Effects of depression on hippocampal memory: A computational model

摘要

Animal studies have shown that chronic stress and depression produce irreversible atrophy of the apical dendrites of CA3 pyramidal neurons. Dysregulations caused by depression also disturbes molecular mechanisms of hippocampal long-term potentiation (LTP). The effect of stress on amygdala is just the opposite of the hippocampus; neuroimaging studies have found both increased baseline activity and a greater amygdala volume in depressed compared to nondepressed individuals. In our study, we have implemented a computational model of CA3 region of the hippocampus to simulate the auto-associative memory impairement caused by depression. In our model, the dendritic atrophy and disturbed synaptic plasticity, is represented by the increase in transmission delay and the increased amygdala activity, in turn, is represented by increased inhibitory input to CA3 region. Our auto-associative CA3 network incorporates 256 excitatory recurrent Hebb's synapses in a 16 times 16 array plus one interneuron representing the inhibition by amygdala. The network has been trained to recognize face patterns. We tested the auto-associative memory function with incomplete patterns and we expected our model to perform the pattern completion function. The pattern completion performance was negatively effected by the increase of the inhibition by amygdala. The increase in information delay due to dendritical atrophy had even more severe consequences on the memory performance. We observed a shutting off of the auto-associative memory for time delays longer than 10 ms. In further studies, our dynamic model will be improved to include the molecular effects of stress on synaptic plasticity.