Toshiyuki Sawaguchi

Dopamine enhances the neuronal activity of spatial short-term memory task in the primate prefrontal cortex.

The influence of dopamine and its antagonists on neuronal activity related to the delay period of a delayed response task was examined in the monkey prefrontal cortex. Iontophoretically applied dopamine enhanced the delay-related neuronal activity, while fluphenazine and haloperidol attenuated the activity. Sulpiride had no effect on the activity. The results suggest that dopamine promotes processing of spatial short-term memory by increasing memory-related activity in the primate prefrontal cortex, probably via D1-type dopamine receptor.

Delayed response deficits produced by local injection of bicuculline into the dorsolateral prefrontal cortex in Japanese macaque monkeys.

SummaryBicuculline (10–30 μg, but usually 30 μg) was injected locally into 20 different sites in the dorsolateral prefrontal cortex (PFC) of 2 Japanese macaque monkeys, while they were performing a delayed response task. The task was initiated by the rotation of a handle to a central zone by the wrist joint and consisted of seven periods: an initial waiting period of 0.3 s, a pre-cue period (central green lamp of 1.0 s), a cue period (left or right green cue of 0.3 s), a delay period of 4.0 s (occasionally 1 s), a go period (central red lamp; rotation of the handle to either the left or right zone within 1.0 s), a hold period (holding of the handle in either the left or the right zone), and a final reward period. The parameters of the task performance, such as the frequency of correct trials, the frequency of directional error trials in which the monkeys rotated the handle in an incorrect direction during the go period, and the frequency of omission error trials, in which the monkeys did not rotate the handle during the go period, were examined before and after the injection of bicuculline. The injections of bicuculline induced a burst of multi-neuronal activity around the sites of injection. Within 5 min of an injection into one of 7 different sites in the PFC, three different kinds of performance deficit were observed: 1) an increase in the frequency of error responses during the go period in both left-cue and right-cue trials, after injection into the dorso-caudal portion of the principal sulcus (2 sites); 2) an increase in the frequency of directional error responses during the go period in either left-cue or right-cue trials, after injection into the bottom of the middle principal sulcus (3 sites), and 3) an increase in the frequency of omission of responses during the go period, after injection into the dorsal region of the caudal principal sulcus (2 sites). Injections at the remaining 13 sites did not induce any deficits, although injections into the dorsal bank of the principal sulcus (3 sites) induced a decrease in the frequency of the task trials as a result of prolonged intertrial intervals (ITIs). Our results suggest that locally disturbed neuronal activity in different small areas of the PFC induces different deficits in the performance of the delayed response task. Neuronal activity in different, localized areas of the PFC may be involved in different processes of a performance that is based on spatial short-term memory.

The Size of the Neocortex in Relation to Ecology and Social Structure in Monkeys and Apes

In an attempt to reveal factors associated with neocortical development in monkeys and apes (anthropoids), relationships between the relative size of the neocortex and differences in ecology and social structure were examined for 24 genera of 11 subfamilies. Relative sizes of the neocortex (RSNs) in a given group were assessed as the difference between actual neocortical volume and the volume expected from an allometric relationship between neocortical volume and the volume of the rest of the brain. We found that RSNs are related to diet and social structure: frugivorous anthropoids had higher values of RSNs than folivorous anthropoids, and polygynous anthropoids had significantly higher values of RSNs than monogynous anthropoids. Furthermore, RSNs were positively correlated with the size of the troop. These results suggest that development of the neocortex is associated with both diet and social structure in anthropoids.

Delayed response deficit in monkeys by locally disturbed prefrontal neuronal activity by bicuculline

Effects of local injection of a gamma-aminobutyric acid antagonist, bicuculline (10-30 micrograms dissolved in saline) in the principal prefrontal cortex on the delayed response task were investigated in two monkeys. On a visual Go signal, the monkeys rotated a handle to the left or to the right (Go period) according to a visual cue (left or right; 1 s) presented 4 s earlier. Bicuculline induced bursting activity at the injected site 1-2 min after the injection and 5 min later the burst activity spread to nearby cortical areas (less than 4 mm diameter). Within 5 min after injection, the monkeys showed errors in Go periods, rotating the handle to the contralateral zone, regardless of the cue side. This tendency continued for 30-40 min and returned to the control level. Electromyographic recordings of forearm muscles did not show any changes. The effect was observed when the drug was injected into a circumscribed area of the bottom of the mid-principalis region. It appears that disturbed neuronal activity in a small group of cortical columns induces performance errors of specific direction of the delayed response.

Correlations of Cerebral Indices for 'Extra' Cortical Parts and Ecological Variables in Primates

Correlations between cerebral indices for extra cortical parts associated with advanced functions (Jersons extra neurons, Nc; Hofmans extra cortical volume, Ve, and Hofmans extra cortical surface, Se) and ecological variables, namely troop size (TS), size of home range of one troop (HRt), and size of home range per individual (HRi) were examined in 12 species of prosimians, 8 species of New World monkeys, and 27 species of Old World monkeys. All three of the cerebral indices, Nc, Ve, and Se were, among the ecological variables examined, positively and most closely correlated with TS in the prosimians, with HRt in the New World monkeys, and with HRi in the Old World monkeys. These results suggest that the cerebral cortex may have expanded in relation to growth of TS for prosimians, in relation to expansion of HRt for New World monkeys, and in relation to expansion of HRi for Old World monkeys. It is, therefore, possible that the cerebral cortex may have expanded in conjunction with changes in different ecological factors in different taxonomic groups of primates.

