The Everted Amygdala of Ray-Finned Fish: Zebrafish Makes a Case

The amygdala, a complex array of nuclei in the forebrain, controls emotions and emotion-related behaviors in vertebrates. Current research aims to understand the amygdala’s evolution in ray-finned fish such as zebrafish because of the region’s relevance for social behavior and human psychiatric disorders. Clear-cut molecular definitions of the amygdala and its evolutionary-developmental relationship to the one of mammals are critical for zebrafish models of affective disorders and autism. In this review, I argue that the prosomeric model and a focus on the olfactory system’s organization provide ideal tools for discovering deep ancestral relationships between the emotional systems of zebrafish and mammals. The review’s focus is on the “extended amygdala,” which refers to subpallial amygdaloid territories including the central (autonomic) and the medial (olfactory) amygdala required for reproductive and social behaviors. Amphibians, sauropsids, and lungfish share many characteristics with the basic amygdala ground plan of mammals, as molecular and hodological studies have shown. Further exploration of the evolution of the amygdala in basally derived fish vertebrates requires researchers to test these “tetrapod-based” concepts. Historically, this has been a daunting task because the forebrains of basally derived fish vertebrates look very different from those of more familiar tetrapod ones. An extreme case are ray-finned fish (Actinopterygii) like zebrafish because their telencephalon develops through a distinct outward-growing process called eversion. To this day, scientists have struggled to determine how the everted telencephalon compares to non-actinopterygian vertebrates. Using the teleost zebrafish as a genetic model, comparative neurologists began to establish quantifiable molecular definitions that allow direct comparisons between ray-finned fish and tetrapods. In this review, I discuss how the most recent discovery of the zebrafish amygdala ground plan offers an opportunity to identify the developmental constraints of amygdala evolution and function. In addition, I explain how the zebrafish prethalamic eminence (PThE) topologically relates to the medial amygdala proper and the nucleus of the lateral olfactory tract (nLOT). In fact, I consider these previously misinterpreted olfactory structures the most critical missing evolutionary links between actinopterygian and tetrapod amygdalae. In this context, I will also explain why recognizing both the PThE and the nLOT is crucial to understanding the telencephalon eversion. Recognizing these anatomical hallmarks allows direct comparisons of the amygdalae of zebrafish and mammals. Ultimately, the new concepts of the zebrafish amygdala will overcome current dogmas and reach a holistic understanding of amygdala circuits of cognition and emotion in actinopterygians.