Stimulus duration in working memory is represented by neuronal activity in the 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)

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Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex

Journal of Neurophysiology ◽

10.1152/jn.00859.2011 ◽

2012 ◽

Vol 108 (2) ◽

pp. 595-609 ◽

Cited By ~ 34

Author(s):

A. V. Zaitsev ◽

N. V. Povysheva ◽

G. Gonzalez-Burgos ◽

D. A. Lewis

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Functional Properties ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Spiking Neurons ◽

Membrane Properties ◽

Layer 2 ◽

Monkey Prefrontal Cortex ◽

Intrinsic Membrane Properties

The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.

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Cholinergic modulation of working memory activity in primate prefrontal cortex

Journal of Neurophysiology ◽

10.1152/jn.00148.2011 ◽

2011 ◽

Vol 106 (5) ◽

pp. 2180-2188 ◽

Cited By ~ 24

Author(s):

Xin Zhou ◽

Xue-Lian Qi ◽

Kristy Douglas ◽

Kathini Palaninathan ◽

Hyun Sug Kang ◽

...

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Neuronal Activity ◽

Visual Processing ◽

Spatial Location ◽

Visually Guided ◽

Electrode Arrays ◽

Dose Dependent Decrease ◽

Higher Cognitive Functions ◽

The Impact

The prefrontal cortex, a cortical area essential for working memory and higher cognitive functions, is modulated by a number of neurotransmitter systems, including acetylcholine; however, the impact of cholinergic transmission on prefrontal activity is not well understood. We relied on systemic administration of a muscarinic receptor antagonist, scopolamine, to investigate the role of acetylcholine on primate prefrontal neuronal activity during execution of working memory tasks and recorded neuronal activity with chronic electrode arrays and single electrodes. Our results indicated a dose-dependent decrease in behavioral performance after scopolamine administration in all the working memory tasks we tested. The effect could not be accounted for by deficits in visual processing, eye movement responses, or attention, because the animals performed a visually guided saccade task virtually error free, and errors to distracting stimuli were not increased. Performance degradation under scopolamine was accompanied by decreased firing rate of the same cortical sites during the delay period of the task and decreased selectivity for the spatial location of the stimuli. These results demonstrate that muscarinic blockade impairs performance in working memory tasks and prefrontal activity mediating working memory.

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

Journal of Neurophysiology ◽

10.1152/jn.1990.63.6.1385 ◽

1990 ◽

Vol 63 (6) ◽

pp. 1385-1400 ◽

Cited By ~ 109

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)

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Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1311310110 ◽

2013 ◽

Vol 111 (1) ◽

pp. 486-491 ◽

Cited By ~ 106

Author(s):

Y. Hara ◽

F. Yuk ◽

R. Puri ◽

W. G. M. Janssen ◽

P. R. Rapp ◽

...

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Estrogen Treatment ◽

Mitochondrial Morphology ◽

Monkey Prefrontal Cortex

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A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia

Schizophrenia Research ◽

10.1016/0920-9964(95)00027-j ◽

1995 ◽

Vol 17 (1) ◽

pp. 25-33 ◽

Cited By ~ 101

Author(s):

Richard S.E. Keefe ◽

Sonia E. Lees Roitman ◽

Philip D. Harvey ◽

Cynthia S. Blum ◽

Rachel L. DuPre ◽

...

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Spatial Working Memory ◽

Monkey Prefrontal Cortex

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

Journal of Neurophysiology ◽

10.1152/jn.00370.2013 ◽

2013 ◽

Vol 110 (11) ◽

pp. 2648-2660 ◽

Cited By ~ 11

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.

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LOW-DIMENSIONAL STRUCTURES: SPARSE CODING FOR NEURONAL ACTIVITY

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545813500028 ◽

2013 ◽

Vol 06 (01) ◽

pp. 1350002 ◽

Cited By ~ 1

Author(s):

YUNHUA XU ◽

WENWEN BAI ◽

XIN TIAN

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Neuronal Activity ◽

Sparse Coding ◽

Neural Coding ◽

Memory Task ◽

Work Memory ◽

Neuronal Ensemble ◽

Coding Method ◽

Low Dimensional

Neuronal ensemble activity codes working memory. In this work, we developed a neuronal ensemble sparse coding method, which can effectively reduce the dimension of the neuronal activity and express neural coding. Multichannel spike trains were recorded in rat prefrontal cortex during a work memory task in Y-maze. As discrete signals, spikes were transferred into continuous signals by estimating entropy. Then the normalized continuous signals were decomposed via non-negative sparse method. The non-negative components were extracted to reconstruct a low-dimensional ensemble, while none of the feature components were missed. The results showed that, for well-trained rats, neuronal ensemble activities in the prefrontal cortex changed dynamically during the working memory task. And the neuronal ensemble is more explicit via using non-negative sparse coding. Our results indicate that the neuronal ensemble sparse coding method can effectively reduce the dimension of neuronal activity and it is a useful tool to express neural coding.

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