Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice

Liu, Yan; Sun, Jiandong; Wang, Yubin; Lopez, Dulce; Tran, Jennifer; Bi, Xiaoning; Baudry, Michel

doi:10.1101/lm.042721.116

Cited by 13 publications

(14 citation statements)

References 21 publications

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“…Calpains, which are localized in spines [ 69 , 70 ], have been suggested to mediate changes in the cytoskeletal structure and organization [ 42 , 71 ] by cleaving substrate proteins [ 60 , 61 ]. The genetic deletions of the calpain 1 / calpain 2 genes resulted in the decline in spine density and dendritic branching complexity in hippocampal CA1 pyramidal neurons, which further impaired the induction of LTP by theta burst stimulation in the CA1 area of the hippocampus [ 44 , 72 , 73 ]. Interestingly, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity [ 45 ]; calpain 1 is required for the induction of LTP while calpain 2 is necessary for this maintenance.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory

et al. 2017

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Memory consolidation, reconsolidation, and extinction have been shown to share similar molecular signatures, including new gene expression. Calpain is a Ca2+-dependent protease that exerts its effects through the proteolytic cleavage of target proteins. Neuron-specific conditional deletions of calpain 1 and 2 impair long-term potentiation in the hippocampus and spatial learning. Moreover, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity. However, the role of hippocampal calpain in memory processes, especially memory consolidation, reconsolidation, and extinction, is still unclear. In the current study, we demonstrated the critical roles of hippocampal calpain in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of calpain in the hippocampus on these memory processes, using the N-Acetyl-Leu-Leu-norleucinal (ALLN; calpain 1 and 2 inhibitor). Microinfusion of ALLN into the dorsal hippocampus impaired long-term memory (24 h memory) without affecting short-term memory (2 h memory). Similarly, this pharmacological blockade of calpain in the dorsal hippocampus also disrupted reactivated memory but did not affect memory extinction. Importantly, the systemic administration of ALLN inhibited the induction of c-fos in the hippocampus, which is observed when memory is consolidated. Our observations showed that hippocampal calpain is required for the consolidation and reconsolidation of contextual fear memory. Further, the results suggested that calpain contributes to the regulation of new gene expression that is necessary for these memory processes as a regulator of Ca2+-signal transduction pathway.

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Section: Discussionmentioning

confidence: 99%

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory

et al. 2017

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“…These data point to a model in which SCOP regulates anxiety by modulating AKT/GSK3β signaling. In addition, SCOP has been shown to regulate K-Ras/ERK signaling in the hippocampus 24 40 . MAPK/ERK signaling in the amygdala has been repeatedly shown to contribute to anxiety regulation in rodents.…”

Section: Discussionmentioning

confidence: 99%

SCOP/PHLPP1β in the basolateral amygdala regulates circadian expression of mouse anxiety-like behavior

Nakano

Shimizu

Shimba

et al. 2016

Sci Rep

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While disruption of the circadian clock triggers a spectrum of affective abnormalities, how the clock regulates mammalian emotionality remains unclear. Here, we characterized the time-of-day-dependent regulation of mouse anxiety-like behaviors. We show that anxiety-like behaviors are expressed in a circadian manner in mice and demonstrate that the clock machineries in the dorsal telencephalon (dTel) are required for the time-of-day-dependent regulation of anxiety-like behaviors. We identify suprachiasmatic nucleus circadian oscillatory protein (SCOP/PHLPP1β) as an essential intracellular signaling molecule mediating this temporal regulation downstream of the clock. Using viral-mediated, basolateral amygdala (BLA)-specific knockout of Scop, we demonstrate that deletion of SCOP in the BLA exerts anxiolytic effects on the elevated plus maze at early subjective night, thereby blunting the circadian variation in the anxiety-like behavior. We conclude that the circadian expression of SCOP in the BLA plays a key role in generating circadian rhythmicity in the anxiety-like behavior. Our results demonstrate SCOP as a regulator of anxiety-like behaviors and reveal its key roles in the anxiogenic functions of the BLA.

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“…These studies have provided clear evidence that calpain-1 plays a critical role in synaptic plasticity and learning and memory, as well as in the maturation of the CNS. Thus, calpain-1 KO mice are impaired in theta burst stimulation-(TBS) induced long-term potentiation (LTP) of synaptic transmission in hippocampus and in various forms of learning and memory (Liu et al, 2016;Heysieattalab et al, 2019). They also exhibit a mild form of cerebellar ataxia resulting from the immaturity of the synaptic contacts between the parallel fibers and the Purkinje neurons in cerebellum (Wang et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer’s Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain

Zhou

Wang

et al. 2020

Front. Genet.

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Calpains represent a family of calcium-dependent proteases participating in a multitude of functions under physiological or pathological conditions. Calpain-1 is one of the most studied members of the family, is ubiquitously distributed in organs and tissues, and has been shown to be involved in synaptic plasticity and neuroprotection in mammalian brain. Calpain-1 deletion results in a number of phenotypic alterations. While some of these alterations can be explained by the acute functions of calpain-1, the present study was directed at studying alterations in gene expression that could also account for these phenotypic modifications. RNA-seq analysis identified 354 differentially expressed genes (DEGs) in brain of calpain-1 knock-out mice, as compared to their wild-type strain. Most DEGs were classified in 10 KEGG pathways, with the highest representations in Protein Processing in Endoplasmic Reticulum, MAP kinase and Alzheimer's disease pathways. Most DEGs were down-regulated and validation of a number of these genes indicated a corresponding decreased expression of their encoded proteins. The results indicate that calpain-1 is involved in the regulation of a significant number of genes affecting multiple brain functions. They also indicate that mutations in calpain-1 are likely to be involved in a number of brain disorders.

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Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice

Cited by 13 publications

References 21 publications

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory

SCOP/PHLPP1β in the basolateral amygdala regulates circadian expression of mouse anxiety-like behavior

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer’s Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain

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