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Research ArticleNew Research, Cognition and Behavior

Plasticity of NMDA Receptors at Ventral Hippocampal Synapses in the Infralimbic Cortex Regulates Cued Fear

Omar Soler-Cedeño, Orlando Torres-Rodríguez, Faviola Bernard, Lizette Maldonado, Anixa Hernández and James T. Porter
eNeuro 14 March 2019, 6 (2) ENEURO.0354-18.2019; DOI: https://doi.org/10.1523/ENEURO.0354-18.2019
Omar Soler-Cedeño
1Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00732
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  • ORCID record for Omar Soler-Cedeño
Orlando Torres-Rodríguez
1Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00732
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Faviola Bernard
2Department of Biology, University of Puerto Rico-Ponce, Ponce, PR 00734
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Lizette Maldonado
1Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00732
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Anixa Hernández
1Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00732
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James T. Porter
1Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00732
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    Figure 1.

    Experimental design to measure vHC EPSCs in IL neurons after fear conditioning and extinction. A, B, ChR2 expression in the vHC and mPFC. C, AMPAR-mediated EPSCs were measured at the peak of the –70-mV current. NMDAR-mediated EPSCs were measured 70 ms after stimulation to minimize the possibility of contamination with AMPAR EPSC. D, Behavioral groups. E, Scheme of the general timeline for the experiments.

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    Figure 2.

    Fear conditioning and extinction induce postsynaptic plasticity in vHC synapses onto IL pyramidal neurons. A, Behavioral responses of all groups. B, Mean AMPA/NMDA ratios measured in IL pyramidal neurons from each group. C, Example traces of vHC EPSCs recorded in IL pyramidal neurons of each group (A, ***p < 0.001, repeated measures ANOVA, COND vs PSEUDO, SAME, and DIFF; B, *p < 0.05, Dunn’s post hoc after significant Kruskal–Wallis test).

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    Figure 3.

    Fear conditioning and extinction induced bidirectional changes in NMDAR currents at vHC synapses onto IL pyramidal neurons. A, B, Average AMPAR-mediated EPSCs and conductance in each group. C, D, Average NMDAR-mediated EPSCs and conductance in each group (**p < 0.01, *p < 0.05; Dunn’s post hoc after significant Kruskal–Wallis test).

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    Figure 4.

    IL neurons from animals that failed to recall extinction showed greater AMPA/NMDA ratios and reduced NMDAR-mediated currents. A, Behavioral data from same context extinction animals that showed successful or failed extinction recall. B, Example vHC EPSCs recorded in IL pyramidal neurons. C, Average AMPA/NMDA ratio in each group. D, E, Average NMDAR-mediated EPSC and conductance in each group. F, G, Average AMPAR-mediated EPSC and conductance in each group (*p < 0.05; Mann–Whitney’s test).

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    Figure 5.

    Contextual fear to context A varies with fear to tones. A, Average freezing during the minute before giving the first test tone on day 3 in the different groups. B, Correlation between freezing before the tones and during the tones on day 3. Rats from the PSEUDO, COND, SUCCESSFUL, and UNSUCCESSFUL groups are plotted.

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    Figure 6.

    In vitro BDNF treatment mimicked fear extinction reversal of conditioning-induced changes in AMPA/NMDA ratio and NMDAR currents. A, Behavioral data. B, Example trace for each group. C, Average AMPA/NMDA ratio for each group. D, Average NMDAR EPSC for each group. E, Average AMPAR EPSCs (p < 0.05, Mann–Whitney’s test).

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Plasticity of NMDA Receptors at Ventral Hippocampal Synapses in the Infralimbic Cortex Regulates Cued Fear
Omar Soler-Cedeño, Orlando Torres-Rodríguez, Faviola Bernard, Lizette Maldonado, Anixa Hernández, James T. Porter
eNeuro 14 March 2019, 6 (2) ENEURO.0354-18.2019; DOI: 10.1523/ENEURO.0354-18.2019

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Plasticity of NMDA Receptors at Ventral Hippocampal Synapses in the Infralimbic Cortex Regulates Cued Fear
Omar Soler-Cedeño, Orlando Torres-Rodríguez, Faviola Bernard, Lizette Maldonado, Anixa Hernández, James T. Porter
eNeuro 14 March 2019, 6 (2) ENEURO.0354-18.2019; DOI: 10.1523/ENEURO.0354-18.2019
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Keywords

  • fear conditioning
  • fear extinction
  • NMDA receptor
  • prefrontal cortex
  • PTSD
  • ventral hippocampus

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