The Zebrafish Amygdaloid Complex – Functional Ground Plan, Molecular Delineation, and Everted Topology

Abstract

In mammals and other tetrapods, a multinuclear forebrain structure, called the amygdala, forms the neuroregulatory core essential for emotion, cognition, and social behavior. Currently, higher circuits of affective behavior in anamniote nontetrapod vertebrates ("fishes") are poorly understood, preventing a comprehensive understanding of amygdala evolution. Through molecular characterization and evolutionary-developmental considerations, we delineated the complex amygdala ground plan of zebrafish, whose everted telencephalon has made comparisons to the evaginated forebrains of tetrapods challenging. In this radical paradigm, thirteen telencephalic territories constitute the zebrafish amygdaloid complex and each territory is distinguished by conserved molecular properties and structure-functional relationships with other amygdaloid structures. Central to our paradigm, the study identifies the teleostean amygdaloid nucleus of the lateral olfactory tract (nLOT), an olfactory integrative structure that links dopaminergic telencephalic groups to the amygdala alongside redefining the putative zebrafish olfactory pallium ("Dp"). Molecular characteristics such as the distribution of substance P and the calcium-binding proteins parvalbumin (PV) and calretinin (CR) indicate, that the zebrafish extended centromedial (autonomic and reproductive) amygdala is predominantly located in the GABAergic and isl1-negative territory. Like in tetrapods, medial amygdaloid (MeA) nuclei are defined by the presence of substance P immunoreactive fibers and calretininpositive neurons, whereas central amygdaloid (CeA) nuclei lack these characteristics. A detailed comparison of lhx5-driven and vGLut2a-driven GFP in transgenic reporter lines revealed ancestral topological relationships between the thalamic eminence (EmT), the medial amygdala (MeA), the nLOT, and the integrative olfactory pallium. Thus, the study explains how the zebrafish amygdala and the complexly everted telencephalon topologically relate to the corresponding structures in mammals indicating that an elaborate amygdala ground plan evolved early in vertebrates, in a common ancestor of teleosts and tetrapods.

Neural pathways of olfactory kin imprinting and kin recognition in zebrafish

“…However, the main advances regarding the amygdaloid complex are as follows. The zebrafish medial amygdala is confirmed to include the Otp-positive Vi described above, but additionally has Otp-negative subdivisions within Vs and Vp as well as in a most dorsal subdivision of Vd (Porter and Mueller 2020 ). The zebrafish central amygdala has several subdivisions, such as the subpallial central nucleus (Vc) and two divisions in parts of Vd dorsal to the striatal one (Porter and Mueller 2020 ).…”

“…The zebrafish medial amygdala is confirmed to include the Otp-positive Vi described above, but additionally has Otp-negative subdivisions within Vs and Vp as well as in a most dorsal subdivision of Vd (Porter and Mueller 2020 ). The zebrafish central amygdala has several subdivisions, such as the subpallial central nucleus (Vc) and two divisions in parts of Vd dorsal to the striatal one (Porter and Mueller 2020 ). Zebrafish bed nuclei of the stria terminalis are identified in the telencephalic strands of dopamine cells along the various subpallial nuclei and in part of Vs (Porter and Mueller 2020 ).…”

“…Finally, a comprehensive study on the entire amygdaloid complex of zebrafish recently provided the most detailed basis to date for a functional neuroanatomical and developmental understanding of the teleostean amygdala and telencephalon in an explicit comparative context with the mammalian (mouse) situation (Porter and Mueller 2020 ). The richness of data and arguments in this study far exceed a thorough discussion here.…”

“…The zebrafish central amygdala has several subdivisions, such as the subpallial central nucleus (Vc) and two divisions in parts of Vd dorsal to the striatal one (Porter and Mueller 2020 ). Zebrafish bed nuclei of the stria terminalis are identified in the telencephalic strands of dopamine cells along the various subpallial nuclei and in part of Vs (Porter and Mueller 2020 ). Interestingly, the cortical amygdala is identified within Dm and the majority of Dm is confirmed as the remaining pallial amygdala (Porter and Mueller 2020 ).…”

“…Zebrafish bed nuclei of the stria terminalis are identified in the telencephalic strands of dopamine cells along the various subpallial nuclei and in part of Vs (Porter and Mueller 2020 ). Interestingly, the cortical amygdala is identified within Dm and the majority of Dm is confirmed as the remaining pallial amygdala (Porter and Mueller 2020 ). This paper represents clearly a milestone in comparative teleostean forebrain research because it solves long-standing questions of homology between mammalian and teleostean telencephala and therefore long-term pressing phylogenetic problems.…”