Biology subjects

Gruenhagen, G. W.

Publications and source records attributed to Gruenhagen, G. W..

4 recordsLinked to original sources

bioRxiv2024

Adult sex change leads to extensive forebrain reorganization in clownfish

Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of neurosexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish. Significance StatementThis study provides key insights into brain sex differences in sex-changing anemonefish (Amphiprion ocellaris), a species that changes sex in adulthood in response to the social environment. Using single nucleus RNA-sequencing, the study provides the first brain cellular atlas showing sex differences in two crucial reproductive areas: the preoptic area and telencephalon. The research identifies notable sex-differences in cell-type proportions and gene expression, particularly in radial glia and glutamatergic neurons that co-express the neuropeptide cholecystokinin. It also highlights differences in preoptic area neurons likely involved in gonadal regulation. This work deepens our understanding of sexual differentiation of the brain in vertebrates, especially those capable of adult sex change, and illuminates key molecular and cellular beginning and endpoints of the process.

neuroscience↗

bioRxiv2023

Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and genetic variation in its receptor gene (Oxtr) is linked to divergent social phenotypes. However, the molecular mechanisms connecting Oxtr genotype to behavioral outcomes remain obscure. Here, we leverage naturally occurring Oxtr polymorphisms in the prairie vole that associate with striatal-specific OXTR density to investigate how OXTR signaling influences brain function. Specifically, we identify OXTR-dependent transcriptomic changes in the natural killer gene complex (NKC) - a genomic region classically associated with peripheral immune function. Centrally, OXTR-regulated NKC genes are positioned to influence microglia-neuron interactions. Consistent with a role for these genes in shaping neuronal connectivity, we show that genetic reduction of OXTR levels leads to increased dendritic spine density on striatal Oxtr-expressing neurons. In addition, we provide support for a similar relation between variation in OXTR mRNA levels and NKC transcription in humans. Together, our findings suggest a role for OXTR signaling in the shaping of neural circuits through transcriptional control of the NKC, outlining a mechanism via which variation in OXTR signaling may influence circuit connectivity to generate diversity in social behaviors.

neuroscience↗

bioRxiv2023

Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking differences in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely everted telencephalon, which has made it challenging to compare brain regions in fish to those in other vertebrates. Here we combine spatial transcriptomics and single-nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell populations in the fish telencephalon and subpallial, hippocampal, and cortical cell populations in tetrapods. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

neuroscience↗

bioRxiv2022

Cellular profiling of a recently-evolved social behavior

Social behaviors are essential for survival and reproduction and vary within and among species. We integrate single nucleus RNA-sequencing (snRNA-seq), comparative genomics, and automated behavior analysis to investigate a recently-evolved social "bower building" behavior in Lake Malawi cichlid fishes. We functionally profile telencephalic nuclei matched to 38 paired behaving/control individuals. Our data suggest bower behavior has evolved in part through divergence in a gene module selectively expressed in a subpopulation of glia lining the pallium. Downregulation of the module is associated with glial departure from quiescence and rebalancing of neuronal subpopulation proportions in the putative homologue of the hippocampus. We show further evidence that behavior-associated excitation of neuronal populations that project to the putative hippocampus mediate glial function and rebalancing. Our work suggests that bower behavior has evolved through changes in glia and region-specific neurogenesis, and more broadly shows how snRNA-seq can generate insight into uncharted behaviors and species.

neuroscience↗