Michikazu Matsumura

Cortical projection to hand-arm motor area from post-arcuate area in macaque monkeys: A histological study of retrograde transport of horseradish peroxidase

In four macaque monkeys horseradish peroxidase (HRP) was injected into physiologically defined hand-arm motor area. Ipsilaterally, HRP labeled neurons were found in both upper and lower limbs of the posterior bank of the arcuate sulcus and in an area surrounding the arcuate spur. Contralaterally, labeled neurons were found in the same areas, though less dense in concentration. Labeled neurons were found mostly in layer III of the cortex.

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.

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.

Glycosaminoglycan-related epitopes surrounding different subsets of mammalian central neurons

Among a panel of monoclonal antibodies generated against monkey brain tissue, a class of antibodies was found to produce perineuronal staining of small subsets of mammalian central neurons. Three antibodies (MAbs 473, 376, 528) we report here define two different, though partially overlapping, neuronal subsets in the monkey neocortex. All 3 antibodies stain in addition certain chondrocytes. The neural immunoreactivities were lost, and the chondral immunoreactivities either lost or enhanced, after treatment of the sections with chondroitinase ABC. Independently, 3 other antibodies (MAbs 1B5, 9A2, 3B3) with established specificity to glycosaminoglycan epitopes also produced perineuronal staining of a related subset of central neurons. Immunoblot experiments with two of the antibodies revealed bands of high molecular weight. These findings indicate that certain glycosaminoglycans occur surrounding mammalian central neurons, and suggest that different neuronal subsets are associated with different combinations of proteoglycan epitopes.

A monoclonal antibody identifies a novel epitope surrounding a subpopulation of the mammalian central neurons.

A monoclonal antibody was obtained by immunizing mice with an extract of monkey brain. The monoclonal antibody 473 stained a small subpopulation of neurons in various regions of monkey and rat central nervous system. The perimeters of neuronal somata and the proximal parts of dendrites bound the antibody. Electron microscopic analysis showed that the immunoreactivity was associated with the outer surface of the cell. The immunoreactivity in the rat cerebral cortex appeared gradually during the second four weeks after birth. The antibody stained fetal cartilages but otherwise was specific to the nervous system. Experiments on the stability of the immunoreactivity to enzymatic and chemical treatments of the sections suggest that the antigen molecule is of proteoglycan nature.

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.

Prefrontal neuron activity during delayed-response performance without imperative GO signals in the monkey

Abstract Prefrontal neuron activity was examined in the monkey during the performance of a delayed-response task without imperative stimuli at the time of left and right-choiced responses. A total of 177 task-related neurons was recorded. Sixty-eight percent of the neurons ( 121 177 ) changed activity during the response period without external stimuli. Seventy percent of these cells ( 84 121 ) showed an activity change during the cue and/or delay as well as response period. These neurons showed a gradual increase or decrease in activity during the delay period. We suggest that this “movement-coupled” activity may be related to changes in motivation or attention of the monkey. Neuron activity between correct and error trials was also examined in a limited sample. Neurons which showed left-right trial differential activity were likely to display differential activity between correct and error trials. From the analysis of neuron firing in error trials, two types of errors were suggested. One type of error may be related to the loss of attention or motivation and the other type may be related to incorrect encoding of the cue position.

Intracellular synaptic potentials of primate motor cortex neurons during voluntary movement

An intracellular recording technique was applied to the precentral motor cortex of the unanesthetized, chronically behaving monkey. Postsynaptic potentials, responsible for an initiation of the voluntary movement, were recorded. In total, 22 pyramidal tract neurons (PTNs) and 40 non-pyramidal tract neurons (non-PTNs) were successfully penetrated in 5 monkeys while the monkey was performing a flexion-extension wrist movement after a visual cue (reaction time, 200--350 msec). The neurons showed a negative membrane potential shift of at least 30 mV for more than 30 sec. A slowly rising PSP appeared 80--180 msec after the visual cue, and was 70--180 msec prior to an onset of the movement. Spike activities were superimposed upon this slow PSP with 20--80 msec rise time and 2--6 mV depolarization (8 PTNs and 6 non-PTNs). Since these depolarizations were variable in magnitude and latency, these were considered to be summated potentials of small EPSPs and hidden IPSPs. Membrane resistance was measured from an IR drop by a hyperpolarizing current (1.2 X 10(-9) A) passed through a recording electrode, and was 3.5 +/- 1.7 Momega in 18 PTNs and 4.5 +/- 2.5 Momega in 28 non-PTNs. There was a linear relationship in PTNs between membrane resistance and antidromic latency from the pontine pyramid. Because of the time course of PSPs, their possible dendritic origins were discussed.