Hiroaki Niki

Prefrontal and cingulate unit activity during timing behavior in the monkey

Single unit activity was recorded from the dorsolateral prefrontal cortex and the anterior cingulate cortex while monkeys were performing a modified differential reinforcement of long latencies (DRLL) task. A total of 252 prefrontal units and 218 anterior cingulate units showed an obvious change in discharge rate (increase or decrease) in association with one or more of the events of a DRLL task. Related units were classified into 3 main groups: S--R event units, reward-error units, and timing units. S--R event units consisted of three subtypes: stimulus-related, response-related, and stimulus--response-related units. Reward-error units contained reward-related units and error-recognition units. Error-recognition units showed a vigorous increase in firing only after incorrect responses. These units were also responsive to omission of reinforcement on correct trials. Three types of timing units were distinguishable. The first one showed an anticipatory change prior to stimulus onset, and the second one exhibited a gradual anticipatory change preceding the time of responding. The third one manifested a sustained change during delay and an abrupt cessation of change in firing at the time of response initiation.

Prefrontal unit activity and delayed response: relation to cue location versus direction of response.

Two monkeys were trained to perform 3 kinds of spatial tasks (right-left DR, up-down DR, and conditional position discrimination with delay). In the conditional position task, the animal was required to respond to the right (left) choice key when the cue had been presented on the upper (lower) position. Single unit activity was recorded from the principalis area of the dorsolateral prefrontal cortex while the animal was performing the tasks. Once a differential delay unit (i.e., unit showing specificity during the delay period for two kinds of trials) was found in right-left DR (or up-down DR), the same unit was tested in the other tasks. A total of 32 differential delay units were investigated sufficiently to allow comparison of all 3 conditions. The results indicate that there are two types of differential delay units. The first type showed a clear dependence on the cue location, while the second type was related to the direction of the impending response. Activity of the second type of differential delay unit during the delay period served to predict the occurrence of errors, whereas this relation between unit discharge and correct or incorrect responses was not seen for the first type of differential delay unit.

Hippocampal unit activity and delayed response in the monkey

Single unit activity was recorded from the hippocampus while Japanese monkeys (Macaca fuscata, n = 4) were performing a delayed response (DR) task. A total of 272 units showed an obvious change in discharge rate in relation to the events of the DR task. These 272 related units were classified into 6 groups: cue-light related units (n = 24), cue- and choice-light related units (n = 41), choice-light related units (n = 21), response-related units (n = 51), reward-error units (n = 17), and delay units (n = 118). Reward-error units contained reward-related and error-related units. Error-related units showed changes in firing after incorrect responses and/or after omission of reward on correct trials. It is noteworthy that 43.4% of the related units are delay units which showed increased or decreased firing preferentially during the delay period. Some units showed a differential firing pattern during cue or delay period depending on the spatial position of the cue. The results of the present study are interpreted as an experimental evidence for the involvement of the hippocampus in DR task.

Prefrontal unit activity during delayed alternation in the monkey. I. Relation to direction of response.

Abstract Single unit activity was recorded from the area midprincipalis of the dorsolateral prefrontal cortex during delayed alternation (DA) in one monkey. Out of 502 units studied in both hemispheres, 198 showed a relation to aspects of the DA task. Half of these related units showed a differential firing pattern depending on the trial (left or right). In 26 units the discharge frequency during delay was different between right and left trials. In no case, however, was such selectivity during delay found in a cue-guided control task. An anticipatory change toward the end of the delay period was observed in many units. Possible functional roles of related units were discussed.

Encoding of behavioral significance of visual stimuli by primate prefrontal neurons: relation to relevant task conditions

Single-unit activity was recorded from the inferior dorsolateral prefrontal cortex of two monkeys while they performed a symmetrically rewarded go/no-go discrimination task. Three different task conditions were used in which the monkeys had to base their response on (1) the color, or (2) the shape, or (3) the position of a cue that was presented during fixation of a light spot. The colors of the fixation spot informed the monkeys which condition was relevant. The monkeys had to make an immediate release (go) or a delayed release (no-go) at the time of the fixation color change (imperative stimulus) depending on the currently relevant condition and the discriminative cue previously presented. The effect of changing the relevant condition on neuronal responses to the discriminative cue was analyzed. Out of 328 neurons tested in two or three conditions, 249 responded differentially at the cue period depending on the particular behavioral meaning of the stimulus (go or no-go) in at least one of the task conditions. This differential cue-period activity was examined across the different task conditions: the majority of neurons (111/154, 72%) showed such activity in all three conditions. In the remaining 43 neurons (28%) the differential activity was observed in two conditions (27/154, 18%) or in one condition (16/ 154, 10%). A few neurons (n = 7) showed feature-specific cue-period activity. In addition, 27 neurons displayed condition-dependent anticipatory activity prior to the cue onset. It is suggested that neurons in the inferior dorsolateral prefrontal cortex may participate in the conversion of sensory information from different visual channels into behavioral information (information on the upcoming response).

