The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

Lee, Bo-Young; Bang, Eunyoung; Yang, Won-Mo; Paydar, Afshin; Ha, Go Eun; Kim, Sujin; Kim, Jong Hyun; Cho, Taesup; Lee, Seung Eun; Lee, Sukchan; Kang, Myoung-Goo; Cheong, Eunji; Kim, Key Sun; Lee, Cheolju; Yu, Myeong Hee; Shin, Hee Sup

doi:10.1038/s41598-018-30589-1

Cited by 9 publications

(20 citation statements)

References 58 publications

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“…To address this important aspect, several groups investigated heterozygous Nbea +/− mice, which exhibit a 30% reduction in forebrain Nbea protein levels 8 , for construct and face validity. In fact, autism-related abnormalities are present in Nbea +/− mice including altered social behaviours, increased self-grooming, delayed spatial learning and memory, increased conditioned fear responses, and impaired fear memory extinction 20,21 . Along with these findings, long-term potentiation (LTP) was enhanced in acute slices of the CA1 region of the hippocampus, an important site for spatial learning 20 .…”

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confidence: 99%

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Muellerleile

Blistein

Rohlmann

et al. 2020

Sci Rep

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Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.

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confidence: 99%

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Muellerleile

Blistein

Rohlmann

et al. 2020

Sci Rep

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“…Consistent with previous findings [11,14], after three days of extinction training morphine-dependent rats did not manifest CPA to the naloxone-paired compartment in the extinction test. The recall of fear and other extinction memories has been reported to alter mTOR activity in the hippocampus [55][56][57]. Nevertheless, mTOR phosphorylation was not altered in the DG of morphine-dependent animals after the extinction test.…”

Section: Discussionmentioning

confidence: 97%

Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus

et al. 2022

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Despite their indisputable efficacy for pain management, opiate prescriptions remain highly controversial partially due to their elevated addictive potential. Relapse in drug use is one of the principal problems for addiction treatment, with drug-associated memories being among its main triggers. Consequently, the extinction of these memories has been proposed as a useful therapeutic tool. Hence, by using the conditioned place aversion (CPA) paradigm in rats, we investigated some of the molecular mechanisms that occurr during the retrieval and extinction of morphine withdrawal memories in the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which control emotional and episodic memories, respectively. The retrieval of aversive memories associated with the abstinence syndrome paralleled with decreased mTOR activity and increased Arc and GluN1 expressions in the DG. Additionally, Arc mRNA levels in this nucleus very strongly correlated with the CPA score exhibited by the opiate-treated rats. On the other hand, despite the unaltered mTOR phosphorylation, Arc levels augmented in the BLA. After the extinction test, Arc and GluN1 expressions were raised in both the DG and BLA of the control and morphine-treated animals. Remarkably, Homer1 expression in both areas correlated almost perfectly with the extinction showed by morphine-dependent animals. Moreover, Arc expression in the DG correlated strongly with the extinction of the CPA manifested by the group treated with the opiate. Finally, our results support the coordinated activity of some of these neuroplastic proteins for the extinction of morphine withdrawal memories in a regional-dependent manner. Present data provide evidence of differential expression and activity of synaptic molecules during the retrieval and extinction of aversive memories of opiate withdrawal in the amygdalar and hippocampal regions that will likely permit the development of therapeutic strategies able to minimize relapses induced by morphine withdrawal-associated aversive memories.

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“…Consistent with previous findings [11,14], after three days of extinction training morphine dependent rats did not manifest CPA to the naloxone-paired compartment in the extinction test. The recall of some kinds of extinction memories has been reported to alter mTOR activity in the hippocampus [61–63]. Nevertheless, mTOR phosphorylation was not altered in in the DG nor the BLA of morphine-dependent animals after the extinction test.…”

Section: Discussionmentioning

confidence: 99%

Disentangling the molecular mechanisms underlying the retrieval and extinction of morphine withdrawal-associated memories in the basolateral amygdala and dentate gyrus

Franco-García

Fernandez-Gomez

Gómez-Murcia

et al. 2022

Preprint

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Despite their indisputable efficacy for pain management, opiates prescription remains highly controversial due to their elevated addictive potential. Relapse in drug use is one of the principal problems for addiction treatment, being drug-associated memories among its main triggers. Consequently, the extinction of these memories has been proposed as a useful therapeutic tool. Hence, by using the conditioned place aversion (CPA) paradigm in rats we investigated some of the molecular mechanisms that occurred during the retrieval and extinction of morphine withdrawal memories in the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which control emotional and episodic memories, respectively. The retrieval of aversive memories associated with the abstinence syndrome paralleled with decreased mTOR activity and increased Arc and GluN1 expressions in the DG. Additionally, Arc mRNA levels in this nucleus very strongly correlated with the CPA score exhibited by the opiate-treated rats. On the other hand, despite the unaltered mTOR phosphorylation Arc augmented in the BLA. After the extinction test, Arc and GluN1 expressions raised in both the DG and BLA of control and morphine-treated animals. Remarkably, Homer1 expression in both areas correlated almost perfectly with the extinction showed by morphine-dependent animals. Also, Arc expression in the DG correlated strongly with the extinction of the CPA manifested by the group treated with the opiate. Finally, our results support coordinated activity of some of these neuroplastic proteins for the extinction of morphine activity in a regional-dependent manner. Present data provide evidence of differential expression and activity of synaptic molecules during the retrieval and extinction of aversive memories of opiate withdrawal in amygdalar and hippocampal regions that will likely permit the development of therapeutic strategies able to minimize relapses induced by drug-associated aversive memories.

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The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

Cited by 9 publications

References 58 publications

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus

Disentangling the molecular mechanisms underlying the retrieval and extinction of morphine withdrawal-associated memories in the basolateral amygdala and dentate gyrus

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