Behavioral and neuropsychological foundations of olfactory fear conditioning

Otto, Tim; Cousens, Graham; Herzog, Christopher R.

doi:10.1016/s0166-4328(99)00190-4

Cited by 99 publications

(68 citation statements)

References 43 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

Learn. Mem.

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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.

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“…Another learning paradigm that appears to require the perirhinal cortex in the rat is fear conditioned learning Sacchetti et al, 1999;Otto et al, 2000;Schulz et al, 2004;Davis, 2006;Albrechet-Souza et al, 2011). Here the perirhinal cortex plays more of an associative role compared to its role in recognition memory (Kholodar-Smith et al, 2008b).…”

Section: The Role Of the Perirhinal Cortex In Fear Conditioningmentioning

confidence: 99%

“…Fear conditioning tasks can be quite varied with different studies using different forms of stimuli across the various sensory modalities to condition subjects and visual, auditory, olfactory, and contextual paradigms have all been explored in the general fear conditioning literature and a number of studies have implicated the perirhinal cortex in visual (Rosen et al, 1992;Campeau et al, 1997;Shi and Davis, 2001), auditory (Campeau et al, 1997;Sacchetti et al, 1999;Kyuhou et al, 2003;Bruchey and GonzalezLima, 2006;Kholodar-Smith et al, 2008a,b;Bang and Brown, 2009a,b), olfactory Otto, 1997, 1998;Otto et al, 2000) and contextual fear conditioning (Sacchetti et al, 1999;Bucci et al, 2000;Burwell et al, 2004a;Kholodar-Smith et al, 2008a,b;SchulzKlaus, 2009). Electrophysiological recordings made in the perirhinal cortex during trace conditioning using auditory stimuli (Furtak et al, 2007c) and immediate early gene imaging shows increased levels of c-Fos in the perirhinal cortex following a fear conditioning task (Campeau et al, 1997).…”

Section: The Role Of the Perirhinal Cortex In Fear Conditioningmentioning

confidence: 99%

“…Yet lesions of the rostral perirhinal cortex cause a complete attenuation of fear conditioned responses (Rosen et al, 1992) and prevent the electrophysiological propagation of auditory stimuli to the motor cortices in a fear conditioning study (Kyuhou et al, 2003). Lesions of the rostral perirhinal cortex also lead to an attenuation of olfactory fear conditioning while sparing contextual fear conditioning Otto, 1997, 1998;Otto et al, 2000) and this sparing of contextual fear conditioning following perirhinal lesions has been confirmed by other groups (Phillips and LeDoux, 1995). However, other studies have shown that similar sized lesions in the same location (Corodimas and LeDoux, 1995) and larger ablations of the entire perirhinal cortex disrupt contextual fear conditioning (Sacchetti et al, 1999;Bucci et al, 2000Bucci et al, , 2002Burwell et al, 2004a).…”

Section: The Role Of the Perirhinal Cortex In Fear Conditioningmentioning

confidence: 99%

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The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

Kealy

Commins

2011

Progress in Neurobiology

106

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“…However, the role of nNOS transmission in an aversive learning to odors is still unknown. Recent studies have shown that odors can be associated with foot shock in the Pavlovian fear conditioning paradigm, and the odor-CS acquires aversive valence to induce fear responses, such as freezing and potentiated startle responses (Otto et al 2000;Paschall and Davis 2002;Jones et al 2005). Olfactory fear processing may differ from contextual or auditory/visual fear.…”

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confidence: 99%

Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization

2013

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Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice lacking nNOS received six training trials, each consisting of an odor-CS co-terminating with a foot shock-US. Mice showed reduced freezing responses to the trained odor 24 h and 7 d after training, compared to wild-type mice. Pretraining systemic injections of the NO donor, molsidomine, rescued fear retention in nNOS knockout mice. In wildtype mice, pretraining systemic injections of L-NAME, a nonspecific nNOS blocker, disrupted odor-CS fear retention in a dose-dependent manner. To evaluate whether NO signaling is involved in generalization of fear memories, nNOS knockout mice and wild-type mice receiving L-NAME were trained to one odor and tested with a series of similar odors. In both cases, we found increased generalization, as measured by increased freezing to similar, unpaired odors. Despite the impairment in fear memory retention and generalization, neither mice receiving injections of L-NAME nor nNOS knockout mice showed any deficits in either novel odor investigation time or odor habituation, suggesting intact olfactory perception and short-term memory olfactory learning. These results support a necessary role for neuronal NO signaling in the normal expression and generalization of olfactory conditioned fear.The ability to learn and retain memories is dependent on several transmitters. Currently, there is much interest in the involvement of nitric oxide (NO) signaling in long-term memory formation (Bredt and Snyder 1992;Hawkins et al. 1994;Garthwaite 2008;Kelley et al. 2011). NO is generated from the amino acid L-arginine by the enzyme NO synthase (NOS) and functions as a retrograde neurotransmitter. Due to the diffusible nature of NO and its relationship with NMDA receptor activation, neurons containing the neuronal isoform of NOS (nNOS) could be involved in driving synaptic strength changes during learning processes such as longterm memory Zhuo et al. 1994;Garthwaite 2008).Fear conditioning is a useful tool in studying the neuronal mechanisms involved in the formation of long-term memory and fear-related systems. Rodents can quickly and reliably learn a fear association between a conditioned stimulus (CS) and an aversive stimulus (US), such as a foot shock (Young and Fanselow 1992). The role nNOS plays in fear learning has been investigated using contextual fear conditioning, as well as visual and auditory cues as the CS (Schafe et al. 2005;Kelley et al. 2010Kelley et al. , 2011Overeem et al. 2010). And although the nNOS inhibitor 7-nitroindazole showed no disruption in the acquisition and expression of the contextual fear conditioning (Maren 1998), it was demonstrated that animals lacking the nNOS gene (Nos1or nNOS knockout) have shown deficits in fear condit...

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Behavioral and neuropsychological foundations of olfactory fear conditioning

Cited by 99 publications

References 43 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

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization

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