Biomedical subjects

Harm J Krugers

Publications and source records attributed to Harm J Krugers.

5 recordsLinked to original sources

PubMed2006

Learning under stress: how does it work?

The effects of stress on learning and memory are not always clear: both facilitating and impairing influences are described in the literature. Here we propose a unifying theory, which states that stress will only facilitate learning and memory processes: (i) when stress is experienced in the context and around the time of the event that needs to be remembered, and (ii) when the hormones and transmitters released in response to stress exert their actions on the same circuits as those activated by the situation, that is, when convergence in time and space takes place. The mechanism of action of stress hormones, particularly corticosteroids, can explain how stress within the context of a learning experience induces focused attention and improves memory of relevant information.

Animals↗

PubMed2006

Stress, corticosteroid hormones and hippocampal synaptic function.

Exposure to stressful events has profound impact on hippocampus-dependent learning and memory processes. Traumatic and stressful experiences are remembered well in general, but have also been reported to suppress learning and memory processes. These bi-directional effects are, at least in part, modulated by corticosteroid hormones that are released during exposure to stressful experiences. An important question that remains to be addressed is how exactly exposure to stressful situations and elevated corticosteroid hormone levels affect learning and memory processes. Evidence is accumulating that exposure to stressful situations and elevated corticosteroid hormone levels modulates fast excitatory amino acid mediated synaptic transmission and synaptic plasticity, which are considered to underlie learning and memory processes in the hippocampus. In particular, exposure to stressful events has been reported to facilitate synaptic plasticity when delivered shortly before or after high frequency stimulation. By contrast, stressful events and elevated corticosteroid hormones suppress synaptic potentiation when stress precedes high frequency stimulation. From the mechanistic point of view, it is potentially important that exposure to stressful events and elevated corticosteroid hormone levels target key mechanisms that are involved in synaptic plasticity, i.e. AMPA receptors and NMDA receptors.

Adrenal Cortex Hormones↗

PubMed2005

Corticosterone shifts different forms of synaptic potentiation in opposite directions.

Calcium entering the cell via different routes, e.g.,N-methyl-D-aspartate (NMDA) receptors or voltage-dependent calcium channels (VDCCs), plays a pivotal role in hippocampal synaptic potentiation. Since corticosteroid hormones have been reported to enhance calcium influx through VDCCs, one may predict that these hormones facilitate hippocampal synaptic efficacy. Surprisingly, though, stress and corticosteroids have so far been found to reduce synaptic potentiation. Here, we addressed this apparent paradox and examined synaptic potentiation in the CA1 area of hippocampal slices from mice with low basal corticosterone levels 1--4 h after a brief in vitro administration of corticosterone. Nifedipine and APV were used to isolate NMDA receptor-mediated and VDCC-mediated long-term potentiations (LTPs), respectively. We report that corticosterone facilitates synaptic potentiation that depends on activation of VDCCs while impairing synaptic plasticity that is mediated by NMDA receptor activation. The glucocorticoid-receptor (GR) antagonist RU 38486 blocked both the effects of corticosterone. These results indicate that the net effect of corticosteroid hormones on synaptic plasticity is determined by the balance between different types of potentiation, a balance that may be region specific and depends on the experimental conditions. We speculate that these opposite effects on synaptic efficacy are involved in the bidirectional modulation of cognitive performance by corticosteroid hormones.

Animals↗

PubMed2004

Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus.

It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.

Animals↗

PubMed2003

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

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.

Animals↗