Effects of dopamine antagonists on neuronal activity related to a delayed response task in monkey prefrontal cortex

1990 ◽  
Vol 63 (6) ◽  
pp. 1401-1412 ◽  
Author(s):  
T. Sawaguchi ◽  
M. Matsumura ◽  
K. Kubota
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Background Activity ◽  
Central Zone ◽  
Companion Paper ◽  
D1 Receptors ◽  
Dopamine Antagonists ◽  
Delayed Response ◽  
Related Activity ◽  
Monkey Prefrontal Cortex

1. Using iontophoretic techniques, we investigated the influence of dopamine (DA) antagonists [haloperidol (HAL), a non-selective DA antagonist; sulpiride (SUL), a selective antagonist for D2 receptors; and fluphenazine (FLU), a potent antagonist for D1 receptors] on neuronal activity related to a delayed response (DR) task in the monkey prefrontal cortex (PFC). The DR task was initiated by the rotation of a handle to a central zone and consisted of seven distinct periods: an initial intertrial interval of 0.3 s, a precue period of 1 s (a center green lamp), a cue period of 1 s (left or right lamp), a delay period of 4 s, a go period (red lamp in the center; rotation of the handle to either the left or right zone), a hold period (holding of the handle in either the left or right zone), and a final reward period. Because it was shown, as described in the companion paper (Sawaguchi et al. 1990), that DA augments the increased activity of prefrontal neurons related to the cue, delay, and go periods of the DR task, effects of the DA antagonists were examined in a total of 61 neurons that showed increases in activity related to these periods and a response to DA. 2. Consistent with previous studies (Sawaguchi et al. 1988a, 1990), iontophoretically applied DA increased DR task-related activity in prefrontal neurons. Iontophoretically applied HAL and FLU antagonized the increased effect of DA on the task-related activity. By contrast, SUL did not have any clear effects on the influence of DA. 3. By themselves, HAL and FLU reduced prefrontal neuronal activity related to the cue, delay, and go periods of the DR task. The ratio of the reduction by HAL and FLU was significantly larger for activity during the cue, delay, or go period than for background activity during the precue period; and, as a result, the signal-to-noise (S/N) ratio of the task-related activity to background activity was reduced during the application of HAL and FLU. In contrast, SUL did not have any clear effects on activity related to the cue, delay, and go periods of the DR task, and the S/N ratio during the application of SUL did not significantly differ from that before the application of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Catecholaminergic effects on neuronal activity related to a delayed response task in monkey prefrontal cortex

1990 ◽  
Vol 63 (6) ◽  
pp. 1385-1400 ◽  
Author(s):  
T. Sawaguchi ◽  
M. Matsumura ◽  
K. Kubota
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Background Activity ◽  
Japanese Macaque ◽  
Central Zone ◽  
Delay Period ◽  
Delayed Response ◽  
Differential Delay ◽  
Hold Period ◽  
Monkey Prefrontal Cortex

1. Using iontophoretic techniques, we investigated the effects of dopamine (DA) and noradrenaline (NA) on neuronal activity related to a delayed response (DR) task in the prefrontal cortex (PFC) of the Japanese macaque monkeys. The DR task was initiated by rotation of a handle to a central zone and consisted of seven distinct time periods: an initial waiting period of 0.3 s, a precue period of 1 s (a central green lamp), a cue period of 1 s (left or right lamp), a delay period of 4 s, a go period of 1 s (red lamp in the center; rotation of the handle to either the left or right zone), a hold period (holding of the handle in either the left or right zone for 0.3 s), and a final reward period. 2. A total of 116 neurons were DR task related. They showed increases in activity during the precue period (Precue-types, n = 19), during both the cue and go periods (Cue/GO-types, n = 17), the go period (GO-types, n = 16), and during the delay period (Delay-types, n = 64). The Delay-type neurons were further divided into differential neurons (n = 33), for which the magnitude of the delay-related activity differed significantly between left- and right-cue trials, and nondifferential neurons (n = 31). Some of the Delay-type neurons also showed increases in activity during the cue (n = 26), go (n = 27), or both the cue and go periods (n = 11). 3. DA or NA, applied iontophoretically with a current of 50 nA, induced increased or decreased responses in most of the DR task-related neurons. DA increased activity of most of the Cue/GO-(16/17), GO-(13/16), and Delay-type neurons (49/64), and NA decreased activity of most of the Precue- (13/19) and non-differential Delay-type neurons (25/31). Thus different types of DR task-related neurons showed different responses to DA and NA. 4. In Cue/GO-, GO-, and/or Delay-type neurons, DA increased the activity related to the cue, go, and delay periods more strongly than it increased background activity. As a result, the ratio [i.e., signal-to-noise (S/N) ratio] of activity related to the cue, go, and delay periods to background activity was increased. 5. In Precue-type or nondifferential Delay-type neurons, NA decreased background activity more strongly than it decreased activity during the precue or delay period.(ABSTRACT TRUNCATED AT 400 WORDS)

