Acute stress, but not corticosterone, disrupts short- and long-term synaptic plasticity in rat dorsal subiculum via glucocorticoid receptor activation

Abstract

The subiculum (SUB) serves as the major output structure of the hippocampus; therefore, exploring synaptic plasticity within this region is of great importance for understanding the dynamics of hippocampal circuitry and hippocampal-cortical interactions. Previous research has shown exposure to acute stress dramatically alters synaptic plasticity within the hippocampus proper. Using in vivo electrophysiological recordings in urethane-anesthetized adult male Sprague-Dawley rats, we tested the effects of either acute restraint stress (30 min) or corticosterone (CORT) injections (3 mg/kg; s.c.) on short- and long-term forms of synaptic plasticity in the Cornu Ammonis 1-SUB pathway. Paired-pulse facilitation and two forms of long-term plasticity (long-term potentiation and late-developing potentiation) were significantly reduced after exposure to acute stress but not CORT treatment. Measurements of plasma CORT confirmed similar levels of circulating hormone in animals exposed to either acute stress or CORT treatment. The disruptive effects of acute stress on both short- and long-term forms of synaptic plasticity are mediated by glucocorticoid receptor (GR) activation as these disruptions were blocked by pre-treatment with the selective GR antagonist RU38486 (10 mg/kg; s.c.). The present results highlight the susceptibility of subicular plasticity to acute stress and provide evidence that GR activation is necessary but not sufficient for mediating these alterations.

Keywords: hippocampus; in vivo electrophysiology; late-developing potentiation; long-term potentiation; paired-pulse facilitation.

Figure 1

(A) A schematic of the experimental design with stimulating electrode placed in dorsal CA1 and recording electrode placed in dorsal subiculum (SUB). (B) A schematic of the experimental conditions. Dotted line represents time spent in home cage and bold line represents time in restraint. All rats were anesthetized at time zero. (C) Representative electrode placements as indicated by black dots. (D) Input–output curve showing the amount of stimulating current (μA) and the evoked fEPSP responses (mV) for the experimental conditions obtained prior to the first paired-pulse facilitation recordings.

Figure 2. Corticosterone (CORT) Assay

(A) Plasma CORT levels taken immediately after anesthesia for control, acute stress, and CORT groups. (B) Plasma CORT levels taken prior to tetanization for control, acute stress, and CORT groups. Asterisk denotes P < 0.05 relative to all other groups.

Figure 3. Initial paired-pulse facilitation (PPF)

(A) Acute stress, but not corticosterone injections, disrupts pre-tetanus PPF values for the averaged 25 and 50 ms inter-pulse intervals, an effect reversed by pre-treatment with RU38486 (10 mg/kg). Asterisk denotes P < 0.05 relative to all other groups. (B) Representative fEPSP traces for control and stress conditions.

Figure 4. Long-term plasticity

(A) High-frequency stimulation-induced LTP is present in control (open circle) and CORT (black triangles) rats but not acutely stressed rats (black circles). (B) High-frequency stimulation-induced LTP following RU38486 treatment (light gray circles) and RU38486-treated rats exposed to acute stress (dark gray circles). (C) Summary of the effects of acute stress, CORT, and RU38486 treatment on HFS-induced long-term plasticity. (D) Low-frequency stimulation-induced late-developing potentiation is present in control (open circles) and CORT (black triangles) but not acutely stressed rats (black circles). (E) Low-frequency stimulation-induced late-developing potentiation following RU38486 treatment (light gray circles) and RU38486 treated rats exposed to acute stress (dark gray circles). (F) Summary of the effects of acute stress, CORT, and RU38486 treatment on LFS-induced long-term plasticity. Asterisk denotes P < 0.05 relative to all other groups.

Figure 5. Changes in paired-pulse facilitation (PPF) following tetanic stimulation

(A) Initial pre-tetanus PPF values (left bars) compared with post-tetanus PPF values (chequered bars). Values are the average PPF for the 25 and 50 ms inter-pulse intervals. Asterisk denotes P < 0.05 relative to pre-tetanus value. (B–F) Correlation and regression plots showing changes in PPF following the induction of potentiation across different experimental conditions. The initial pre-tetanus PPF is plotted on the x-axis and the PPF difference scores are plotted on the y-axis.