Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition

Abstract

It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

Keywords: Pavlovian conditioning; cerebellum; eyeblink conditioning; fear conditioning; inhibitory avoidance; neocortex; thalamic reticular nucleus.

Figure 1

Schematic of Pavlovian conditioning paradigms. (A) In delay-conditioning, the conditioned stimulus (CS) (e.g., tone, whisker stimulation) co-terminates with the unconditioned stimulus (US) (e.g., mild footshock, eye shock). (B) In trace-conditioning, there is a stimulus-free separation in time between the CS and US.

Figure 2

Schematic of amygdala involvement in a two process model for memory consolidation. In phase 1 of the model, the amygdala, receiving event information, increases the saliency of the event to motor and sensory regions, thus facilitating memory consolidation and behavioral response to the event. In phase 2 of the model, motor and sensory regions, primed with amygdala activation from phase 1, begin to solidify the memory and generate appropriate behavioral responses.

Figure 3

Schematic of amygdala and thalamic reticular nucleus involvement with eyeblink conditioning. Information from the conditioned stimuli (CS) first projects to the thalamus, where it will then project to the neocortex and thalamic reticular nucleus. The thalamic reticular nucleus can then compare information from the neocortex, amygdala, and thalamus. Then, via selective inhibition of thalamic activity, the thalamic reticular nucleus can modulate what information the neocortex receives. Modulation of neocortical input would modulate neocortical activation of the pontine nuclei that directly assists in generating the appropriate conditioned response “Blink.” Note in the above illustration, the amygdala can facilitate appropriate behavioral responses by not only modulating neocortical activation of the pontine nuclei via thalamic reticular nuclear stimulation, but also via direct projections to the pontine nuclei.