Elsevier

Brain Research

Volume 789, Issue 2, 13 April 1998, Pages 245-255
Brain Research

Research report
Acute cold stress leading to elevated corticosterone neither enhances synaptic efficacy nor impairs LTP in the dentate gyrus of freely moving rats

https://doi.org/10.1016/S0006-8993(97)01265-1Get rights and content

Abstract

Exposure to stress has previously been found to impair long-term potentiation (LTP) in the hippocampus. Exposure to stress has also been proposed to induce an LTP-like effect. We examined the effect of acute cold stress on synaptic transmission, neuronal excitability, and LTP induction in the medial perforant path-granule cell synapse of freely moving rats. After obtaining baseline recordings of evoked field potentials at room temperature (23°C), rats were transferred to an environmental cage maintained at 4°C (cold group) or 23°C (control group) and, 90 min later, high-frequency stimulation (HFS) was applied to the medial perforant path. Serum corticosterone measured in trunk blood from rats without implanted electrodes was significantly elevated in cold exposed (28.7 μg/dl) rats relative to control (6.6 μg/dl). Despite increased corticosterone levels indicative of stress activation, cold exposed rats exhibited LTP of the fEPSP slope and population spike of similar magnitude and time course as controls. In addition, there was no stress-specific effect on the fEPSP slope or population spike and no effect on paired-pulse plasticity. Surprisingly, despite extensive cage acclimation, transferring rats to the environmental cage was associated with a reduction in population spike amplitude and an enhancement in paired-pulse facilitation. The results show that acute cold stress leading to elevated serum corticosterone levels neither induces LTP-like increases in synaptic efficacy nor impairs tetanus-evoked LTP in the dentate gyrus of freely moving rats. Thus, impaired working memory during cold stress is not due to an inability of perforant path synapses to express LTP.

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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