Heterogeneity in the pyramidal network of the medial prefrontal cortex

Wang, Yun; Markram, Henry; Goodman, Philip H.; Berger, Thomas; Ma, Jun; Goldman‐Rakic, Patricia S.

doi:10.1038/nn1670

Cited by 441 publications

(511 citation statements)

References 43 publications

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“…However, we found that most of the layer 5 P-P connections exhibited similar short-term depression in both PFC and V1 (28) although some connections in PFC exhibited larger recovery EPSCs (see Fig. 2C, 11th EPSC) than those in V1, as previous reported (26). Because NMDARs are highly localized near the soma and proximal dendrites (29), we believe that the possible difference of somatodendritic morphologies of pyramidal neurons in PFC and V1 (26) would not cause such a distinct difference in rise time and decay time constants in the NMDA currents (16).…”

Section: Discussionsupporting

confidence: 89%

“…Previous studies indicated that multiple mechanisms might contribute to the slow process of persistent activity in prefrontal circuit. For instance, a subset of PFC recurrent excitatory synapses exhibiting pronounced shortterm facilitation (26,27) and augmentation (28) can play a role in persistent activity. However, we found that most of the layer 5 P-P connections exhibited similar short-term depression in both PFC and V1 (28) although some connections in PFC exhibited larger recovery EPSCs (see Fig.…”

Section: Discussionmentioning

confidence: 99%

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A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Wang

Stradtman

Wang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

185

252

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In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, immunocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders.cortical development ͉ persistent activity ͉ working memory ͉ recurrent excitation W hat are the microcircuit properties that enable the prefrontal cortex (PFC) to subserve cognitive functions such as working memory and decision making in contrast to early sensory coding and processing in primary sensory areas? To address this central question, physiologists have focused on a salient feature of PFC, namely self-sustained persistent activity, as a candidate neural mechanism for short-term working memory in primates (1-3) and rodents (4). It has been hypothesized that persistent activity is generated by sufficiently strong recurrent excitation among prefrontal neurons (5). The N-methyl-Daspartate receptors (NMDARs) may be critically involved in persistent activity, as indicated by the findings that NMDAR antagonists impaired performance on delayed response tasks in rat PFC (6, 7). Recently, computational models confirmed that only the slow kinetics of NMDARs could stabilize the active maintenance of memory trace (8-10), and their voltage dependences could enhance the stimulus selectivity of persistent activity (11). Therefore, modeling work suggests that a distinctive feature of PFC is its slow reverberating neural dynamics that depend on the NMDARs in the local recurrent circuits.This raises the question of whether PFC neurons are endowed with a substantially higher number of NMDARs, or with NMDARs that express distinct biophysical properties, compared with those in a sensory area such as the primary visual cortex V1 (10). One anatomical study has reported a higher level of mRNA for NMDARs in PFC than in other cortices in human postmortem brain tissues (12). Physiologically, little is known about the functional properties of NMDARs in the prefrontal local recurrent circuits. Because prefrontal functions mature more slowly than the visual cortex, and thi...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Wang

Stradtman

Wang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

185

252

View full text Add to dashboard Cite

show abstract

“…The time constant of the synaptic facilitation is adjusted by the parameter τ F . The values for the baseline utilization factor U (0.15) and for τ F (2 s) are similar to values reported experimentally and used elsewhere (13,23).…”

Section: Methodssupporting

confidence: 70%

Neural and computational mechanisms of postponed decisions

Martínez-García

Rolls

Deco

2011

Proc. Natl. Acad. Sci. U.S.A.

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We consider the mechanisms that enable decisions to be postponed for a period after the evidence has been provided. Using an information theoretic approach, we show that information about the forthcoming action becomes available from the activity of neurons in the medial premotor cortex in a sequential decisionmaking task after the second stimulus is applied, providing the information for a decision about whether the first or second stimulus is higher in vibrotactile frequency. The information then decays in a 3-s delay period in which the neuronal activity declines before the behavioral response can be made. The information then increases again when the behavioral response is required. We model this neuronal activity using an attractor decision-making network in which information reflecting the decision is maintained at a low level during the delay period, and is then selectively restored by a nonspecific input when the response is required. One mechanism for the short-term memory is synaptic facilitation, which can implement a mechanism for postponed decisions that can be correct even when there is little neuronal firing during the delay period before the postponed decision. Another mechanism is graded firing rates by different neurons in the delay period, with restoration by the nonspecific input of the low-rate activity from the higher-rate neurons still firing in the delay period. These mechanisms can account for the decision making and for the memory of the decision before a response can be made, which are evident in the activity of neurons in the medial premotor cortex.attractor network | delayed response | recall

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“…For this model to be compatible with experimental delay durations, facilitation has to be stable for the entire delay period. Some forms of facilitation, such as synaptic augmentation, that are driven by high-frequency bursts of presynaptic firing, can persist for periods of many seconds (Hempel et al, 2000;Zucker and Regehr, 2002;Wang et al, 2006). We therefore propose that the firing rates in the stimulus period, which can reach values of more then 100 Hz (Fig.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Population Coding of Parametric Working Memory

Barak

Tsodyks²,

Romo³

2010

Journal of Neuroscience

173

162

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Comparing two sequentially presented stimuli is a widely used experimental paradigm for studying working memory. The delay activity of many single neurons in the prefrontal cortex (PFC) of monkeys was found to be stimulus-specific, however, population dynamics of stimulus representation has not been elucidated. We analyzed the population state of a large number of PFC neurons during a somatosensory discrimination task. Using the tuning curves of the neurons, we derived a compact characterization of the population state. Stimulus representation by the population was found to degrade after stimulus termination, and emerge in a different form toward the end of the delay. Specifically, the tuning properties of neurons were found to change during the task. We suggest a mechanism whereby information about the stimulus is contained in activity-dependent synaptic facilitation of recurrent connections.

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Heterogeneity in the pyramidal network of the medial prefrontal cortex

Cited by 441 publications

References 43 publications

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Neural and computational mechanisms of postponed decisions

Neuronal Population Coding of Parametric Working Memory

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