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 restrainttailshock 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.

Functional Connectivity from the Amygdala to the Hippocampus Grows Stronger after Stress

“…In particular, stress appears to shift control over area CA1 from the CA3 area to LA, which may explain some of the previously reported effects of stress on hippocampal place cells and spatial learning and memory (Kim et al, 2007). Importantly, some of these changes persist even 10 d after the cessation of stress, raising the possibility of a prolonged rewiring of the amygdala-hippocampal network.…”

“…First, neuroanatomical data point to extensive direct and indirect interconnections between the LA/BLA and area CA1 (McDonald, 1998;Pikkarainen et al, 1999). Second, both lesions and pharmacological inactivation of the BLA prevent stressinduced impairment of hippocampal LTP and spatial memory in rats (Kim et al, 2001(Kim et al, , 2005. Third, in vivo electrical activation of the amygdala, but not corticosterone treatment, mimics the effects of stress on CA1 place cells (Kim et al, 2012).…”

“…Indeed, behavioral and pharmacological evidence suggests that the amygdala may mediate certain stress effects on hippocampal LTP and memory (Kim et al, 2001(Kim et al, , 2005. These findings highlight the need to examine the potential impact of stress on directional influences between the hippocampus and amygdala.…”

Stressful Experience and Learning Across the Lifespan

“…The effects of stress on this type of learning are somewhat varied and depend on the type of stressor, but even more so on when the stressor is experienced. For example, animals that are exposed to a stressful event of brief intermittent tailshocks learn to navigate in the Morris water maze and do so at the same rate as animals that are unstressed (Kim et al 2005). There are also examples of enhanced learning in the Morris water maze after a stressful experience.…”

Stress Impairs 5-HT2A Receptor-Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala

“…Activity of projection neurons in the BLA is under strong inhibitory control by GABAergic synaptic transmission (Royer et al, 1999;Szinyei et al, 2000). Manipulation of this neurotransmission within the BLA has a critical influence on behavioral, emotional sequelae resulting from stress (Jasnow and Huhman, 2001;Kim et al, 2005;Sanders and Shekhar, 1995;Van Nobelen and Kokkinidis, 2006). Therefore, the occurrence of stress-associated psychiatric syndromes has been closely associated with changes in the GABAergic system in the BLA.…”