Our current research is focused on the neuronal networks in the basal ganglia which control eye movements. We have shown that sensory and cognitive signals carried by neurons in the basal ganglia are strongly modified by expected reward. We hypothesized that the reward-dependent modulation occurs within the basal ganglia. Specifically, excitatory inputs from the cerebral cortical areas to the caudate nucleus (CD), which carry spatial signals, are modulated by inputs from midbrain dopamine (DA) neurons. To test this model, we conducted two kinds of experiments by injecting DA antagonists and electrically stimulate the CD.? DA antagonist injections: According to the model, the sensorimotor activity of CD projection neurons is modulated by the concurrent DA input and the result is expressed as the reward modulation of CD neuronal activity and consequently as the reward modulation of saccadic behavior. Then, if the DA input is blocked, the reward modulation of saccade behavior as well as CD neuronal activity would be eliminated. Among at least five types of DA receptors, mainly D1 and D2 receptors are expressed in CD projection neurons, D1 predominantly in direct-pathway neurons and D2 predominantly in indirect-pathway neurons. We injected a D1 antagonist and a D2 antagonist into the region of the CD where saccade-related neurons are clustered while the monkey performed a reward-biased saccade task. We found that D1 antagonist, not D2 antagonists, attenuates the reward modulation of saccade behavior. The results suggest that: 1) the reward modulation of saccade behavior is originated from the CD; 2) the DA input to CD projection neurons is responsible for the reward modulation; 3) the DA effect is mediated by D1 receptors. However, the results do not indicate that the DA-input to CD projection neurons is the only source of the reward modulation of saccade behavior. ? Saccade-associated CD electrical stimulation: The result of the first experiment was encouraging, but might not completely support the model which claims the importance of the concurrent activation of cortical and DA inputs. For example, the blockade of D1 receptor activation might change the general condition of CD projection neurons and disable their plasticity. The second experiment tested whether the reward modulation of saccade behavior can be promoted, rather than blocked. While the monkey was engaged in a visually guided saccade task, the saccade-related area of the CD was electrically stimulated only after the monkey made a saccade and only when the saccade was directed to a particular position. After repeating the trials, the latency became gradually shorter for the saccade that was associated with electrical stimulation and the effect remained even after the stimulation was stopped. The results may be interpreted as in the following. Many CD neurons around the stimulating electrode may become active at the time of the saccade, perhaps responding to cortical inputs. If electrical stimulation is applied further around such CD neurons, the neurons? response to the cortical input is enhanced plastically. However, the electrical stimulation would activate various neuronal elements around the CD neurons. At this moment it is unclear which element is responsible for the plastic change of CD neuronal responses.
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