Kazuko Nakao

Appetitive and Aversive Information Coding in the Primate Dorsal Raphé Nucleus

Serotonin is known to play a key role in the regulation of emotional behavior. There have been conflicting hypotheses about whether the central serotonergic system is involved in positive or negative emotional information processing. To reveal whether and how such opposing information processing can be achieved by single neurons in the dorsal raphé nucleus (DRN), the major source of serotonin in the forebrain, we recorded the activity of DRN neurons while monkeys were conditioned in a Pavlovian procedure with two distinct contexts: an appetitive block where a reward was available; and an aversive one where an airpuff was delivered. We found that single DRN neurons were involved in several aspects of both appetitive and aversive information processing. First, more than half of the recorded DRN neurons discriminated between appetitive and aversive contexts by tonic changes in their activity. In the appetitive context, they then kept track of the expected reward value indicated by the conditioned stimuli. Some of them also encoded an error between the obtained and expected values. In the aversive context, the same neurons maintained tonic modulation in their activity throughout the block. However, modulation of their responses to aversive task events depending on airpuff probability was less common. Together, these results indicate that single DRN neurons encode both appetitive and aversive information, but over differing time scales: relatively shorter for appetitive, and longer for aversive. Such temporally distinct processes of value coding in the DRN may provide the neural basis of emotional information processing in different contexts.

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.

Neuronal coding of rewarding and aversive stimuli in the primate dorsal raphe nucleus

Neuronal activity in the dorsal raphé nucleus (DRN), a major source of serotonin, is modulated by the received reward size. To investigate whether DRN neurons code rewarding or aversive stimuli and/or positive or negative prediction error, we recorded single-unit activity in the DRN of two monkeys performing the trace conditioning task. This task consisted of two blocks with distinct contexts. In the appetitive block, liquid reward was used as an unconditioned stimulus (US). In the aversive block, air-puff directed at the monkey face was used as a negative US. In both blocks, three visual stimuli (conditioned stimuli: CSs) were paired with the US, with probabilities of 100, 50 and 0%, respectively. To confirm that monkeys learned the association of each specific CS with the US, we monitored licking behavior and anticipatory eye blinking. In 50 and 0% trials, tone was presented as a neutral stimulus in the absence of reward or air-puff. We recorded 211 task-related neurons. It was found that DRN neurons responded to the CSs in the appetitive block more often than in the aversive block; 38% (n = 81) responded to the rewarding CS with 100% probability, while 9% (n = 19) responded to the aversive CS with 100% probability. Among them, 13 neurons responded to both rewarding and aversive CSs. Many DRN neurons also responded to the USs (n = 176); either to reward only (n = 35), to air-puff only (n = 57) or to both (n = 84). In the appetitive block, rewardrelated activity was modulated by its probability with stronger response to the unpredicted than the predicted US. In the aversive block, short-latency response to air-puff delivery was frequently observed regardless of the CS-US predictability. These results suggest that the primate DRN codes information about both rewarding and aversive stimuli, and some DRN neurons exhibited activity similar to reward prediction error reported for dopamine neurons.