Laminar distributions of neurons sensitive to acetylcholine, noradrenaline and dopamine in the dorsolateral prefrontal cortex of the monkey

Sensitivities of neurons to acetylcholine (ACh), noradrenaline (NA) and dopamine (DA) were investigated at different depths of the dorsolateral prefrontal cortex (PFC) in awake or halothane-anesthetized macaque monkeys, using microiontophoretic techniques with multi-barreled electrodes. The laminar locations of tested neurons (n = 403) were estimated by reconstructing electrode tracks based on the microlesion made by passing a current through the recording barrel, which contained a carbon fiber. Iontophoretically applied drugs induced excitatory or inhibitory responses. Neurons excited by ACh (n = 105) were located mainly in layers III and V, and those inhibited by ACh (n = 126) were in layers III and IV. The majority of the NA-sensitive neurons (n = 123) were NA-inhibited neurons (n = 100), and were found most often in layers III and IV. The ratio of DA-sensitive neurons (excited, n = 74; inhibited, n = 63) to tested neurons was higher in the deep layers than in the superficial ones. These results indicate that sensitivities of the PFC neurons to ACh, NA and DA are not uniform between cortical layers, suggesting that each of these substances may predominantly influence the neuronal activity of particular layers of the monkey PFC.

Dopamine modulates neuronal activities related to motor performance in the monkey prefrontal cortex

Effects of iontophoretically applied dopamine were investigated in prefrontal neurons of the monkey which showed activity changes during a visual reaction time task. The task consisted of an initial waiting phase (3.0 s), a warning phase (green lamp, 1.5-3.5 s), a lever-release GO phase (red lamp) and a reward phase. The neurons (n = 99) showed their activity changes during the warming (n = 31), GO (n = 43) or reward (n = 25) phase. Among those, dopamine predominantly influenced the GO phase-related activities (39/43) and the activity changes were enhanced by dopamine. Further, fluphenazine attenuated the GO phase-related activity changes. Results suggest that prefrontal dopamine may be involved in modulations of neuronal activities related to motor performance.

Relationships between Cerebral Indices for 'Extra' Cortical Parts and Ecological Categories in Anthropoids

The relationships between cerebral indices for extra cortical parts associated with advanced functions [Jerisons extra neurons (Nc), Hofmans extra cortical volume (Ve)] and ecology and social structure were examined for a total of 86 species of anthropoids (28 species of New World monkeys, 48 species of Old World monkeys and 10 species of apes). The species were divided into a total of 39 congeneric groups of species which share common ecology and social structure (in most cases, congeneric groups are synonymous with genera). Both Nc and Ve were significantly larger for polygynous congeneric groups than for monogynous congeneric groups in the case of New World monkeys. In the case of Old World monkeys, both Nc and Ve were significantly larger for terrestrial congeneric groups than for arboreal congeneric groups. In the case of apes, although complete analyses could not be performed because of the limited size of the sample for which data were available, both Nc and Ve appeared to be larger for polygynous/terrestrial apes than for monogynous/arboreal apes. These results suggest that the expansion of the cerebral cortex in anthropoids may be associated with terrestriality and polygyny.

A hypothesis on the primate neocortex evolution: Column-multiplication hypothesis

A hypothesis is proposed, that the primate neocortex has evolved by the multiplication of cortical columns. As the column size is similar across primate species, it is considered that the columns have multiplied to expand the neocortex during primate evolution. This hypothesis would explain the expansion of neocortical sensory-motor-associational areas and multiple sensory and motor areas which had occurred during evolution. Further, the hypothesis predicts the existence of columns neutral for the fitness, genetic control upon the columns, and intraspecies variations of the columns.

Catecholamine sensitivities of motor cortical neurons of the monkey

The effects of noradrenaline (NA) and dopamine (DA) were examined in 139 neurons of the motor cortex (area 4) of the monkey, using multibarreled micropipettes. Sampled neurons were those spontaneously active and sensitive to iontophoretically applied glutamate (30-50 nA). Iontophoretically applied NA and DA induced excitatory and inhibitory responses in 91 neurons (NA: excitatory, n = 17; inhibitory, n = 53; DA: excitatory, n = 16; inhibitory, n = 37). Cortical depth was determined in 121 neurons tested. Neurons sensitive to NA (excitatory, n = 13; inhibitory, n = 46) were distributed uniformly across the cortical layers, while neurons sensitive to DA (excitatory, n = 14; inhibitory, n = 30) were numerous in layers V and VI. This suggests that NA may influence various neuronal activities, and that DA may predominantly influence neuronal activities of layers V and VI in the monkey motor cortex.