In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Biology

In the

School of Biological Sciences

Brianna Hegarty

Will defend her dissertation

MOLECULAR AND SPATIAL PROFILING OF THE CICHLID BRAIN REVEALS CONSERVED NEURAL SIGNATURES UNDERLYING SOCIAL COURTSHIP BEHAVIORS

Tuesday, October 24th, 2023

10 AM

https://gatech.zoom.us/j/93188231383

 Thesis Advisor:

Jeffrey Todd Streelman, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Patrick McGrath, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Liang Han, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Alberto Stolfi, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Zachary Johnson, Ph.D.

Department of Psychiatry and Behavioral Sciences

Emory University

ABSTRACT:

Teleost ray-finned fish represent the largest and most behaviorally diverse vertebrate group, comprising roughly half of all extant vertebrate species. Several regions in the teleost telencephalon have been compared to mammalian forebrain regions involved in advanced cognition and social behavior, but these investigations have been challenging due to the uniquely everted morphology of teleost telencephalon and the large evolutionary distance between fish and other vertebrates. Mchenga conophoros (MC) cichlids are a teleost species that perform a goal-directed social courtship behavior called bower-building, wherein males manipulate the sand and construct bowers (mating structures) to attract mates. This work utilizes advanced genomics technologies to 1) uncover molecular signatures in the MC telencephalon underlying bower-building behavior, and 2) identify transcriptionally conserved populations in the vertebrate forebrain.

To transcriptionally profile the MC telencephalon during bower-building behavior, we employed single nucleus RNA-sequencing and revealed neuronal and non-neuronal populations exhibiting building-associated gene expression, neurogenesis, and excitation. We found evidence that genome divergence associated with bower-building has altered a subpopulation of radial glia which exhibit a behavior-associated departure from quiescence and contribute to downstream neurogenesis and neuronal balancing in specific glutamatergic populations. To further investigate the heterogeneity of MC telencephalic cell types, we performed spatial transcriptomics, a technique that provides gene expression information within anatomical context. We identified the spatial locations of cell types sequenced at single-cell resolution, generating a comprehensive molecular and spatial atlas of the MC telencephalon. We then performed comparative analyses with forebrain datasets from amphibians, reptiles, and mammals and identified neuronal and non-neuronal populations in the teleost brain that exhibit conserved gene expression across vertebrate clades. We mapped populations exhibiting neuronal balancing to the teleost Dl region and revealed significant transcriptional similarity between these cell types and mammalian hippocampal and neocortical populations implicated in spatial memory and cognition. This result is striking in light of ongoing debates regarding the existence of neocortical-like populations in non-mammals. In summary, by incorporating molecular, spatial, and behavioral evidence, we gain a uniquely comprehensive perspective on the teleost telencephalon and offer new insights into conserved properties of the vertebrate brain.