Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory

Abstract

The prefrontal cortex (PFC), a key brain region controlling cognition and emotion, is strongly influenced by stress. While chronic stress often produces detrimental effects on these measures, acute stress has been shown to enhance learning and memory, predominantly through the action of corticosteroid stress hormones. We used a combination of electrophysiological, biochemical, and behavioral approaches in an effort to identify the cellular targets of acute stress. We found that behavioral stressors in vivo cause a long-lasting potentiation of NMDAR-and AMPAR-mediated synaptic currents via glucocorticoid receptors (GRs) selectively in PFC pyramidal neurons. This effect is accompanied by increased surface expression of NMDAR and AMPAR subunits in acutely stressed animals. Furthermore, behavioral tests indicate that working memory, a key function relying on recurrent excitation within networks of PFC neurons, is enhanced by acute stress via a GR-dependent mechanism. These results have identified a form of long-term potentiation of synaptic transmission induced by natural stimuli in vivo, providing a potential molecular and cellular mechanism for the beneficial effects of acute stress on cognitive processes subserved by PFC.AMPA receptors ͉ corticosterone ͉ NMDA receptors

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

“…This design enabled assessment of the immediate effects of restraint stress and GR activation on early reversal learning [10], as well as the long-term effects on late reversal learning in a manner similar to that reported previously [11,12]. We hypothesized that blocking GRs would prevent the immediate influence of stress on reversal learning as GRs become saturated by elevated CORT levels following stress and blocking GRs reverses the effect of acute stress on cognitive functioning in previous studies [6,13].…”

“…Eighteen rats were injected with the GR antagonist RU38486 (10 mg/kg; Sigma-Aldrich, Oakville, Ontario) while the other 19 were injected with vehicle (50:50 DMSO:95% ethanol; 2 ml/kg). The dose of RU38486 was determined from previous studies [10,13,22].…”

“…However, the influence of acute stress on forms of cognition dependent on prefrontal cortex (PFC) is less well defined [1]. Research regarding the influence of acute stress on PFC-dependent executive processing and cognitive/behavioral flexibility have been inconsistent, with some studies showing impaired performance [6][7][8][9] while others show facilitated performance [10][11][12][13][14], depending on the specific task and stressor.…”

Rapid-onset antidepressant efficacy of glutamatergic system modulators: The neural plasticity hypothesis of depression

“…If stress occurs before a spatial learning task, it impedes both memory formation and retrieval [64] . However, briefly exposing the rats to acute stress, as measured by the T-maze, increases working memory performance, and the effects are acute, lasting <2 days [41] . Therefore, stress can either facilitate or impair memory formation and (or) retrieval depending on the timing and the severity, possibly due to the effects on neural plasticity [65] .…”

“…Stress can cause rapid glucocorticoid receptor-mediated alterations in presynaptic glutamate release and slower changes in postsynaptic glutamate receptor expression and function [41] , which can affect LTP and LTD. In addition, stress may induce changes in functional plasticity by shifting the balance between synaptic and extrasynaptic glutamate receptors that are thought to contribute to potentiation and depression, respectively [42,43] .…”