Fear learning, where a neural cue or environment (CS) is paired with a fearful event such as a shock (US), is a widely used model for investigating the mechanism of learning. Although learning typically involves plastic changes in individual neurons, the activated neural circuitry varies depending on the learning paradigm.

We here present learning-specific neural activation patterns using the engram tagging technique in prefrontal cortices and the hippocampus - regions implicated in converting learned information into long-term memories. Engram tagging allows for labelling of neurons that become active during specific phases of learning. We employed a technique called robust activity marking to label neurons active during the learning or retrieval of classical fear conditioning, trace conditioning, cued and contextual conditioning.

While many published studies have tagged neurons active in classical fear conditioning to identify the “learning engram”, our data suggests that the activity patterns during the learning stage reflects the sensory processing of cues and the shock. In contrast, tagging of neurons active during the retrieval of the learned fear revealed significantly more activity in hippocampal areas for encoding contextual and trace conditioned fear. Retrieval of trace conditioning also led to significantly more activity in the anterior cingulate cortex.

Together, this dataset reveals neural activation patterns that are highly dependent on the learning modality and underscores the importance of considering learning-paradigms that drive specific neural circuits. Further, the neural circuits active during learning may not represent a true memory, but rather an ensemble of activated neurons encoding sensory information.