Applying gene regulatory network logic to the evolution of social behavior

Abstract

Animal behavior is ultimately the product of gene regulatory networks (GRNs) for brain development and neural networks for brain function. The GRN approach has advanced the fields of genomics and development, and we identify organizational similarities between networks of genes that build the brain and networks of neurons that encode brain function. In this perspective, we engage the analogy between developmental networks and neural networks, exploring the advantages of using GRN logic to study behavior. Applying the GRN approach to the brain and behavior provides a quantitative and manipulative framework for discovery. We illustrate features of this framework using the example of social behavior and the neural circuitry of aggression.

Keywords: development; evolution; gene regulatory networks; neural networks; social behavior network.

Fig. 1.

GRN and SBN circuits. (A) Circuit diagram representing the GRN controlling forebrain specification at midlate gastrula stage. The diagram shows the regulatory activity of key developmental transcription factors implicated in the specification of the different forebrain domains. Modified from ref. . (B) Simplified circuit diagram representing the core social behavior neural network for aggression, plus several key regions in the mesolimbic reward pathway. Some individual cell populations within these regions that play a known role in aggression are outlined within each structure. Dotted gray lines represent known physical connections between the brain regions. The black line represents one functional connection that has been recently quantified in mice, the inhibitory projection from lateral septum (LS) to the ventrolateral portion of the ventromedial nucleus of the hypothalamus (VMHvl) (67). The pallium is shaded in blue, medial ganglion eminence (MGE) and anterior entopeduncular area (AEP) are shaded in yellow, lateral ganglionic eminence (LGE) is shaded in red, the preoptic area (POA) is shaded in orange, the hypothalamus is shaded in purple, and the midbrain is shaded in gray. HIP, hippocampus; NAcc, nucleus accumbens; OB/VNO, olfactory bulb and vomeronasal organ; VTA, ventral tegmental area.

Fig. 2.

Conservation of the SBN across vertebrates. Evolutionary depiction illustrating the conservation of telencephalic brain regions within the SBN. Shown is a schematic of transverse sections from the major vertebrate groups, with colors indicating homologous developmental fields. The pallium is shaded in blue, the ventral pallium (intermediate zone) is shaded green, medial ganglion eminence (MGE) and anterior entopeduncular area (AEP) are shaded yellow, lateral ganglionic eminence (LGE) is shaded red, and the preoptic area (POA) is shaded orange. blAMY, basolateral amygdala; BNST, bed nucleus of the stria terminalis; Dl, lateral part of the dorsal telencephalon; Dm, medial part of the dorsal telencephalon; HIP, hippocampus; meAMY, medial amygdala; NAcc, nucleus accumbens; Str, striatum; Vc, central part of the ventral telencephalon; Vd, dorsal part of the ventral telencephalon; Vl, lateral part of the ventral telencephalon; Vs, supracommissural part of the ventral pallium; Vv, ventral part of the ventral telencephalon; VP, ventral pallidum (VP). Reprinted from ref. .