Investigation of context-dependent decision making along the olfactory pathway

Abstract

Contrary to the long-held belief that the prefrontal cortex (PFC) is critical for working memory and decision- making, recent findings suggest a negligible engagement of this area, especially in the context of olfactory delayed match-to-sample (DMS) tasks. This study reevaluates the neural substrates for working memory and decision- making by extending the focus beyond the PFC to the entire olfactory pathway. I delve into the possibility that early sensory cortices, in addition to traditional downstream areas like the hippocampus, might play a pivotal role in context-dependent sensory processing, influencing behavioral outcomes directly. Furthermore, this study addresses the intricate challenge of disentangling match/nonmatch signals from choice (action selection) signals in neural responses. Traditional task paradigms have often blurred these distinctions, leaving ambiguity in interpreting whether neural activities represent stimulus coding or choice. To answer these questions, our approach includes a comprehensive survey of neuronal activity across various brain regions using advanced recording techniques (Neuropixels) to encompass a wide array of areas efficiently and unique analytical technique. To effectively collect neuronal data across various brain regions from well-trained mice in a time-efficient manner, reducing training time should be prioritized. To achieve this, I first developed an automated side bias correction system in an olfactory DMS task, where the lickport positions and the ratio of left- and right-rewarded trials are dynamically adjusted to counterbalance mouse’s biased licking responses during training. This algorithm successfully reduced the training period for the DMS task to one-third of that reported in the previous study conducted under similar experimental settings. The comprehensive survey of neuronal activity reveals that in well-trained mice, early sensory areas such as the Anterior Olfactory Nucleus (AON) show significant involvement in memory retention and decision-making processes. This involvement contrasts with the minimal representation observed in traditionally acknowledged PFC sub-regions (prelimbic, infralimbic, orbito-frontal cortex). Notably, the correlation between working memory representation in upstream areas like the AON and CA1 with behavioral performance challenges the conventional view of higher-order cortical areas as the primary sites of working memory and decision-making. Our results suggest a paradigm shift, advocating for a new perspective where sensory areas are integrally involved in sensory encoding, working memory, match/nonmatch, and choice, thus challenging the traditional hierarchical model of neural processing in perceptual decision making.