Pedunculopontine tegmental nucleus neurons provide reward, sensorimotor, and alerting signals to midbrain dopamine neurons

Abstract

Dopamine (DA) neurons in the midbrain are crucial for motivational control of behavior. However, recent studies suggest that signals transmitted by DA neurons are heterogeneous. This may reflect a wide range of inputs to DA neurons, but which signals are provided by which brain areas is still unclear. Here we focused on the pedunculopontine tegmental nucleus (PPTg) in macaque monkeys and characterized its inputs to DA neurons. Since the PPTg projects to many brain areas, it is crucial to identify PPTg neurons that project to DA neuron areas. For this purpose we used antidromic activation technique by electrically stimulating three locations (medial, central, lateral) in the substantia nigra pars compacta (SNc). We found SNc-projecting neurons mainly in the PPTg, and some in the cuneiform nucleus (CuN). Electrical stimulation in the SNc-projecting PPTg regions induced a burst of spikes in presumed DA neurons, suggesting that the PPTg-DA(SNc) connection is excitatory. Behavioral tasks and clinical tests showed that the SNc-projecting PPTg neurons encoded reward, sensorimotor and arousal/alerting signals. Importantly, reward-related PPTg neurons tended to project to the medial and central SNc, whereas sensorimotor/arousal/alerting-related PPTg neurons tended to project to the lateral SNc. Most reward-related signals were positively biased: excitation and inhibition when a better and worse reward was expected, respectively. These PPTg neurons tended to retain the reward value signal until after a reward outcome, representing ‘value state’; this was different from DA neurons which show phasic signals representing ‘value change’. Our data, together with previous studies, suggest that PPTg neurons send positive reward-related signals mainly to the medial-central SNc where DA neurons encode motivational values and sensorimotor/arousal signals to the lateral SNc where DA neurons encode motivational salience.

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

“…Responses similar to those described above were also reported by Hong and Hikosaka [161] in a task in which monkeys had to perform a saccade toward a rewarded or not rewarded target. In this study different PPTg neurons were found that were phasically excited by reward- related cues, that tonically increased firing from cue to reward release, and that phasically increased firing when the reward was delivered.…”

“…Interestingly, some of the PPTg neurons in the Hong and Hikosaka' study [161] could be neurons projecting to thalamic targets because they were not antidromically activated from the substantia nigra.…”

“…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.…”

Neuronal Reward and Decision Signals: From Theories to Data

“…Positive dopamine prediction error response components may arise from direct excitatory inputs from pedunculopontine neurons (131) responding to sensory stimuli, reward-predicting cues, and rewards (136,228,396,410). In support of this possibility, inactivation of pedunculopontine neurons reduces dopamine stimulus responses (410).…”

“…Some neurons in the pedunculopontine nucleus are activated by both predicted and unpredicted rewards and by conditioned stimuli (136,396,410) but fail to show depressions to omitted rewards and thus process reward without producing a clear error signal (281). Pedunculopontine neurons with midbrain projections above substantia nigra show bidirectional error responses to reward versus no-reward-predicting cues, but only positive prediction error responses to the reward (228). Positive responses to unpredicted but not predicted rewards occur in norepinephrine neurons as part of their attentional sensitivity (22), and in nucleus basalis Meynert neurons (466).…”