Chronic unpredictable stress impairs long‐term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro

Abstract

Rises in corticosteroid levels, e.g. after acute stress, impair synaptic plasticity in the rat hippocampus when compared with the situation where levels are basal, i.e. under rest. We here addressed the question whether basal and raised levels of corticosterone affect synaptic plasticity similarly in animals that experienced chronic stress prior to corticosterone application. To this end, rats were exposed to a 21-day variable stress paradigm. Synaptic plasticity was examined in vitro in the dentate gyrus and CA1 hippocampal region, 24 h after exposure to the last stressor, i.e. when corticosterone levels are basal (low). First we observed that long-term potentiation was greatly impaired in both CA1 and dentate gyrus after 3 weeks of exposure to variable stress, when recorded under conditions where plasma corticosterone levels are low. Second, administration of 100 nm corticosterone in vitro reduced synaptic plasticity in CA1 of control rats, but induced no further impairment of synaptic plasticity in chronically stressed rats. Third, in the dentate gyrus, corticosterone incubation did not affect synaptic plasticity in slices from both control and stressed animals. We conclude that: (i) exposure to chronic variable stress per se reduces synaptic plasticity both in CA1 and dentate gyrus; and (ii) acute rises in corticosterone level induce no additional impairment of synaptic plasticity in the CA1 region of chronically stressed rats. It is tempting to speculate that the stress-induced reduction of hippocampal efficacy provides a cellular substrate for cognitive deficits in hippocampus-dependent learning tasks seen after prolonged exposure to stressful events.

Brief RU 38486 Treatment Normalizes the Effects of Chronic Stress on Calcium Currents in Rat Hippocampal CA1 Neurons

“…This is in agreement with an earlier set of experiments where we used the same protocol (eg Alfarez et al, 2003;Van Riel et al, 2003). Previously we found a similar relative increase in the basal corticosterone level after chronic stress as well as considerable variability among animals.…”

“…Indeed, our data clearly indicate that during the 21 days of unpredictable stress rats were exposed to elevated plasma corticosterone levels. Thus, in agreement with earlier studies (eg Herman et al, 1995;Alfarez et al, 2003), their gain in bodyweight was decreased and adrenal sizeFboth absolute and relative to body weightFwas increased. The absolute Ca-currents evoked in CA1 neurons from naïve rats by a voltage step to À20 mV are significantly increased 1-4 h after a brief (20 min) administration of corticosterone in vitro (cort; n ¼ 12 cells), compared to the vehicle treated group (veh; n ¼ 11; left panel).…”

“…For instance, a similar protocol was earlier found to impair LTP (Alfarez et al, 2003) and to suppress responses to serotonin in the CA1 region (Van Riel et al, 2003). In other brain areas too, effects of 21 days of stressFrestraint, social, unpredictable or other types of stressFon cell characteristics have been described (see for reviews McEwen and Chattarji (2004), Joëls et al (2004)).…”

“…This paradigm clearly affects the function of CA1 neurons . For instance, long-term potentiation is impaired after chronic unpredictable stress (Alfarez et al, 2003). Likewise, responses of CA1 pyramidal cells to serotonin are attenuated (Van Riel et al, 2003).…”

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

“…In addition, chronic stress in adults negatively affects long-term potentiation (LTP) in hippocampal subfields [109,3], including the commissural-associational projections in field CA3 [109]. The structural foundation of these functional deficits may derive from the actions of chronic stress in adults on dendritic trees.…”