Serotonin Modulation of Prefronto-Hippocampal Rhythms in Health and Disease

Abstract

There is mounting evidence that most cognitive functions depend upon the coordinated activity of neuronal networks often located far from each other in the brain. Ensembles of neurons synchronize their activity, generating oscillations at different frequencies that may encode behavior by allowing an efficient communication between brain areas. The serotonin system, by virtue of the widespread arborisation of serotonergic neurons, is in an excellent position to exert strong modulatory actions on brain rhythms. These include specific oscillatory activities in the prefrontal cortex and the hippocampus, two brain areas essential for many higher-order cognitive functions. Psychiatric patients show abnormal oscillatory activities in these areas, notably patients with schizophrenia who display psychotic symptoms as well as affective and cognitive impairments. Synchronization of neural activity between the prefrontal cortex and the hippocampus seems to be important for cognition and, in fact, reduced prefronto-hippocampal synchrony has been observed in a genetic mouse model of schizophrenia. Here, we review recent advances in the field of neuromodulation of brain rhythms by serotonin, focusing on the actions of serotonin in the prefrontal cortex and the hippocampus. Considering that the serotonergic system plays a crucial role in cognition and mood and is a target of many psychiatric treatments, it is surprising that this field of research is still in its infancy. In that regard, we point to future investigations that are much needed in this field.

A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance

“…Our study suggests that helplessness might be associated with impaired theta engagement. This is consistent with reports that uncontrollable stress induces brain-wide serotonergic activation, which is the main modulatory system that suppresses theta (Maier and Watkins, 1998;Puig and Gener, 2015;Vertes and Kocsis, 1997). Serotonin-induced effects related to helplessness arise mostly from the dorsal raphe nucleus (Maier and Watkins, 2005), which receives regulatory projections from the mPFC (Pollak Dorocic et al, 2014).…”

Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

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Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments

“…Recently, long-range inhibitory projections originating from GABAergic neurons that terminate selectively on inhibitory interneurons in their respective target areas could also contribute to an important mechanism for inter-regional synchronization (Melzer et al, 2012). Furthermore, the neuromodulatory system plays an important role in the gating of oscillations and synchrony: Gamma oscillations and their synchronization depend critically on the activation of muscarinic (Rodriguez et al, 2004), dopaminergic, and 5-HT receptors (Dzirasa et al, 2013; Dzirasa et al, 2009; Puig and Gener, 2015). All these molecular mechanisms could affect the levels of neural activity, oscillations, and synchronization in the PFC, thereby providing a possible mechanism for mediating inter-regional communication, information selection, and processing involving PFC (Benchenane et al, 2011).…”