Table 1.
Rodent models of impaired fear extinction linked to mPFC–amygdala circuitry abnormalities
| Category of model | Link to mPFC–amygdala circuit | Reference |
|---|---|---|
| Subpopulation or strain | ||
| Poor extinction C57BL/6 mice | mPFC/BLA hypoactivation, prolonged mPFC long-term depression | Herry and Mons, 2004 |
| Poor extinction Sprague Dawley rats | Increased prelimbic cortex neuronal firing, reduced infralimbic cortex neuronal bursting | Burgos-Robles et al., 2007; 2009 |
| Poor extinction transgenic rats | Hypoactivation of infralimbic cortex inputs to BLA, hyperactivation of prelimbic cortex inputs to BLA | Knapska et al., 2012 |
| 129S1/SvImJ inbred strain | Infralimbic cortex/BLA/CeL hypoactivation, prelimbic cortex/CeM hyperactivation, prelimbic cortex/infralimbic cortex neuronal hyperactivity | Hefner et al., 2008; Whittle et al., 2010; Camp et al., 2012; Fitzgerald et al., 2014 |
| High-anxiety behavior rats | Infralimbic cortex/BLA hypoactivity, CeM hyperactivity | Muigg et al., 2008 |
| Adolescent rats and mice | Infralimbic cortex hypoactivation, impaired infralimbic cortex synaptic plasticity | Kim et al., 2011; Pattwell et al., 2012 |
| Environmental insult | ||
| Chronic alcohol | Infralimbic cortex dendritic hypertrophy, reduced infralimbic cortex NMDA receptor function, infralimbic cortex neuronal hypoactivity | Holmes et al., 2012 |
| Forced swim stress | Infralimbic cortex dendritic hypotrophy | Izquierdo et al., 2006 |
| Restraint stress | Infralimbic cortex neuronal hypoactivity, prelimbic cortex neuronal hyperactivity, BLA synaptic hyperactivity | Wilber et al., 2011; Chauveau et al., 2012 |
| Elevated platform stress | BLA dendritic hypotrophy/spinogenesis, infralimbic cortex GR up-regulation | Maroun and Richter-Levin, 2003; Maroun, 2006; Deschaux et al., 2013; Maroun et al., 2013 |
| Social defeat stress | Increased mPFC 2-AG levels | Dubreucq et al., 2012 |
| Chronic corticosterone | mPFC NMDA/AMPA receptor down-regulation | Gourley et al., 2009 |
| Prenatal stress or corticosterone | Infralimbic cortex GR down-regulation | Bingham et al., 2013 |
| Maternal separation | Infralimbic cortex GR up-regulation/NMDA receptor down-regulation | Wilber et al., 2009 |
| Post-natal footshock stress | Ishikawa et al., 2012 | |
| Adolescent stress | Prelimbic cortex/BA hyperactivation, impaired mPFC synaptic plasticity | Judo et al., 2010; Toledo-Rodriguez et al., 2012; Saito et al., 2013 |
| ‘Immediate extinction effect’ | Reduced mPFC neuronal bursting, mPFC neuronal hypoactivity, prelimbic cortex hyperactivity | Chang et al., 2010; Kim et al., 2010; Stafford et al., 2013 |
| Genetic manipulation | ||
| Reelin haploinsufficient | Abnormal mPFC synaptic plasticity/spine density | Iafrati et al., 2013 |
| 5-HT transporter knockout | Infralimbic cortex dendritic hypertrophy, increased BLA spine density, increased LA-mPFC theta activity | Wellman et al., 2007; Narayanan et al., 2011; Nietzer et al., 2011 |
| Pet-1 knockout | BLA dendritic hypertrophy | Wellman et al., 2013 |
