Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine

eLife

Alexis Monical¹  Daniel McGehee¹  Jessica Koranda²  Mark Sheffield²  Xiaoxi Zhuang²  Chad Heer²  Anastasia Sorokina³  Bobby Kasthuri³  Gregg Wildenberg³ 

[1] Department of Anesthesia & Critical Care, University of Chicago, Chicago, United States;Department of Neurobiology, University of Chicago, Chicago, United States;Department of Neurobiology, University of Chicago, Chicago, United States;Argonne National Laboratory, Lemont, United States;

关键词: connectomics;    dopamine;    cocaine;    electron microscopy;    anatomy;    mouse;    Mouse;   

DOI  :  10.7554/eLife.71981

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.

【 授权许可】

CC BY