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brainCOGS - circuits of COGnitive Systems. Carlos Brody. Mechanisms of neural circuit dynamics in working memory and decision-making

Abstract 2:

Title: The role of the hippocampus in context-dependent decision-making

Abstract: Many decisions depend on context; for example, “which shirt should I wear?” depends on whether you are going to work or a party. Decision-making (DM) thus often requires individuals to evaluate the consequences of multiple actions based on stored contextual memories. How does the mammalian brain make such context-dependent decisions? On the one hand, cellular recordings in rodents have characterized the neural circuit mechanisms involved in DM in multiple frontoparietal brain regions. On the other hand, lesion and inactivation studies have shown that the hippocampus (HC) is necessary for context-specific memory retrieval. Yet, the role of the HC in guiding context-dependent DM is unknown. We developed a virtual-reality T-maze navigation task in which head-fixed mice are required to make context-dependent spatial decisions. In one T-maze context, mice are trained to turn toward a visible turn guide; in the other context, mice are trained to turn away from a turn guide. This task is decomposable into sensory (e.g., visual cues), behavioral (e.g., running speed) and cognitive (e.g., context) components. While mice perform this task, we plan to conduct i) cellular-resolution two-photon imaging of the dentate gyrus (DG) HC subfield, ii) time-dependent optogenetic inactivation of the DG, iii) activity-dependent optogenetic reactivation of context-specific DG neural populations, and iv) electrophysiological recordings of prefrontal brain regions known to be involved in DM (e.g., premotor cortex) during simultaneous optogenetic inactivation or reactivation of DG. We hope these data could contribute to:

1.  Models of HC contextual separation, such as attractor neural networks or autoassociative memory models.
2. The development of models characterizing how HC contextual separation might drive DM-related activity in cortical brain regions.

With regard to the second point, for instance, HC context representations might gate or modulate the entire DM process itself, such that all DM computations occur in a context-dependent manner. Alternatively, HC contextual separation might gate or modulate only the output of DM-related processes, to decide the most suitable action given the current context. Adjudicating between these alternatives would strongly benefit from a flexible theoretical model that links HC contextual separation to DM computations at different stages of the DM process, which could then be constrained through targeted experimental manipulations.

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