Contextual Fear Conditioning Is Associated With Lateralized Expression of the Immediate Early Gene c-fos in the Central and Basolateral Amygdalar Nuclei (original) (raw)
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Brain Research, 2008
Rats selectively bred for high or low levels of emotionality represent an important and powerful tool to investigate the role of genetic variables in the occurrence of different anxiety disorders. In the present study, albino rats were selectively bred for differences in defensive freezing behavior in response to contextual cues previously associated with footshock, an animal model of general anxiety disorder. The results indicate that these two new lines of rats, which we refer to as Carioca High-Freezing (CHF) and Carioca Low-Freezing (CLF), show a reliable difference in conditioned freezing after three generations of selection.
Amygdala, hippocampus, and unconditioned fear
Experimental Brain Research, 2001
Embedded within contemporary views of emotional learning is a well-founded agreement that the amygdala plays a pivotal role in the formation and consolidation of aversive memories formed during fear conditioning. However, it is important to determine whether observed deficits are reflective of a memory impairment or whether they are simply attributable to a deficit in the performance of unconditioned fear responses such as freezing. Within the neurobiology of learning and memory literature, there is an ongoing debate concerning the potential role of the amygdala in the performance of unconditioned fear responses. A view put forth by Vazdarjanova and McGaugh (1998) suggests that the amygdala is not required for the formation and consolidation of the aversive memories formed during fear conditioning, but is essential in the performance of unconditioned fear responses. Data provided by Maren (1999) counter this view by positing that the amygdala is not required for the performance of fear responses, but its role is of a mnemonic nature in the conditioning of fear to neutral cues. To clarify the amygdala's participation in these two processes, a useful approach would involve a situation where animals with amygdala damage were examined for their unconditioned fear responses in reaction to footshock as well as the conditioning of these reactions to previously neutral cues paired with the aversive event. We have previously reported that rats with amygdala or hippocampal damage are impaired in discriminative fear conditioning to context. In the present experiment, we report the initial unconditioned fear responses to footshock by these same animals as well as the conditioned responses during testing. In both groups, the fear responses assessed (freezing, urination, defecation, and locomotion) were not impaired and did not differ from those expressed by the sham animals. The impairment of discriminative fear conditioning to context, in combination with the present experiment, represents a dissocia-tion where damage to specific memory structures (amygdala or hippocampus) debilitates the mnemonic processes involved in fear conditioning, but not the performance of the fear responses per se.
After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry. After fear conditioning and extinction to an auditory conditioned stimulus (CS), rats were presented with the extinguished CS in either the extinction context or a second context, and then sacrificed. Presentation of the CS in the extinction context yielded low levels of conditioned freezing and induced c-Fos expression in the infralimbic division of the medial prefrontal cortex, the intercalated nuclei of the amygdala, and the dentate gyrus (DG). In contrast, presentation of the CS outside of the extinction context yielded high levels of conditioned freezing and induced c-Fos expression in the prelimbic division of the medial prefrontal cortex, the lateral and basolateral nuclei of the amygdala, and the medial division of the central nucleus of the amygdala. Hippocampal areas CA1 and CA3 exhibited c-Fos expression when the CS was presented in either context. These data suggest that the context specificity of extinction is mediated by prefrontal modulation of amygdala activity, and that the hippocampus has a fundamental role in contextual memory retrieval.
Neurobiology of Learning and Memory, 2008
The current study examined the effects of temporary inactivation of the DH on freezing, rearing, ambulating, grooming, and whisking behavior in an explicitly nonspatial contextual fear conditioning paradigm in which olfactory stimuli served as temporally and spatially diffuse contexts. Prior either to training, testing, or both, male Sprague-Dawley rats received bilateral microinfusions of saline or the GABA A agonist muscimol into the DH. Results indicate that temporary inactivation of DH produced both anterograde and retrograde deficits in contextually conditioned freezing, while sparing the acquisition and expression of freezing to a discrete auditory or olfactory CS. These data suggest that there is a decidedly nonspatial component to the role of DH in contextual conditioning, and that olfactory contextual conditioning is a fruitful means of further exploring this function.
Neurobiology of learning and memory, 2013
While a number of early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus often impairs recall across a wide range of training-testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previously-acquired memories may differ according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the offset of an initially neutral cue or cues and the onset of an aversive stimulus is separated by a temporal (trace) interval. Specifically, either saline or the GABA-A agonist muscimol was infused into DH or VH prior to testing either 1, 7, 28, or 42 days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any timepoint, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pretesting inactivation of VH had no effect on the performance of previously-acquired delay conditioning, suggesting that the deficits observed in trace conditioning cannot be attributed to a deficit in performance of the freezing response. Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997
The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.
Brain c-Fos immunocytochemistry and cytochrome oxidase histochemistry after a fear conditioning task
Psicothema, 2007
The involvement of the basolateral and the medial amygdala in fear conditioning was evaluated using different markers of neuronal activation. The method described here is a combination of cytochrome oxidase (CO) histochemistry and c-Fos immunocytochemistry on fresh frozen brain sections. Freezing behavior was used as an index of auditory and contextual fear conditioning. As expected, freezing scores were significantly higher in rats exposed to tone-shock pairings in a distinctive environment (conditioned; COND), as compared to rats that did not receive any shocks (UNCD). CO labeling was increased in the basolateral and medial amygdala of the COND group. Conversely, c-Fos expression in the basolateral and medial amygdala was lower in the COND group as compared to the UNCD group. Furthermore, c-Fos expression was particularly high in the medial amygdala of the UNCD group. The data provided by both techniques indicate that these amygdalar nuclei could play different roles on auditory a...
Hippocampus and Contextual Fear Conditioning: Recent Controversies and Advances
Hippocampus, 2001
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.