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Research ArticleResearch Article: New Research, Cognition and Behavior

Hippocampal Disinhibition Reduces Contextual and Elemental Fear Conditioning While Sparing the Acquisition of Latent Inhibition

Stuart A. Williams, Miriam Gwilt, Rebecca Hock, Charlotte Taylor, Joanna Loayza, Carl W. Stevenson, Helen J. Cassaday and Tobias Bast
eNeuro 3 January 2022, 9 (1) ENEURO.0270-21.2021; https://doi.org/10.1523/ENEURO.0270-21.2021
Stuart A. Williams
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Miriam Gwilt
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Rebecca Hock
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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  • ORCID record for Rebecca Hock
Charlotte Taylor
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Joanna Loayza
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Carl W. Stevenson
2School of Biosciences, University of Nottingham, Sutton Bonington LE12 5RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Helen J. Cassaday
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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Tobias Bast
1School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom
3Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, United Kingdom
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    Figure 1.

    Infusion sites in the VH. A, Illustrative coronal brain section showing infusion site in the VH. Approximate locations of infusion cannula tips (black dots) mapped onto coronal sections adapted from the Paxinos and Watson (1998) rat brain atlas for rats in experiments 1 (B) and 2 (C). Numbers on the right indicate posterior distance from bregma in millimeters.

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    Figure 2.

    Experiment 1: ventral hippocampal disinhibition during pre-exposure and conditioning impairs the acquisition of contextual and elemental fear conditioning. A, Design of experiment 1. B, Mean (±SEM) latency to first lick values (s; log transformed) in the conditioning chamber following the aversive conditioning session for NPE (white bars) and PE (gray bars) rats in the saline and picrotoxin groups. Saline NPE rats show longer latencies compared with all other groups indicating increased conditioning to the conditioning context. Picrotoxin-infused rats show reduced latencies compared with saline-infused animals indicating impaired conditioning to the conditioning context. C, Mean suppression ratio (±SEM) to the light CS for NPE (white) and PE (gray) rats in the saline and picrotoxin groups. Saline-infused rats displayed LI, with PE rats showing markedly less fear than NPE rats. Picrotoxin-infused rats show similarly low levels of fear conditioning in both NPE and PE groups reflecting picrotoxin infusion abolished conditioning to the CS. Asterisks indicate statistically significant differences between groups (F > 9, p < 0.005; simple main effects analysis following significant interaction of infusion and pre-exposure).

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    Figure 3.

    Experiment 2: VH disinhibition during pre-exposure does not impair the acquisition of LI. A, Design of experiment 2, with the time point of the VH picrotoxin or saline infusion before the pre-exposure stage indicated. B, Mean (±SEM) latency to first lick (s; log transformed) in the conditioning chamber, during reshaping, following the aversive conditioning session for NPE (white bars) and PE (gray bars) rats in the saline and picrotoxin groups. All groups show similar levels of contextual conditioning, indicated by similar latencies to first lick. C, Mean suppression ratio (±SEM) to the light CS for control NPE (white) and PE (gray) rats in the saline and picrotoxin groups. Pre-exposure reduced fear responding to the CS in both saline and picrotoxin-infused rats compared with NPE rats, reflecting LI in both saline and picrotoxin-infused rats. Asterisk indicates significant main effect of pre-exposure during test (F(1,24) = 8.44, p = 0.008).

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    Figure 4.

