Rapamycin attenuates reconsolidation of a backward conditioned fear memory

Trask, Jared (2024) Rapamycin attenuates reconsolidation of a backward conditioned fear memory. Masters thesis, Memorial University of Newfoundland.

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Abstract

The mechanistic target of rapamycin (mTOR) kinase has been implicated in the consolidation and reconsolidation of aversive memories. Most studies in this area employ a forward conditioning (FW) paradigm (Pavlovian or auditory fear conditioning) which consists of a conditioned stimulus (CS) that precedes the unconditioned stimulus (US). Little is known, however, about the neurobiological underpinnings of the reverse, backward (BW) conditioning paradigms, particularly in female mice. In BW conditioning, the CS does not become directly associated with the US; it instead evokes conditioned fear by reactivating a memory of the conditioning context and indirectly retrieving a memory of the aversive US. Our studies confirm and extend the findings on BW-conditioned fear memory processes to female mice. We show that conditioned freezing to a BW CS is mediated by fear to the conditioning context. Furthermore, the mTOR inhibitor rapamycin (RAPA), when given immediately following BW conditioning, impairs consolidation of both cued and contextual fear memory. Similarly, RAPA given following retrieval of a BW CS blocks context recall and CS retrieval is necessary to see the effects of RAPA on context memory recall. In sum, our study provides novel evidence that indirect retrieval cues are sensitive to RAPA in female mice.

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