Abstract
Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC), a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking) interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT2 receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT1 receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.
Highlights
The prefrontal cortex (PFC) is a central brain region controlling high-level executive functions and goal-directed behaviors [1]
To understand the effect of serotonin on the excitability of cortical neuronal populations, we conducted whole-cell currentclamp recordings to examine the action potential (AP) firing in FS interneurons and pyramidal neurons located at layer 3–5 of PFC
We have revealed the effect of serotonin and fluoxetine on the intrinsic excitability of PFC FS interneurons and pyramidal neurons
Summary
The prefrontal cortex (PFC) is a central brain region controlling high-level executive functions and goal-directed behaviors [1]. Neuropsychological, and imaging studies have indicated that several neuropsychiatric disorders, including depression, anxiety and schizophrenia, are related to the deficits in cognitive and emotional processes subserved by PFC [2,3,4,5]. PFC activity is control by the excitability of two major neuronal populations: glutamatergic excitatory pyramidal neurons and GABAergic inhibitory interneurons [16]. Specific deficits in PFC FS interneurons have been found in schizophrenia patients [21]. Alterations of prefrontal cortical activity are considered as an important causal factor for major depression [22], which provides a basis for the treatment of depression with brain stimulation [23]
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