Research reportAcute cold stress leading to elevated corticosterone neither enhances synaptic efficacy nor impairs LTP in the dentate gyrus of freely moving rats
Introduction
Acute exposure to stress is associated with impairment of hippocampal-dependent memory formation in rat and human subjects 12, 27, 49, 50, 52. Acute stress in rats is also associated with impairment of hippocampal long-term potentiation (LTP), an increase in synaptic efficacy induced by high-frequency electrical stimulation of afferent fibers. Suppression of LTP induction has been demonstrated in freely moving rats exposed to a novel environment 10, 11, and in hippocampal slices obtained from rats subjected to restraint and electric shock 17, 47. Although the physiological roles of LTP are far from established 29, 46, much evidence suggests that LTP-like mechanisms are important in hippocampal-dependent memory formation 13, 28. Stress-induced memory deficits may therefore be related to suppression of LTP.
The mechanisms of LTP suppression following stress have not been fully elucidated. The adrenal cortical hormone corticosterone is probably the factor that has received most attention to date 12, 25, 31, although opioid peptides and epinephrine released from the adrenal medulla have also been implicated 20, 45. Corticosterone levels are reliably elevated under stressful conditions, and the hippocampus contains high densities of both glucocorticoid and mineralocorticoid receptors 18, 25, 31, 39. High, stress levels of corticosterone or selective activation of glucocorticoid receptors is associated with impairment of LTP induction 3, 9, 26, 36, 37, 40. However, with the exception of the novelty stress study of Diamond et al. [11], this work has focused on manipulating corticosterone levels by peripheral injection of the hormone or implanted food pellets, and effects on LTP were assessed in anesthetized animals or hippocampal slices. To the best of our knowledge, there have been no studies examining the effect of stress on LTP during the acute elevation of corticosterone in behaving rats.
An alternative view of stress is that it induces a long-lasting enhancement of synaptic transmission similar to tetanus-evoked LTP 42, 46, 48. According to this model, stress leads to the expression of LTP at saturating levels in the hippocampus, effectively occluding further enhancement by tetanic stimulation [42]. However, this hypothesis has not been supported by direct electrophysiological measurement of changes in synaptic efficacy in the CA1 region of the hippocampus during exposure to stress [43].
The following study carried out in the medial perforant path-granule cell input to the dentate gyrus of freely moving rats had two main objectives: (1) to assess changes in LTP induction during stress-induced elevations of corticosterone, and (2) to assess changes in synaptic efficacy and neuronal excitability during development of the stress response. Acute exposure to mild cold (4°C) was used as a stressor because it impairs hippocampal-dependent working memory in rats and human subjects 1, 2, 15, 49, 50, 52, and because evoked field potentials are readily monitored during exposure to the stressor.
Section snippets
Subjects
Fifty-eight male Sprague–Dawley albino rats (Taconic, Germantown, NY) weighing between 250–350 g were used as experimental subjects. Animals were group housed (4/cage) in a temperature- and light-controlled vivarium (23±0.5°C, lights on 0700 h–lights off 1900 h) and supplied with food and water ad libitum.
Surgery and electrode implantation
Rats were anesthetized (secobarbital, 40 mg/kg, i.p.) and placed in a stereotaxic headholder with the incisor bar adjusted to the skull-flat position. Rectal temperature was maintained at 37°C
Effect of acute cold exposure on serum corticosterone
Mean serum corticosterone levels obtained after a 90 min cold exposure (28.7 μg/dl) were significantly elevated above control (6.6 μg/dl) (Fig. 2; P<0.05, 2-tailed t-test for independent samples, n=7 in both groups). The effect was not attributable to handling or cage transfer per se because controls received identical treatment at room temperature.
Effect of cold stress on LTP induction
In the first set of LTP experiments, HFS parameters shown previously to induce robust LTP lasting at least 5 days in freely moving rats were used [7]
Discussion
Stress, including exposure to a novel environment or inescapable footshock, has previously been reported to suppress LTP induction in the hippocampus 10, 11, 17, 47. Exposure to stress has also been suggested to induce a form of synaptic enhancement akin to LTP [46]. In the present study, we have investigated the effect of acute cold stress on synaptic transmission and tetanus-evoked LTP in the medial perforant path input to dentate granule cells of freely moving rats. To the best of our
Acknowledgements
We gratefully acknowledge Tim Teyler for the gift of the Labman software, and Bolek Srebro for comments on the manuscript. This study was supported by NMRDC Work Unit 61153N MR04120 OOD 1383 (S.T.A.), Navy Contract MDA905-92-Z-0004 (S.T.A. and J.M.S), NIH NS23865 (J.M.S.) and USUHS RO75BZ (J.M.S.). The opinions and assertions expressed herein are those of the authors and are not to be construed as official or reflecting the views of the Department of Defense, the USUHS, the Department of Navy,
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2013, NeuroscienceCitation Excerpt :Stress hormones such as corticosterone have featured particularly strongly in this regard (Kim and Yoon, 1998). Thus, prior delivery of corticosterone in vivo or in vitro can up- or down-regulate LTP depending on the synapses under study and the timing of the events, and these effects can be replicated by substituting behavioral stress for the hormone administration (Foy et al., 1987; Shors et al., 1989; Diamond et al., 1992; Pavlides et al., 1993, 1996; Shors and Dryver, 1994; Bramham et al., 1998; Kim and Diamond, 2002; Kavushansky and Richter-Levin, 2006; Kavushansky et al., 2006). One of the key issues for the metaplasticity field now is whether metaplasticity occurs in vivo in a way that is relevant to behavioral phenomena such as learning and memory (Hulme et al., 2013).
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Department of Physiology, University of Bergen, Årstadveien 19, N-5009 Bergen, Norway.