Learning, sleep replay and consolidation of contextual fear memories: A neural network model

Abstract

Contextual fear conditioning is an experimental framework widely used to investigate how aversive experiences affect the valence an animal associates with an environment. While the initial formation of associative context-fear memories is well studied - dependent on plasticity in hippocampus and amygdala - the neural mechanisms underlying their subsequent consolidation remain less understood. Recent evidence suggests that the recall of contextual fear memories shifts from hippocampal-amygdalar to amygdalo-cortical networks as they age. This transition is thought to rely on sleep. In particular, neural replay during hippocampal sharp-wave ripple events seems crucial, though open questions regarding the involved neural interactions remain. Here, we propose a biologically informed neural network model of context-fear learning. It expands the scope of previous models through the addition of a sleep phase. Hippocampal representations of context, formed during wakefulness, are replayed in conjunction with cortical and amygdalar activity patterns to establish long-term encodings of learned fear associations. Additionally, valence-coding synapses within the amygdala undergo overnight adjustments consistent with the synaptic homeostasis hypothesis of sleep. The model reproduces experimentally observed phenomena, including context-dependent fear renewal and time-dependent increases in fear generalisation. Few neural network models have addressed fear memory consolidation and to our knowledge, ours is the first to incorporate a neural mechanism enabling it. Our framework yields testable predictions about how disruptions in synaptic homeostasis may lead to pathological fear sensitization and generalisation, thus potentially bridging computational models of fear learning and mechanisms underlying anxiety symptoms in disorders such as PTSD. Author SummaryHow do we learn to fear certain environments? Why do some fear memories fade while others persist or even grow stronger over time? Scientists have long used laboratory experiments to study how animals associate danger with a particular context. These studies have helped identify brain regions involved in fear learning, including the amygdala, hippocampus, and cortex, and have inspired many computational models of how fear is acquired in the brain. However, most models focus only on what happens when fear is first learned, overlooking how these memories evolve in the days that follow and the role of sleep in this process. In this work, we present a neural network model that captures how fear memories are strengthened or reshaped during sleep. It builds on earlier models by incorporating memory replay and synaptic homeostasis, two brain processes believed to support emotional memory consolidation. Our model identifies neural processes that help make fear memories persistent, suggests that sleep is necessary to maintain adaptive behaviour after threatening experiences, and proposes that sleep disruptions mediate the harmful impact of stress on emotional regulation. By extending amygdala-based models of fear learning to include post-learning dynamics, our work offers new insight into how emotional memories are stabilised.