Pattern of distribution of serotonergic fibers to the thalamus of the rat

Abstract

It is well established that serotonergic (5-hydroxytryptamine, 5-HT) fibers, mainly originating from the dorsal and median raphe nuclei of the brainstem, distribute throughout the forebrain, most heavily to 'limbic' forebrain structures. Few reports have examined the distribution of 5-HT fibers to the thalamus and none to our knowledge using immunoprocedures for the detection of the serotonin transporter (SERT)-a very sensitive marker for 5-HT fibers. Using immunohistochemical methods for SERT, we examined the pattern of distribution of 5-HT fibers to the thalamus in the rat. We show that serotonergic fibers are heavily concentrated in midline, intralaminar and association nuclei of the thalamus, and with the exception of the lateral geniculate complex, weakly distributed to principal nuclei of thalamus. Specifically, we demonstrate that 5-HT fibers are densely concentrated in the anteroventral, anteromedial and interanteromedial nuclei of the anterior thalamus, the paraventricular, rhomboid and reuniens nuclei of the midline thalamus, the central medial and central lateral nuclei of the intralaminar thalamus, the intermediodorsal nucleus, the lateral dorsal nucleus, and the dorsal and ventral lateral geniculate nuclei and intergeniculate leaflet of the LGN complex. Less densely innervated sites include the mediodorsal, paracentral, parafascicular, lateral posterior and submedial nuclei of thalamus. Remaining regions of the thalamus, largely consisting of principal nuclei, contained few 5-HT fibers. This pattern of 5-HT innervation indicates that serotonin/ serotonergic fibers mainly affect thalamic nuclei with connections to 'non-principal' or limbic regions of the cortex (or forebrain). This suggests that serotonergic fibers to the thalamus may exert a significant influence on affective and cognitive functions, possibly complementing the actions of 5-HT fibers to other parts of the brain involved in emotional and cognitive behaviors.

Pattern of distribution of serotonergic fibers to the orbitomedial and insular cortex in the rat

“…Studies examining the 5-HT innervation of thalamus using immunostaining for 5-HT or SERT have shown that serotonergic axons are much more heavily concentrated in 'limbic' (nonspecific) than in principal (relay) nuclei of the thalamus (Cropper et al, 1984;Lavoie and Parent, 1991;Vertes et al, 2010). For instance, using antisera to SERT, we demonstrated that 5-HT fibers are densely distributed in the anterior, midline, intralaminar and mediodorsal nuclei of thalamus (Vertes et al, 2010).…”

“…Nielsen et al (2006) showed that SERT as a biomarker for 5-HT produces a stronger signal than antisera to serotonin. We found that both 5-HT and SERT immunohistochemistry produce similar patterns of serotonergic labeling, but that SERT immunostaining, by heightening signal to background, provided a bolder representation of labeled 5-HT fibers (Vertes et al, 2010).…”

“…For instance, using antisera to SERT, we demonstrated that 5-HT fibers are densely distributed in the anterior, midline, intralaminar and mediodorsal nuclei of thalamus (Vertes et al, 2010). By contrast, 'non-limbic areas' of the thalamus, largely consisting of relay nuclei, contained few 5-HT fibers -the only exception being the lateral geniculate complex.…”

GPCR Modulation of Extrasynapitic GABAA Receptors

“…Thalamic 5-HT projections mainly originate from the small-to-medium sized 5-HT neurons located in the DR and MR nuclei (Dahlstroem and Fuxe 1964;Vertes et al 1999). Several studies have described a dense and heterogeneous distribution of 5-HT fibers within the thalamus; serotonergic fibers are heavily concentrated in midline, intralaminar and association thalamic nuclei, and with the exception of the dLGN, they are also weakly distributed in principal thalamic nuclei (Vertes et al 2010;Rodriguez et al 2011).…”

Role of Midline Thalamic Circuits in Limbic Seizures

“…Some structures of the ventral forebrain, such as the ventral pallidum and globus pallidus also send GABAergic projections in (Churchill 1996), as does the substantia nigra pars reticulata (Tanibuchi 2009). The midline thalamus also receives serotonergic (Vertes 2010), dopaminergic (Garcia-Cabezas et al 2009) and adrenergic (Vogt et al 2008) inputs as well, indicating that midline thalamic output is regulated in a complicated manner.…”