ReviewSerotonergic modulation of the limbic system
Section snippets
Overview
The limbic system is composed of cortical as well as subcortical structures, which are intimately interconnected. The major structures of the limbic system include prefrontal cortex, cingulate cortex, entorhinal cortex, hippocampus, nucleus accumbens (ventral striatum), ventral pallidum, amygdala, and anterior hypothalamus (see Swanson and Petrovich, 1998, Kandel et al., 2000, Heimer, 2003). Connections between these structures form complex circuits. Furthermore, projections between structures
Two distinct central serotonergic systems
Serotonin-containing neuronal cell bodies are restricted to discrete groups of cells or nuclei located along the midline of the brainstem. Their axonal projections, however, innervate nearly every area of the central nervous system. Dahlström and Fuxe (1964), using the Falck–Hillarp technique of histofluorescence, observed that the majority of serotonergic soma were found in cell body groups previously designated by Taber et al. (1960) as the raphe nuclei based on cytoarchitectural criteria,
Ascending serotonergic projections to limbic structures
The dorsal periventricular path and the ventral tegmental radiations are the two main ascending serotonergic pathways from the midbrain raphe nuclei to the forebrain. Both pathways converge in the caudal hypothalamus where they join the medial forebrain bundle and axons of dopaminergic (A8, A9, A10) and noradrenergic (A6) cell body groups (Moore et al., 1978, Parent et al., 1981; see also Molliver, 1987, Vertes, 1991).
The dorsal and median raphe nuclei give rise to distinct serotonergic
Volume transmission
The action of neurotransmitters may be restricted to the synaptic cleft, specifically referred to as hard-wired neurotransmission, or may require that the neurotransmitter diffuse to remote receptor sites, referred to as diffuse, volume or paracrine transmission. Important factors determining the type of neurotransmission include the location of receptors with respect to release sites, the amount of neurotransmitter released, rate of diffusion away from the release site, and the removal or
Disorders of limbic system and treatment strategies
In humans, disorders associated with dysfunction within the limbic system include schizophrenia, major depression, and anxiety disorders. Drugs used in the treatment of these disorders modulate or alter serotonergic neurotransmission (see Jones and Blackburn, 2002).
Some considerations in the treatment of disorders of the limbic system
Serotonergic projections from the dorsal and median raphe differ in the topographical organization and density of their respective innervation of forebrain structures. With regard to the treatment of affective disorders, i.e. major depression and anxiety disorders, it is an intriguing possibility that these two distinct serotonergic systems are differentially modulated by drugs that block serotonin reuptake (e.g. tricyclic antidepressants and selective serotonin reuptake inhibitors). Indeed,
Acknowledgements
This work was supported by US PHS grants MH 52369 and funds from the National Association for Research on Schizophrenia and Depression (NARSAD).
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