Amygdala-dependent and amygdala-independent pathways for contextual fear conditioning

Ponnusamy, Ravikumar; Poulos, Andrew M.; Fanselow, Michael S.

doi:10.1016/j.neuroscience.2007.04.026

Cited by 57 publications

(47 citation statements)

References 76 publications

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“…These results not only are replicated by the present work but also are extended to show the continued involvement of the amygdala in weanling aged animals-a finding that is consistent with adult fear conditioning literature about the amygdala (Fanselow and LeDoux 1999;Davis 2000;LeDoux 2000;Otto et al 2000;Gale et al 2004;Ponnusamy et al 2007). …”

Section: Development Of Fear Conditioningsupporting

confidence: 91%

Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence

Raineki¹,

Shionoya²,

Sander³

et al. 2009

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Both odor-preference and odor-aversion learning occur in perinatal pups before the maturation of brain structures that support this learning in adults. To characterize the development of odor learning, we compared three learning paradigms: (1) odor-LiCl (0.3M; 1% body weight, ip) and (2) odor-1.2-mA shock (hindlimb, 1sec)-both of which consistently produce odor-aversion learning throughout life and (3) odor-0.5-mA shock, which produces an odor preference in early life but an odor avoidance as pups mature. Pups were trained at postnatal day (PN) 7-8, 12-13, or 23-24, using odor-LiCl and two odor-shock conditioning paradigms of odor-0.5-mA shock and odor-1.2-mA shock. Here we show that in the youngest pups (PN7-8), odor-preference learning was associated with activity in the anterior piriform (olfactory) cortex, while odor-aversion learning was associated with activity in the posterior piriform cortex. At PN12-13, when all conditioning paradigms produced an odor aversion, the odor-0.5-mA shock, odor-1.2-mA shock, and odor-LiCl all continued producing learning-associated changes in the posterior piriform cortex. However, only odor-0.5-mA shock induced learning-associated changes within the basolateral amygdala. At weaning (PN23-24), all learning paradigms produced learning-associated changes in the posterior piriform cortex and basolateral amygdala complex. These results suggest at least two basic principles of the development of the neurobiology of learning: (1) Learning that appears similar throughout development can be supported by neural systems showing very robust developmental changes, and (2) the emergence of amygdala function depends on the learning protocol and reinforcement condition being assessed.Even in utero, infant rats rapidly learn to avoid odors paired with malaise (LiCl) as expressed by learning an odor aversion (Garcia et al. 1966(Garcia et al. , 1974Hennessey et al. 1976;Haroutunian and Campbell 1979;Smotherman 1982;Stickrod et al. 1982;Rudy and Cheatle 1983;Kucharski and Spear 1984;Smotherman and Robinson 1985, 1990;Alleva and Calamandrei 1986;Miller et al. 1990b; Best 1992, 1993;Richardson and McNally 2003;Gruest et al. 2004;Shionoya et al. 2006). In contrast to adult odor-LiCl learning, which relies on the amygdala (Touzani and Sclafani 2005), this early-life, odoraversion learning relies on the olfactory bulb until the pup approaches weaning age, when the amygdala is incorporated into the learning circuitry (Shionoya et al. 2006). In contrast, if infant rats receive an odor paired with a moderately painful stimulus (0.5-mA foot or tail shock, or tail pinch) the amygdala appears to be incorporated into this learning circuitry around postnatal day Here we expand assessment of the developing pups' odoraversion learning circuit by including the anterior and posterior piriform cortex, which have previously been demonstrated to be important for both pup and adult odor learning (Litaudon et al. 1997;Barkai and Saar 2001;Mouly et al. 2001;Mouly and Gervais 2002;Tronel and Sara 2002;Moriceau and Su...

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Section: Development Of Fear Conditioningsupporting

confidence: 91%

Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence

Raineki¹,

Shionoya²,

Sander³

et al. 2009

Learn. Mem.

View full text Add to dashboard Cite

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“…However, in line with previous studies (Matus-Amat et al 2007), we found that similar manipulations within the BLA disrupt learning to fear a moderately familiar context. Further, we have shown that such manipulations in the BLA also disrupt learning to fear a highly familiar context as well as relearning to fear a dangerous context or an extinguished context but, as noted previously, only when the extinguished or the dangerous context receives a limited amount of pairings with the shock US (Maren 1999(Maren , 2001aPonnusamy et al 2007;Pistell and Falls 2008). Thus, both neuronal activity and synaptic plasticity in the BLA are necessary for learning and relearning context-conditioned fear.…”

Section: Cshlporg Downloaded Fromsupporting

confidence: 77%

Infusion of the NMDA receptor antagonist, DL-APV, into the basolateral amygdala disrupts learning to fear a novel and a familiar context as well as relearning to fear an extinguished context

