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)

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 Prefrontal and Parietal Attractor Networks Mediate Working Memory Judgments

2020 ◽  
Author(s):  
Sihai Li ◽  
Christos Constantinidis ◽  
Xue-Lian Qi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Critical Role ◽  
Memory Task ◽  
Delayed Response ◽  
Persistent Activity ◽  
Neural Basis ◽  
Brain Areas ◽  
Dorsolateral Prefrontal

ABSTRACTThe dorsolateral prefrontal cortex plays a critical role in spatial working memory and its activity predicts behavioral responses in delayed response tasks. Here we addressed whether this predictive ability extends to categorical judgments based on information retained in working memory, and is present in other brain areas. We trained monkeys in a novel, Match-Stay, Nonmatch-Go task, which required them to observe two stimuli presented in sequence with an intervening delay period between them. If the two stimuli were different, the monkeys had to saccade to the location of the second stimulus; if they were the same, they held fixation. Neurophysiological recordings were performed in areas 8a and 46 of the dlPFC and 7a and lateral intraparietal cortex (LIP) of the PPC. We hypothesized that random drifts causing the peak activity of the network to move away from the first stimulus location and towards the location of the second stimulus would result in categorical errors. Indeed, for both areas, when the first stimulus appeared in a neuron’s preferred location, the neuron showed significantly higher firing rates in correct than in error trials. When the first stimulus appeared at a nonpreferred location and the second stimulus at a preferred, activity in error trials was higher than in correct. The results indicate that the activity of both dlPFC and PPC neurons is predictive of categorical judgments of information maintained in working memory, and the magnitude of neuronal firing rate deviations is revealing of the contents of working memory as it determines performance.SIGNIFICANCE STATEMENTThe neural basis of working memory and the areas mediating this function is a topic of controversy. Persistent activity in the prefrontal cortex has traditionally been thought to be the neural correlate of working memory, however recent studies have proposed alternative mechanisms and brain areas. Here we show that persistent activity in both the dorsolateral prefrontal cortex and posterior parietal cortex predicts behavior in a working memory task that requires a categorical judgement. Our results offer support to the idea that a network of neurons in both areas act as an attractor network that maintains information in working memory, which informs behavior.

scholarly journals Stable population coding for working memory coexists with heterogeneous neural dynamics in prefrontal cortex

2016 ◽  
Vol 114 (2) ◽  
pp. 394-399 ◽  
Author(s):  
John D. Murray ◽  
Alberto Bernacchia ◽  
Nicholas A. Roy ◽  
Christos Constantinidis ◽  
Ranulfo Romo ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Neural Circuit ◽  
Temporal Dynamics ◽  
Population Level ◽  
Population Coding ◽  
Neural Dynamics ◽  
Stable Population ◽  
Neuron Activity ◽  
Delayed Response

Working memory (WM) is a cognitive function for temporary maintenance and manipulation of information, which requires conversion of stimulus-driven signals into internal representations that are maintained across seconds-long mnemonic delays. Within primate prefrontal cortex (PFC), a critical node of the brain’s WM network, neurons show stimulus-selective persistent activity during WM, but many of them exhibit strong temporal dynamics and heterogeneity, raising the questions of whether, and how, neuronal populations in PFC maintain stable mnemonic representations of stimuli during WM. Here we show that despite complex and heterogeneous temporal dynamics in single-neuron activity, PFC activity is endowed with a population-level coding of the mnemonic stimulus that is stable and robust throughout WM maintenance. We applied population-level analyses to hundreds of recorded single neurons from lateral PFC of monkeys performing two seminal tasks that demand parametric WM: oculomotor delayed response and vibrotactile delayed discrimination. We found that the high-dimensional state space of PFC population activity contains a low-dimensional subspace in which stimulus representations are stable across time during the cue and delay epochs, enabling robust and generalizable decoding compared with time-optimized subspaces. To explore potential mechanisms, we applied these same population-level analyses to theoretical neural circuit models of WM activity. Three previously proposed models failed to capture the key population-level features observed empirically. We propose network connectivity properties, implemented in a linear network model, which can underlie these features. This work uncovers stable population-level WM representations in PFC, despite strong temporal neural dynamics, thereby providing insights into neural circuit mechanisms supporting WM.

scholarly journals Role of prefrontal cortex and the midbrain dopamine system in working memory updating

2012 ◽  
Vol 109 (49) ◽  
pp. 19900-19909 ◽  
Author(s):  
K. D'Ardenne ◽  
N. Eshel ◽  
J. Luka ◽  
A. Lenartowicz ◽  
L. E. Nystrom ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dopamine System ◽  
Memory Updating ◽  
Working Memory Updating ◽  
Midbrain Dopamine
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