Cue- versus reward-encoding basolateral amygdala projections to nucleus accumbens
Data files
Oct 18, 2023 version files 89.02 KB
Abstract
In substance use disorders, drug use as unconditioned stimulus (US) reinforces drug taking. Meanwhile, drug-associated cues (conditioned stimulus, CS) also gain incentive salience to promote drug seeking. The basolateral amygdala (BLA) is implicated in both US- and CS-mediated responses. Here, we show that two genetically distinct BLA neuronal types, expressing Rspo2 versus Ppp1r1b, respectively, project to the nucleus accumbens (NAc) and form monosynaptic connections with both dopamine D1 and D2 receptor-expressing neurons. While intra-NAc stimulation of Rspo2 or Ppp1r1b presynaptic terminals establishes intracranial self-stimulation (ICSS), only Ppp1r1b-stimulated mice exhibit cue-induced ICSS seeking. Furthermore, increasing versus decreasing the Ppp1r1b-to-NAc, but not Rspo2-to-NAc, subprojection increases versus decreases cue-induced cocaine seeking after cocaine withdrawal. Thus, while both BLA-to-NAc subprojections contribute to US-mediated responses, the Ppp1r1b subprojection selectively encodes CS-mediated reward and drug reinforcement. Such differential circuit representations may provide insights into precise understanding and manipulation of drug- versus cue-induced drug seeking and relapse.
README: Cue- versus reward-encoding basolateral amygdala projections to nucleus accumbens
https://doi.org/10.5061/dryad.gqnk98stv
The data sheet contains raw data for the summarized results in each figure.
Description of the data and file structure
The data sheet is organized in line with the summarized data in figures. Please also see figure legends for more technical details.
- Fig. 1L: Summaries showing EPSC amplitudes in individual D1 versus D2 MSNs (cells 1-9) from Rspo2 mice before and during perfusion of NBQX+APV.
- Fig. 1X: Summaries showing EPSC amplitudes in individual D1 versus D2 MSNs (cells 1-9) from carpet mice before and during perfusion of NBQX+APV.
- Fig. 1Z: Summaries showing the paired pulse ratio results with the pulse durations of 25, 50, 100 and 200 ms. The ratios were provided for each of the 6 recorded cells in D1 and D2 MSNs from Respo2 mice as well as D1 and D2 MSNs from Cartpt mice.
- Fig. 2B: Summaries showing the numbers of operant responses of Rspo2 control mice (without ChR2 expression) to the active lever or inactive lever upon optogenetic stimulation at 20 or 40 Hz.
- Fig. 2C: Summaries showing the numbers of operant responses of Ppp1r1b control mice (without ChR2 expression) to the active lever or inactive lever upon optogenetic stimulation at 20 or 40 Hz.
- Fig. 2D: Summaries showing the numbers of operant responses of Rspo2-ChR2 mice to the active lever or inactive lever upon optogenetic stimulation at 20 or 40 Hz.
- Fig. 2E: Summaries showing the numbers of operant responses of Ppp1r1b-ChR2 mice (without ChR2 expression) to the active lever or inactive lever upon optogenetic stimulation at 20 or 40 Hz.
- Fig. 2F: Summaries showing the number of operant responses to the active and inactive lever in individual Rspo2-ChR2 mice upon optogenetic stimulation over three training sessions and three extinction sessions.
- Fig. 2G: Summaries showing the number of operant responses to the active and inactive lever in individual Ppp1r1b-ChR2 mice upon optogenetic stimulation over three training sessions and three extinction sessions.
- Fig. 2H: Summaries showing combined results of operant responses to the active and inactive lever in Rspo2-ChR2 mice upon optogenetic stimulation over training and extinction sessions.
- Fig. 2I: Summaries showing combined results of operant responses to the active and inactive lever in Ppp1r1b-ChR2 mice upon optogenetic stimulation over training and extinction sessions.
- Fig. 3F: Summaries showing the numbers of operant responses to active versus inactive levers in all 10 Rspo2 mice during the baseline and manipulation phases.
- Fig. 3G: Summaries showing the numbers of operant responses to active versus inactive levers in all 6 Ppp1r1b mice during the baseline and manipulation phases.
- Fig. 3K: Summaries showing the scores (numbers of operant responses to active or inactive lever presses) of all Rspo2 mice with or without DREADD-mediated inhibition during the 10 days of cocaine self-administration training.
- Fig. 3L: Summaries showing the number of cocaine infusions of all Rspo2 mice with or without DREADD-mediated inhibition during the 10 days of cocaine self-administration training.
- Fig. 3M: Summaries showing the scores (numbers of operant responses to active or inactive lever presses) of all Ppp1r1b mice with or without DREADD-mediated inhibition during the 10 days of cocaine self-administration training.
- Fig. 3N: Summaries showing the number of cocaine infusions of all Ppp1r1b mice with or without DREADD-mediated inhibition during the 10 days of cocaine self-administration training.
- Fig. 4M: Summaries showing the scores (number of operant responses to active or inactive lever presses) of all tested Rspo2-hM4D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4N: Summaries showing the numbers of cocaine infusions of all tested Rspo2-hM4D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4O: Summaries showing scores (number of operant responses to active or inactive levers) in Rspo2-hM4D mice with intra-NAc injection of saline (control) or CNO over a 3 days of extinction tests.
- Fig. 4P: Summaries showing the scores (number of operant responses to active or inactive lever presses) of all tested Ppp1r1b-hM4D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4Q: Summaries showing the numbers of cocaine infusions of all tested Ppp1r1b-hM4D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4R: Summaries showing scores (number of operant responses to active or inactive levers) in Ppp1r1b-hM4D mice with intra-NAc injection of saline (control) or CNO over a 3 days of extinction tests.
- Fig. 4S: Summaries showing the scores (number of operant responses to active or inactive lever presses) of all tested Rspo2-hM3D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4T: Summaries showing the numbers of cocaine infusions of all tested Rspo2-hM3D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4U: Summaries showing scores (number of operant responses to active or inactive levers) in Rspo2-hM3D mice with intra-NAc injection of saline (control) or CNO over a 3 days of extinction tests.
- Fig. 4V: Summaries showing the scores (number of operant responses to active or inactive lever presses) of all tested Ppp1r1b-hM3D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4W: Summaries showing the numbers of cocaine infusions of all tested Ppp1r1b-hM3D mice with intra-NAc injection of saline (control) or CNO.
- Fig. 4X: Summaries showing scores (number of operant responses to active or inactive levers) in Ppp1r1b-hM3D mice with intra-NAc injection of saline (control) or CNO over a 3 days of extinction tests.