Student Theses and Dissertations

Date of Award

2021

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Freiwald Laboratory

Abstract

Utilizing the immense strengths of the common marmoset (Callithrix jacchus) as a model organism, we executed three efforts with the common goal of revealing key insights into dissecting the social brain. First, we examined the hypothesis that there is a neural, functional architecture underlying face processing. Faces form a unique category of stimuli that bridge visual perception and social cognition. They are processed in dedicated areas of cortex, face patches, which are organized into an interconnected network. While insight into neurons within face patches has been explored through extracellular electrophysiology, the functional architecture of local ensembles of cells has remained elusive. Recently discovered face patches in the lissencephalic common marmoset brain provide the cortical access necessary in order to employ optical techniques to resolve both the functional properties as well as the spatial organization of these neural ensembles. Unique to marmoset face patches, the cortical boundaries of these patches overlap with areas usually attributed to early stage visual processing. In particular, the occipitally located face patch “O” overlaps with V2, an area usually thought to be composed of neurons with tuning properties to low-level visual stimuli such as, but not limited to, orientation and direction. Here, in the anesthetized marmoset, we demonstrated the areal parcelization of function along the dimensions of low-level visual stimuli and high-level visual stimuli including faces, objects, and bodies using two-photon microscopy. We found that the functional architecture revealed best supports naturalistic stimuli processing more so than face processing. This suggests the interpretation that face patch “O” is a selective measure of recurrent activity or feedback activity into natural scene processing of faces rather than an area of pure face perception. As an area of natural scene processing, there may be cell-type specific populations supporting such segregation and suppression of low-level feature responses. We developed a novel approach to characterize the entire region using iterative antibody staining with volumetric immunohistochemistry. From a genetic and circuits approach, social cognition has been implicated in numerous circuits across brain structures. One such circuit includes pyramidal neurons projecting from layer V of the medial prefrontal cortex (mPFC) to the nucleus accumbens (NAc), given its involvement in social-reward behaviors and depression in rodents and primates. This circuit presents an opportunity not only to study the genetic blueprint of a socially relevant circuit, but also to determine how it is conserved across rodents and non-human primates. Here we established retrograde viral Translating Ribosome Affinity Purification (retro-vTRAP), using techniques previously implemented only in rodents. retro-vTRAP enables sequencing of mRNA bound to EGFP-tagged polyribosomes from chosen projection neurons that have been virally labeled with an EGFP-L10a transgene. retro-vTRAP facilitates the study of gene expression patterns in specific neural cell types to be studied in the complex, heterogeneous tissue of the cortex, shedding new light on transcriptional differences in cognitively relevant cells across species. We implemented retro-vTRAP in marmosets, macaques, rats, and mice and found a single conserved, enriched gene ontology set across marmosets and the rodents. This gene set is involved in negative regulation of endoplasmic reticulum stress induced apoptosis and is implicated in depression and mechanisms of treatment. This enrichment specific to this projection may be part of a genetic signature of this projection and provide functional modulation in times of social stress. Lastly, from a developmental approach, we detailed a critical embryonic period of protracted growth resulting in a developmental delay in the marmoset compared to other species, relative to gestation length. This was revealed through use of highresolution, serial ultrasound scans of developing marmosets. We demonstrated that this delay period occurs during gastrulation and before neural tube closure. During this protracted period, the amnion undergoes massive restructuring and growth, creating a unique opportunity to utilize this window to introduce genetic manipulations creating a proxy of a transgenic animal without conventional transgenic methodologies. This may be transformative to building more accurate models of disorders, particularly cognitive disorders that cannot be fully replicated in rodent models.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Download

Included in

Life Sciences Commons

Share

COinS