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Serotonin and Prefrontal Cortex Function: Neurons, Networks, and Circuits

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Abstract

Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expression and brain waves have been observed. Furthermore, many psychiatric drug treatments target serotonergic receptors in the PFC. Thus, understanding the role of serotonergic neurotransmission in PFC function is of major clinical importance. Here, we review recent findings concerning the powerful influences of serotonin on single neurons, neural networks, and cortical circuits in the PFC of the rat, where the effects of serotonin have been most thoroughly studied.

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Acknowledgments

We are grateful to Francesc Artigas, Miquel Bosch, Pau Celada, and Yasuo Kawaguchi for their guidance and support. We also thank Daniel Avesar for contributing the data for Fig. 2. This work has been supported by a number of grants and fellowships from the Spanish, Japanese and U.S. governments. These include a fellowship from the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; M.V.P), a fellowship from the Japan Society for the Promotion of Science (JSPS, M.V.P.), a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation (A.T.G.) and PHS grant R01 MH83806 (A.T.G.).

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The authors declare that they have no conflict of interest.

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  1. The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    M. Victoria Puig

  2. Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, NH, 03756, USA

    Allan T. Gulledge

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  1. M. Victoria Puig
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  2. Allan T. Gulledge
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Correspondence to M. Victoria Puig.

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Puig, M.V., Gulledge, A.T. Serotonin and Prefrontal Cortex Function: Neurons, Networks, and Circuits. Mol Neurobiol 44, 449–464 (2011). https://doi.org/10.1007/s12035-011-8214-0

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