Cocaine-seeking neuronal ensembles
Previous research has established that neural ensembles, or sparse populations of neurons activated synchronously, can be specifically linked to drug-related behaviors (Cruz et al., 2013). After characterizing cocaine-seeking ensembles in the nucleus accumbens core (Bobadilla et al., 2020), a key region of the brain reward pathway, we aim to causally link the ensembles to seeking behaviors (Figure 1), and compare ensemble-specific structural (Figure 2, Figure 3) and functional plasticity between drug and natural rewards.
We use the targeted recombination in active populations (TRAP) strategy (Guenthner et al., 2013; DeNardo et al., 2018; Ye et al., 2016) and the FosCreERxAi14 mouse line (cFos-TRAP), which allows Cre-dependent expression of tdTomato (Tom+) in neurons expressing the immediate early gene Fos only in the presence of 4-hydroxytamoxifen (4-OHT), resulting in durable labeling of the neurons specifically activated during cocaine seeking.
FIGURE 1
In this figure, we see expression of the designer receptors exclusively activated by a designer drug (DREADD) virus, tagged in yellow, or mCitrine, allowing us to activate (Gq-DREADD) or silence (Gi-DREADD) the cocaine-seeking ensemble (tagged in red, or Tomato) to show the role of the ensemble on seeking behavior. *=Tom+ mCitrine+ cell, bar= 20 μm.
FIGURE 2
Ensemble-specific structural spine plasticity measurements. cFos-TRAP2 neuron tagged during cocaine seeking reveals adequate morphology to measure spine plasticity. White arrows within the insert feature dendritic spines.
FIGURE 3
Detail of a dendritic spine and spine analysis on the imaging software IMARIS. Acquired by undergraduate student Skylar Hodgins.
