The habenula as an evolutionary conserved link between basal ganglia, limbic, and sensory systems—A phylogenetic comparison based on anuran amphibians

Abstract

Based on anatomical and functional data, the habenula—a phylogenetically old brain structure present in all vertebrates—takes part in the integration of limbic, sensory, and basal ganglia information to guide effective response strategies appropriate to environmental conditions. In the present study, we investigated the connections of the habenular nuclei of the oriental fire‐bellied toad, Bombina orientalis, and compared them with published data from lampreys, chondrichthyes, teleosts, reptiles, birds, and mammals. During phylogenetic development, the primordial habenula circuitry underwent various evolutionary adaptations and in the tetrapod line, the circuit complexity increased. The habenula circuitry of anuran amphibians, decedents of the first land‐living tetrapods, seem to exhibit a mix of ancient as well as modern features. The anuran medial and lateral habenula homologs receive differential input from the septum, nucleus of the diagonal band of Broca, preoptic area, hypothalamus, rostral pallium, nucleus accumbens, ventral pallidum, and bed nucleus of the stria terminalis. Additional input arises from a border region in the ventral prethalamus, here discussed as a putative homolog of the entopeduncular nucleus of rodents. The habenular subnuclei also differentially innervate the interpeduncular nucleus, raphe nuclei, substantia nigra pars compacta and ventral tegmental area homologs, superficial mamillary area, laterodorsal tegmental nucleus, locus coeruleus, inferior and superior colliculus homologs, hypothalamus, preoptic area, septum, nucleus of the diagonal band of Broca, and main olfactory bulb. It seems likely that the main connectivity between the habenula and the basal ganglia, limbic, and sensory systems was already present in the common tetrapod ancestor.

Refinement of the dopaminergic system of anuran amphibians based on connectivity with habenula, basal ganglia, limbic system, pallium, and spinal cord

“…In a previous study, we identified prominent projections from the dorsal and ventral habenula to the posterior tubercle, mesencephalic tegmentum, and raphe nuclei in Bombina orientalis (Freudenmacher et al, ). But direct habenula projections to dopaminergic, serotonergic, and histaminergic neurons were not identified.…”

“…This appears to be mediated by GABAergic neurons in the rostromedial tegmental nucleus (RMTg) and opposes the reward and motor‐activating functions of dopaminergic midbrain neurons (Jhou, Geisler, Marinelli, Degarmo, & Zahm, ). While a structure homologous to the RMTg—located in the dorsal mamillary area—was identified in lampreys (Stephenson‐Jones et al, ), we could identify the superficial mamillary area as a putative RMTg homolog in anuran amphibians (Freudenmacher et al, ). In order to address the question whether the MHb/LHb–(RMTg)–VTA/SNc/raphe circuitry is as well present in anuran amphibians, this study investigated these regions and their topographic and immunohistochemical organization in more detail.…”

“…The brains were isolated by a ventral approach and transferred into a dish with Ringer's solution (75 mM NaCl, 25 mM NaHCO 3 , 2 mM CaCl 2 , 2 mM KCl, 0.5 mM MgCl 2 , 11 mM D‐glucose), which was adjusted with carbogen (95% O 2 , 5% CO 2 ) to a pH of 7.4 and stored at 5°C. The majority of the brain preparations were also used in a prior study (Freudenmacher et al, ). The project is registered after §4 of the Animal Protection Act under the title “NeuroAnura,” approval number 4.16.004.…”

“…The amphibian homologs of the A9–A10 cell groups might therefore represent an early stage in the evolution of these structures. However, in a recent study we could identify a differential innervation of the SNc/VTA homologs by the ventral and dorsal habenula in Bombina orientalis (Freudenmacher, Twickel, & Walkowiak, ). This closely resembles the situation found in many mammals (Akagi & Powell, ; Araki, McGeer, & Kimura, ; Brinschwitz et al, ; Herkenham & Nauta, ; Omelchenko, Bell, & Sesack, ; Phillipson, ; Way & Kaelber, ).…”

“…The in‐depth analysis of the habenula circuitry in anuran amphibians could therefore provide new insights into the evolution of dopaminergic systems. In all mammals for which data are available, the habenula comprises medial (MHb) and lateral parts (LHb; reviewed by Hikosaka, ), which correspond—in terms of their connectivity—to the dorsal (DHb) and ventral habenula (VHb) of anuran amphibians (Freudenmacher et al, ).…”