A chemogenetic toolbox with multimodal imaging and motion tracking for free marmoset behavior

A chemogenetic technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), offers a valuable means to remotely control neural activity in living animals. This technique has great potential for investigating the link between neural activity and behavior in marmosets, although its application has yet to be established. Here, we report repetitive and minimal-invasive DREADD manipulation of the neural system in marmosets using a selective and highly potent DREADD agonist, deschloroclozapine (DCZ). We applied multimodal neuroimaging techniques to monitor DREADD expression and DREADD-induced activity change in vivo. To quantify DREADD-induced behavioral change, we also developed a marker-less motion tracking system (ml-MTS) consisting of four depth cameras with deep-learning algorithm. Two marmosets were injected with an adeno-associated viral vector expressing hM3Dq, an excitatory DREADD, into unilateral substantia nigra (SN). Several weeks after the injection, the marmosets underwent a positron emission tomography (PET) scan with [11C]DCZ, confirming in vivo hM3Dq expression at the injection site. Following a low-dose DCZ oral administration (10 µg/kg), the marmosets turned and eventually rotated in a contralateral direction to the injected side. This behavioral change was quantified by ml-MTS, illustrating that the contralateral rotation was significant 30-90 min after DCZ administration, but not in the following days without DCZ. PET imaging demonstrated that an intravenous injection of DCZ (3 µg/kg) decreased binding of [11C]raclopride, a dopaminergic receptor ligand, specifically at the ipsilateral striatum, a projection site of dopaminergic neurons in SN. Resting-state functional magnetic resonance imaging (rs-fMRI) further revealed that the DCZ administration significantly increased BOLD signal in the ipsilateral striatum, suggesting that enhancement of the nigro-striatal DA system may drive the rotation behavior. These results demonstrated that DREADD manipulation of neural activity can be applied to marmosets. Our set of methodologies should be beneficial for studying the link between neural activity and non-restricted behavior of marmosets in a variety of contexts including social interaction.Marmoset Bioscience Symposium 201