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Heterogeneity in the pyramidal network of the medial prefrontal cortex


The prefrontal cortex is specially adapted to generate persistent activity that outlasts stimuli and is resistant to distractors, presumed to be the basis of working memory. The pyramidal network that supports this activity is unknown. Multineuron patch-clamp recordings in the ferret medial prefrontal cortex showed a heterogeneity of synapses interconnecting distinct subnetworks of different pyramidal cells. One subnetwork was similar to the pyramidal network commonly found in primary sensory areas, consisting of accommodating pyramidal cells interconnected with depressing synapses. The other subnetwork contained complex pyramidal cells with dual apical dendrites displaying nonaccommodating discharge patterns; these cells were hyper-reciprocally connected with facilitating synapses displaying pronounced synaptic augmentation and post-tetanic potentiation. These cellular, synaptic and network properties could amplify recurrent interactions between pyramidal neurons and support persistent activity in the prefrontal cortex.

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Figure 1: Facilitating connections in the mPFC.
Figure 2: Recorded and modeled synaptic connections in the mPFC and visual cortex.
Figure 3: Distribution of model parameters (DFUA) of all connections studied in the mPFC and visual cortex.
Figure 4: Excitatory synaptic subtypes in the mPFC.
Figure 5: Synaptic augmentation and post-tetanic potentiation (PTP) in different types of excitatory connections in the mPFC.
Figure 6: Functional and structural architecture of the layer 5 pyramidal network in the mPFC.


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This paper is dedicated to Patricia S. Goldman-Rakic, who wholeheartedly supported and supervised this study before she passed away suddenly on July 31 2003. She will always be an inspiration for our work. We are grateful to D.A. McCormick, T. Koos and W.J. Gao for comments on the experimental design; O. Melamed for testing mathematical synaptic modeling; and M. Pappy and A. Begovic for technical assistance. We also thank M. Tsodyks for performing preliminary network modeling studies to better understand the potential functions of facilitation and PTP in recurrent excitation and for his comments on the paper. This work was supported by the National Institute of Mental Health (grant RO1), the Natalie V. Zucker Award, the Charlton Research grants to Tufts University School of Medicine and, in part, by the National Alliance for Autism Research.

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Correspondence to Yun Wang.

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Supplementary information

Supplementary Fig. 1

Facilitating time constant (F) vs. ages of the ferrets. (PDF 56 kb)

Supplementary Fig. 2

Synaptic facilitation between layer 5 pyramidal neurons in different cortical areas of juvenile rats (p13 – p17). (PDF 57 kb)

Supplementary Fig. 3

The EPSP amplitudes and patterns of three E–types of excitatory connections during the train stimulations. (PDF 46 kb)

Supplementary Table 1

Structural and functional architecture of the layer 5 pyramidal networks in ferret mPFC and VC. (PDF 104 kb)

Supplementary Table 2

E-Types vs. multiple parameters of PCs and synaptic connections. (PDF 57 kb)

Supplementary Table 3

Quantitative comparison of complex and simple PCs in the ferret mPFC. (PDF 74 kb)

Supplementary Table 4 (PDF 45 kb)

Supplementary Methods (PDF 322 kb)

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Wang, Y., Markram, H., Goodman, P. et al. Heterogeneity in the pyramidal network of the medial prefrontal cortex. Nat Neurosci 9, 534–542 (2006).

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