Footshock intensity and generalization in contextual and auditory-cued fear conditioning in the rat

Baldi, Elisabetta; Lorenzini, Carlo Ambrogi; Bucherelli, Corrado

doi:10.1016/j.nlm.2004.02.004

Cited by 150 publications

(97 citation statements)

References 17 publications

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“…Moreover, during retrieval testing, the very good conditioned freezing response both to acoustic CS and to context exhibited by all S control groups (Fig. 3) was quite similar to that previously reported (Sacchetti et al 1999a(Sacchetti et al ,b, 2002(Sacchetti et al , 2003Baldi et al 2004Baldi et al , 2007. It may be concluded that the shorter freezing response of TTX-injected rats is due to the amnesic effect of the NBM inactivation performed during consolidation.…”

Section: Methodological Considerationssupporting

confidence: 87%

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

Baldi¹,

Mariottini²,

Bucherelli³

2007

Learn. Mem.

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The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.

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Section: Methodological Considerationssupporting

confidence: 87%

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

Baldi¹,

Mariottini²,

Bucherelli³

2007

Learn. Mem.

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“…Thus, the selectivity of this treatment targeting memory reconsolidation is evidenced by the fact that there is no effect on memory reconsolidation when the pharmacological intervention is applied in the absence of the reactivation procedure (exposure to a different context). The generalization phenomenon to other context outside the conditioning environment has been previously reported in animals previously trained with high-intensity footshocks (Baldi et al, 2004). Therefore, it seems appropriate to suggest that increasing the fear status due to earlier aversive experience or by increasing footshock intensity during training promotes the onset of the generalization phenomenon or of an excessive unconditioned freezing response to novel stimuli.…”

Section: Discussionmentioning

confidence: 82%

Previous Stress Attenuates the Susceptibility to Midazolam's Disruptive Effect on Fear Memory Reconsolidation: Influence of Pre-Reactivation D-Cycloserine Administration

Bustos

Giachero

Maldonado

et al. 2009

Neuropsychopharmacol

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It is well known that, under certain boundary conditions, the retrieval of a stable consolidated memory results into a labile one. During this unstable phase, memory can be vulnerable to interference by a number of pharmacological agents, including benzodiazepines. One of the goals of this study was to evaluate the vulnerability to midazolam (MDZ) after reactivation of recent and remote contextual fear memories in animals that experienced a stressful situation before learning. Animals were subjected to a restraint session and trained in a contextual fear paradigm the following day; consolidated memories were reactivated at different times after learning and different MDZ doses (1.5, 3.0 mg/kg) were administered to rats after reactivation. Our results show that MDZ did not affect memory reconsolidation in older-than-one-day memories of stressed animals, even after the administration of a higher MDZ dose and a longer reactivation session (5 min). In contrast, MDZ was effective in blocking reconsolidation at all memory ages in unstressed animals. In addition, the current research investigated whether activating NMDA sites before reactivation promotes the destabilization of resistant memories such as those of stressed animals. We tested the influence of pre-reactivation D-cycloserine (DCS), a partial NMDA agonist, on MDZ's effect on fear memory reconsolidation in stressed animals. Our findings indicate that DCS before reactivation promotes retrieval-induced lability in resistant memory traces, as MDZ-induced memory impairment in stressed rats became evident with pre-reactivation DCS but not after pre-reactivation sterile isotonic saline.

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“…One potential issue with these results lies in the fact that higher doses of oxotremorine have been shown to have analgesic effects in mice (Wess et al 2003), making them less sensitive to the shock. However, this is likely not an issue here as our dose of oxotremorine was lower than the effective doses for inducing analgesia in the above study.While these results demonstrate that olfactory generalization can be modulated by mAChRs during olfactory aversive learning, generalization can also be affected by other factors such as CS intensity, US intensity, and training conditions (Baldi et al 2004;Cleland et al 2009;Chen et al 2011). While our paradigm serves as the starting point for investigations into cholinergic influence on olfactory generalization, future experiments manipulating these factors are needed to fully characterize generalization of olfactory fear learning.…”

mentioning

confidence: 88%

“…While these results demonstrate that olfactory generalization can be modulated by mAChRs during olfactory aversive learning, generalization can also be affected by other factors such as CS intensity, US intensity, and training conditions (Baldi et al 2004;Cleland et al 2009;Chen et al 2011). While our paradigm serves as the starting point for investigations into cholinergic influence on olfactory generalization, future experiments manipulating these factors are needed to fully characterize generalization of olfactory fear learning.…”

mentioning

confidence: 88%

Cholinergic modulation during acquisition of olfactory fear conditioning alters learning and stimulus generalization in mice

et al. 2012

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We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly reduced freezing. To test whether cholinergic manipulation affected fear generalization, mice were presented with odors similar to the trained odor. Generalization was increased following pretraining scopolamine, while the muscarinic agonist oxotremorine decreased generalization. These results suggest that muscarinic neurotransmission during the acquisition of olfactory association modulates both the strength and specificity of learning.The olfactory system receives cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) (Zaborszky et al. 1986). Blocking olfactory system cholinergic receptors disrupts several aspects of olfactory processing including olfactory shortterm memory (Hunter and Murray 1989;Paolini and McKenzie 1993;Miranda et al. 2009), perceptual learning, and discrimination (Ravel et al. 1992;Fletcher and Wilson 2002;Linster and Cleland 2002;Mandairon et al. 2006). Despite this, relatively little is known about the role of cholinergic activation during acquisition of olfactory aversive learning. While a recent study has demonstrated that cholinergic blockade during acquisition reduces odor-evoked displays of defensive responses to the learned odor (Kroon and Carobrez 2009), the cholinergic contribution to the magnitude and specificity of olfactory fear learning is currently unknown.Sensory cue-evoked fear conditioning has long been used in the study of the neural mechanisms underlying associative memory. In the standard fear-conditioning paradigm, a neutral stimulus is associated with an aversive foot shock, allowing the conditioned stimulus to acquire an aversive valence and induce fear responses, such as freezing (LeDoux 2003). Olfactory cues have been used as an effective conditioned stimulus in promoting fear-conditioned responses (Otto et al. 2000;Jones et al. 2005;Kroon and Carobrez 2009) and studies in other sensory systems have shown that cholinergic neurotransmission is involved in fear learning (Tinsley et al. 2004). For example, in auditory-cued fear conditioning, blockade of muscarinic receptors disrupts the acquisition of the tone-fear conditioning (Young et al. 1995;Anagnostaras et al. 1999;Feiro and Gould 2005), while blocking nicotinic activation does not affect this learning (Feiro and Gould 2005). Despite this, it remains to be seen whether nicotinic and muscarinic receptors can also mediate conditioned freezing responses to olfactory stimuli.In this study, we found that pretraining injections of the nicotinic receptor antagonist (nAChR) mecamylamine had no effect on olfactory fear learning. However, pretraining injections of the muscarinic antagonist scopolamine (mAChR) significantly reduced freezing to the trained od...

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Footshock intensity and generalization in contextual and auditory-cued fear conditioning in the rat

Cited by 150 publications

References 17 publications

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

Previous Stress Attenuates the Susceptibility to Midazolam's Disruptive Effect on Fear Memory Reconsolidation: Influence of Pre-Reactivation D-Cycloserine Administration

Cholinergic modulation during acquisition of olfactory fear conditioning alters learning and stimulus generalization in mice

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