Context-Dependent Encoding of Fear and Extinction Memories in a Large-Scale Network Model of the Basal Amygdala

Abstract

The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

Author Summary

The amygdaloid complex is one of the key brain structures involved in fear-related processes. A typical way to study neural correlates of fear expression (e.g. freezing response) in the amygdala is to perform a fear conditioning paradigm, which yields a conditioned fear response. This response can be reversed by another procedure called fear extinction. Thanks to the experimental approaches to date we have some understanding about the putative roles of specific subnuclei within the amygdala in the formation of these fear and extinction memories. Here, we complement the experimental studies by providing a computational model that addresses the question of how fear and extinction memories are encoded in the amygdala, and specifically, in the basal nucleus (BA). We propose a specific neural mechanism to explain how the BA may integrate information about a salient, conditioned stimulus and the environment, thereby enabling it to switch the state of the animal from low to high fear and vice versa. We also provide possible explanations for various other behavioral findings, such as the recovery of fear after it had been extinguished (renewal). Finally, we make specific, experimentally testable predictions that need to be addressed in future work.