Neuronal networks for control of eye movement

National Eye Institute

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Abstract

Choosing valuable objects is critical for survival, but their values may change flexibly or remain stable. Therefore, animals should be able to update the object values flexibly by recent experiences and retain them stably by long-term experiences. However, it is unclear how the brain encodes the two conflicting forms of values and controls behavior accordingly. We found that distinct circuits of the primate caudate nucleus control behavior selectively in the flexible and stable value conditions. Single caudate neurons encoded the values of visual objects in a regionally distinct manner: flexible value coding in the caudate head and stable value coding in the caudate tail. Monkeys adapted in both conditions by looking at objects with higher values. Importantly, inactivation of each caudate subregion disrupted the high-low value discrimination selectively in the flexible or stable context. This parallel complementary mechanism enables animals to choose valuable objects in both flexible and stable conditions. The lateral habenula (LHb) plays an important role in motivational decision making. Neurons in the primate LHb signal negative 'reward prediction errors' and inhibit midbrain dopamine (DA) neurons. These negative reward prediction error signals in the LHb are, at least partly, provided by a distinct group of neurons in the border region of the globus pallidus internal segment (GPb). However, it is still unclear whether other basal ganglia nuclei provide the LHb with reward signals, either through the GPb or through different circuits. As a first step to answer this question, we electrically stimulated various parts of the basal ganglia and monitored the neural activity in the LHb in the awake monkey. First, we found that low intensity stimulations in the GPb and the internal segment of the globus pallidus (GPi) evoked a short latency (5 ms) excitatory response in LHb neurons. Second, LHb neurons were inhibited by stimulations in the ventral pallidum (VP). These results suggest that reward-related signals are transmitted to the LHb mainly through excitatory connections from the GPb and inhibitory connections from the VP. Finally, excitations or inhibitions are induced in LHb neurons from diverse but patchy regions in the striatum. These effects have considerably longer latencies, suggesting that they may be mediated by the GPb or the VP. The patchy nature of the stimulation effect raises the possibility that the striosomes are the source of reward-related signals transmitted to the LHb. 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. 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. The basal ganglia are equipped with inhibitory and disinhibitory mechanisms that enable a subject to choose valuable objects and actions. Notably, a value can be determined flexibly by recent experience or stably by prolonged experience. Recent studies have revealed that the head and tail of the caudate nucleus selectively and differentially process flexible and stable values of visual objects. These signals are sent to the superior colliculus through different parts of the substantia nigra so that the animal looks preferentially at high-valued objects, but in different manners. Thus, relying on short-term value memories, the caudate head circuit allows the subject's gaze to move expectantly to recently valued objects. Relying on long-term value memories, the caudate tail circuit allows the subject's gaze to move automatically to previously valued objects. The basal ganglia also contain an equivalent parallel mechanism for action values. Such flexible-stable parallel mechanisms for object and action values create a highly adaptable system for decision making.