Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Dong, Zhifang; Han, Hyounkoo; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoge; Zhou, Weihui; Jin, Wu-Yang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

doi:10.1172/jci77888

Cited by 146 publications

(135 citation statements)

References 51 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, a preliminary study from Sacktor's laboratory showed that the constitutive knockout of PKC/PKMζ resulted in a compensatory increase in phospho-Thr403 PKCι/λ under basal conditions (Tsokas et al, 2012), and PKCι/λ has been shown to be involved in the maintenance of LTP (Ren et al, 2013a). Others also found that ZIP may have an inhibitory effect on PKCι/λ (Ren et al, 2013a), and using PKMζ-shRNA to reduce the expression of PKMζ without influencing PKCι/ λ abolished the fear memory (Dong et al, 2014). In our Figure 4 PKMζ overexpression in the PrL potentiates the fear conditioning-induced increase in membrane GluA2 expression.…”

Section: Discussionsupporting

confidence: 62%

Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

Xue

Zhu

Han

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Neuroplasticity in the prefrontal cortex (PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory. Protein kinase Mζ (PKMζ), an isoform of protein kinase C with persistent activity, is involved in the formation and maintenance of memory. However, less is known about the role of PKMζ in the PFC in the formation of fear memory. We investigated whether the overexpression of PKMζ enhances the formation of auditory fear memory in rats. We found that microinfusion of lentiviral vector-expressing PKMζ into the prelimbic cortex (PrL) selectively enhanced the expression of PKMζ without influencing the expression of other isoforms of PKC. The overexpression of PKMζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas the overexpression of PKMζ in the infralimbic cortex had no effect on either short-term or long-term fear memory. The overexpression of PKMζ in the PrL had no effect on anxiety-like behavior or locomotor activity. We also found that PKMζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL. These results demonstrate that the overexpression of PKMζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory, and PKMζ in the PrL may be involved in the formation of fear memory.

show abstract

Section: Discussionsupporting

confidence: 62%

Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

Xue

Zhu

Han

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Furthermore, in these knockout experiments plasticity and memory were still sensitive to ZIP. In these animals PKCi/l, also a target of ZIP (Frankland and Josselyn 2013;Ren et al 2013;Dong et al 2014), was present. We postulate that the redundancy between these two kinases and possible compensation might account for the seeming inconsistency between these recent experiments and the plethora of previous experimental results.…”

Section: A "Molecular Switch" Resulting From the Interaction Between mentioning

confidence: 89%

Atypical PKCs in memory maintenance: the roles of feedback and redundancy

Jalil¹,

Sacktor

Shouval³

2015

Learn. Mem.

Self Cite

View full text Add to dashboard Cite

Memories that last a lifetime are thought to be stored, at least in part, as persistent enhancement of the strength of particular synapses. The synaptic mechanism of these persistent changes, late long-term potentiation (L-LTP), depends on the state and number of specific synaptic proteins. Synaptic proteins, however, have limited dwell times due to molecular turnover and diffusion, leading to a fundamental question: how can this transient molecular machinery store memories lasting a lifetime? Because the persistent changes in efficacy are synapse-specific, the underlying molecular mechanisms must to a degree reside locally in synapses. Extensive experimental evidence points to atypical protein kinase C (aPKC) isoforms as key components involved in memory maintenance. Furthermore, it is evident that establishing long-term memory requires new protein synthesis. However, a comprehensive model has not been developed describing how these components work to preserve synaptic efficacies over time. We propose a molecular model that can account for key empirical properties of L-LTP, including its protein synthesis dependence, dependence on aPKCs, and synapse-specificity. Simulations and empirical data suggest that either of the two aPKC subtypes in hippocampal neurons, PKMz and PKCi/l, can maintain L-LTP, making the system more robust. Given genetic compensation at the level of synthesis of these PKC subtypes as in knockout mice, this system is able to maintain L-LTP and memory when one of the pathways is eliminated.

show abstract

“…Given that consolidation decreases the fragility of memory traces, theories and studies related to memory should address consolidation as an infl uential phenomenon in this process (Brown, 2002). From a neurophysiological perspective, forgetting eventually mobilizes physiological mechanisms that mediate time-dependent forgetting (Dong et al, 2016;Sachser et al, 2016;Villareal, Do, Haddad, & Derrick, 2002). According to these recent fi ndings, memory can last indefi nitely, provided it is protected from the active forgetting associated with specifi c neurochemical mechanisms.…”

Section: Resultsmentioning

confidence: 99%

Retroactive Interference: Forgetting as an Interruption of Memory Consolidation

Alves¹,

Bueno²

2017

Temas Psicol.

View full text Add to dashboard Cite

Although experimenting with forgetting is complex, forgetting is not only a condition experienced by individuals every day but also an extremely important concept in memory science. Some theories that attempt to defi ne the science of forgetting are presented in this study; however, we have focused here on the theory of interference, retroactive interference (RI) in particular. RI is the interference that occurs when a task or piece of information is inserted between the presentation of target information and its subsequent recall. Although RI can be explained as competition between items, some have now proposed that it results from the interruption of the process of memory consolidation, through which information become stable; neural processes following the initial recording of information contribute to the defi nitive-or, at least, longer lasting-record of this information. RI disrupts post-learning processes, resulting in the loss of these materials. This study proposes a deeper investigation of RI and memory consolidation to obtain a better understanding of this important concept, seeking to deepen knowledge of this hypothesis and other possible causes of forgetting.Keywords: Forgetting, long-term memory, interference theory, memory consolidation. Interferência Retroativa: O Esquecimento como uma Interrupção na Consolidação da MemóriaResumo O esquecimento é uma condição vivenciada diariamente pelos indivíduos e um conceito de extrema importância para a ciência da memória, apesar de sua experimentação ser complexa. Algumas teorias que tentam defi nir a ciência do esquecimento são apresentadas neste estudo, todavia, aqui focamos na Teoria da Interferência, principalmente na Interferência Retroativa (IR). A IR é a interferência que ocorre quando uma informação ou tarefa é inserida entre a apresentação de uma informação-alvo e sua posterior recordação. A IR pode ser explicada como uma competição de itens, mas atualmente surge a proposta que ela seja fruto da interrupção de um outro processo, chamado de Consolidação da Memória. A consolidação da memória é o processo através do qual as informações tornam-se estáveis, a partir de processos neurais posteriores ao registro inicial de uma informação que contribuem para o registro defi nitivo -ou, ao menos, mais duradouro -desta informação. A IR perturbaria estes processos posteriores à aprendizagem, resultando na perda destes materiais. O presente estudo visa propor a possibilidade 1 Mailing address: Rua Botucatu, 862, Vila Clementino. São Paulo, SP, Brazil 04023062. Phone: (11) 21490155.

show abstract

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Cited by 146 publications

References 51 publications

Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

Atypical PKCs in memory maintenance: the roles of feedback and redundancy

Retroactive Interference: Forgetting as an Interruption of Memory Consolidation

Contact Info

Product

Resources

About