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

eLife

Anastasia Sorokina¹  Alexis Monical¹  Mark Sheffield²  Xiaoxi Zhuang³  Daniel McGehee³  Chad Heer³  Bobby Kasthuri³  Gregg Wildenberg³  Jessica Koranda³ 

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

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

DOI  :  10.7554/eLife.71981

来源: DOAJ

【 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】

Unknown