The prefrontal cortex is essential for both executive function and emotional regulation. The interrelationships among these behavioral domains are increasingly recognized, as well as their sensitivity to serotonin (5-hydroxytryptamine, 5-HT). Prefrontal cortex receives serotonergic inputs from the dorsal and median raphe nuclei and is modulated by multiple subtypes of 5-HT receptor across its layers and cell types. Extremes of serotonergic modulation alter mood regulation in vulnerable individuals, yet the impact of serotonin under more typical physiological parameters remains unclear. In this regard, new tools are permitting a closer examination of the behavioral impact of the serotonin system. Optogenetic and chemogenetic manipulations of dorsal raphe 5-HT neurons reveal that serotonin has a greater impact on executive function than previously appreciated. Domains that appear sensitive to fluctuations in 5-HT neuronal excitability include patience and cognitive flexibility. This work is broadly consistent with ex vivo research investigating how 5-HT regulates prefrontal cortex and its output projections. A growing literature suggests 5-HT modulation of these prefrontal circuits is unexpectedly flexible to alteration during development by genetic, behavioral, environmental or pharmacological manipulations, with lasting repercussions for cognition and emotional regulation. Here, we review the cellular and circuit mechanisms of prefrontal serotonergic modulation, investigate recent research into the cognitive consequences of the serotonergic system, and probe the lasting consequences of developmental perturbations. Understanding both the complexity of the prefrontal serotonin system and its sensitivity during development are essential to learn more about the vulnerabilities of this system in mood and anxiety disorders and the underappreciated cognitive consequences of these disorders and their treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acschemneuro.9b00073 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress.
Epigenetics
December 2025
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA.
The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content, which induce stress-specific phenotypes in their offspring. However, how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring.
View Article and Find Full Text PDFUnlabelled: Motivated behaviors are regulated by distributed forebrain networks. Traditional approaches have often focused on individual brain regions and connections that do not capture the topographic organization of forebrain connectivity. We performed co-injections of anterograde and retrograde tract tracers in rats to provide novel high-spatial resolution evidence of topographic connections that elaborate a previously identified closed-loop forebrain circuit implicated in affective and motivational processes.
View Article and Find Full Text PDFHow the prefrontal hemispheres coordinate to adapt to spatial working memory (WM) demands remains an open question. Recently, two models have been proposed: A specialized model, where each hemisphere governs contralateral behavior, and a redundant model, where both hemispheres equally guide behavior in the full visual space. To explore these alternatives, we analyzed simultaneous bilateral prefrontal cortex recordings from three macaque monkeys performing a visuo-spatial WM task.
View Article and Find Full Text PDFTau pathology in the locus coeruleus (LC) is associated with several neurodegenerative conditions including Alzheimer's disease and frontotemporal dementia. Phosphorylated tau accumulates in the LC and results in inflammation, synaptic loss, and eventually cell death as the disease progresses. Loss of LC neurons and noradrenergic innervation is thought to contribute to the symptoms of cognitive decline later in disease.
View Article and Find Full Text PDFThe fine-grained functional organization of the human lateral prefrontal cortex (PFC) remains poorly understood. Previous fMRI studies delineated focal domain-general, or multiple-demand (MD), PFC areas that co-activate during diverse cognitively demanding tasks. While there is some evidence for category-selective (face and scene) patches, in human and non-human primate PFC, these have not been systematically assessed.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!