Our lab focuses on multi-modal brain mapping of the common marmoset to study large-scale brain network development and dynamics underlying social behavior and brain disorders, including the following research directions:
Marmoset Brain Mapping Project (marmosetbrainmapping.org)
The common marmoset (Callithrix jacchus), a New World primate, has rapidly emerged as a promising animal model for biomedical and neuroscience research. As phylogenetically closer to humans, the marmoset allows for studying higher cognitive brain function that rodents cannot sufficiently model. With a short life span and high reproduction rates, the marmoset has pivotal advantages over macaques in gene-editing models for human brain diseases. Most importantly, the marmosets are one of the smallest primates with small and smooth brains, which provide practical advantages for comprehensively mapping normal and disrupted brain circuits. However, these advantages are also accompanied by potential difficulties in translating results from marmosets to humans.
The Marmoset Brain Mapping Project was launched in 2016, aiming at building comprehensive MRI-based marmoset brain atlases and tools to facilitate neuroimaging and translational studies. The first phase included three versions of atlas tools: the first version (cortical parcellation) was published as the cover paper on the Apr 2018 issue of Neuroimage; the second version (white matter pathways) as the cover paper on the Feb 2019 issue of Nature Neuroscience; and the third version (population tools) will be released soon. Our lab will lead the second phase of the project. Besides improving atlases for adult marmosets, we will emphasize the brain development and cross-species translation: how to translating results acquired from the small and smooth marmoset brain to the large and gyrificated macaque and human brains.
Connectomic Basis and Functional Mechanisms of the Default Mode Network
Based on the atlas tools from the Marmoset Brain Mapping Project, we will explore large-scale functional brain networks using marmosets, especially the default mode network (DMN).
As a major association network that is particularly vulnerable to mental illnesses, the DMN has triggered significant interests in human neuroimaging studies over the past two decades. However, the connectomic basis and functional mechanisms of the DMN are poorly understood, due to scarce insights from non-human primate (NHPs) studies. NHPs allow more direct and invasive approaches to investigate the structural and functional architectures of the DMN that human studies could not fully elucidate. With a small and nearly smooth brain, the common marmoset provides considerable practical advantages to map large-scale brain networks. Our pioneer study (Liu, et al, 2019) reported anatomical and functional evidence of the DMN-like networks in the marmoset brain. We aim to elucidate the connectomic basis and functional mechanisms of the DMN by using awake fMRI and other techniques including MEMRI, neuronal tracing, electrophysiology and optogenetics.
Social experience and stress in brain development and disorders.
One of the putative key functions of the DMN is self and social cognition, and abnormal social cognition is also a prominent phenotype of many brain disorders. Social experience during brain development is essential for social cognition formation. Rodent animal models have provided significant insights, but there are huge translational and evolutional gaps between rodents and humans, especially concerning social experience and cognition.
Marmoset is a promising animal model to fill the translational gaps, which shares many similarities in their prosocial behavior and social structure with humans. Both species are socially monogamous primates and demonstrate cooperatively breeding and alloparent care that only exists in only 3% of mammals. The short-life span (sex maturation in 14-18 months) of marmosets makes longitudinal studies of brain development and social stress more practical than macaques. Additionally, marmosets rely heavily on their rich vocalization for social communication, which can be monitored to evaluate social behaviors. Based on these features, we will use the marmoset to probe the brain networks underlying prosocial behaviors and how social experience and stress contribute to brain development and brain disorders.