Evolutionary and Developmental Contributions for Understanding the Organization of the Basal Ganglia

Abstract

Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons containing LANT6). Based on the presence of neurons containing enkephalin or SP, it is possible that the pallidum of these animals also includes the Islet1 lineage cell subpopulation, and both neuron subtypes were likely present in the pallidum of the first jawed vertebrates. In contrast, lampreys (jawless fishes) appear to lack the pallidal embryonic domain and the Nkx2.1 lineage cell population that mainly characterize the pallidum in jawed vertebrates. In the absence of data in other jawless fishes, the ancestral condition in vertebrates remains to be elucidated. Perhaps, a major event in telencephalic evolution was the novel expression of Nkx2.1 in the subpallium, which has been related to Hedgehog expression and changes in the regulatory region of Nkx2.1.

Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)

“…By comparison with tetrapods, this Nkx2.1-labeled region is topologically the counterpart of the septopallidal region of tetrapods [Moreno et al, 2009;Medina et al, 2014]. Therefore, the nitrergic cell populations observed in the Vv in our study would correspond to the septopallidal populations observed in tetrapods ( Table 2).…”

Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells

“…See online version for colors and list for abbreviations. From this comparison, it appears that the Ceov is rather aligned with the radial dorsal part of the Pa (Pad), which includes the BSTL at a periventricular position (note that the GP is not a reference, since in birds it is displaced dorsally, as explained in Puelles et al [2007]; Abellán and Medina [2009] and Medina et al [2014]). It would be interesting to study what led the striatal cells of the Ceov to migrate ventrally during development, and what advantages (if any) this might have implied.…”

“…Scattered Stv-derived cells were also observed in the globus pallidus (GP; fig. 2 c; in chicken, the GP is ectopically located within the striatal radial division Abellán and Medina, 2009;Medina et al, 2014]). …”

From network architecture of forebrain systems to brain wide web

“…The main tenets of Medina's research focuses on (1) the phylogenic conservation of the forebrain modulator systems (including cholinergic and catecholaminergic) in vertebrates and (2) strict segregation of neuronal groups within the basal ganglia and amygdalar structures, with identification of distinctive sites of their ontogenetic origin and discrete migrational paths, already defined during the early phylogeny (Medina et al, 2014). The unparalleled advances made recently in exploring the architecture and connectivity of forebrain systems, without a doubt, reflect recent developments in imaging tools and recombinant technologies that enabled tracing and visualization of individual neurons with their development and plasticity.…”