Table 3.
Studies examining neural mechanisms of safety signal learning (via conditioned inhibition)
| Publication | Sample | Region of interest | Methods | Results |
|---|---|---|---|---|
| Kazama, Heuer, Davis, & Bachevalier, 2012 (117) | Non-human primates | Amygdala | Neonatal neurotoxic lesion | Delayed, but not abolished, acquisition of fear No effect on summation test |
| Falls & Davis, 1995 (118) | Rodents | CE | Bilateral electrolytic lesion | No interference with acquisition of conditioned fear inhibition by safety cues |
| Sangha, Chadick, & Janak, 2013 (116) | Rodents | BLA | In vivo single unit recordings | Subpopulation of neurons in the BLA selectively responsive to safety cues |
| Ng, Pollock, Urbanczyk, & Sangha, 2018 (207) | Rodents | BLA | Altering dopamine (D1) receptors | D1 receptor alterations (agonist and antagonist) experimentally impair suppression of fear during a safety cue |
| Sangha, Robinson, Greba, Davies, & Howland, 2014 (122) | Rodents | vmPFC (PL and IL separately) | Inactivation using muscimol/baclofen mixture | Disrupted summation test following IL inactivation |
| Rhodes & Killcross, 2007 (123) | Rodents | vmPFC (IL) | Lesion | No effect on the summation test, but disrupted retardation |
| Gewirtz, Falls, & Davis, 1997 (124) | Rodents | Large PFC region | Lesion | No effect on safety learning, extinction, or retardation |
| Kazama et al., 2014 (127) | Non-human primates | OFC | Neonatal neurotoxic lesions | No deficits in modulating fear responses in the presence of safety signals |
| Sarlitto et al., 2018 (135) | Rodents | vlOFC | Inactivation using muscimol/baclofen mixture | No effect on discrimination if inactivated during acquisition; inactivation after acquisition and prior to recall impaired discrimination with the behavioral fear response prevailing |
| Fernando, Urcelay, Mar, Dickinson, & Robbins, 2014 (136) | Rodents | NAc shell | Infusion of d-amphetamine | Reduced inhibition of avoidance behavior |
| Josselyn, Falls, Gewirtz, Pistell, & Davis, 2005 (131) | Rodents | NAc | Electrolytic lesion | No impact on acquisition or expression of conditioned inhibition during fear-potentiated startle |
| Rogan, Leon, Perez, & Kandel, 2005 (132) | Rodents | Striatum | Electrophysiological recording | Enhanced responses in safety but weakened in fear conditioning, suggesting that safety cues may instigate an approach behavior |
| Christianson et al., 2008 (133) | Rodents | Posterior insula | Excitotoxic lesion | Blocked inhibition via safety cues if lesioned prior to acquisition |
| Christianson et al., 2011 (134) | Rodents | Posterior insula | Inactivation using muscimol | Abolished stress-mitigating effects of the safety signal learning, but not the behavioral control, if lesioned during exposure to uncontrollable stress |
| Pollak et al., 2008 (115) | Rodents | Hippocampus | Immunohistochemistry and x-irradiation treatment | Increased neurogenesis following safety signal learning. Inhibiting neurogenesis prevented the behavioral effects of safety signal learning |
| Kazama et al., 2012 (117) | Non-human primates | Hippocampus | Neonatal lesion | No impact on safety signal learning |
| Meyer & Odriozola et al., 2019 (107) | Rodents and humans | Ventral hippocampus | Fiber photometry and fMRI | Summation test passed in both humans and mice. VH activation related to conditioned inhibition in both humans and mice. Activation of VH neurons projecting to PL associated with conditioned inhibition and correlated with freezing in rodents. Functional connectivity of VH-dACC associated with conditioned |
BLA, basolateral amygdala; CE, central nucleus of the amygdala; vmPFC, ventromedial prefrontal cortex; PFC, prefrontal cortex; IL, infralimbic cortex; PL, prelimbic cortex; OFC, orbitofrontal cortex; vlOFC, ventrolateral orbitofrontal cortex; NAc, nucleus accumbens; VH, ventral hippocampus; dACC, dorsal anterior cingulate cortex.