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Scientific article
Open access
English

Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Published ineLife, vol. 10, e66048
Publication date2021-10-05
First online date2021-10-05
Abstract

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here, we used single-cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.

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Keywords
  • Calcium imaging
  • Cocaine
  • Dopamine
  • Mouse
  • Neuroscience
  • Nucleus accumbens
  • Population coding
  • Spiny projection neuron
  • Animals
  • Cocaine / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Female
  • Locomotion / drug effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
Citation (ISO format)
VAN ZESSEN, Ruud et al. Dynamic dichotomy of accumbal population activity underlies cocaine sensitization. In: eLife, 2021, vol. 10, p. e66048. doi: 10.7554/eLife.66048
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Article (Published version)
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Identifiers
ISSN of the journal2050-084X
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