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Research ArticleNew Research, Cognition and Behavior

Chemogenetic Silencing of Prelimbic Cortex to Anterior Dorsomedial Striatum Projection Attenuates Operant Responding

Megan L. Shipman, Gregory C. Johnson, Mark E. Bouton and John T. Green
eNeuro 11 September 2019, 6 (5) ENEURO.0125-19.2019; https://doi.org/10.1523/ENEURO.0125-19.2019
Megan L. Shipman
1Department of Psychological Science
2Neuroscience Graduate Program, University of Vermont, Burlington, VT 05405
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Gregory C. Johnson
1Department of Psychological Science
2Neuroscience Graduate Program, University of Vermont, Burlington, VT 05405
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Mark E. Bouton
1Department of Psychological Science
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John T. Green
1Department of Psychological Science
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  • Figure 1.
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    Figure 1.

    A, Acquisition of lever-press response over six training sessions with one retraining session in between the two test sessions. Mean ± SEM. B, Test session results for rats that had received the DREADD or control (GFP) construct in the PL. CNO or vehicle was infused into the aDMS before the first test session, and rats received the opposite infusate before the second test session. Order of infusion was counterbalanced in each group; *p < 0.05.

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    Figure 2.

    A, Location (left panel) and representative images (right panels) of cell bodies expressing DREADDs-mCherry construct (left) or GFP control construct (right) in the PL (area 32) at 40×. Blue is DAPI nuclear stain. B, Location (left panel) and representative images (right panels) of axon terminals in aDMS expressing DREADDs-mCherry (left) or GFP (right) at 60×. Scale bars = 50 μm.

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    Figure 3.

    Location and representative DREADDs-mCherry (A) and GFP (B) spread in the PL (area 32) at 20×. Top panels are the infusion site and bottom panels are estimated posterior-most spread. Stitching was done with a 3% overlap in the images and each frame within the final image was 2048 × 2048 pixels. Scale bars = 100 μm.

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    Figure 4.

    Left panel, Infusion sites in aDMS. Numbers are anterior-posterior distance in mm from bregma. Right panel, Example cannula placement. Shown is the right hemisphere, and guide cannula (CN) track. Guide cannula tips were above the DMS. The thin white bar shows where the infusion cannula (which protruded 1 mm below the tip of the guide cannula) was. STR, striatum; LV, lateral ventricle. Scale bar = 500 μm.

  • Figure 5.
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    Figure 5.

    A, Excitability curve shows spikes elicited to progressively larger current injection of DREADDs-mCherry-expressing PL pyramidal cells before and after CNO (10 μM) exposure. B, Example image of DREADDs-mCherry-expressing PL pyramidal cell in fluorescent (left) and infrared (right). C, Excitability curve shows spikes elicited to progressively larger current injection of GFP-expressing PL pyramidal cells before and after CNO (10 μM) exposure. D, Example image of GFP-expressing PL pyramidal cell in fluorescent (left) and infrared (right). E, Example trace of DREADDs-expressing PL neuron; 4 min of CNO exposure caused a reduction in spike frequency to current injection compared to baseline, while removal of CNO from the bath caused a partial recovery of spike frequency. Scale bars = 20 mV and 100 ms, and stimulation was 250 and 350 pA for 1 s.

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    Table 1.

    Data structure, type of test used to analyze the data, and observed power of key results

    Data structureType of testPower (Cohen’s d)
    aNormal distributionRepeated-measures ANOVAMain effect session: 1.784
    bNormal distributionRepeated-measures ANOVAInteraction (drug × vector): 0.247
    cNormal distributionPaired samples
    t test
    Main effect drug: 0.745
    dNormal distributionPaired samples
    t test
    Not significant
    eNormal distributionRepeated-measures ANOVAMain effect CNO: 0.388
    Interaction (drug × current): 0.262
    fNormal distributionPaired samples t testsMain effects current:
    200 pA: 1.204
    250 pA: 3.095
    300 pA: 2.807
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eneuro: 6 (5)
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September/October 2019
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Chemogenetic Silencing of Prelimbic Cortex to Anterior Dorsomedial Striatum Projection Attenuates Operant Responding
Megan L. Shipman, Gregory C. Johnson, Mark E. Bouton, John T. Green
eNeuro 11 September 2019, 6 (5) ENEURO.0125-19.2019; DOI: 10.1523/ENEURO.0125-19.2019

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Chemogenetic Silencing of Prelimbic Cortex to Anterior Dorsomedial Striatum Projection Attenuates Operant Responding
Megan L. Shipman, Gregory C. Johnson, Mark E. Bouton, John T. Green
eNeuro 11 September 2019, 6 (5) ENEURO.0125-19.2019; DOI: 10.1523/ENEURO.0125-19.2019
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Keywords

  • action
  • dorsomedial striatum
  • DREADD
  • instrumental conditioning
  • operant conditioning
  • prelimbic cortex

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