Posttraining handling facilitates memory for auditory-cue fear conditioning in rats

Hui, Isabel R.; Hui, Gabriel K.; Roozendaal, Benno; McGaugh, James L.; Weinberger, Norman M.

doi:10.1016/j.nlm.2006.02.002

Cited by 39 publications

(27 citation statements)

References 22 publications

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“…Although males are handled for 3 days postoperatively, and daily during behavioral testing, our females experienced slightly more handling during the few days between postoperative care and the start of fear conditioning as a necessary result of estrous cycle monitoring. As handling experience can affect behavior in a number of different paradigms (Hoffman et al, 2010;Hui et al, 2006), it is possible that the slight discrepancy in handling of males vs females could have affected the outcome in our study. However, sex differences in handling effects are most commonly reported in animals exposed to handling during prepubertal periods (Kosten et al, 2007;Raineki et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

Rey

Lipps

Shansky

2013

Neuropsychopharmacol

104

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Post-traumatic stress disorder (PTSD) is twice as common in women as in men; it is a major public health problem whose neurobiological basis is unknown. In preclinical studies using fear conditioning and extinction paradigms, women and female animals with low estrogen levels exhibit impaired extinction retrieval, but the mechanisms that underlie these hormone-based discrepancies have not been identified. There is much evidence that estrogen can modulate dopaminergic transmission, and here we tested the hypothesis that dopamine-estrogen interactions drive extinction processes in females. Intact male and female rats were trained on cued fear conditioning, and received an intraperitoneal injection of a D1 agonist or vehicle before extinction learning. As reported previously, females that underwent extinction during low estrogen estrous phases (estrus/metaestrus/diestrus (EMD)) froze more during extinction retrieval than those that had been in the high-estrogen phase (proestrus; PRO). However, D1 stimulation reversed this relationship, impairing extinction retrieval in PRO and enhancing it in EMD. We also combined retrograde tracing and fluorescent immunohistochemistry to measure c-fos expression in infralimbic (IL) projections to the basolateral area of the amygdala (BLA), a neural pathway known to be critical to extinction retrieval. Again we observed diverging, estrous-dependent effects; SKF treatment induced a positive correlation between freezing and IL-BLA circuit activation in EMD animals, and a negative correlation in PRO animals. These results show for the first time that hormone-dependent extinction deficits can be overcome with non-hormone-based interventions, and suggest a circuit-specific mechanism by which these behavioral effects occur.

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Section: Discussionmentioning

confidence: 99%

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

Rey

Lipps

Shansky

2013

Neuropsychopharmacol

104

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“…One would therefore need an account with mechanisms that prevent a labile memory from being updated with the new information that occurs during the extinction trial. Some studies suggest that even minimally invasive procedures during periods of memory consolidation can strengthen the fear response (Hui et al 2006), as can other behavioral and pharmacological enhancements of the stress response (McGaugh 2006;McGaugh and Roozendaal 2009). Thus, the simple experience of being returned to a fearful context while the organism is in an aroused state may prevent extinction.…”

Section: Discussionmentioning

confidence: 99%

Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

et al. 2013

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An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact. Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate -early gene c-Fos within fear conditioning and extinction circuits. Our results show that long-term extinction is impaired when it occurs during time periods during which the memory should be most vulnerable to disruption (soon after conditioning or retrieval). These behavioral effects are correlated with hyperactivation of medial prefrontal cortex and amygdala subregions associated with fear expression rather than fear extinction. These findings demonstrate that behavioral experiences during periods of heightened fear prevent extinction and prolong the conditioned fear response.

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“…Changes in physiological arousal produced by epinephrine in pre-exposed animals resulted in very high rates of freezing to the CS that were quite similar to that observed in non-pre-exposed animals tested in experiments 1 and 2. In addition, when physiological arousal is increased by handling following cued fear conditioning (Hui et al 2006), administering epinephrine or corticosterone after learning tasks such as object recognition Dornelles et al 2007), viewing a series of neutral slides (Cahill and Alkire 2003), or receiving a footshock in a distinct context (Introini-Collison and McGaugh 1988), memory for the CS, the location of objects, slides viewed, or the context where given a footshock is improved. The findings from experiment 3 further suggest heightened states of arousal impact memory.…”

Section: Discussionmentioning

confidence: 99%

Novelty-induced arousal enhances memory for cued classical fear conditioning: Interactions between peripheral adrenergic and brainstem glutamatergic systems

King¹,

Williams²

2009

Learn. Mem.

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Exposure to novel contexts produce heightened states of arousal and biochemical changes in the brain to consolidate memory. However, processes permitting simple exposure to unfamiliar contexts to elevate sympathetic output and to improve memory are poorly understood. This shortcoming was addressed by examining how novelty-induced changes in peripheral and/or central arousal modulates memory for Pavlovian fear conditioning. Male rats were either exposed to the conditioning chamber for 5-min or given no exposure 24 h before conditioning with five tone-shock (0.35 mA) pairings. Retention was assessed 48 h later in a different context. Non-pre-exposed animals exhibited significantly greater freezing during conditioned stimulus (CS) presentations than did pre-exposed animals (P < 0.05). The improvement in retention produced by novelty was attenuated by pretraining a blockade of peripheral b-adrenergic receptors with sotalol (6 mg/kg, i.p.). Study 2 revealed that novelty-induced increases in peripheral autonomic output are conveyed to the brain by visceral afferents that synapse upon brainstem neurons in the nucleus tractus solitarius (NTS). Blocking AMPA receptor activity in the NTS with CNQX (1.0 mg) significantly reduced freezing to the CS in non-pre-exposed animals (P < 0.01). Study 3 showed that elevating epinephrine levels in habituated animals influences learning through mechanisms similar to those produced by novelty-induced arousal. Pre-exposed animals given epinephrine (0.1 mg/kg) froze significantly more than saline controls (P < 0.01), and this effect was attenuated by intra-NTS infusion of CNQX. The findings demonstrate that novelty-induced arousal or increasing sympathetic activity with epinephrine in preexposed animals enhances memory through adrenergic mechanisms initiated in the periphery and transmitted centrally via the vagus/NTS complex.

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Posttraining handling facilitates memory for auditory-cue fear conditioning in rats

Cited by 39 publications

References 22 publications

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

Novelty-induced arousal enhances memory for cued classical fear conditioning: Interactions between peripheral adrenergic and brainstem glutamatergic systems

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