Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

  1. Ruud van Zessen
  2. Yue Li
  3. Lucile Marion-Poll
  4. Nicolas Hulo
  5. Jérôme Flakowski
  6. Christian Lüscher  Is a corresponding author
  1. Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Switzerland
  2. Institute of Genetics and Genomics of Geneva (IGE3), University of Geneva, Switzerland
  3. Clinic of Neurology, Dept. of Clinical Neurosciences, Geneva University Hospital, Switzerland
6 figures and 1 additional file

Figures

Figure 1 with 2 supplements
Acute changes in accumbal neuronal activity in response to cocaine.

(A) Schematic of calcium imaging setup. Inset graph shows calcium recording trace, gray line indicates zoomed area in lower graph. Top trace horizontal bar is 60 s, bottom trace horizontal bar is 1 …

Figure 1—figure supplement 1
Schematic overview of fiber / GRIN placement for different experimental groups.

(A) GRIN lens placement for animals used in cocaine sensitization experiment (Figures 14) N = 13 D1R-cre animals, N = 12 D2R/A2a-cre animals. Green lines indicate D1R-cre, red lines indicate …

Figure 1—figure supplement 2
Diverse movement and calcium activity responses after cocaine.

(A) Average distance moved over 5-min bins around saline/cocaine injections in the cocaine-treated group. Green bars indicate moments of calcium imaging. N = 14 animals. Spread shows S.E.M. (B) …

Figure 2 with 1 supplement
Recruitment of cocaine-responsive neurons during cocaine sensitization.

(A) Schematic overview of methodology to identify responsive neurons. Calcium transients are detected from traces (green trace shows raw trace, green ticks show calcium transients), and activity …

Figure 2—figure supplement 1
Analysis of the cocaine response, accounting for individual animals.

(A) Standard deviation of the activity change (i.e. Δ transients/min = (number of transients within 5 min after injection – number of transients within 5 min before injection)/5 min), for all …

Profiling cocaine responsive neurons over cocaine treatments.

(A) Example of identified neurons on two different sessions in the same animal. Green indicates neurons present on both session (see Methods). (B) Example trace of a single neuron that was present …

Figure 4 with 1 supplement
Movement-related activity of NAc neurons does not change during cocaine sensitization.

(A) Example trace showing velocity over time and the activity of D1R neurons recorded during a saline-treated session. Ticks below each trace indicate detected calcium transients. (B) Schematic …

Figure 4—figure supplement 1
Movement around calcium transients in all recorded neurons over days.

(A) Left Panel: average movement velocity change over time around calcium transient for all NAc D1R SPNs, during saline, or cocaine-treated sessions. Right panel: box plot of the average movement …

Cocaine-evoked NAc dopamine levels remain stable during cocaine sensitization.

(A) Experimental setup. Wild-type mice were injected with an AAV9 CAG-dLight construct in the NAc, and an optic fiber was placed above the area. Trace represents dLight fluorescence over time. …

Figure 6 with 1 supplement
Blocking ERK signaling pathway decreases the fraction of sensitized D1R SPN responses, leaves sensitized D2R SPN responses unaffected, and abolishes LS.

(A) Schematic overview of experimental setup. Animals are pre-treated with SL327 (30 mg/kg) 30 min before the first cocaine injection. Green squares indicate recording days (top) and 5-min recording …

Figure 6—figure supplement 1
Blocking ERK signaling pathway prevents D1R sensitization on day 8.

Fraction of significantly responsive D1R neurons over days, with and without SL327 treatment (comparison of data presented in Figures 2D and 6C). D1R cocaine without SL327 n = 525/507/580 neurons …

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