A descending dopamine pathway conserved from basal vertebrates to mammals

Abstract

Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson's disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine's role in locomotion.D opaminergic neurons represent a vital neuromodulatory component essential for vertebrate motor control, and their loss in neurodegenerative disease is devastating. The meso-diencephalic dopamine (DA) neurons are known to provide ascending projections to the basal ganglia, which, in turn, provide input to cortical structure in mammals but also project caudally to the mesencephalic locomotor region (MLR), a highly conserved structure that controls locomotion in all vertebrates investigated to date (1-7; for review, see ref. 8). A growing body of evidence supports the view that basal ganglia connectivity is highly conserved among vertebrates, from lampreys to mammals (9-11; for review, see ref. 12), with some interspecies differences recently highlighted (13). As such, the homology between DA cell populations remains to be resolved in vertebrates. As a general rule, DA neurons from the meso-diencephalon send projections to the striatum in all vertebrates. In lampreys and teleosts, those neurons are located only in the diencephalon (posterior tuberculum), but in tetrapods and cartilaginous fishes (14) they are located in both the diencephalon and the mesencephalon. An increasing number of authors seem to agree with the hypothesis that at least some of the mesodiencephalic DA neurons located in the diencephalon are homologous in all vertebrates, and thus, homologous to at least a portion of the mammalian substantia nigra pars compacta (SNc)/ ventral tegmental area (VTA) (13, 15-19; for review, see ref. 20). Alternatively, it was suggested that the posterior tuberculum DA neurons projecting to the striatum in zebrafish are homologs of the mammalian DA neurons of the A11 group (21). This will be discussed below in light of the results of the present study.In lampreys, only a few meso-diencephalic DA neurons send ascending projections to the striatum (9, 22); the majority ...

Organization of the catecholaminergic systems in two basal actinopterygian fishes, Polypterus senegalus and Erpetoichthys calabaricus (Actinopterygii: Cladistia)

“…Therefore, the presence of a prethalamic dopaminergic population seems to be a conserved feature in the evolution of DA system. Interestingly, in mammals, the expression of the genes Arx and Isl1 is required for the development of prethalamic dopaminergic cells (Filippi, Jainok, & Driever, 2012), and Isl1 is strongly expressed in the prethalamus of cladistians (personal observation) like in amphibians and lungfishes (Moreno et al, 2018;Moreno, Domínguez, Rétaux, & González, 2008 The most conspicuous dopaminergic cell population in the diencephalon of cladistians is situated in the posterior tubercle, within the basal part of p3, similarly to the observations reported in teleosts (Bhat & Ganesh, 2017;Forlano & Sisneros, 2016;Karoubi et al, 2016;Rink & Wullimann, 2001, 2002a, 2002bRyczko et al, 2016;, and other groups of fishes as chondrosteans (Adrio et al, 2002), elasmobranchs (Carrera et al, 2012;Molist et al, 1993), and lampreys (Pierre et al, 1997;Pombal et al, 1997). The amphibians also present a remarkable TH/DA-ir cell population in the posterior tubercle , whereas in lungfishes this dopaminergic group is less developed (López & González, 2017).…”

Pattern of nitrergic cells and fibers organization in the central nervous system of the Australian lungfish,Neoceratodus forsteri(Sarcopterygii: Dipnoi)

“…Comparatively, a more prominent and numerous nitrergic cell group is observed in the TP of actinopterygian fishes and amphibians, although a few exceptions have been noted in urodeles and some teleosts (Gaikwad et al, ; González et al, ). In addition, the TP of actinopterygians also houses a remarkable TH‐ir (dopaminergic) cell population that, at less in part, is considered equivalent to the ventral tegmental area/substantia nigra complex of amniotes by its ascending projections to the subpallium (Forlano, Kim, Krzyminska, & Sisneros, ; Karoubi, Segev, & Wullimann, ; López et al, ; López, Lozano, Morales, & González, ; Rink & Wullimann, ; Ryczko et al, ; Tay, Ronneberger, Ryu, Nitschke, & Driever, ; Yamamoto & Vernier, ). Of note, a comparable connectivity from TP/mesencephalic tegmentum to basal ganglia has been corroborated in amphibians (Marín, Smeets, & González, , ).…”

Organization of the catecholaminergic systems in the brain of lungfishes, the closest living relatives of terrestrial vertebrates

“…The TH/DA‐ir cell population of the posterior tubercle observed in lungfishes, seems to be less developed than in actinopterygian fishes (Rink & Wullimann, ,b; Yamamoto et al, ; Forlano, Kim, Krzyminska, & Sisneros, ; Karoubi et al, ; Ryczko et al, ). This group of dopaminergic neurons in the basal part of p3 are a caudal continuation of the cells in the retromammillary region and do not extend into p2.…”