HT Innervation of the Basal Ganglia

The 5-HT innervation of the basal ganglia comes from midbrain raphe nuclei (Azmitia and Segal 1978). The most rostral raphe nuclei, i.e., the dorsal raphe nucleus (DRN) and the caudal linear nucleus predominantly innervate the basal ganglia. Fibers ascend to innervate all areas of the basal ganglia, including the striatum, GP, SN, and STN. The 5-HT ascending pathway gives collaterals to each region as it travels to the frontal cortex (Van der Kooy and Hattori 1980). The medial raphe nuclei (MRN) also send fibers to the basal ganglia, in particular to the SN and the nucleus accumbens. However, despite the existence of some 5-HT cell bodies in the MRN, the projection of MRN to the basal ganglia does not seem to be serotonergic. High densities of 5-HT terminals, studied by anterograde labeling, immunohistochemistry (Steinbush 1984), postmortem tissue content, or 5-HT transporter binding, have been found in the SN, the GPi, the STN, the GPe, the nucleus accumbens, and the striatum. However, the 5-HT axon terminals are not homogeneously distributed in the basal ganglia. Gradients of innervations can be observed even in a single region. Notably, the ventral striatum presents higher densities of 5-HT fibers compared with the medial and lateral striatum (Soghomonian et al. 1989). Overall, the 5-HT system is present in all regions of the basal ganglia with a higher density found in associative and limbic territories compared with sensorimotor areas. Ultrastructurally, the morphology of nerve endings differs among regions. In the striatum, varicosities predominate and make en passant synapses, whereas classical nerve endings are less often observed, particularly in the lateral striatum (Soghomonian et al. 1989). Conversely, a higher proportion of true nerve endings have been described in the SNr and SNc, and these make synapses on dentrites and cell bodies of various neuronal types (Corvaja et al. 1993; Moukhles et al. 1997).

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