. Information collected at the baseline examinations in 1958 and 1959 included recalled weight at age 20, present weight, height, smoking status, and other CHD risk factors. To decrease the effect of intraindividual variation, the mean values of the 1958 and 1959 baseline examinations were used in analyses. Change in body mass index ($\Delta$BMI) during young adulthood was the primary exposure variable and was measured as BMI at baseline (kg/m$\sp2)$ minus BMI at age 20 (kg/m$\sp2).$ Proportional hazards regression analysis was used to generate relative risks of CHD mortality by category of $\Delta$BMI and cigarette smoking status after adjustment for age, family history of CVD, major organ system disease, BMI at age 20, and number of cigarettes smoked per day. Adjustment was not performed for systolic blood pressure or total serum cholesterol as these were regarded as intervening variables. Vital status was known for all men on the 25th anniversary of their baseline examinations. 705 deaths (including 319 CHD deaths) occurred over 40,136 person-years of experience. $\Delta$BMI was positively associated with risk of CHD mortality in never-smokers, but not in ever-smokers (p for interaction = 0.067). For never-smokers with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 1.62, 1.61, and 2.78, respectively (p for trend = 0.010). For ever-smokers, with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 0.74, 1.07, and 1.06, respectively (p for trend = 0.422). These results support the research hypothesis that cigarette smoking modifies the association between weight gain and CHD mortality. Current estimates of the magnitude of effect of obesity and physical inactivity on risk of coronary mortality may have been seriously underestimated due to inadequate handling of cigarette smoking. ^