Role of post-learning auditory thalamic and cortical circuit pathways in fear memory consolidation

Abstract

Coordinated activities of inter-regional brain networks during the post-learning period are thought to be critical for consolidation of memories. Previous studies have investigated whether the amygdala consolidates a variety of memories through interaction with other brain regions after learning, but relatively little has been known about the neural network mechanism for the consolidation of fear memories. It has been well established that auditory input to the lateral nucleus of amygdala (LA) is essential for acquisition and retrieval of auditory fear memory. Accumulating evidence suggests that fear conditioning induces associative plasticity not only in the amygdala but also in regions outside the amygdala, including various stages of the auditory pathways. Despite these findings, it is unknown whether auditory inputs to the LA are necessary during a post-learning period for consolidation of fear memory. To investigate this question, I optogenetically silenced the inputs from both auditory cortex (AuV/TeA) and thalamus (MGm/PIN) in the lateral amygdala (LA) for 15 min immediately following auditory fear conditioning (FC) and examined its effect on fear memory formation in mice. Optogenetic inhibition of both inputs impaired fear memory formation tested 24 h after FC. This effect was specific to long-term auditory fear memory such that the same inhibition did not affect short-term memory and context-dependent memory. Moreover, long-term memory was intact if both auditory inputs were inhibited at much later time points after FC (3 h or 1 d after FC), indicating that 15 min inhibition itself does not produce any non-specific harmful effect on fear memory retrieval. Selective inhibition of thalamic input was sufficient to impair consolidation of auditory fear memory. In contrast, selective inhibition of cortical input disrupted consolidation of remote fear memory without affecting recent memory. These results reveal a dissociated role of auditory pathways to the LA during early post-learning periods for consolidation of long-term fear memory.