The role of the rat hippocampal system in several effects of context in extinction.

Abstract

The effect of fornix lesions on some effects of manipulating the context on performance in extinction were studied. In renewal, subjects' responding to an extinguished conditioned stimulus (CS) recovered when the CS was presented in the context in which it had been conditioned after extinction in a different context. In reinstatement, it recovered when the CS was tested after independent presentation of the unconditioned stimulus (US; an effect mediated by contextual conditioning.) In spontaneous recovery, it recovered after the passage of time, that is, when the CS was tested in a new temporal context. In the conditioned suppression method, fornix lesions had no effect on conditioning, extinction, renewal, or spontaneous recovery; however, they abolished the reinstatement effect. The results suggest that the hippocampal system may be important in the formation of context-US associations, but not in other types of learning about the context.

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…On the basis of these findings, the subgenual vmPFC region has been proposed to be a potential human homologue of the rodent IL region (Hartley and Phelps, 2013;Milad et al, 2007a;Milad and Quirk, 2012), and may diminish fear expression via its projections to the amygdala. Context-dependent retrieval of extinction is associated with increased BOLD activation in the hippocampus (Kalisch et al, 2006;Milad et al, 2007b), and hippocampal lesions impair context-dependent fear reinstatement (LaBar and Phelps, 2005), a finding that parallels observations in rodents (Wilson et al, 1995).…”

Mechanisms of fear extinction

“…The hippocampus has long been implicated in contextual fear conditioning 108,109 and it is widely believed that the hippocampus processes contextual information and sends configural representations of context to the amygdala, where they are associated with footshock. 110 Consistent with this general framework, reinstatement of extinguished fear, a context-specific phenomenon thought to be mediated primarily by context-US associations, is disrupted by pretraining radiofrequency lesions of fimbria-fornix 111 or pretraining electrolytic lesions of hippocampus. 112 Hippocampal involvement in renewal is more complex.…”

“…112 Hippocampal involvement in renewal is more complex. Studies involving permanent, pretraining lesions of fimbria-fornix 111 or hippocampus 112,113 have reported inconsistent effects, but studies employing temporary inactivation of hippocampus via localized infusions of the GABA A receptor agonist muscimol have reported specific deficits. When animals are tested in a novel context (AAB or ABC renewal) and muscimol is infused into hippocampus before test, renewal is not observed (i.e., freezing is equally low in all contexts).…”

“…In most experiments there is no effect of these manipulations 112,113,118 but there is one report of a decrease in freezing across an extinction training session following pretraining electrolytic lesions 113 and one report of a disruption of within-session extinction following pre-extinction training infusions of muscimol. 114 Two recent physiological studies by Garcia and co-workers indicate that long-term potentiation (LTP) is induced in the output pathways of the dorsal 119 and ventral 120 hippocampus by extinction training; that extinction is impaired by application of depotentiation-inducing low-frequency stimulation to the dorsal hippocampus following extinction training; 119 and that application of LTP-inducing high-frequency stimulation to the dorsal hippocampus shortly after depotentiation induction restores extinction behavior.…”

Selective Modification of Short-Term Hippocampal Synaptic Plasticity and Impaired Memory Extinction in Mice with a Congenitally Reduced Hippocampal Commissure

“…Contextual fear extinction was impaired in mice with a reduced HC (strain 9XCA/ Wah). Like fear conditioning, extinction has been proposed to be a form of new learning rather than an erasure of existing memories (for review, see Bouton, 1993), and it is dependent on hippocampal function (Wilson et al, 1995;Frohardt et al, 2000) (see also Fox and Holland, 1998). In addition, extinction is NMDA receptor dependent (Lee and Kim, 1998;Santini et al, 2001) (but see Berman and Dudai, 2001) and requires protein synthesis (Flood et al, 1977;Berman and Dudai, 2001;Vianna et al, 2001), similar to fear conditioning.…”