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New technologies for examining the role of neuronal ensembles in drug addiction and fear

Abstract

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. In addition, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches — Daun02 inactivation, FACS sorting of activated neurons and Fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — Fos-tTA transgenic mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear.

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Figure 1: Neuronal ensembles in the mesocorticolimbic dopamine reward system.
Figure 2: The Daun02 inactivation method.
Figure 3: FACS sorting of activated neurons.
Figure 4: Electrophysiology of activated neurons using the Fos-GFP rat.
Figure 5: Manipulating activated fear-encoding neuronal ensembles in the hippocampus and amygdala.

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Acknowledgements

The writing of this article was supported by the US National Institute on Drug Abuse, Intramural Research Program. We thank the members of the Hope, Lupica and Shaham laboratories who contributed to the development and implementation of the new technologies described in this article.

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Correspondence to Bruce T. Hope.

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Cruz, F., Koya, E., Guez-Barber, D. et al. New technologies for examining the role of neuronal ensembles in drug addiction and fear. Nat Rev Neurosci 14, 743–754 (2013). https://doi.org/10.1038/nrn3597

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