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.

Structural attributes and principles of the neocortical connectome in the marmoset monkey

“…The marmoset connectivity data consists of the first complete large-scale cortico-cortical connectivity dataset which is available through the Marmoset Brain Connectivity Atlas portal (http://marmosetbrain.org). The detailed methods regarding data collection have been described elsewhere 17,53 . In brief, 143 retrograde tract-tracing experiments were performed in 52 young adult Similarly, in the marmoset most of the projections are from within the injected area, but here we don't consider these connections.…”

Single unit activity in marmoset posterior parietal cortex in a gap saccade task

“…By contrast, some have suggested the marmoset LIP to be an area that includes both banks of the IPS, based on the presence of calbindin-rich deep layers (Bourne et al, 2007). In addition to cytoarchitecture, functional connectivity and tracing studies have supported the presence of an LIP homologue in the marmoset PPC, given its connections with the FEF and the SC (Reser et al, 2013;Majka et al, 2016;Ghahremani et al, 2017). In macaque monkeys, the LIP stands out as the only parietal region that projects directly to the SC (Lynch et al, 1985;Andersen et al, 1990).…”

“…In macaque monkeys, reciprocal connections exist between the FEF and the LIP and VIP, but not MIP (Stanton et al, 1995(Stanton et al, , 2005. By contrast, in the marmoset, all three areas as defined by the atlas are reciprocally connected with area 8aV (Reser et al, 2013;Majka et al, 2016), the putative marmoset FEF. Thus, the existence of an area homologous to the macaque LIP in the marmoset PPC is supported by studies of cytoarchitecture and connectivity, but its precise boundary remains unclear and appears to extend beyond the lateral bank of the IPS.…”

“…In comparison, the generation of express saccades can be explained by motor preparation alone as demonstrated in the SC (Dorris et al, 1997;Everling et al, 1998), the FEF (Everling and Munoz, 2000) and area LIP in macaque monkeys (Chen et al, 2013(Chen et al, , 2016. Given that the marmoset PPC directly projects to the SC (Collins et al, 2005) and is reciprocally connected with frontal areas which may correspond to the marmoset FEF (Reser et al, 2013;Majka et al, 2016), we hypothesize that it contains an area that plays a similar role in the motor preparation preceding the gap effect and express-like saccades as area LIP in macaques.…”

The NanoZoomer Connectomics Pipeline for Tracer Injection Studies of the Marmoset Brain

“…Comparable state-of-the-art brain mapping activities include: Majka et al (2016) who describe a method to register marmoset brain data from retrograde tracer experiments into a standard atlas built from Nissl histology slices. In comparison, our experiments used anterograde tracer, we individually annotate each brain, and we have subcortical structures delineated in our common space.…”