Altered gating of Kv1.4 in the nucleus accumbens suppresses motivation for reward
- University of Kentucky, United States
- University of South Carolina, United States
Figures
Figure 1 with 1 supplement
Characterization of behavioral variability on a progressive ratio task.
(A) Scatterplot: Individual breakpoints of rats tested on the PR schedule of reinforcement (N = 111. Black bar: median. Red bars: upper and lower interquartile ranges. Bar histograms: Breakpoints …
Figure 1—figure supplement 1
Cohort to cohort variability and FR-PR correlation.
(A) Seven cohorts of rats were used in the study. Cohort size was 8, 16 or 24 subjects. For each cohort, the highS group was identified as the top quartile of the interquartile distribution and lowS …
Figure 2
Progressive ratio performance does not depend on individual stress levels.
(A) Plasma corticosterone levels do not differ between lowS, highS, and intermediate performance (midS) rats. (B) Breakpoint values on the PR schedule do not correlate with plasma corticosterone …
Figure 3
Divergent transcriptome profile in lowS and highS rats.
(A) A clustergram summary of top differentially expressed genes (DEGs) between lowS, highS, and midS rats. Each column represents RNA sequencing of NAc tissue from a single animal. Log2fold values …
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Figure 3—source data 1
Divergent transcriptome profile in highS and lowS rats.
Full gene list of DEGs between lowS vs highS, and lowS vs midS groups, including log2fold change values, p-values, and q-value (p-value adjusted to FDR). Genes with log2fold change of ≥0.5 and FDR < 0.05 and those with log2fold change of ≤0.5 and FDR < 0.05 were considered differentially expressed. Negative log2fc values indicate transcripts that were downregulated in the highS or midS groups relative to the lowS group. Positive log2fc values indicate transcripts that were upregulated in the highS or midS groups relative to the lowS group.
- https://doi.org/10.7554/eLife.47870.006
Figure 4 with 2 supplements
Low motivation for sucrose is associated with increased SPN excitability.
(A) Left, representative traces from NAc SPNs in lowS and highS animals at a depolarizing (+200 mV) current step. Right, action potential output across a range of injected current steps is …
Figure 4—figure supplement 1
Membrane excitability measures do not differ between lowS and highS groups.
There were no significant differences in: membrane resistance (Rm, t(16)=0.54, p=0.6), resting membrane potential (RMP, t(16)=0.28, p=0.78), rheobase (t(16)=1.18, p=0.26), spike threshold (t(16)=1.4,…
Figure 4—figure supplement 2
Spike output and K+ currents in midS animals align closely with the highS group.
All highS and lowS data are duplicated from Figure 5 for comparison. (A) Action potential output of NAc shell SPN from midS animals (n = 7, N = 4) is significantly lower than in lowS animals (**p<0.0…
Figure 5 with 2 supplements
NAc neurons from lowS animals are uniquely sensitive to Kv1.4 antagonist, UK-78,282.
(A) Action potential frequency was measured after application of UK-78,282 (100 nM) and expressed as percent change from frequency before UK-78,282 in the same cell (n = 7, N = 4/group). UK-72,282 …
Figure 5—figure supplement 1
UK-78,282 effects on membrane excitability measures.
(A) In the lowS group, UK-78,282 (100 nM) application had no significant effect on: membrane resistance (Rm, t(6)=0.61, p=0.85), resting membrane potential (RMP, t(6)=0.2, p=0.85), rheobase (t(6)=0.3…
Figure 5—figure supplement 2
UK-78,282 effects on spike output, AHP, and potassium channel currents.
(A) UK-78,282 (100nM) application had no significant effect on action potential output or (B) afterhyperpolarization area in midS animals (n = 8, N = 4). (C) UK-78,282 (100 nM) had no significant …
Figure 6 with 1 supplement
Selective effect of Kv1.4 antagonism on PR performance in lowS animals.
(A) In lowS animals (N = 6), microinjection of UK-78,282 into the NAc shell dose-dependently increased: i) breakpoints, ii) active lever presses and iii) pellets earned, but not iv) inactive lever …
Figure 6—figure supplement 1
Histological verification of placements for UK-78,282 microinjection experiments.
(A) Photomicrograph of cresyl violet-stained coronal section (150 µM thick) showing a representative placement of the tip of the guide cannula (white arrow) and microinjector (black arrow) in the …
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.47870.015
