NIGRO-COLLICULAR PATHWAYS FOR APPETITIVE AND THREAT RESPONSES

Animals make decisions in response to environmental cues motivated by different internal states. In auditory-based decision making, the tail of striatum (TS) is involved in both reward seeking and threat avoidance behaviors, but the neural circuits mediating each of these behaviors remain unknown. To investigate the mechanisms by which the TS controls appetitive and threat responses, we developed two behavioral paradigms for mice. The first is a two-alternative forced choice (2AFC) task (Fig. 1a), in which auditory or visual cues are presented in blocks (Fig. 1b), allowing the direct comparison of behavioral outcomes following circuit inhibition. We found that the TS is required for executing auditory-guided, but not visually-guided choices (Fig. 1c). Modeling of the 2AFC task reveals that animals exhibit distinct behavioral states that they differentially occupy across modalities (Fig. 1d,e). The second paradigm is an escape task (Fig. 1f), in which animals display distinct fear-related behaviors, including freezing and escaping (Fig. 1g). Across days, animals learn to suppress their escapes (Fig. 1h). In ongoing experiments we are generating a brain-wide activity map using cfos staining and light-sheet imaging to reveal the brain areas specifically active in auditory-guided decisions. To causally investigate the relevant circuits downstream the TS, we are employing chemogenetic approaches to manipulate nigro-collicular (Fig. 1i) projections across both behavioral paradigms. This will allow us to understand if there is a dissociation in basal ganglia output pathways by which the TS controls these core behaviors, and to examine how different motivational contexts shape auditory-driven decision making.