Catecholamine sensitivities of neurons related to a visual reaction time task in the monkey prefrontal cortex

1987 ◽  
Vol 58 (5) ◽  
pp. 1100-1122 ◽  
Author(s):  
T. Sawaguchi
Keyword(s):  
Prefrontal Cortex ◽  
Reaction Time ◽  
Background Activity ◽  
Reaction Time Task ◽  
Visual Reaction Time ◽  
Related Activity ◽  
Time Task ◽  
Visual Reaction ◽  
Monkey Prefrontal Cortex ◽  
A Current

1. Using microiontophoretic techniques and conscious monkeys, sensitivities to noradrenaline (NA) and dopamine (DA) of neurons of the prefrontal cortex (PFC), which showed changes in activity during a visual reaction time task, were investigated. The visual reaction time task was initiated by the pressing of a lever and consisted of four phases: an initial waiting phase of 3.0 s, a warning phase (green light of variable duration of 1.5-3.5 s), a lever release go phase (red light), and a final reward phase. 2. A total of 153 neurons, which showed changes in activity during one or two phase(s) of the task, were sampled. Of these neurons, 39 changed their activity during the warning phase, 48 changed their activity during the go phase, 38 changed their activity during both the warning and the go phases, and 28 changed their activity during the reward phase. 3. Iontophoretically applied NA and DA (with a current of 30-70 nA, but usually with a current of 50 nA) induced excitatory and/or inhibitory responses in 141 of the 153 task-related neurons. NA induced responses in 99 neurons, and these responses were predominantly inhibitory (n = 90). DA induced excitatory (n = 62) and inhibitory (n = 30) responses in 92 neurons. Fifty neurons were sensitive to both NA and DA. 4. The neurons showing changes in activity during different phases of the task showed different sensitivities to NA and DA applied with 50 nA. The warning phase-related neurons were primarily sensitive to NA (36/39), the go phase-related neurons were primarily sensitive to DA (44/48), neurons related to both the warning and go phases were sensitive to both NA and DA (33/38), and the reward phase-related neurons were primarily sensitive to NA (23/28). 5. In the neurons that showed increased changes in activity during the warning phase, NA reduced the background activity to a greater extent than the activity during the warning phase and increased the ratio of the warning phase-related activity to the background activity. In the neurons that showed decreased changes during the warning phase, NA reduced the activity during the warning phase to a great extent than the background activity, and increased ratio of the background activity to the warning phase-related activity. Furthermore, the latency of onset of the change in activity tended to become shorter by application of NA. Thus, NA enhanced the change in activity during the warning phase, irrespective of whether the direction of the change was toward an increase or a decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks

2002 ◽  
Vol 87 (1) ◽  
pp. 567-588 ◽  
Author(s):  
Kazuyoshi Takeda ◽  
Shintaro Funahashi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Neuron Activity ◽  
Delayed Response ◽  
Related Activity ◽  
Visual Cue ◽  
Response Period ◽  
Dorsolateral Prefrontal

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.

The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task

1994 ◽  
Vol 71 (2) ◽  
pp. 515-528 ◽  
Author(s):  
T. Sawaguchi ◽  
P. S. Goldman-Rakic
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Injection Site ◽  
Target Location ◽  
Dopamine Antagonists ◽  
Dopamine Antagonist ◽  
Delayed Response ◽  
Intracerebral Injection ◽  
Control Task

1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 micrograms) and SCH39166 (1-5 micrograms) and/or the nonselective dopamine antagonist haloperidol (10-100 micrograms) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuronal Activity Representing Temporal Prediction of Reward in the Primate Prefrontal Cortex

2005 ◽  
Vol 93 (6) ◽  
pp. 3687-3692 ◽  
Author(s):  
Satoshi Tsujimoto ◽  
Toshiyuki Sawaguchi
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Behavioral Control ◽  
Delayed Response ◽  
Temporal Prediction ◽  
Reward Delivery ◽  
Dorsolateral Prefrontal ◽  
Future Events ◽  
Response Task ◽  
Reward Delay

