Addiction Connectomes in Macaques and Mice

Advances in neuroimaging have given us the ability to assess the connectivity patterns of the whole brain – in essence, its roadmap – in a relatively efficient manner. The idealized complete map of the brain’s connections – the connectome – can be collected in experimental and control conditions and compared. A connectome offers a valuable tool for examining the effects of any intervention that alters brain activity. For this reason, the connectome has proven to be an extremely valuable tool for a large number of psychiatric and neurological diseases. We propose to add addiction to this list. The addiction connectome will be a resource that can be used by anyone interested in the relationship between connectivity and chronic drug exposure.

The core dataset will involve the direct comparison of the effects of stimulants and opiates on the connectomes of mice and monkeys. We are currently leveraging the extensive neuroimaging expertise at the University of Minnesota to collect (1) diffusion-weighted scans to assess structural connectivity and (2) resting state functional MRI to assess functional connectivity from both species before and after chronic self-administration of stimulants and opiates. Our mice are be from the innovative Targeted Recombination of Active Populations (TRAP) line, which will allow us to visualize active populations of neurons and their connections. Thus, in the same animals, we are partnering with the SCC to determine which neurons are active in response to drug administration. Finally, in a subset of the same animals, we have partnered with the ICBC to collect wide field-of-view optical imaging to the effects of drug-exposure on a meso- and macro-scale. All of these structural and functional data will be combined and analyzed not just within method, but to find novel relationships across methods. Data will be linked to behavioral phenotypes describing drug-seeking behavior.