Immediate-early gene expression in the amygdala following footshock stress and contextual fear conditioning

Rosen, Jeffrey B.; Fanselow, Michael S.; Young, Stacey L.; Sitcoske, Martina; Maren, Stephen

doi:10.1016/s0006-8993(98)00294-7

Cited by 182 publications

(149 citation statements)

References 39 publications

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“…The BLA receives a strong LC projection, and is known to be activated during stress (Cullinan et al, 1995;Rosen et al, 1998;Chowdhury et al, 2000;Akirav et al, 2001;Dayas et al, 2001). In addition, the vSub is activated by BLA inputs (Lipski and Grace, 2011).…”

Section: Discussionmentioning

confidence: 99%

Activation and Inhibition of Neurons in the Hippocampal Ventral Subiculum by Norepinephrine and Locus Coeruleus Stimulation

Lipski

Grace

2012

Neuropsychopharmacol

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The ventral subiculum (vSub) has been implicated in a wide range of neurocognitive functions, including responses to fear, stress, and anxiety. The vSub receives dense noradrenergic (NE) inputs from the locus coeruleus (LC), and the LC-NE system is heavily implicated in attention and is known to be activated by stressors. However, the way in which the neurons in the vSub respond to activation of the LC-NE is not well understood. In this study, the direct LC innervation of the vSub was investigated. The effect of norepinephrine (NE) on single vSub neurons was examined using microiontophoresis combined with electrophysiological recordings in anesthetized rats, and this response compared with the effect of electrical stimulation of the LC. Iontophoretic NE inhibited all vSub neurons tested, whereas LC stimulation inhibited 16% and activated 38% of neurons. Inhibition was mediated primarily by alpha-2 receptors, whereas activation was mediated by beta-adrenergic receptors. Furthermore, this effect was not mediated via the LC-basolateral amygdala (BLA) pathway, because BLA inactivation did not block LC stimulation-evoked activation of the vSub. These results indicate that the LC-NE system is a potent modulator of vSub activity. Based on these findings, stress-induced activation of the LC-NE system is expected to evoke inhibition and activation in the vSub, both of which may contribute to stress adaptation, whereas an imbalance of this system may lead to pathological stress responses in mental disorders.

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Section: Discussionmentioning

confidence: 99%

Activation and Inhibition of Neurons in the Hippocampal Ventral Subiculum by Norepinephrine and Locus Coeruleus Stimulation

Lipski

Grace

2012

Neuropsychopharmacol

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“…However, it is possible that a footshock induces IEG expression in the brain within minutes after the experience (Rosen et al, 1998), and we missed this early induction in the previous studies. There is, in fact, evidence that Arc is present in the cell nucleus within minutes of a behavioral experience or neural stimulation (Guzowski et al, 1999;Vazdarjanova and Guzowski, 2004).…”

Section: C-fos Expressionmentioning

confidence: 94%

Amygdala Regulation of Immediate-Early Gene Expression in the Hippocampus Induced by Contextual Fear Conditioning

et al. 2006

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The basolateral nuclei of the amygdala (BLA) are thought to modulate memory storage in other brain regions (McGaugh, 2004). We reported that BLA modulates the memory for both an explored context and for contextual fear conditioning. Both of these memories depend on the hippocampus. Here, we examined the hypothesis that the BLA exerts its modulatory effect by regulating the expression of immediate-early genes (IEGs) in the hippocampus. The main findings of these experiments were: (1) Arc activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) and c-fos mRNA are induced in the hippocampus after a context exposure, or context plus shock experience, but not after an immediate shock; and (2) BLA inactivation with muscimol attenuated the increase in Arc and c-fos mRNA in the hippocampus associated with contextual fear conditioning but did not influence Arc mRNA associated with context exploration. These results support the hypothesis that the amygdala modulates contextual fear memory by regulating expression of IEGs in the hippocampus.

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“…Second-order olfactory fear conditioning could also be useful in the analysis of gene expression following associative fear conditioning, as investigations of S2 stimuli would not be confounded by shock-induced gene expression (e.g., Campeau et al 1991;Rosen et al 1998). Thus, second-order olfactory fear conditioning could shed light on how seemingly innocuous stimuli become associated with traumatic events, and are then capable of eliciting fear responses in individuals suffering from anxiety disorders such as phobias and PTSD.…”

Section: Paschall and Davismentioning

confidence: 99%

Second-Order Olfactory-Mediated Fear-Potentiated Startle

Paschall¹,

Davis²

2002

Learn. Mem.

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Recently, we reported that discrete (4-sec) olfactory cues paired with footshock serve as effective conditioned stimuli (CSs) for potentiating the acoustic startle response in rats using the fear-potentiated startle paradigm. Because odors are such salient cues for the rat, and because of the robust olfactory conditioning observed previously, the current studies investigated second-order fear conditioning using olfactory and visual cues. In Experiments 1 and 2, we used a small number of first-order and second-order training trials on separate days to investigate second-order fear-potentiated startle. Significant potentiated startle was observed in animals receiving Paired/Paired training in both studies, but surprisingly, control animals in the Unpaired/Paired group (Exp. 1) also showed significant potentiated startle to a light S2 at testing. These findings are addressed in the Discussion. Overall, the results of both experiments suggest that olfactory cues serve as efficient S1 and S2 stimuli in second-order fear-potentiated startle paradigms when only a small number of first and second-order training trials are presented.Recently, we reported that discrete (4-sec) olfactory cues paired with footshock serve as effective conditioned stimuli (CSs) for potentiating the acoustic startle response in rats using the fear-potentiated startle paradigm (Paschall and Davis 2002). In those studies, amyl acetate (5%) had no significant effect on startle in untrained rats, but potentiated startle in animals receiving 1, 2, 5, or 10 odor-shock pairings. Olfactory-mediated fear-potentiated startle decreased, but was still significant up to 40 d after conditioning, and could be measured using test trials separated by as little as 30 sec. Those studies confirmed a previous report by Richardson et al. (1999), showing that ambient odors are also effective CSs for potentiating the startle response. Because odors are such salient cues for the rat, and because of the robust olfactory conditioning observed previously, the current studies investigated second-order olfactory fear conditioning.Pavlov (1927) proposed that once a stimulus has been conditioned, it can serve the role of an unconditioned stimulus (US). In first-order Pavlovian conditioning, a previously neutral stimulus (i.e., a light), is paired with a biologically significant US that can be either aversive (i.e., footshock) or rewarding (i.e., food). The animal learns an association between the CS and the US, and later exhibits a conditioned response (CR) to that stimulus in the absence of the US. Conditioning of a second neutral stimulus (S2) with the previously conditioned (and now excitatory) firstorder stimulus (S1) is known as higher-order (or secondorder) conditioning. When later tested with S2, the animal exhibits a CR, although S2 was never paired directly with the US.The existence of second-order conditioning is important, as it increases the range of situations in which classical conditioning occurs, even without a primary unconditioned stimulus (cf. Domjan 1998...

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Immediate-early gene expression in the amygdala following footshock stress and contextual fear conditioning

Cited by 182 publications

References 39 publications

Activation and Inhibition of Neurons in the Hippocampal Ventral Subiculum by Norepinephrine and Locus Coeruleus Stimulation

Activation and Inhibition of Neurons in the Hippocampal Ventral Subiculum by Norepinephrine and Locus Coeruleus Stimulation

Amygdala Regulation of Immediate-Early Gene Expression in the Hippocampus Induced by Contextual Fear Conditioning

Second-Order Olfactory-Mediated Fear-Potentiated Startle

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