Kae Nakamura

Parallel neural networks for learning sequential procedures

Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism.

Reward-dependent modulation of neuronal activity in the primate dorsal raphe nucleus

The dopamine system has been thought to play a central role in guiding behavior based on rewards. Recent pharmacological studies suggest that another monoamine neurotransmitter, serotonin, is also involved in reward processing. To elucidate the functional relationship between serotonin neurons and dopamine neurons, we performed single-unit recording in the dorsal raphe nucleus (DRN), a major source of serotonin, and the substantia nigra pars compacta, a major source of dopamine, while monkeys performed saccade tasks in which the position of the target indicated the size of an upcoming reward. After target onset, but before reward delivery, the activity of many DRN neurons was modulated tonically by the expected reward size with either large- or small-reward preference, whereas putative dopamine neurons had phasic responses and only preferred large rewards. After reward delivery, the activity of DRN neurons was modulated tonically by the received reward size with either large- or small-reward preference, whereas the activity of dopamine neurons was not modulated except after the unexpected reversal of the position–reward contingency. Thus, DRN neurons encode the expected and received rewards, whereas dopamine neurons encode the difference between the expected and received rewards. These results suggest that the DRN, probably including serotonin neurons, signals the reward value associated with the current behavior.

Role of Dopamine in the Primate Caudate Nucleus in Reward Modulation of Saccades

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position–reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus.

Coding of Task Reward Value in the Dorsal Raphe Nucleus

The dorsal raphe nucleus and its serotonin-releasing neurons are thought to regulate motivation and reward-seeking. These neurons are known to be active during motivated behavior, but the underlying principles that govern their activity are unknown. Here we show that a group of dorsal raphe neurons encode behavioral tasks in a systematic manner, tracking progress toward upcoming rewards. We analyzed dorsal raphe neuron activity recorded while animals performed two reward-oriented saccade tasks. There was a strong correlation between the tonic activity level of a neuron during behavioral tasks and its encoding of reward-related cues and outcomes. Neurons that were tonically excited during the task predominantly carried positive reward signals. Neurons that were tonically inhibited during the task predominantly carried negative reward signals. Neurons that did not change their tonic activity levels during the task had weak reward signals with no tendency for a positive or negative direction. This form of correlated task and reward coding accounted for the majority of systematic variation in dorsal raphe response patterns in our tasks. A smaller component of neural activity reflected detection of reward delivery. Our data suggest that the dorsal raphe nucleus encodes participation in a behavioral task in terms of its future motivational outcomes.

Facilitation of Saccadic Eye Movements by Postsaccadic Electrical Stimulation in the Primate Caudate

Sensorimotor experience followed by positive feedback leads to motor learning. Although the striatum, an input channel of the basal ganglia, has been implicated to play a key role in motor learning, little is known about how reward information modulates the neuronal processes in the striatum that causes behavioral changes. Here, we report that direct manipulation of the neuronal signal in the primate caudate yields behavioral changes comparable with those induced by natural reward. Electrical stimulation in the oculomotor region of the caudate immediately after saccades to a fixed direction led to selective facilitation of saccades in that direction. The facilitation remained even after stimulation was stopped, indicating a plastic change. These effects were observed when stimulation was applied after, not before, saccades. We propose that the caudate plays a causal role in behavioral changes by integrating selective sensorimotor and reward information in a temporally specific manner.

Cerebromalacia with Epilepsy and Cortical Blindness in a Laboratory Japanese Macaque (Macaca fuscata)

The authors performed a pathological examination of a 5-year-old female laboratory Japanese monkey who developed cortical blindness and epileptic seizures. Generalized, tonic-clonic seizures started to occur during behavioral training to get the animal to enter a carrying cage for future psychological experiments. Blindness was suspected because of a lack of approaching behavior toward foods such as fruits. Although the monkey was extensively treated with anticonvulsants, the clinical signs did not improve. An increased serum creatine phosphokinase (CPK) level and bilateral occipital brain atrophy were detected. Histopathologically, a severe degree of cerebromalacia was detected bilaterally in the occipital lobe, and necrosis and gliosis were seen mainly in the temporal lobe. Focal inflammation was found in the meninges. No other changes were observed in other nervous tissues or organs, and no signs of a parasitic or viral infection were found in the systemic organs. Spontaneously occurring lesions in the central nervous system have been rarely reported in laboratory monkeys. In the present case, the cause of cerebromalacia could not be confirmed, but the relationship between symptoms such as abnormal vision and the presence of brain lesions was distinct. The authors believe that this case is a valuable historical control case for the laboratory Japanese macaque.