Prefrontal unit activity during delayed alternation in the monkey. II. Relation to absolute versus relative direction of response

Abstract Single unit activity was recorded from the area principalis of the dorsolateral prefrontal cortex during DA in 3 monkeys in order to analyze further the nature of observed differential changes in relation to the different positions of the choice keys (directional selectivity). Out of 354 related units obtained from 170 penetrations, 182 showed directional selectivity. A total of 111 directionally selective units were investigated in sufficient detail to determine whether the observed directional selectivity was related to the absolute or to the relative position of the choice keys. Twenty of these 111 units showed directional selectivity during the delay period and all of these units showed clear dependence on the relations between choice keys. For the remaining units, whose directional selectivity became apparent only after the choice keys were illuminated, dependence on relative factors was less marked. All units showed some dependence on the location of the choice keys, independent of the relations between choice keys.

Increased fearfulness of Fyn tyrosine kinase deficient mice

Fyn-deficient mice were produced by inserting the beta-galactosidase gene (lacZ) into the fyn gene locus. The homozygously Fyn kinase-deficient (fynz/fynz) mice exhibited stronger light aversion in the light-dark choice test and higher fear-response scores in the novelty preference and passive avoidance tests than did the heterozygously Fyn-deficient (+/fynz) mice. These results indicate that fynz/fynz mice are hyperresponsive to fear-inducing stimuli.

Radial maze performance, open-field and elevated plus-maze behaviors in Fyn-kinase deficient mice: Further evidence for increased fearfulness

Fyn-deficient mice produced by inserting the beta-galactosidase gene (lacZ) into the fyn gene locus were tested in a radial maze, an open field and an elevated plus-maze. In the radial maze, the homozygous Fyn-deficient (fynz/fynz) mice showed no impairment in spatial learning, although they showed a stronger avoidance tendency for those arms located closer to the experimenter during pretraining (adaptation). In the open-field test, the fynz/fynz mice defecated more frequently in the bright condition than did the +/fynz mice, and they were less active during the first 10-min test period than the +/fynz mice. In addition, the temporal pattern of locomotor activity for fynz/fynz mice was altered by changing the illumination while the pattern for +/fynz mice remained relatively unchanged. Scores reflecting the fear-response in the elevated plus-maze were higher in the fynz/fynz mice. These results indicate that Fyn deficiency increased fear-response, but did not impair spatial learning in the radial maze. It is suggested that we should take account of effects of emotional factors in the learning experiment using mutant mice.

Spatial selectivity of go/no-go neurons in monkey prefrontal cortex

We examined single-unit activity in the inferior prefrontal cortex during a visual go/no-go discrimination task under maintained visual fixation. The monkeys had to base their response on either the color, shape, or position of a discriminative cue, and the relevant task condition was indicated by the color of the fixation spot. We analyzed the spatial selectivity of 128 go/no-go neurons showing a marked differential cue-period activity that depended on whether the stimulus signaled a go or no-go response. Most of these neurons (n = 106, 83%) showed asymmetry between their responses to stimuli in the contralateral and ipsilateral visual fields. Seventy-seven of these neurons had a contralateral preferential field, and 29 had an ipsilateral preferential field. These results show that in many inferior prefrontal neurons a degree of differentiation in their responses to go and no-go stimuli depends on the cue positions, and that the coding of behavioral meaning is carried out mainly in the contralateral hemisphere.

Enhanced susceptibility of audiogenic seizures in Fyn-kinase deficient mice

Mice with a mutation in fyn genes were examined for their susceptibility to acoustically primed audiogenic seizures. Homozygous mutant (fynz/fynz) mice were significantly more likely to have seizures and to show the stronger seizure syndrome (clonus). These results indicate that the susceptibility of acoustically primed audiogenic seizures is enhanced in the Fyn kinase deficient mice.