Anxiety induced working memory disruption is mediated by amygdala-ventral hippocampal circuit

Abstract

Cognitive functions can be impacted by anxiety. In particular, anxiety is regarded to restrict a capacity of working memory by competing with task-relevant processes. Previous studies have shown that there would be an interaction between anxiety and working memory function. However, it is still elusive that how anxiety-related brain circuits affect working memory dysfunction. In this study, mice were allowed to conduct working memory task after inducing anxiety by an anxiogenic drug or optogenetic stimulation. Simultaneous electrophysiological recordings were also performed to verify neural underpinnings of working memory dysfunction in anxious period. During the nonmatch-to-place T-maze task, one of the typical behavior tasks for measuring working memory function, mice showed significantly reduced performance when the anxiogenic drug (picrotoxin) was injected intraperitoneally. Optogenetic inhibition of the circuit from the basolateral amygdala (BLA) to the ventral hippocampus (vHPC), which was previously reported as an anxiogenic circuit, restored the working memory dysfunction by the drug. In the same vein, optogenetic excitation of the circuit also significantly reduced the working memory function during the task. Moreover, delay period-specific excitation also significantly reduced working memory function and the impairments depended on the delay time (the longer delay time, the more impairments), suggesting that anxiety might be a disturbance factor for maintaining the working memory ability. Results of local field potentials and single unit recordings in the medial prefrontal cortex (mPFC) and the vHPC was showed that coherence between two regions was significantly weakened during the maintaining period of working memory in anxious situations. In addition, pattern of the mPFC units distorted when the mice showed working memory deficit in anxious status and the distortion was restored after the bilateral inhibition of the BLA to vHPC circuit. Thus, these data suggest that the BLA to the vHPC circuit mediates working memory disruption in anxiety-dependent manner and the dysfunction involved changes of electrophysiological features in the mPFC.