Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism

Abstract

SUMMARY The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in seven out of eight sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions.

The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas

“…The next challenge in applying these methods for anatomical studies is to develop computational methods for automated reconstruction, registration, anatomical segmentation, and data analysis of the whole brain datasets, which range in scale from hundreds of gigabytes for spatially down-sampled STPT brains (Kim et al, 2017; Oh et al, 2014; Ragan et al, 2012) to more than 10 terabytes for full resolution mouse brains imaged, for example, at 0.3 × 0.3 × 1 Pm either by STPT (Economo et al, 2016) or the BPS system (Gong et al, 2016). Computational efforts have led to the development of new neuroinformatics tools necessary for standardized digital atlasing of mouse brain datasets, which became known as the Allen Brain Atlas (ABA) and Mouse Common Coordinate Framework (CCF) (Hawrylycz et al, 2011; Kuan et al, 2015; Ng et al, 2009; Ng et al, 2007; Oh et al, 2014).…”

“…The Ultratracer is an alternative approach for automated neuronal reconstructions in whole-brain datasets based on maximum likelihood estimation (MLE) (Peng et al, 2017). Finally, in addition to the morphological reconstructions, the Osten lab has also established STPT- and CNN-based imaging and computational pipeline for automated and quantitative mapping of cell type distribution, including precise cell counts and cell densities for all anatomical regions of the mouse brain (Kim et al, 2017). This early work thus demonstrates the power of such unbiased brain-wide anatomical studies in translating the cell type knowledge into a deeper understanding of the organization of brain structure.…”

Signatures of sex: Sex differences in gene expression in the vertebrate brain

“…Sex dimorphism, or a qualitative sex difference, describes a trait that is predominantly distinct between the sexes, such as mating behavior, or the increased size of vocal control brain areas in male songbirds (McCarthy et al, 2012). There are minimal anatomic dimorphisms between mammalian female and male brains, and these dimorphisms relate to reproductive physiology and behavior (Bao & Swaab, 2011;Kim et al, 2017;Morris, Jordan, & Marc Breedlove, 2004). Sexual dimorphism in gene expression in the brain has been observed for genes on sex chromosomes (Armoskus et al, 2014;Xu, Burgoyne, & Arnold, 2002).…”

Sex differences: Transcriptional signatures of stress exposure in male and female brains

“…Connectivity has been shown to be different in the sexes in the frontal cortex, whereas neuronal activity differs in the hippocampus, hypothalamus, frontal cortex, amygdala, and pituitary gland . Cell composition of the frontal cortex, amygdala, and hypothalamus and the transcriptional profile of the pituitary gland, frontal cortex, hippocampus, hypothalamus, and amygdala, were also found to be sex specific…”

“…15,16 Similarly, other regions, such as the hippocampus and the amygdala, have higher activation for women in response to negative emotions. 17,18 Many of these regions also show sex dimorphism in structure, [19][20][21][22][23][24][25][26][27] connectivity, 28 cell composition, 29,30 and transcriptional profile [31][32][33][34][35][36] (Figure 1).…”