Evidence of Contextual Fear after Lesions of the Hippocampus: A Disruption of Freezing But Not Fear-Potentiated Startle

McNish, Kenneth A.; Gewirtz, Jonathan C.; Davis, Michael

doi:10.1523/jneurosci.17-23-09353.1997

Cited by 244 publications

(177 citation statements)

References 45 publications

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“…The difference between this value and the baseline motor activity (measured during the habituation period, see above) was used as a measure of "freezing." Preliminary studies in this laboratory as well as in other laboratories (Leaton and Borszcz, 1985;McNish et al, 1997) showed that this kind of measure is highly correlated with freezing quantified by an observer.…”

Section: Methodsmentioning

confidence: 58%

“…It should be noted that freezing was not directly observed, but attenuation of motor activity in the startle test chamber was measured, which is highly correlated with freezing (Leaton and Borszcz, 1985;McNish et al, 1997). The question now is why the studies of Davis and colleagues (Miserendino et al, 1990;Campeau et al, 1992;) revealed contradictory results.…”

Section: Discussionmentioning

confidence: 98%

“…Because a fearconditioned context enhances the baseline startle response (McNish et al, 1997;Frankland et al, 1998), the amount of fear potentiation by the discrete CS could be attenuated by a mixed conditioning procedure. This could be an important point because the injection sites of the studies by Davis and colleagues (Miserendino et al, 1990;Campeau et al, 1992; were located in the basolateral nucleus of the amygdala (also see below), and the basolateral nucleus is a critical nucleus for contextual fear conditioning (LeDoux, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Injections of the NMDA Receptor Antagonist Aminophosphonopentanoic Acid into the Lateral Nucleus of the Amygdala Block the Expression of Fear-Potentiated Startle and Freezing

Fendt

2001

J. Neurosci.

103

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NMDA receptors within the amygdala play an important role in the acquisition and expression of conditioned fear. Because amygdaloid injections of NMDA receptor antagonists did not block the expression of every behavioral sign of fear, a discussion arose as to whether amygdaloid NMDA receptors play different roles in different kinds of fear-conditioning tasks. To clarify the exact role of amygdaloid NMDA receptors, the present study measured the effects of amygdaloid NMDA receptor blockade on the two major animal models of conditioned fear. An experimental design was used that allowed simultaneous measurement of fear-potentiated startle and freezing during the same test session after animals had undergone identical training procedures. The present study clearly demonstrates that injections of the NMDA receptor antagonist AP-5 into the lateral nucleus of the amygdala significantly attenuated both behavioral fear responses (i.e., the amygdaloid NMDA receptors are necessary for the expression of fearpotentiated startle and freezing). The present results together with others from the literature indicate that NMDA receptors within the lateral amygdala are critically involved in normal synaptic transmission. It appears then that NMDA receptor antagonists may block the acquisition of fear conditioning by directly interfering with normal synaptic transmissions in the amygdala. Possible reasons for some discrepant results in earlier studies are also discussed. Key words: amygdala; AP-5; conditioned fear; expression; freezing; glutamate; NMDA receptor; plasticity; startleFear conditioning is the learning of an association between an initially neutral stimulus and a potentially threatening stimulus [unconditioned stimulus (US)]. After a few pairings of these stimuli, the neutral stimulus becomes a conditioned stimulus (CS) capable of eliciting behavioral, autonomic, and endocrine fear responses that normally occur in threatening situations. (In rats, these responses include freezing, ultrasonic vocalization, potentiation of reflexes, defecation, etc.) Because fearful experiences are rapidly learned and long remembered, fear conditioning also has become an excellent model to investigate the processes and mechanisms underlying learning Fendt and Fanselow, 1999;LeDoux, 2000).A variety of studies have painted a relatively clear picture of the neuroanatomy and neurochemistry of conditioned fear. The amygdala is thought to play an essential role in the acquisition and expression of conditioned fear (Blanchard and Blanchard, 1972;Davis et al., 1993;Lavond et al., 1993;Fendt and Fanselow, 1999;LeDoux, 2000). Specifically, the amygdala has been hypothesized as the interface between the sensory systems carrying the information about the CS and the US and the different motor and autonomic pathways eliciting the conditioned fear responses. The sensory inputs to the amygdala mainly terminate in the lateral nucleus of the amygdala (LA) (Doron and LeDoux, 1999), and lesions of the LA blocked acquisition as well as the expression of condit...

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Section: Methodsmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Injections of the NMDA Receptor Antagonist Aminophosphonopentanoic Acid into the Lateral Nucleus of the Amygdala Block the Expression of Fear-Potentiated Startle and Freezing

Fendt

2001

J. Neurosci.

103

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“…Although there is a lack of support for the hyperactivity account of contextual freezing deficits, McNish et al (1997) presented data showing that context-potentiated startle was not affected by DH lesions made immediately after training. This suggests that the deficits in contextual fear we have observed may be specific to the freezing response.…”

Section: Performance Account Of Contextual Freezing Deficits After Himentioning

confidence: 91%

Hippocampus and contextual fear conditioning: Recent controversies and advances

2001

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ABSTRACT:Dorsal hippocampal (DH) lesions produce a severe deficit in recently, but not remotely, acquired contextual fear without impairing memory of discrete training stimuli, i.e., DH lesions produce an anterograde and time-limited retrograde amnesia specific to contextual memory. These data are consistent with the standard model which posits temporary involvement of the hippocampus in recent memory maintenance. However, three recent controversies apparently weaken the case for a selective mnemonic role for the hippocampus in contextual fear. First, although retrograde amnesia (from posttraining lesions) is severe, anterograde amnesia (from pretraining lesions) may be mild or nonexistent. Second, a performance, rather than mnemonic, account of contextual freezing deficits in hippocampal-lesioned animals has been offered. Third, damage to the entire hippocampus, including the ventral hippocampus, can produce a dramatic and temporally stable disruption of context and tone fear. These data are reviewed and explanations are offered as to why they do not necessarily challenge the standard model of hippocampal memory function in contextual fear. Finally, a more complete description of the hippocampus' proposed role in contextual fear is offered, along with new data supporting this view. In summary, the data support a specific mnemonic role for the DH in the acquisition and consolidation of contextual representations. Hippocampus 2001;11:8 -17.

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“…Not all studies find that lesions of the hippocampus affect context conditioning (Frankland et al 1998;McNish et al 1997;Winocur 1997). Recent preclinical evidence indicates that context conditioning is hippocampus-dependent for complex but not simple environments (Moses et al 2007).…”

Section: Context Conditioningmentioning

confidence: 99%

Models and mechanisms of anxiety: evidence from startle studies

2007

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Rationale-Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).Objective-To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety.Results-The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to nonphobic anxiety disorders.Conclusions-Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

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Evidence of Contextual Fear after Lesions of the Hippocampus: A Disruption of Freezing But Not Fear-Potentiated Startle

Cited by 244 publications

References 45 publications

Injections of the NMDA Receptor Antagonist Aminophosphonopentanoic Acid into the Lateral Nucleus of the Amygdala Block the Expression of Fear-Potentiated Startle and Freezing

Injections of the NMDA Receptor Antagonist Aminophosphonopentanoic Acid into the Lateral Nucleus of the Amygdala Block the Expression of Fear-Potentiated Startle and Freezing

Hippocampus and contextual fear conditioning: Recent controversies and advances

Models and mechanisms of anxiety: evidence from startle studies

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