| GAD67 knockdown | BLA specific | Heldt et al., 2012 |
| Plaur knockout | Reduced mPFC interneurons | Bissonette et al., 2014 |
| Dynorphin knockout | Infralimbic cortex/BLA hypoactivation | Bilkei-Gorzo et al., 2012 |
| GRP receptor knockout | mPFC hypoactivation, BLA hyperactivation and increased synaptic plasticity | Martel et al., 2012 |
| TrkB knockdown | BLA specific knockdown | Chhatwal et al., 2006 |
| Stathmin knockout | mPFC hyperactivation, BLA hypoactivation | Martel et al., 2012 |
| Pharmacological manipulation | ||
| 6-hydroxdopamine | mPFC dopamine depletion | Morrow et al., 1999; Fernandez Espejo, 2003; Hugues et al., 2007; Saito et al., 2013 |
| Dopamine D1 antagonist | Intra-BLA or intra-infralimbic cortex infusion | Hikind and Maroun, 2008; Fiorenza et al., 2012 |
| Dopamine D2 antagonist | Intra-infralimbic cortex infusion | Mueller et al., 2010 |
| Dopamine D4 antagonist | Intra-mPFC infusion | Pfeiffer and Fendt, 2006 |
| Noradrenaline | Intra-BLA infusion | Berlau and McGaugh, 2006; Fiorenza et al., 2012 |
| β-adrenoceptor agonist | Intra-mPFC or intra-BLA infusion | Fiorenza et al., 2012 |
| β-adrenoceptor antagonist | Intra-infralimbic cortex infusion | Mueller et al., 2008 |
| GABAA agonist | Intra-infralimbic cortex or intra-BLA infusion | Sierra-Mercado et al., 2006; 2011; Laurent and Westbrook, 2008; 2009a; 2010; Laurent et al., 2008; Parkes and Westbrook, 2010; Sotres-Bayon et al., 2012; Holmes and Singewald, 2013; Holmes et al., 2013 |
| Benzodiazepine agonist | Intra-BLA infusion | Hart et al., 2009; 2010 |
| AMPA receptor internalization inhibition | Intra-BLA infusion | Kim et al., 2007b; Dalton et al., 2008 |
| mGluA1 antagonist | Intra-BLA infusion | Kim et al., 2007a |
| mGluA5 antagonist | Intra-BLA infusion | Fontanez-Nuin et al., 2011; Sepulveda-Orengo et al., 2013 |
| NMDA receptor antagonist | Intra-BLA or intra-mPFC infusion | Falls et al., 1992; Lee and Kim, 1998; Lin et al., 2003c; Burgos-Robles et al., 2007; Laurent and Westbrook, 2008; 2009b; Laurent et al., 2008; Zimmerman and Maren, 2010; Parkes and Westbrook, 2011; Fiorenza et al., 2012; Holmes et al., 2012 |
| GluN2B antagonist | Intra-BLA or intra-mPFC infusion | Sotres-Bayon et al., 2007; 2009; Laurent and Westbrook, 2008; Laurent et al., 2008; Dalton et al., 2012 |
| Glucocorticoid receptor antagonist | Intra-BLA | Yang et al., 2006 |
| NPY-Y1 antagonist | Intra-BLA infusion | Gutman et al., 2008 |
| NPS antagonist | Intra-BLA infusion | Jungling et al., 2008 |
| KOP receptor antagonism | mPFC and BLA hypoactivation | Bilkei-Gorzo et al., 2012 |
| MOP receptor ablation | ICN specific | Likhtik et al., 2008 |
| Oxytocin | Intra-BLA infusion | Likhtik et al., 2008 |
| CCK2 receptor agonist | BLA CCK-B receptor dependent | Chhatwal et al., 2009 |
| CB1 receptor antagonist | Intra-BLA infusion | Kuhnert et al., 2013 |
| H2 receptor antagonist | Intra-BLA or mPFC infusion | Fiorenza et al., 2012 |
| CaV1.x antagonist | Intra-BLA infusion, BLA MAPK hypoactivation | Davis and Bauer, 2012 |