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4.1 How Do We Choose A Model System?

Animal models are used to understand biological phenomena and behaviors that can be applied to a broad range of species. The choice of model organisms is based on behavioral characteristics, breeding, ease of handling and/or exceptional abilities. Animal research must follow strict guidelines and be approved by an ethics committee called IACUC. While animal models have a proven track record in saving human lives, there are emerging alternatives such as organoids that may reduce the need for animal testing.

4.2 How Do We Compare Brains?

To date, there is still no clear consensus as to what structures are homologous to the mammalian cortex and their equivalent in birds. We reviewed one unresolved case that highlights the challenges that arise from attempting to define homologous neural structures across distantly related lineages. This is not to say that neuroscientists simply argue about homologies. Rather, we selected this topic because unresolved cases demonstrate the many kinds of perspectives we might use to define homology. Some perspectives place an emphasis on adult structure whereas others place an emphasis on developmental processes that give rise to adult structures.

4.3 How Do Brains Vary in Size?

The size of the brain and parts are relatively large in humans compared with other species. Cross-species comparisons across diverse species show that brain regions sometimes vary allometrically (Finlay and Darlington, 1995; Finlay et al., 2011; Barton and Harvey, 2000), but grade shifts are also possible, which means that regions are larger or smaller than allometry would predict given their brain size. Sensory and motor specializations carve out cortical territories so that the relative size of brain parts is dictated by allometry, lifestyle, and environment.

4.4 How Do Connections Differ Across Species?

We discussed methods used to study brain pathways. It’s a tricky subject and most of the pathways we study in human neuroscience are inferred from model systems. Some methods are only available in model systems (e.g., tracers) but others (e.g., diffusion imaging) are also available for use in humans. The map of human brain pathways remains a work-in-progress. Due to the inherent limitations of methods for studying human brain connectivity, many researchers use the principle of conservation to make inferences about connectivity profiles in humans. We rely on features that are constant across diverse mammalian species to extrapolate the map of human brain pathways. Yet, some pathways should be specific to humans, and we have yet to identify many of the pathway types that are unique to humans. Some researchers have turned to integration of large-scale maps from neuroimaging with genetics to identify how pathways have evolved across species (Charvet et al., 2022).

4.5 How Can Diverse Species Help Us Make Inferences about Human Neurobiology?

As is evident from our overview of the development and neural basis of social bonds, the selection of model systems depends on the biological program of interest. Groups of closely related species offer advantages in understanding human neurobiology as is the case of voles. Non-human primates also enable probing into our biological processes due to their phylogenetic proximity to humans. We discussed how we can use early postnatal development from macaques to study human fetal development.

4.6 How Can Brain Organoids Help Us Make Inferences about Brain Evolution?

The use of brain organoids coupled with RNA sequencing technology have provided new insights into the evolution of the human brain. Comparative analyses have converged on the finding that brain maturation in humans is extended relative to great apes. Questions remain as to how information gained from brain organoids relates to the individual. Nevertheless, these methods are exciting and open new avenues of research. Indeed, there is much left to learn about the evolution of the nervous systems. The field of comparative neuroscience is well positioned to make important contributions to many areas of biomedical sciences.

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