Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning

Abstract

Stress is a biologically significant factor shown to influence synaptic plasticity and memory functioning in the hippocampus. This study examined the role of the amygdala, a brain structure implicated in coordinating stress behaviors and modulating memory consolidation, in mediating stress effects on hippocampal long-term potentiation (LTP) and memory in rats. Electrolytic lesions of the amygdala effectively blocked the adverse physiological and behavioral effects of restraint and tailshock stress, without impeding the increase in corticosterone secretion to stress. Physiologically, hippocampal slices from stressed animals exhibited impaired LTP relative to slices from unstressed control animals, whereas hippocampal slices from stressed animals with amygdalar lesions exhibited normal LTP. Behaviorally, stressed animals were impaired in retention of a hippocampal-dependent hidden platform version of the Morris water maze task, and this impairment was blocked by amygdalar lesions. In a fixed location-visible platform water maze task that can be acquired by independent hippocampal and nonhippocampal memory systems, stress enhanced the use of nonhippocampal-based memory to acquire the task. These results indicate that an intact amygdala is necessary for the expression of the modulatory effects of stress on hippocampal LTP and memory.

Fig. 1.

Photomicrograph showing a transverse brain section stained with cresyl violet and Prussian blue from a rat with amygdalar lesions.

Fig. 2.

Effects of amygdalar lesions and stress on Schaffer collateral–commissural-CA1 LTP and corticosterone secretion.A, Synaptic strength in the CA1 area of the hippocampus from sham-control (open circles, n = 6), sham-stress (filled circles,n = 6), lesion-control (open triangles, n = 8), and lesion-stress (filled triangles, n = 8) animals is expressed as a percentage of the average pretetanus f-EPSP over time (in minutes). Inset, two representative f-EPSPs from lesion-stress group, taken 10 min before and 50–60 min after LTP are shown. B, Trunk blood corticosterone levels assayed (I¹²⁵ radioimmunoassay) from the four groups used in the hippocampal slice experiment.

Fig. 3.

Effects of amygdalar lesions and stress on spatial memory and fear conditioning. A, Mean (±SE) latencies to find a submerged platform from sham-control (open circles, n = 8), sham-stress (filled circles, n = 9), lesion-control (open triangles, n = 9), and lesion-stress (filled triangles,n = 9) animals during acquisition and a single retention test. B, Mean (±SE) swim speed (centimeters per second) of four groups during acquisition and a single retention test. C, Mean (±SE) percentage postshock (PSK) freezing during the 1 min baseline (BL) and during the three 1 min intershock intervals.

Fig. 4.

Left, Fixed location–visible platform water maze paradigm for assessing stress effects on the relative use of S-R and spatial memory.A, Mean (±SE) latency to find a submerged platform marked with a visually salient pole from control (open circles, n = 10) and stress (filled circles, n = 10) animals during the acquisition trials (1–8) and on a single test trial (9). B, Mean (±SE) distance to find a submerged platform marked with a visually salient pole on a single test trial. C, Mean number of old quadrant entry (where the platform was located during training).