Cocaine and habit training cause dendritic spine rearrangement in the prelimbic cortex

Michelle K Sequeira; Andrew M Swanson; Henry W Kietzman; Shannon L Gourley

doi:10.1016/j.isci.2023.106240

Cocaine and habit training cause dendritic spine rearrangement in the prelimbic cortex

iScience. 2023 Feb 20;26(4):106240. doi: 10.1016/j.isci.2023.106240. eCollection 2023 Apr 21.

Authors

Michelle K Sequeira^{1

2}, Andrew M Swanson^{1

2}, Henry W Kietzman^{1

2}, Shannon L Gourley^{1

2}

Affiliations

¹ Graduate Program in Neuroscience, Emory National Primate Research Center, Departments of Pediatrics and Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, GA 30329, USA.
² Children's Healthcare of Atlanta, Atlanta, GA 30329, USA.

Abstract

Successfully navigating dynamic environments requires organisms to learn the consequences of their actions. The prelimbic prefrontal cortex (PL) formulates action-consequence memories and is modulated by addictive drugs like cocaine. We trained mice to obtain food rewards and then unexpectedly withheld reinforcement, triggering new action-consequence memory. New memory was disrupted by cocaine when delivered immediately following non-reinforcement, but not when delayed, suggesting that cocaine disrupted memory consolidation. Cocaine also rapidly inactivated cofilin, a primary regulator of the neuronal actin cytoskeleton. This observation led to the discovery that cocaine also within the time of memory consolidation elevated dendritic spine elimination and blunted spine formation rates on excitatory PL neurons, culminating in thin-type spine attrition. Training drug-naive mice to utilize inflexible response strategies also eliminated thin-type dendritic spines. Thus, cocaine may disrupt action-consequence memory, at least in part, by recapitulating neurobiological sequalae occurring in the formation of inflexible habits.

Keywords: Behavioral neuroscience; Biological sciences; Molecular neuroscience; Neuroscience.

Abstract

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