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

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.

The Native Serotonin 5-HT5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

“…Serotonergic inhibition of the prefrontal cortex is important for coordinating emotional behaviors (Puig and Gulledge, 2011). To date, this inhibition has been attributed entirely to 5-HT 1A receptors, despite evidence suggesting the presence of an additional, unidentified, inhibitory 5-HT effect (Amargó s- Bosch et al, 2004, Villalobos et al, 2005Zhong and Yan, 2011).…”

Brain imaging research on psychopathy: Implications for punishment, prediction, and treatment in youth and adults

“…Responsible for a wide range of functions, it is perhaps best known as the center of "executive functioning", functions which include behavioral flexibility, learning, sustained attention, and working memory (Puig & Gulledge, 2011). It is also part of a wider neural circuit underlying moral decision making and reward/punishment processing (e.g.…”

Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

“…Previous evidence supports the idea that the PFC is related to emotional control (MyersSchulz and Koenigs 2012), regulating executive tasks of higher order, such as learning, memory, categorization, inhibitory control and executive flexibility, among others (Puig and Gulledge 2011). Also the PFC seems to play a pivotal role in the regulation of mood and anxiety-related responses (Drevets et al 2008, Fredericks et al 2006, Milad and Rauch 2006, Price and Drevets 2010.…”

“…According to in vitro studies performed with rat brain slices, PFC pyramidal neurons co-express serotonin 1A and 2A receptors (Puig and Gulledge 2011). It is thus possible that the increases in Fosir in the PFC caused by tryptophan overload are related to the activation of serotonin receptors in PFC neurons.…”

“…It is thus possible that the increases in Fosir in the PFC caused by tryptophan overload are related to the activation of serotonin receptors in PFC neurons. This may be one of the mechanisms by which the supplementation of tryptophan in clinical trials alters mood, cognition and behavior (Puig and Gulledge 2011, Miller and Cohen 2001, Fuster 1997, 2001.…”