Subthreshold basis for reward-predictive persistent activity in mouse prefrontal cortex

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.

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Persistent Activity in Prefrontal Cortex during Trace Eyelid Conditioning: Dissociating Responses That Reflect Cerebellar Output from Those That Do Not

Journal of Neuroscience ◽

10.1523/jneurosci.1238-13.2013 ◽

2013 ◽

Vol 33 (38) ◽

pp. 15272-15284 ◽

Cited By ~ 28

Author(s):

J. J. Siegel ◽

M. D. Mauk

Keyword(s):

Prefrontal Cortex ◽

Eyelid Conditioning ◽

Persistent Activity

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Representation of remembered stimuli and task information in the monkey dorsolateral prefrontal and posterior parietal cortex

Journal of Neurophysiology ◽

10.1152/jn.00413.2014 ◽

2015 ◽

Vol 113 (1) ◽

pp. 44-57 ◽

Cited By ~ 12

Author(s):

Xue-Lian Qi ◽

Anthony C. Elworthy ◽

Bryce C. Lambert ◽

Christos Constantinidis

Keyword(s):

Prefrontal Cortex ◽

Parietal Cortex ◽

Posterior Parietal Cortex ◽

Spatial Working Memory ◽

Persistent Activity ◽

Relative Preference ◽

Task Effects ◽

Dorsolateral Prefrontal ◽

Posterior Parietal ◽

And Task

Both dorsolateral prefrontal and posterior parietal cortex have been implicated in spatial working memory and representation of task information. Prior experiments training animals to recall the first of a sequence of stimuli and examining the effect of subsequent distractors have identified increased ability of the prefrontal cortex to represent remembered stimuli and filter distractors. It is unclear, however, if this prefrontal functional specialization extends to stimuli appearing earlier in a sequence, when subjects are cued to remember subsequent ones. It is also not known how task information interacts with persistent activity representing remembered stimuli and distractors in the two areas. To address these questions, we trained monkeys to remember either the first or second of two stimuli presented in sequence and recorded neuronal activity from the posterior parietal and dorsolateral prefrontal cortex. The prefrontal cortex was better able to represent the actively remembered stimulus, whereas the posterior parietal cortex was more modulated by distractors; however, task effects interfered with this representation. As a result, large proportions of neurons with persistent activity and task effects exhibited a preference for a stimulus when it appeared as a distractor in both areas. Additionally, prefrontal neurons were modulated to a greater extent by task factors during the delay period of the task. The results indicate that the prefrontal cortex is better able than the posterior parietal cortex to differentiate between distractors and actively remembered stimuli and is more modulated by the task; however, this relative preference is highly context dependent and depends on the specific requirements of the task.

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Temporally Irregular Mnemonic Persistent Activity in Prefrontal Neurons of Monkeys During a Delayed Response Task

Journal of Neurophysiology ◽

10.1152/jn.00949.2002 ◽

2003 ◽

Vol 90 (5) ◽

pp. 3441-3454 ◽

Cited By ~ 149

Author(s):

Albert Compte, ◽

Christos Constantinidis ◽

Jesper Tegnér ◽

Sridhar Raghavachari ◽

Matthew V. Chafee ◽

...

Keyword(s):

Prefrontal Cortex ◽

Power Spectrum ◽

Spike Train ◽

Temporal Structure ◽

Spike Trains ◽

Delay Period ◽

Delayed Response ◽

Persistent Activity ◽

Response Task ◽

Delayed Response Task

An important question in neuroscience is whether and how temporal patterns and fluctuations in neuronal spike trains contribute to information processing in the cortex. We have addressed this issue in the memory-related circuits of the prefrontal cortex by analyzing spike trains from a database of 229 neurons recorded in the dorsolateral prefrontal cortex of 4 macaque monkeys during the performance of an oculomotor delayed-response task. For each task epoch, we have estimated their power spectrum together with interspike interval histograms and autocorrelograms. We find that 1) the properties of most (about 60%) neurons approximated the characteristics of a Poisson process. For about 25% of cells, with characteristics typical of interneurons, the power spectrum showed a trough at low frequencies (<20 Hz) and the autocorrelogram a dip near zero time lag. About 15% of neurons had a peak at <20 Hz in the power spectrum, associated with the burstiness of the spike train; 2) a small but significant task dependency of spike-train temporal structure: delay responses to preferred locations were characterized not only by elevated firing, but also by suppressed power at low (<20 Hz) frequencies; and 3) the variability of interspike intervals is typically higher during the mnemonic delay period than during the fixation period, regardless of the remembered cue. The high irregularity of neural persistent activity during the delay period is likely to be a characteristic signature of recurrent prefrontal network dynamics underlying working memory.

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Persistent activity in the prefrontal cortex during working memory

Trends in Cognitive Sciences ◽

10.1016/s1364-6613(03)00197-9 ◽

2003 ◽

Vol 7 (9) ◽

pp. 415-423 ◽

Cited By ~ 1085

Author(s):

Clayton E. Curtis ◽

Mark D'Esposito

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Persistent Activity

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Exploring the Inner Workings of Neuron Circuits That Exhibit Persistent Activity To Explain How Working Memory and Executive Function Are Implemented in The Brain

10.1101/2021.07.05.451167 ◽

2021 ◽

Author(s):

Paul Gomez

Keyword(s):

Decision Making ◽

Working Memory ◽

Prefrontal Cortex ◽

Executive Function ◽

Memory Task ◽

Persistent Activity ◽

Storage Mechanism ◽

Minimum Number ◽

Task Processing ◽

The Brain

In this research we explore in detail how a phenomenon called sustained persistent activity is achieved by circuits of interconnected neurons. Persistent activity is a phenomenon that has been extensively studied (Papoutsi et al. 2013; Kaminski et. al. 2017; McCormick et al. 2003; Rahman, and Berger, 2011). Persistent activity consists in neuron circuits whose spiking activity remains even after the initial stimuli are removed. Persistent activity has been found in the prefrontal cortex (PFC) and has been correlated to working memory and decision making (Clayton E. Curtis and Daeyeol Lee, 2010). We go beyond the explanation of how persistent activity happens and show how arrangements of those basic circuits encode and store data and are used to perform more elaborated tasks and computations. The purpose of the model we propose here is to describe the minimum number of neurons and their interconnections required to explain persistent activity and how this phenomenon is actually a fast storage mechanism required for implementing working memory, task processing and decision making.

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