Amygdalar inactivation blocks stress-induced impairments in hippocampal long-term potentiation and spatial memory

Abstract

Electrolytic lesions to the amygdala, a limbic structure implicated in stress-related behaviors and memory modulation, have been shown to prevent stress-induced impairments of hippocampal long-term potentiation (LTP) and spatial memory in rats. The present study investigated the role of intrinsic amygdalar neurons in mediating stress effects on the hippocampus by microinfusing the GABA(A) receptor agonist muscimol into the amygdala and examining stress effects on Schaffer collateral/commissural-CA1 LTP and spatial memory. The critical period of the amygdalar contribution to stress effects on hippocampal functions was determined by applying muscimol either before stress or immediately after stress. Our results indicate that intra-amygdalar muscimol infusions before uncontrollable restraint-tailshock stress effectively blocked stress-induced physiological and behavioral effects. Specifically, hippocampal slices prepared from vehicle-infused stressed animals exhibited markedly impaired LTP, whereas slices obtained from muscimol-infused stressed animals demonstrated robust LTP comparable with that of unstressed animals. Correspondingly, vehicle-infused stressed animals displayed impaired spatial memory (on a hidden platform version of the Morris water maze task), whereas muscimol-infused stressed animals revealed unimpaired spatial memory. In contrast to prestress muscimol effects, however, immediate poststress infusions of muscimol into the amygdala failed to interfere with stress impairments of LTP and spatial memory. Together, these results suggest that the amygdalar neuronal activity during stress, but not shortly after stress, is essential for the emergence of stress-induced alterations in hippocampal LTP and memory.

Figure 1.

Time intervals from intra-amygdalar MUSC infusions to stress presentation to hippocampal slice preparation in experiments 1 and 2.

Figure 2.

Photomicrograph showing a transverse brain section stained with cresyl violet from a rat infused with muscimol bilaterally into the amygdala and used in the hippocampal slice experiment. Arrowheads indicate infusion cannula tip positions.

Figure 3.

Examples of the USV raster plots; each dot represents a time-stamped episode of vocalization. USV emissions are shown from a typical ACSF- and muscimol-infused animal during 60 min of stress. The y-axis represent block of time; each block represent 5 min (12 blocks × 5 min = 60 min of stress).

Figure 4.

Effects of intra-amygdalar infusions of muscimol and stress on Schaffer collateral/commissural-CA1 LTP. Synaptic strength in the CA1 area of the hippocampus from ACSF-CONTROL, ACSF-STRESS, MUSC-CONTROL, and MUSC-STRESS animals is expressed as a percentage of the average pretetanus f-EPSP over time (in minutes).

Figure 5.

Prestress and immediate poststress intra-amygdalar infusions of muscimol and stress effects on Schaffer collateral/commissural-CA1 LTP. Synaptic strength in the CA1 area of the hippocampus from STRESS-ACSF, MUSC-STRESS, and STRESS-MUSC animals is expressed as a percentage of the average pretetanus f-EPSP over time (in minutes).

Figure 6.

Photomicrograph showing a transverse brain section stained with cresyl violet from a rat with bilateral guide cannulas implanted in the amygdala and used in the behavioral experiment. Arrowheads indicate infusion cannula tip positions.

Figure 7.

Effects of intra-amygdala infusions of muscimol and stress on spatial memory. A, Mean (±SE) latencies to find a submerged platform from ACSF-CONTROL, ACSF-STRESS, MUSC-CONTROL, MUSC-STRESS, and STRESS-MUSC animals during acquisition and a single retention test. B, Mean (±SE) swim speed of five groups during acquisition and a single retention test.