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Distinct prefrontal-amygdala connectivity drives consolidated fear memories

Created on 20 Aug 2026

Authors

Kenna, M., Kesby, J. P., Xu, L., Sullivan, R., Marek, R., Sah, P.

Abstract

Elucidating the neuronal circuitry that underpins memory formation is critical to understanding how organisms use past experience to guide adaptive behaviour. While memory formation has long been framed as the reactivation of a static ensemble of neurons established during initial learning, growing evidence suggests that memory traces are highly dynamic and undergo substantial reorganisation during consolidation. During the formation of auditory fear memory, initial acquisition is primarily mediated by the basolateral amygdala (BLA), whereas long-term expression relies on the medial prefrontal cortex (mPFC). However, the circuit motifs that coordinate this systemic redistribution remain poorly understood. Here, using targeted anatomical tracing and electrophysiology, we show that the reciprocal connectivity between the mPFC and BLA is organised as a parallel topography along the rostro-caudal axis. Leveraging this novel anatomical understanding of reciprocal communication between the amygdala and prefrontal cortex, we reveal an underlying circuitry mechanism by which fear memory traces are redistributed into subcortical-cortical networks after learning. Using activity-dependent engram capture and optogenetic manipulation, we demonstrate that post-learning engagement of a distinct sub-circuit linking the rostral BLA and rostral mPFC is a hallmark of the consolidated fear memory. These insights reveal that the consolidated engram requires the targeted engagement of a post-learning engram circuit, rather than a simple reactivation of neurons engaged during initial learning.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 20 Aug 2026.

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