Temporal prediction of future events, especially regarding reward delivery, is critical for controlling/learning purposeful behavior. The dorsolateral prefrontal cortex (DLPFC) has been considered to be involved in behavioral control based on prospective coding for future events, including reward. Thus this area is likely to have a neuronal mechanism responsible for temporal prediction of forthcoming reward. To address this hypothesis, we recorded the neuronal activity from the DLPFC of macaque monkeys while they performed an oculomotor delayed-response task under two conditions regarding the time of reward delivery. In this task, when the subjects made a correct response, the reward was delivered after a reward-delay period of 0.5 or 2 s. At the behavioral level, the onset latency for saccades was significantly faster in the shorter reward-delay trials (0.5 s) than in longer reward-delay trials (2 s), indicating that our subjects actually predicted the time of reward delivery. At the neuronal level, we found that many DLPFC neurons showed differential activity depending on the predicted time of reward delivery during the cue and/or delay periods. These results suggest that a fraction of neurons in the DLPFC represent the temporal prediction of reward and probably a variety of other future events.

scholarly journals Working memory performance and neural activity in prefrontal cortex of peripubertal monkeys

2013 ◽  
Vol 110 (11) ◽  
pp. 2648-2660 ◽  
Author(s):  
Xin Zhou ◽  
Dantong Zhu ◽  
Xue-Lian Qi ◽  
Cynthia J. Lees ◽  
Allyson J. Bennett ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Neural Activity ◽  
Developmental Stages ◽  
Memory Performance ◽  
Large Fraction ◽  
Early Adulthood ◽  
Delayed Response ◽  
Distractor Stimulus

The dorsolateral prefrontal cortex matures late into adolescence or early adulthood. This pattern of maturation mirrors working memory abilities, which continue to improve into adulthood. However, the nature of the changes that prefrontal neuronal activity undergoes during this process is poorly understood. We investigated behavioral performance and neural activity in working memory tasks around the time of puberty, a developmental event associated with the release of sex hormones and significant neurological change. The developmental stages of male rhesus monkeys were evaluated with a series of morphometric, hormonal, and radiographic measures. Peripubertal monkeys were trained to perform an oculomotor delayed response task and a variation of this task involving a distractor stimulus. We found that the peripubertal monkeys tended to abort a relatively large fraction of trials, and these were associated with low levels of task-related neuronal activity. However, for completed trials, accuracy in the delayed saccade task was high and the appearance of a distractor stimulus did not impact performance significantly. In correct trials delay period activity was robust and was not eliminated by the presentation of a distracting stimulus, whereas in trials that resulted in errors the sustained cue-related activity was significantly weaker. Our results show that in peripubertal monkeys the prefrontal cortex is capable of generating robust persistent activity in the delay periods of working memory tasks, although in general it may be more prone to stochastic failure than in adults.

scholarly journals Neuronal activity in the monkey prefrontal cortex during a duration discrimination task with visual and auditory cues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Chiba ◽  
Kazunori Morita ◽  
Ken-ichi Oshio ◽  
Masahiko Inase
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
Visual Cues ◽  
Discrimination Task ◽  
Early Stage ◽  
Duration Discrimination ◽  
Visual Signals ◽  
Final Decision ◽  
Monkey Prefrontal Cortex ◽  
Duration Discrimination Task

AbstractTo investigate neuronal processing involved in the integration of auditory and visual signals for time perception, we examined neuronal activity in prefrontal cortex (PFC) of macaque monkeys during a duration discrimination task with auditory and visual cues. In the task, two cues were consecutively presented for different durations between 0.2 and 1.8 s. Each cue was either auditory or visual and was followed by a delay period. After the second delay, subjects indicated whether the first or the second cue was longer. Cue- and delay-responsive neurons were found in PFC. Cue-responsive neurons mostly responded to either the auditory or the visual cue, and to either the first or the second cue. The neurons responsive to the first delay showed activity that changed depending on the first cue duration and were mostly sensitive to cue modality. The neurons responsive to the second delay exhibited activity that represented which cue, the first or second cue, was presented longer. Nearly half of this activity representing order-based duration was sensitive to cue modality. These results suggest that temporal information with visual and auditory signals was separately processed in PFC in the early stage of duration discrimination and integrated for the final decision.

scholarly journals The Prefrontal Cortex and Oculomotor Delayed Response: A Reconsideration of the “Mnemonic Scotoma”

