Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template

Abstract

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for co-registration of retrograde tracing data on connections of cortical areas into a 3-dimensional marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We have applied this procedure to 17 injections, placed in the frontal lobe of 9 marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as supplementary materials. Comparison between the results of the automated and human-based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated (r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large data sets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain.

Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood

“…Cortical brain regions were defined by adapting a digital reference template based on histological sections of the marmoset brain ( Majka et al 2016 ), itself based on a comprehensive atlas ( Paxinos et al 2012 ). The unilateral labels of this dataset were flipped symmetrically about the midline to produce a symmetric atlas of the entire cortex.…”

High-resolution data-driven model of the mouse connectome

“…In between these two extremes is mesoscopic structural connectivity: a coarser scale than that of single neurons or cortical columns but finer than whole-brain regions (Bohland et al, 2009). Facilitated by new tracing techniques, image-processing algorithms, and high-throughput methods, mesoscale data with partial to full brain coverage exist in animals such as the fly (Jenett et al, 2012; Shih et al, 2015) and mouse (Gămănuţ et al, 2018; Oh et al, 2014; Zingg et al, 2014), and such data are being collected from other model organisms such as rat (Bota, Dong, & Swanson, 2003) and marmoset (Majka et al, 2016). …”

Mapping the Architecture of Ferret Brains at Single-Cell Resolution

“…In addition, our integrated pipeline only performs single en-bloc Nissl staining although allows uniform true 3D reconstruction at cellular level. In contrast, the traditional neuro-histological method with MRIguided registration allows multiple modalities (e.g., Nissl, Myelin and tract-tracing) to realize 3D reconstruction (Majka et al, 2016;Lin et al, 2019). Thus, the integrated pipeline is more suitable for construction cytoarchitectonic atlas at cellular resolution with single modality approach.…”