RGD Reference Report - Enhanced apoptosis and decreased ampa receptors are involved in deficit in fear memory in rin1 knockout rats. - Rat Genome Database

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Enhanced apoptosis and decreased ampa receptors are involved in deficit in fear memory in rin1 knockout rats.

Authors: Ma, Linchuan  Chen, Xinzhao  Zhao, Beiying  Shi, Yuxiu  Han, Fang 
Citation: Ma L, etal., J Affect Disord. 2020 May 1;268:173-182. doi: 10.1016/j.jad.2020.02.040. Epub 2020 Feb 27.
RGD ID: 126790555
Pubmed: PMID:32174475   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jad.2020.02.040   (Journal Full-text)


BACKGROUND: Ras and Rab interactor 1 (Rin1) is predominantly expressed in memory-related brain regions, and has been reported to play an important role in fear memory. Increased expression of Rin1 in an animal model of posttraumatic stress disorder (PTSD) has been associated with enhanced acquisition of fear memories, but the exact mechanism of Rin1 in memory regulation are not clear.
METHODS: Here, we used Rin1-knockout rats to examine the effect of Rin1 on fear memories by fear conditional test and the molecular mechanisms that regulate these effects by immunofluorescence, western blotting and TUNEL.
RESULTS: Our results show that Rin1-knockout rats have a deficit in formation and extinction of Auditory fear memories. Lack of Rin1 results in enhanced apoptosis in the hippocampus through a pathway related to the mitochondria rather than the endoplasmic reticulum-related pathway. Importantly, the lack of Rin1 induces a decrease in α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) found in the cytoplasm, but not in those found in the membrane. Expression of CaMKII (which is important for insertion of cytoplasmic AMPAR into the membrane) and stargazin (which is important for immobilization of AMPAR in the membrane) was not changed. The lack of Rin1 also induced changes in AMPAR distribution, from diffuse spread in the cells to clusters around the edge of the cell. Additionally, clustered AMPAR distribution showed a high degree of overlap with actin distribution.
CONCLUSION: These findings indicate that Rin1 affects not only apoptosis, but also the concentration and distribution pattern of AMPAR, which are important in the formation and extinction of fear memory.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
long-term memory  IMP 126790555 RGD 
negative regulation of hippocampal neuron apoptotic process  IMP 126790555 RGD 
short-term memory  IMP 126790555 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal learning/memory/conditioning  IMP 126790555; 126790555; 126790555 RGD 
decreased freezing behavior  IMP 126790555; 126790555; 126790555 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)
Rin1  (Ras and Rab interactor 1)
Rin1em1Hcz  (Ras and Rab interactor 1; TALEN induced mutant 1, Hcz)

Strains
SD-Rin1em1-/-Hcz  (NA)


Additional Information