Acute stress effects on cognition and synaptic plasticity

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My Discovery Grant Program is designed to elucidate the mechanisms underlying the effects of experience on neurophysiology and cognitive functions such as memory. Neurophysiological processes and memory are strongly influenced by a variety of experiences, such as acute stress. However, definitive links between the effects of experience on particular neurophysiological processes, such as patterns of synaptic plasticity, and memory are lacking. The specific experiments in the present proposal are designed to determine the effects of one particular experience, that of acute stress, on memory retrieval in rodents. We have recently developed sensitive behavioral tests that may be used to reliably assess two types of memory, recognition and temporal order memory, in rodents. When these tests are conducted with different stimuli (spatial information or objects), normal memory performance depends on well understood, dissociable circuits involving a number of brain areas including the hippocampus, perirhinal cortex, and medial prefrontal cortex. In an initial series of experiments, the effects of acute stress on memory retrieval in these tests will be examined. We believe that acute stress will disrupt normal memory retrieval on these tests thereby providing novel information regarding the specific types of memory and neural substrates influenced by acute stress. In separate electrophysiological experiments, the effects of acute stress on synaptic plasticity in the neural circuits important for performance of these tests will be characterized. Given the results of previous experiments, acute stress is predicted to enable the induction of a cellular model of synaptic plasticity known as long-term depression in the hippocampus, perirhinal cortex, and medial prefrontal cortex. Finally, the effects of a number of highly specific inhibitors known to inhibit long-term depression in other preparations will be used to block the electrophysiological and behavioral effects of acute stress. An integration of the fundamental behavioral and electrophysiological effects of acute stress on learning and memory will allow theories regarding the neural mechanisms mediating cognition in both normal and challenging circumstances to be developed.