Preliminary Investigations in the Effect of Continually Changing Reinforcement on Learning and Extinction

A great deal of research has been done in the gener­al area of manipulating reinforcement parameters. However, reinforcement per se has rarely been varied systematically from trial to trial. The research exceptions have been indicated. In these experiments , the nutritive value, the delay, or the units of reinforcement have been systematical­ly varied and the results are not always conclusive as re­gards the experimental variable itself. The present study attempts to control for these factors and yet vary systema­tically properties of the reinforcing agent alone. Pigeons were the experimental subjects and they worked for food while they were at a controlled drive level. Since the caloric value in the food reward was kept constant from trial to trial, a Hullian prediction would be that the groups would show no difference in either conditioning or extinc­tion as all groups would be drive-reduced similarly (Hull, 1943). On the basis of most of the stimulus variation ex­periments it is possible to predict that the more the cue change in reinforcement, the slower the rate of acquisition and the lower the subjects\u27 performance level. It is pos­sible to predict further that the groups with more ex­tensive reinforcement variation should resist extinction longer much the same as is shown in the stimulus change and also in the partially-delayed reinforcement experiments. In other words, they have been conditioned to changing cues and extinction can be viewed as another cue change. There is of course a third possibility. The more reinforcement variation, the higher the level of performance due to a sort of grab­ bag motivating effect. This third alternative would fit in with the amount or bits research and the novel stimu­lation research. The more stimulus change groups should be similar to getting more units for their efforts in terms of more cue-change. Specific directional predictions were not made although on the basis of previous pilot study work (see Chapter II) a trend could be predicted

A circuit for video-tape interviewing and its recording reliability

A circuit to automate fully a standardized video-taped interview (SVTI) is developed. Data are reported demonstrating good instrument reliability

Antidepressants act by inducing autophagy controlled by sphingomyelin\u2013ceramide

Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days