Danger Changes the Way the Mammalian Brain Stores Information About Innocuous Events: A Study of Sensory Preconditioning in Rats

Abstract

The amygdala is a critical substrate for learning about cues that signal danger. Less is known about its role in processing innocuous or background information. The present study addressed this question using a sensory preconditioning protocol in male rats. In each experiment, rats were exposed to pairings of two innocuous stimuli in stage 1, S2 and S1, and then to pairings of S1 and shock in stage 2. As a consequence of this training, control rats displayed defensive reactions (freezing) when tested with both S2 and S1. The freezing to S2 is a product of two associations formed in training: an S2-S1 association in stage 1 and an S1-shock association in stage 2. We examined the roles of two medial temporal lobe (MTL) structures in consolidation of the S2-S1 association: the perirhinal cortex (PRh) and basolateral complex of the amygdala (BLA). When the S2-S1 association formed in a safe context, its consolidation required neuronal activity in the PRh (but not BLA), including activation of AMPA receptors and MAPK signaling. In contrast, when the S2-S1 association formed in a dangerous context, or when the context was rendered dangerous immediately after the association had formed, its consolidation required neuronal activity in the BLA (but not PRh), including activation of AMPA receptors and MAPK signaling. These roles of the PRh and BLA show that danger changes the way the mammalian brain stores information about innocuous events. They are discussed with respect to danger-induced changes in stimulus processing.

Keywords: amygdala; associative learning; consolidation; danger; memory; sensory preconditioning.

Figure 1.

Experiment 1. The neural substrates involved in consolidation of a sensory preconditioned association depend on the context. The mean (±SEM) levels of freezing in groups control (n = 7), safe-BLA-bupi (n = 8), safe-PRh-bupi (n = 8), danger-BLA-bupi (n = 8), and danger-PRh-bupi (n = 8) during test presentations of S2 (left panel) and S1 (right panel) in experiment 1, relative to the baseline. When sensory preconditioning occurred in a safe context, consolidation of the S2-S1 memory required neuronal activity in the PRh but not the BLA; but when it occurred in a dangerous context, consolidation of the same memory required neuronal activity in the BLA but not the PRh. There was no evidence in any protocol that an infusion of bupivacaine impaired the encoding and/or storage of the S1-shock association. Horizontal arrows in the design schematic (top of figure) indicate transitions between experimental stages, and the vertical arrow indicates an infusion of bupivacaine or vehicle into the PRh or BLA.

Figure 2.

Experiment 2. The role of AMPA receptors and MAPK signaling in consolidation of an S2-S1 memory. The mean (±SEM) levels of freezing during test presentations of S2 (left panel) and S1 (right panel) in experiments 2A (top row) and 2B (bottom row), relative to the baseline. Experiment 2A: when sensory preconditioning occurred in a safe context, consolidation of the S2-S1 memory required activation of AMPA receptors and MAPK signaling in the PRh [groups vehicle (n = 12), NBQX (n = 8), and U0126 (n = 8)]. Experiment 2B: when sensory preconditioning occurred in a dangerous context, consolidation of the S2-S1 memory required activation of AMPA receptors and MAPK signaling in the BLA [groups vehicle (n = 15), NBQX (n = 8), and U0126 (n = 7)]. Horizontal arrows in the design schematics indicate transitions between experimental stages, and the vertical arrows indicate an infusion of NBQX, U0126 or vehicle into the PRh or BLA.

Figure 3.

Experiment 3. Experience of danger shortly after a learning event changes how the brain stores information about that event. The mean (±SEM) levels of freezing during test presentations of S2 (left panel) and S1 (right panel) in experiments 3A (top row) and 3B (bottom row), relative to the baseline. Experiment 3A: a shocked exposure to the context after sensory preconditioning renders consolidation of the S2-S1 memory independent of neuronal activity in the PRh [groups vehicle (n = 8), danger-Bupi (n = 10), and safe-Bupi (n = 10)]. Experiment 3B: a shocked exposure to the context after sensory preconditioning renders consolidation of the S2-S1 memory dependent on neuronal activity in the BLA. This engagement of the BLA requires that the shocked context exposure occurs immediately after sensory preconditioning. Under these circumstances, the effect of the shocked context exposure is blocked when the BLA is inactivated before the shock [groups vehicle (n = 19), Bupi-shock-10 (n = 7) and shock-Bupi-10 (n = 7), and shock-Bupi-24 (n = 11)]. Horizontal arrows in the design schematics indicate transitions between experimental stages, and the vertical arrows indicate an infusion of bupivacaine or vehicle into the PRh or BLA.

Figure 4.

Experiment 4. The role of AMPA receptors and MAPK signaling in consolidation of an S2-S1 memory. The mean (±SEM) levels of freezing during test presentations of S2 (left panel) and S1 (right panel) in experiment 4, relative to the baseline. When danger is experienced shortly after sensory preconditioning, consolidation of the S2-S1 memory requires activation of AMPA receptors and MAPK signaling in the BLA. Groups vehicle (n = 15), NBQX (n = 8), and U0126 (n = 8). Horizontal arrows in the design schematic indicate transitions between experimental stages, and the vertical arrow indicates an infusion of NBQX, U0126 or vehicle into the BLA.

Figure 5.

Approximate placements of microinfusion cannulas in the BLA for 124 rats (left) and PRh (right) for 76 rats. The cannula locations were verified on Nissl-stained coronal sections with reference to the atlas of Paxinos and Watson (1997; p 145).