Contextual Fear Conditioning Retrieval Research Articles

The dorsal subiculum is required for contextual fear conditioning consolidation in rats

The hippocampal formation has a well-known role in contextual fear conditioning. The dorsal subiculum connects the hippocampus to the entorhinal cortex through pathways that seemingly rely on NMDA-dependent synaptic plasticity. The role of the dorsal subiculum in contextual fear conditioning retrieval, but not acquisition, has been previously reported. However, most of the critical biological phenomena involved in memory formation occur in the consolidation phase. The present study aimed to assess the effects of intra-dorsal subiculum muscimol or AP5 infusion on contextual fear conditioning consolidation. Our data show that dorsal subiculum integrity, as well as NMDA transmission in this region, seem to be necessary for contextual fear conditioning consolidation.

Contextual fear retrieval-induced Fos expression across early development in the rat: An analysis using established nervous system nomenclature ontology.

The neural circuits underlying the acquisition, retention and retrieval of contextual fear conditioning have been well characterized in the adult animal. A growing body of work in younger rodents indicates that context-mediated fear expression may vary across development. However, it remains unclear how this expression may be defined across the full range of key developmental ages. Nor is it fully clear whether the structure of the adult context fear network generalizes to earlier ages. In this study, we compared context fear retrieval-induced behavior and neuroanatomically constrained immediate early-gene expression across infant (P19), early and late juvenile (P24 and P35), and adult (P90) male Long-Evans rats. We focused our analysis on neuroanatomically defined subregions and nuclei of the basolateral complex of the amygdala (BLA complex), dorsal and ventral portions of the hippocampus and the subregions of the medial prefrontal cortex as defined by the nomenclature of the Swanson (2004) adult rat brain atlas. Relative to controls and across all ages tested, there were greater numbers of Fos immunoreactive (Fos-ir) neurons in the posterior part of the basolateral amygdalar nuclei (BLAp) following context fear retrieval that correlated statistically with the expression of freezing. However, Fos-ir within regions having known connections with the BLA complex was differentially constrained by developmental age: early juvenile, but not adult rats exhibited an increase of context fear-dependent Fos-ir neurons in prelimbic and infralimbic areas, while adult, but not juvenile rats displayed increases in Fos-ir neurons within the ventral CA1 hippocampus. These results suggest that juvenile and adult rodents may recruit developmentally unique pathways in the acquisition and retrieval of contextual fear. This study extends prior work by providing a broader set of developmental ages and a rigorously defined neuroanatomical ontology within which the contextual fear network can be studied further.

Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval

In the present study we test the hypothesis that extinction is not a consequence of retrieval in unreinforced conditioned stimulus (CS) presentation but the mere perception of the CS in the absence of a conditioned response. Animals with cannulae implanted in the CA1 region of hippocampus were subjected to extinction of contextual fear conditioning. Muscimol infused intra-CA1 before an extinction training session of contextual fear conditioning (CFC) blocks retrieval but not consolidation of extinction measured 24 h later. Additionally, this inhibition of retrieval does not affect early persistence of extinction when tested 7 d later or its spontaneous recovery after 2 wk. Furthermore, both anisomycin, an inhibitor of ribosomal protein synthesis, and rapamycin, an inhibitor of extraribosomal protein synthesis, given into the CA1, impair extinction of CFC regardless of whether its retrieval was blocked by muscimol. Therefore, retrieval performance in the first unreinforced session is not necessary for the installation, maintenance, or spontaneous recovery of extinction of CFC.

S17-03 Memory reorganization by synaptic protein degradation

An accumulating body of evidence shows that the retrieval process of long-term memory is not static and requires de novo protein synthesis. Thus long-term memories are dynamic and particularly become fragile during its retrieval. Importantly, memory retrieval is regarded as a step necessary for incorporating new information into preexisting memories. We have examined whether protein degradation is involved in the memory reorganization or not. In this presentation I will present the evidence that synaptic proteins are degraded by polyubiquitination and proteasome pathway in the hippocampus after the retrieval of contextual fear conditioning. In addition, we found that the infusion of a proteasome inhibitor into the hippocampus prevented the memory impairment induced by anisomycin, a protein synthesis inhibitor. This indicates that ubiquitin/proteasome-dependent protein degradation is involved in destabilization processes accompanying the memory retrieval. It also supports our hypothesis that preexisting memory is disrupted by synaptic protein degradation before updated memory is strengthened by protein synthesis. Our data also showed that synaptic protein degradation plays a critical role in fear memory extinction, a simple form of memory reorganization. Taken together, synaptic protein degradation is critically involved in the reorganization of the preexisting memories.

Behavioral impairments caused by injections of the protein synthesis inhibitor anisomycin after contextual retrieval reverse with time.

Recent accounts of memory suggest that retrieval of a learning experience transforms that memory into a labile state that requires a period of protein synthesis to be reconsolidated into a fixed state. In this article, we show that the impairments in behavior caused by the protein synthesis inhibitor anisomycin given after retrieval are temporary and are thus not likely to reflect disruptions in a protein synthesis-dependent reconsolidation process. Mice received injections of anisomycin after either initial acquisition or retrieval of contextual fear conditioning. When anisomycin injections followed acquisition, freezing was impaired during memory tests the next day and 21 days later. When anisomycin injections followed normal retrieval of contextual fear conditioning, freezing was impaired the next day but recovered to levels of control mice when testing occurred 21 days later. This recovery effect occurred after short or long durations of exposure during the retrieval period and was specific to the conditioning context. These results suggest that anisomycin injections after retrieval do not retroactively affect the memory from conditioning.