The differential effects of basal and stress levels of glucocorticoids (GCs) on cognition can be explained by the presence of two types of GC receptors, the type I mineralocorticoid receptor (MR) which has a high affinity for GCs and mediates the beneficial effects of GC secretion on cognition. In contrast, the type II glucocorticoid receptor has a low affinity for GCs and is only activated at a high GC concentration, which is implicated in impairing spatial discrimination and synaptic plasticity. This research proposal aims are to construct a vector expressing the MR and characterize the effects of overexpression on basal cognitive functions and synaptic plasticity. In addition, we will assess the neuroprotective potential of MR overexpression against stress-induced memory impairments and synaptic plasticity. A modified herpes simplex virus amplicon system has made it feasible to introduce and overexpress foreign DNA into the central nervous system. In the present study we will use a HSV amplicon overexpressing MR to investigate its neuroprotective potential against stress-induced impairments in hippocampal-dependent cognition and its potential to enhance cognition and synaptic plasticity. ? ?
