Persistent Increases of PKMζ in Sensorimotor Cortex Maintain Procedural Long-Term Memory Storage

Gao, Peng; Goodman, Jeffrey H.; Francis, Joseph T.

doi:10.1016/j.isci.2018.07.002

Cited by 28 publications

(16 citation statements)

References 42 publications

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“…In contrast to LTP in which PKMζ preferentially increases in the projection fields of the tetanically stimulated fibers (Figure S1), spatial conditioning increases PKMζ throughout CA1 (Figures 2 and 3, Figures S3-S4). This localization of persistent increases in PKMζ to the output neurons of the hippocampal formation in this spatial task is analogous to similar increases in the output neurons of the motor cortex during long-term retention of a reaching task (Gao et al, 2018). Neocortical PKMζ also appears to increase in active place avoidance memory at both superficial and deep layers at the earlier time point, but less so at the superficial layers in remote memory, while increasing at deep layers of the retrosplenial cortex during remote memory, but not at the earlier time point (Wesierska et al, 2009).…”

supporting

confidence: 54%

Persistent increases of PKMζ in memory‐activated neurons trace LTP maintenance during spatial long‐term memory storage

Hsieh

Tsokas

Grau‐Perales

et al. 2021

Eur J of Neuroscience

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PKMζ is an autonomously active PKC isoform crucial for the maintenance of synaptic long-term potentiation (LTP) and long-term memory. Unlike other kinases that are transiently stimulated by second messengers, PKMζ is persistently activated through sustained increases in protein expression of the kinase. Therefore, visualizing increases in PKMζ expression during long-term memory storage might reveal the sites of its persistent action and thus the location of memory-associated LTP maintenance in the brain. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we examined the amount and distribution of PKMζ in subregions of the hippocampal formation of wild-type mice during LTP maintenance and spatial long-term memory storage. During LTP maintenance in hippocampal slices, PKMζ increases in the pyramidal cell body and stimulated dendritic layers of CA1 for at least 2 hr. During spatial memory storage, PKMζ increases in CA1 pyramidal cells for at least 1 month, paralleling the persistence of the memory. During the initial expression of the memory, we tagged principal cells with immediate-early gene Arc promoterdriven transcription of fluorescent proteins. The subset of memory-tagged CA1 cells selectively increases expression of PKMζ during memory storage, and the increase persists in dendritic compartments within stratum radiatum for 1 month, indicating long-term storage of information in the CA3-to-CA1 pathway. We conclude that persistent increases in PKMζ trace the molecular mechanism of LTP maintenance and thus the sites of information storage within brain circuitry during long-term memory.

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supporting

confidence: 54%

Persistent increases of PKMζ in memory‐activated neurons trace LTP maintenance during spatial long‐term memory storage

Hsieh

Tsokas

Grau‐Perales

et al. 2021

Eur J of Neuroscience

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“…In this study, while aiming to explore the layer-specific long-term memory-dependent dynamics of cortical neural activities, we specifically selected layers II/III and layer V for a number of reasons. In particular, both layers II/III and deep cortical layers have been shown to play important roles in learning and memory in previous studies (Xie et al, 2014; Hayashi-Takagi et al, 2015; Gao et al, 2018; Wang et al, 2019) and the quality of the data under study is good in multiple locations scanned down to layer V (more specifically, to layer Vb). Thus, layers II, III, Va and Vb turned out to be the good candidates for this study.…”

Section: Discussionmentioning

confidence: 90%

Multimodal Memory Components and Their Long-Term Dynamics Identified in Cortical Layers II/III but Not Layer V

Liu

Wang

Xie

et al. 2019

Front. Integr. Neurosci.

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Activity patterns of cerebral cortical regions represent the current environment in which animals receive multi-modal inputs. These patterns are also shaped by the history of activity that reflects learned information on past multimodal exposures. We studied the long-term dynamics of cortical activity patterns during the formation of multimodal memories by analyzing in vivo high-resolution 2-photon mouse brain imaging data of Immediate Early Gene (IEG) expression, resolved by cortical layers. Strikingly, in superficial layers II/III, the patterns showed similar dynamics across structurally and functionally distinct cortical areas and the consistency of dynamic patterns lasted for one to several days. By contrast, in deep layer V, the activity dynamics varied across different areas, and the current activities were sensitive to the previous activities at different time points, depending on the cortical locations, indicating that the information stored in the cortex at different time points was distributed across different cortical areas. These results suggest different roles of superficial and deep layer neurons in the long-term multimodal representation of the environment.

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“…In previous studies, the presence of PKMζ was always considered as a necessary factor for long-term synaptic potentiation, successful learning and memory consolidation 30 , 31 , 33 , 35 , 36 , 39 , 40 , 48 , 52 . On the contrary, a decreased quantity of PKMζ was associated with the long-term synaptic depression, impaired learning and weakening of the existing memory trace 32 , 33 , 35 , 40 , 47 , 52 , 71 – 73 . Previously, it was described in details that consolidation of some types of memory requires both long-term potentiation and long-term depression (LTD) 74 .…”

Section: Discussionmentioning

confidence: 95%

Histone acetylation determines transcription of atypical protein kinases in rat neurons

Borodinova

Kuznetsova

Alekseeva

et al. 2019

Sci Rep

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It is widely accepted that memory consolidation requires de-novo transcription of memory-related genes. Epigenetic modifications, particularly histone acetylation, may facilitate gene transcription, but their potential molecular targets are poorly characterized. In the current study, we addressed the question of epigenetic control of atypical protein kinases (aPKC) that are critically involved in memory consolidation and maintenance. We examined the patterns of expression of two aPKC genes (Prkci and Prkcz) in rat cultured cortical neurons treated with histone deacetylase inhibitors. Histone hyperacetylation in the promoter region of Prkci gene elicited direct activation of transcriptional machinery, resulting in increased production of PKCλ mRNA. In parallel, histone hyperacetylation in the upstream promoter of Prkcz gene led to appearance of the corresponding PKCζ transcripts that are almost absent in the brain in resting conditions. In contrast, histone hyperacetylation in the downstream promoter of Prkcz gene was accompanied by a decreased expression of the brain-specific PKMζ products. We showed that epigenetically-triggered differential expression of PKMζ and PKCζ mRNA depended on protein synthesis. Summarizing, our results suggest that genes, encoding memory-related aPKC, may represent the molecular targets for epigenetic regulation through posttranslational histone modifications.

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Persistent Increases of PKMζ in Sensorimotor Cortex Maintain Procedural Long-Term Memory Storage

Cited by 28 publications

References 42 publications

Persistent increases of PKMζ in memory‐activated neurons trace LTP maintenance during spatial long‐term memory storage

Persistent increases of PKMζ in memory‐activated neurons trace LTP maintenance during spatial long‐term memory storage

Multimodal Memory Components and Their Long-Term Dynamics Identified in Cortical Layers II/III but Not Layer V

Histone acetylation determines transcription of atypical protein kinases in rat neurons

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