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The lateral hypothalamus (LH), which plays a role in homeostatic functions such as appetite regulation, is also linked to arousal and motivational behavior. However, little is known about how these components are encoded in the LH. Thus cynomolgus monkeys were conditioned with two distinct contexts, i.e., an appetitive context with available rewards and an aversive context with predicted air puffs. Different LH neuron groups encoded different degrees of expectation, predictability, and risks of rewards in a specific manner. A nearly equal number of one-third of the recorded LH neurons showed a positive or negative correlation between their response to visual conditioned stimuli (CS) that predicted the probabilistic delivery of rewards (0%, 50%, and 100%) and the associative values. For another one-third of recorded neurons, a nearly equal number showed a positive or negative correlation between their responses to rewards [appetitive unconditioned stimulus (US)] and reward predictability. Some neurons exhibited their highest or lowest trace-period responses in the 50% reward trials. These response modulations were represented independently and overlaid on a consistent excitatory or inhibitory response across the conditioning events. LH neurons also showed consistent responses in the aversive context. However, the responses to aversive conditioning events depending on the air puff value and predictability were less common. The multifaceted modulation of consistent activity related to outcome predictions may reflect motivational and arousal signals. Furthermore, it may underlie the role the LH plays in the integration and relay of signals to cortices for adaptive and goal-directed physiological and behavioral responses to environmental changes.    NEW &amp; NOTEWORTHY The lateral hypothalamus (LH) is implicated in motivational and arousal behavior; however, the detailed information carried by single LH neurons remains unclear. We demonstrate that primate LH neurons encode multiple combinations of signals concerning different degrees of expectation, appreciation, and uncertainty of rewards in consistent responses across conditioning events and between different contexts. This multifaceted modulation of activity may underlie the role of the LH as a critical node integrating motivational signals with arousal signals.

Encoding prediction signals during appetitive and aversive Pavlovian conditioning in the primate lateral hypothalamus