    Experiment 1: an analysis limited to the rats that did not show seizure-related behavioral signs still reveals that ventral hippocampal disinhibition during pre-exposure and conditioning impairs the acquisition of contextual and elemental fear conditioning. A, Mean (±SEM) latency to first lick values (s; log transformed) in the conditioning chamber following the aversive conditioning session for NPE (white bars) and PE (gray bars) rats in the saline and picrotoxin groups. Saline NPE rats show longer latencies compared with all other groups indicating increased conditioning to the conditioning context, similar to the pattern of results obtained from the whole sample (compare Fig. 2B). B, Mean suppression ratios (±SEM) to the light CS for NPE (white) and PE (gray) rats in the saline and picrotoxin groups. Picrotoxin-infused rats show similarly low levels of fear conditioning in both NPE and PE groups reflecting picrotoxin infusion abolished conditioning to the CS, very similar to the pattern of results obtained from the whole sample (compare Fig. 2C); ^ indicates statistically significant differences between saline and picrotoxin infused NPE rats (F(1,46) = 5.330, p = 0.026; simple main effects analysis following a trend toward interaction of infusion and pre-exposure, F(1,46) = 3.614, p = 0.0636). Asterisks indicate statistically significant differences between groups (F > 8, p < 0.01; simple main effects analysis following significant interaction of infusion and pre-exposure).

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    Figure 5.

    Experiment 1: data excluding rats with cannula placements in the ventral subiculum confirm that ventral hippocampal disinhibition during pre-exposure and conditioning impairs contextual and elemental fear conditioning. A, Mean (±SEM) latency to first lick values (s; log transformed) in the conditioning chamber following the aversive conditioning session for NPE (white bars) and PE (gray bars) rats in the saline and picrotoxin groups. Picrotoxin-infused rats show numerically reduced latencies as compared with saline-infused rats, especially in the NPE groups, indicating impaired conditioning to the context, similar to the pattern of results from the whole sample (compare Fig. 2B). B, Mean suppression ratio (±SEM) to the light CS for NPE (white) and PE (gray) rats in the saline and picrotoxin groups. Picrotoxin-infused rats show similarly low levels of fear conditioning in both NPE and PE groups reflecting picrotoxin infusion abolished conditioning to the CS. The pattern of results is very similar to the pattern obtained from the whole sample (compare Fig. 2C). Asterisks indicate statistically significant differences between groups (F > 6, p < 0.03; simple main effects analysis following significant interaction of infusion and pre-exposure).

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    Table 1

    Final number of rats included in data analysis per group for each stage of both experiments

    Experiment 1Experiment 2
    GroupReshapingTestReshapingTest
    Saline NPE141477
    Saline PE131088
    Picrotoxin NPE151566
    Picrotoxin PE171777
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    Table 2

    Seizure-related behavioral signs observed after VH picrotoxin microinfusions

    Observed behaviorOverall totalExperiment 1 totalExperiment 1Experiment 2 total
    Infusion 1Infusion 2
    Facial twitching33120
    Wet dog shakes19151174
    Wild running109821
    Clonic limb movement10001
    • The type of behavior observed is indicated in column one. Total number of rats experiencing seizure-related behavior signs overall during experiment 1 or 2 is shown in column two. The number of rats experiencing seizure-related signs during experiment 1 is detailed in column 3, with these signs separated to show the effects after the two individual infusions in columns 4 and 5. Column 6 details the total number of rats showing seizure-related signs after the one infusion of experiment 2.

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January/February 2022
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Hippocampal Disinhibition Reduces Contextual and Elemental Fear Conditioning While Sparing the Acquisition of Latent Inhibition
Stuart A. Williams, Miriam Gwilt, Rebecca Hock, Charlotte Taylor, Joanna Loayza, Carl W. Stevenson, Helen J. Cassaday, Tobias Bast
eNeuro 3 January 2022, 9 (1) ENEURO.0270-21.2021; DOI: 10.1523/ENEURO.0270-21.2021

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Hippocampal Disinhibition Reduces Contextual and Elemental Fear Conditioning While Sparing the Acquisition of Latent Inhibition
Stuart A. Williams, Miriam Gwilt, Rebecca Hock, Charlotte Taylor, Joanna Loayza, Carl W. Stevenson, Helen J. Cassaday, Tobias Bast
eNeuro 3 January 2022, 9 (1) ENEURO.0270-21.2021; DOI: 10.1523/ENEURO.0270-21.2021
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Keywords

  • conditioning
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