Cocaine Place Conditioning Strengthens Location-Specific Hippocampal Coupling to the Nucleus Accumbens

• Published in: Neuron (Cambridge, Mass.) Vol. 98; no. 5; pp. 926 - 934.e5
• Main Authors: Sjulson, Lucas, Peyrache, Adrien, Cumpelik, Andrea, Cassataro, Daniela, Buzsáki, György
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-06-2018; Elsevier Limited
• Subjects: accumbens; addiction; Addictions; Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiology; Cocaine; Cocaine-Related Disorders; conditioned place preference; Conditioning, Classical - physiology; corticostriatal; Disease Models, Animal; Dopamine Uptake Inhibitors; Hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Hippocampus - physiology; Interneurons - metabolism; Mice; Neural Pathways; Neurons - metabolism; Nucleus accumbens; Nucleus Accumbens - cytology; Nucleus Accumbens - metabolism; Nucleus Accumbens - physiology; Place preference conditioning; plasticity; Potentiation; Pyramidal Cells - metabolism; Receptors, Dopamine D2 - metabolism; Rodents; Sleep; Spiny neurons; accumbens; hippocampus; conditioned place preference; addiction; plasticity; corticostriatal; Cocaine
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2018.04.015

Conditioned place preference (CPP) is a widely used model of addiction-related behavior whose underlying mechanisms are not understood. In this study, we used dual site silicon probe recordings in freely moving mice to examine interactions between the hippocampus and nucleus accumbens in cocaine CPP. We found that CPP was associated with recruitment of D2-positive nucleus accumbens medium spiny neurons to fire in the cocaine-paired location, and this recruitment was driven predominantly by selective strengthening of coupling with hippocampal place cells that encode the cocaine-paired location. These findings provide in vivo evidence suggesting that the synaptic potentiation in the accumbens caused by repeated cocaine administration preferentially affects inputs that were active at the time of drug exposure. This provides a potential physiological mechanism by which drug use becomes associated with specific environmental contexts.
•Cocaine place conditioning increases subsequent firing in D2R medium spiny neurons•Accumbens neurons decode spatial information from hippocampal inputs•Increased accumbens firing is due to location-selective coupling with hippocampus
Sjulson et al. demonstrate that cocaine place conditioning recruits location-dependent firing of medium spiny neurons in the nucleus accumbens. This recruitment is mediated primarily through selective coupling with hippocampal inputs that encode the cocaine-paired location, providing a possible substrate for storage of drug-location associations.