DCN Seminar by Dr. Masakazu Taira

GABAergic neurons in lateral hypothalamus (LHGABA) are critical for learning about reward cues. We have shown that LHGABA neurons differently regulate learning about reward cues depending on the relative distance of the cues to rewards. This led to our hypothesis that LHGABA neurons bias behaviours toward cues closest to reward and away from distal cues. To formally investigate this in rats, we adapted the “Daw two-step task”, which quantifies the ability of human subjects to use complex task structure to predict rewards. This task enables us to measure the weights of distal and proximal cues on future choices. Rats first receive one of two distal cues that are further from reward followed by presentation of two levers. Rats press one of the levers and then receive one of two proximal cues. The distal cues inform different state transitions from the levers to the proximal cues. In turn, the proximal cues inform the fluctuating reward probabilities (high/low). We found that rats can guide their choices by using the transitional structure of the task. We also found that using different outcomes following distal cues promoted rats to better use the task structure. Lastly, optogenetic inhibition of lateral orbitofrontal cortex during distal cues and outcome delivery in the task reduced the ability of rats to use the task structure to modulate performance, while the optogenetic inhibition during proximal cues did not affect their abilities of using the task structure. Overall, these results validate the task for optogenetic investigation of model-based behaviour as dictates by distal and proximal cues. Next, we will investigate the contribution of LHGABA neurons to the different components of this task.