Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks

Abstract

The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target (FT), then made saccades to the peripheral saccade target and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity continued until the disappearance of the saccade target (ST) after reward delivery. Thus, for these neurons, the tonic activity might be related to maintaining attention to complete fixation behavior. These results suggest that, in addition to the reward value information, some PPTg neurons might contribute to the execution of conditioned task behavior.

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

“…These neurons did not give any response to unexpected reward. However, when the target cue was kept on after reward delivery, instead of being turned off, a subpopulation of PPTg neurons showed sustained activity, indicating that the monkey continued fixating on the saccade target even after the reward delivery [163]. This may be indicative of the existence of PPTg neurons that sustain attention toward the actual task event rather than toward reward.…”

“…The tonic reward-related responses consisted of either a sustained increase of discharge [161][162][163], or sustained depression [162]. Most of the sustained increased activity developed from the onset of the initial fixation target until reward delivery, and the magnitude of the response was higher when the shape of the fixation target cued the animal to expect a large reward.…”

Deep brain stimulation and eye movements

“…It acts as an integrator of activity from BG, cerebellum, and motor cortex and is an important part of at least three distinct systems: rostral locomotion region, arousal system, and behavioural state control. Indeed, neurophysiological studies in monkeys showed an alteration of firing rate in PPN neurons not only before and during voluntary movements, but also during reflexive and voluntary saccades and fixation (Kobayashi, Inoue, Inoue, Yamamoto, Isa, & Aizawa, 2002; Okada & Kobayashi, 2009, 2014, 2016). The PPN influence upon saccades is probably due to direct PPN projections to SC (PPN cholinergic neurons; Kobayashi, Yoshida, Yoshida, & Inouye, 2009) and STN (predominately inhibitory, GABAergic PPN neuron projections; Mena‐Segovia & Bolam, 2017).…”