2012 ◽  
Vol 24 (3) ◽  
pp. 627-635 ◽  
Author(s):  
Satoshi Tsujimoto ◽  
Bradley R. Postle
Keyword(s):  
Prefrontal Cortex ◽  
Target Location ◽  
Delayed Response ◽  
Short Term ◽  
Neuroscience Research ◽  
Analysis Window ◽  
Corrective Saccade ◽  
Response Task ◽  
Monkey Prefrontal Cortex

The concept of the “mnemonic scotoma,” a spatially circumscribed region of working memory impairment produced by unilateral lesions of the PFC, is central to the view that PFC is critical for the short-term retention of information. Presented here, however, are previously unpublished data that offer an alternative, nonmnemonic interpretation of this pattern of deficit. In their study, Wajima and Sawaguchi [Wajima, K., & Sawaguchi, T. The role of GABAergic inhibiton in suppressing perseverative responses in the monkey prefrontal cortex. Neuroscience Research, 50(Suppl. 1), P3–P317, 2004] applied the GABAA antagonist bicuculline methiodide unilaterally to the PFC of two monkeys while they performed an oculomotor delayed-response task. Consistent with previous studies, errors for the initial memory-guided saccade were markedly higher when the cued location fell into the region of the visual field affected by the infusion. These erroneous saccades tended to select an alternative target location (out of a possible 16) that had not been cued on that trial. By extending the analysis window, however, it was observed that the second, “corrective” saccade often acquired the location that had been cued on that trial. Further analysis of the erroneous initial saccades indicated that they tended to be directed to a location that had been relevant on the previous trial. Thus, the deficit was not one of “forgetting” the cued location. Rather, it was one of selecting between currently and previously relevant locations. These findings suggest a need for a reconsideration of the concept of the mnemonic scotoma, which in turn invites a reconsideration of functional interpretations of sustained neuronal activity in PFC.

scholarly journals Neuronal activity related to saccadic eye movements in the monkey's dorsolateral prefrontal cortex

1991 ◽  
Vol 65 (6) ◽  
pp. 1464-1483 ◽  
Author(s):  
S. Funahashi ◽  
C. J. Bruce ◽  
P. S. Goldman-Rakic
Keyword(s):  
Prefrontal Cortex ◽  
Eye Movements ◽  
Visual Field ◽  
Tuning Curve ◽  
Saccadic Eye Movements ◽  
Neuron Activity ◽  
Delayed Response ◽  
Visually Guided ◽  
Related Activity ◽  
Vertical Meridian

1. Single-neuron activity was recorded from the prefrontal cortex of monkeys performing saccadic eye movements in oculomotor delayed-response (ODR) and visually guided saccade (VGS) tasks. In the ODR task the monkey was required to maintain fixation of a central spot throughout the 0.5-s cue and 3.0-s delay before making a saccadic eye movement in the dark to one of four or eight locations where the visual cue had been presented. The same locations were used for targets in the VGS tasks; however, unlike the ODR task, saccades in the VGS tasks were visually guided. 2. Among 434 neurons recorded from prefrontal cortex within and surrounding the principal sulcus (PS), 147 changed their discharge rates in relation to saccadic eye movements in the ODR task. Their response latencies relative to saccade initiation were distributed between -192 and 460-ms, with 22% exhibiting presaccadic activity and 78% exhibiting only postsaccadic activity. Among PS neurons with presaccadic activity, 53% also had postsaccadic activity when the monkey made saccadic eye movements opposite to the directions for which the presaccadic activity was observed. 3. Almost all (97%) PS neurons with presaccadic activity were directionally selective. The best direction and tuning specificity of each neuron were estimated from parameters used to fit a Gaussian tuning curve function. The best direction for 62% of the neurons with presaccadic activity was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (23%) or along the vertical meridian (15%). 4. Most postsaccadic activity of PS neurons (92%) was also directionally selective. The best direction for 48% of these neurons was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (36%) or along the vertical meridian (16%). Eighteen percent of the neurons with postsaccadic activity showed a reciprocal response pattern: excitatory responses occurred for one set of saccade directions, whereas inhibitory responses occurred for roughly the opposite set of directions. 5. Sixty PS neurons with saccade-related activity in the ODR task were also examined in a VGS task. Forty of these neurons showed highly similar profiles of directional specificity and response magnitude in both tasks, 13 showed saccade-related activity only in the ODR task, and 7 changed their response characteristics between the ODR and VGS tasks.(ABSTRACT TRUNCATED AT 400 WORDS)

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