Molecules, Brains and Social Behavior:

Integrative Insights into Neural Plasticity

The research in the Hofmann laboratory seeks to understand the molecular and hormonal mechanisms that underlie social behavior and its evolution. African cichlid fishes are an ideal model system to address these questions because of their recent, repeated and rapid radiations that have resulted in hundreds of phenotypically diverse species. When appropriate, we utilize other model systems as well. Our work uses a broad spectrum of approaches, ranging from ecological studies in the East African Great Lakes to functional genomics using custom-made cDNA microarrays for gene expression profiling in the brain. We also employ hormonal perturbations, neuroanatomical techniques and advanced microscopy, laser micro-dissection and bioinformatics tools. Although we have been working on a variety of topics in several model systems, current projects focus on two main areas:

1) Identifying genes that are involved in implementing social dominance and sex roles in the Tanganyikan mouthbrooder Astatotilapia burtoni. We have conducted a molecular systems analysis of the preoptic area (POA), a neuroendocrine integration center in the forebrain. We identified numerous clusters of coregulated genes that are associated with specific phenotypic traits, such as aggression, courtship behavior or condition. We are now identifying the molecular signatures involved in the transition from one social phenotype to the other by collecting animals at various time points throughout the transition period.

2) Understanding the role of the neuropeptide somatostatin in regulating aggressive behavior in Astatotilapia burtoni. We have previously shown that somatostatin (in the past known for its inhibitory role in somatic growth) and several of it receptor subtypes carry out important functions in the regulation of aggressive behavior in dominant males. We are now investigating whether the subtype 2 receptor acts as an autoreceptor in the POA and whether somatostatin can reduce androgen production despite high levels of GnRH.

3) Explaining a complex behavior at all levels of biological organization. In collaboration with the laboratory of Dr. Thomas Preuss (Albert-Einstein College of Medicine), we have found that startle escape behavior is socially regulated in Astatotilapia burtoni. The escape response is controlled by a paired neuron, the Mauthner cell, a huge neuron with massive dendrites and axon. We are currently using behavioral pharmacology and electrophysiology to investigate the role of serotonin in modulating M-cell function and have adapted single-cell molecular techniques for identifying the molecular correlates of social regulation at the level of a single cell.

4) Analyzing the reproductive physiology of female reproduction and behavior. We have established an experimental paradigm that enables us to record the behavior of eight females simultaneously as they progress through the reproductive cycle (~30 days). We have also established protocols that allow the reliable measurement of several steroid hormones in the water. These techniques, together with laser microdissection of the POA, are currently being used to obtain a detailed description of the female reproductive cycle (as well as changing male responses). Next, we will pharmacologically manipulate this system in order to determine the respective role of each hormone in regulating, e.g., oocyte maturation and/or proceptive or receptive behaviors.

5) A comparative analysis of the ecological, neuroanatomical and molecular basis and evolution of divergent social organization (monogamy vs. polygamy) in a group of closely related (monophyletic) species, the Ectodini cichlids from Lake Tanganyika. We have constructed a new and robust phylogeny that shows that there have been at least four independent transitions from polygamy to monogamy in this clade. We have also shown for this clade that the size of certain brain structures is associated with quantitative measures of the physical or social environment. We have also conducted a comprehensive molecular evolution study of the arginine vasotocin (AVT) pathway in 12 species. In collaboration with the laboratory of Dr. Caroly Shumway (Boston University & The Nature Conservancy), we are currently assessing AVT regulation at the peptide level. Finally, we are using functional genomic tools to assess whether the same or different molecular pathways are being recruited in these independent transitions.

By carefully and systematically querying the brains of these fish using genomic, behavioral and physiological approaches we can identify the molecular building blocks of complex behavior and their evolution within an integrative and organismic framework