Anatomical and functional neuroimaging in awake, behaving marmosets

Abstract

The common marmoset (Callithrix jacchus) is a small New World monkey that has gained significant recent interest in neuroscience research, due in great part for its compatibility with gene editing techniques, but also due to its tremendous versatility as an experimental animal model. Neuroimaging modalities, including anatomical (MRI) and functional magnetic resonance imaging (fMRI), complemented by two-photon laser scanning microscopy and electrophysiology, have been at the forefront of unraveling the anatomical and functional organization of the marmoset brain. High resolution anatomical MRI of the marmoset brain can be obtained with remarkable cytoarchitectonic detail. Functional MRI of the marmoset brain has been used to study various sensory systems, including somatosensory, auditory and visual pathways, while resting-state fMRI studies have unraveled functional brain networks that bear great correspondence to those previously described in humans. Two-photon laser scanning microscopy of the marmoset brain has enabled the simultaneous recording of neuronal activity from thousands of neurons with single cell spatial resolution. In this article, we aim to review the main results obtained by our group and our colleagues in applying neuroimaging techniques to study the marmoset brain.

Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey

“…Here we explored the existence of direct interconnections between auditory areas and V1 in the marmoset monkey (Callithrix jacchus), a New World monkey which is attracting increasing interest as a model species for studies of neural systems that are highly developed or specialized in the primate brain (Solomon and Rosa 2014;Mitchell and Leopold 2015;Majka et al 2016;Miller et al 2016;Eliades and Miller 2017;Hagan et al 2017;Oikonomidis et al 2017;Okano et al 2016;Okano and Kishi 2017;Silva 2017). Previous work in this species has indicated that sparse projections from auditory cortex target the middle temporal visual area (MT; Palmer and Rosa 2006a), but studies of V1 connections have not reported afferents from the auditory cortex (Rosa and Tweedale 2000;Lyon and Kaas 2001).…”

Why marmosets?

“…As Eliades and Miller discuss in this Issue, marmosets are also highly voluble, engaging in near tonic levels of vocal communication (Eliades and Miller, 2017). This degree of social signaling again shares parallels to humans, while the discovery of the "face-patch" system in marmosets described by Silva in this Issue (Silva, 2017) underlines the significance of visual signaling common to all primates (Tsao et al, 2006(Tsao et al, , 2008Hung et al, 2015a). Beyond the social dimensions of their behavioral repertoire, marmosets are proficient hunters, relying on their speed and precision to quickly grab fast moving insects that make up a large portion of their natural diet (Schiel et al, 2010).…”

“…This characteristic is particularly beneficial for several neural recording techniques, such as multielectrode arrays and laminar electrodes, functional neuroimaging (Silva et al, 2011;Hung et al, 2015b;Mundiano et al, 2016), as well as modern multi-photon imaging techniques (Sadakane et al, 2015;Santisakultarm et al, 2016). Recent pioneering work applying 2-Photon Ca 1 imaging in marmosets is discussed in detail by both Watakabe et al (2017) and Silva (2017) in this Issue. Furthermore, adeno-associated viruses (AAV) express robustly in marmosets (Watakabe et al, , 2017, providing opportunities to apply modern optogenetic and pharmacogenetic techniques to the study of primate brain circuitry (MacDougall et al, 2016).…”

Generation of genetically engineered non‐human primate models of brain function and neurological disorders

“…We are currently pursuing the establishment of a cohort of GCaMP transgenic marmosets, owing to their short intergeneration time and prolific reproductive capacity (Tardif et al, 2003). Various neuroimaging modalities, including anatomical (MRI) and functional magnetic resonance imaging (fMRI) together with two-photon laser scanning microscopy and electrophysiology have been applied to study the marmoset brain, which will be eventually used to better understanding of corresponding functional network of the human brain (Huang, Merson, & Bourne, 2016; Silva, 2017). Fully grown GCaMP transgenic marmosets have been trained for ongoing awake fMRI studies (Belcher et al, 2016; Hirano et al, 2018; Silva, 2017; Yen, Papoti, & Silva, 2018) and we are currently working on developing multimodal neuroimaging studies to unveil the functional brain networks in marmoset.…”

“…Various neuroimaging modalities, including anatomical (MRI) and functional magnetic resonance imaging (fMRI) together with two-photon laser scanning microscopy and electrophysiology have been applied to study the marmoset brain, which will be eventually used to better understanding of corresponding functional network of the human brain (Huang, Merson, & Bourne, 2016; Silva, 2017). Fully grown GCaMP transgenic marmosets have been trained for ongoing awake fMRI studies (Belcher et al, 2016; Hirano et al, 2018; Silva, 2017; Yen, Papoti, & Silva, 2018) and we are currently working on developing multimodal neuroimaging studies to unveil the functional brain networks in marmoset. We believe these transgenic marmosets will be invaluable NHP models in neuroscience, allowing the monitoring of neural activity in awake behaving animals with functional confocal and multi-photon optical microscopy imaging of intracellular calcium dynamics (Santisakultarm et al, 2016).…”