Laurent

Westbrook²

2009

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Ample evidence suggests that activation of NMDA receptors (NMDAr) in the basolateral complex of the amygdala (BLA) is necessary for context fear conditioning. The present series of experiments examined whether this activation was still required when the to-be-shocked context had a history. We found that BLA infusion of the selective NMDAr antagonist DL-APV impaired the acquisition of fear responses to a novel context, a moderately familiar context, or a highly familiar context. The same treatment also impaired the reacquisition of fear responses to a dangerous context, a context extinguished to criterion, or a context massively extinguished. Importantly, DL-APV persistently suppressed fear responses, suggesting that the NMDAr antagonist disrupted basal synaptic transmission in the BLA. Therefore, we conclude that neuronal activity in the BLA is critical for learning and relearning context-conditioned fear. This finding is consistent with current neural models that attribute context fear conditioning to interactions among several brain regions, most notably the hippocampus and the BLA.Activation of N-methyl-D-aspartate receptors (NMDAr) is critical for many forms of learning (Riedel et al. 2003). One example is the use of spatial information to locate the hidden platform in the Morris maze. Learning to use this information is impaired by intracerebroventricular (i.c.v) infusion of the NMDAr antagonist DL-APV (Morris 1989;Bannerman et al. 1995). A second example is the acquisition and extinction of Pavlovian conditioned fear responses. Acquisition occurs in subjects exposed to a context or stimulus paired with an aversive unconditioned stimulus (US), while extinction occurs when they are repeatedly exposed to the conditioned context or stimulus (CS) in the absence of the aversive US. The acquisition of such fears and their inhibition by the learning produced by extinction are each disrupted by infusion of DL-APV into the basolateral complex of the amygdala (BLA) (Miserendino et al. 1990;Campeau et al. 1992;Maren et al. 1996;Lee and Kim 1998;Lee et al. 2001;Laurent et al. 2008). Infusion of DL-APV into the dorsal hippocampus spares acquisition of fears to a CS paired with shock while disrupting acquisition to the context where the pairings occurred (Sanders and Fanselow 2003;Quinn et al. 2005). These findings suggest that activation of NMDAr in various brain regions is necessary to trigger the signal transduction cascade that leads to the long-term stabilization of spatial, fear, and fear inhibition memories (Martin et al. 2000;Blair et al. 2001;Myers and Davis 2007).Nevertheless, there is also evidence that components of the learning produced by these tasks can occur under blockade of NMDAr. For instance, rats that had learned to locate a hidden platform in one Morris maze were able to use spatial information to locate a hidden platform in a second maze in spite of the fact that training in the second maze occurred under an i.c.v infusion of DL-APV (Bannerman et al. 1995). Similarly, rats that had learned to fear ...

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“…Previous findings have found that in the absence of the BLA, animals are able to form compensatory fear memories, provided they are given adequate training (41,42). This compensation was shown to require the bed nuclei of the stria terminalis (43), a structure already implicated in fear-related behavior (44,45) and positioned in an ideal neuroanatomical location to mediate contextual processing in the DH and midbrain regions controlling freezing (46,47).…”

Section: Discussionmentioning

confidence: 98%

Prefrontal microcircuit underlies contextual learning after hippocampal loss

Zelikowsky

Bissière

Hast³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

155

147

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Specific brain circuits have been classically linked to dedicated functions. However, compensation following brain damage suggests that these circuits are capable of dynamic adaptation. Such compensation is exemplified by Pavlovian fear conditioning following damage to the dorsal hippocampus (DH). Although the DH normally underlies contextual fear and fear renewal after extinction, both can be learned in the absence of the DH, although the mechanisms and nature of this compensation are currently unknown. Here, we report that recruitment of alternate structures, specifically the infralimbic and prelimbic prefrontal cortices, is required for compensation following damage to the hippocampus. Disconnection of these cortices in DH-compromised animals and immediate early gene induction profiles for amygdala-projecting prefrontal cells revealed that communication and dynamic rebalancing within this prefrontal microcircuit is critical. Additionally, the infralimbic cortex normally plays a role in limiting generalization of contextual fear. These discoveries reveal that plasticity through recruitment of alternate circuits allows the brain to compensate following damage, offering promise for targeted treatment of memory disorders.anxiety | recovery of function | amnesia | medial prefrontal cortex A widely accepted view is that the brain is comprised of multiple independent circuits dedicated to performing specific functions and encoding specific information. This view is exemplified in the field of learning and memory, where it is held that different circuits specialize in integrating and storing different classes of memories (1). However, studies looking at learning following brain damage clearly demonstrate that the brain can also behave dynamically. For example, in Pavlovian fear conditioning, contextual memories can be formed in the absence of circuits classically thought to underpin integration and storage of information about an animal's environment or context (2).In fear conditioning, contexts play two key roles in controlling fear learning and expression. First, a context can act as a conditional stimulus (CS), to which fear can be directly conditioned when an aversive experience, such as a foot shock [unconditional stimulus (US)] is signaled by the context. Second, contexts can modulate responding to a discrete cue, such as a tone-CS, which has acquired multiple meanings. For example, in extinction, a tone previously conditioned to elicit fear is presented in the absence of the aversive foot shock US, such that the conditional fear response begins to extinguish. However, because extinction is not an erasure of the original fear but rather new learning that interferes with retrieval of the original fear memory, an extinguished cue has multiple meanings (shock/no shock), which compete for behavioral expression (3). This competition is mediated by context, as fear renewal occurs when an extinguished stimulus is presented outside of the extinction context (4).These context-sensitive effects provide excellent models t...

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Amygdala-dependent and amygdala-independent pathways for contextual fear conditioning

Cited by 57 publications

References 76 publications

Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence

Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence

Infusion of the NMDA receptor antagonist, DL-APV, into the basolateral amygdala disrupts learning to fear a novel and a familiar context as well as relearning to fear an extinguished context

Prefrontal microcircuit underlies contextual learning after hippocampal loss

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