• S Hong and O Hikosaka.
• McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA.
• Neuroscience. 2014 Dec 12; 282: 139-55.

AbstractDopamine (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. 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. Published by Elsevier Ltd.

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