Calcium-Permeable AMPA Receptors Mediate the Induction of the Protein Kinase A-Dependent Component of Long-Term Potentiation in the Hippocampus

Park, Pojeong; Sanderson, Thomas M.; Amici, Mascia; Choi, Sun-Lim; Bortolotto, Zuner A.; Zhuo, Min; Kaang, Bong‐Kiun; Collingridge, Graham L.

doi:10.1523/jneurosci.3625-15.2016

Cited by 84 publications

(130 citation statements)

References 36 publications

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“…Depending on the stimulation paradigms, LTP can be divided into two forms: a PKA and protein-synthesisdependent form and a PKA and protein-synthesis-independent form (Park et al, 2016). The induction of PKA-sensitive LTP requires multiple episodes of stimuli with proper interepisode intervals (Woo et al, 2003;Kim et al, 2010;Park et al, 2014;Park et al, 2016). In our experiments, LTP was induced by TBS with relatively short intervals, which may not be sensitive to protein synthesis and PKA inhibitors.…”

Section: Discussionmentioning

confidence: 77%

“…Furthermore, we showed that miR-9-3p inhibition did not affect NMDAR function, suggesting that miR-9-3p is involved in LTP induction, very likely through regulating AMPAR trafficking. Depending on the stimulation paradigms, LTP can be divided into two forms: a PKA and protein-synthesisdependent form and a PKA and protein-synthesis-independent form (Park et al, 2016). The induction of PKA-sensitive LTP requires multiple episodes of stimuli with proper interepisode intervals (Woo et al, 2003;Kim et al, 2010;Park et al, 2014;Park et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The EGFP-CXCR4 control sponge has seven bulged binding sites for artificial miRNA based on a sequence from the CXCR4 gene. AAVs expressing each sponge were produced as described previously (Choi et al, 2014). Briefly, human embryonic kidney (HEK)-293T cells were transfected with an AAV vector expressing each sponge, AAV2/1, and pAdDeltaF6 using calcium phosphate.…”

Section: Methodsmentioning

confidence: 99%

“…miR-134, which is specifically expressed in the brain, was shown to regulate the size of dendritic spines, excitatory synaptic transmission, and synaptic plasticity (Schratt et al, 2006;Gao et al, 2010). The role of another brain-specific miRNA, miR-124, was studied in the marine snail Aplysia californica (Rajasethupathy et al, 2009). It is exclusively expressed in the sensory neuron and regulates serotonin-mediated synaptic plasticity through the regulation of CREB (Rajasethupathy et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The role of another brain-specific miRNA, miR-124, was studied in the marine snail Aplysia californica (Rajasethupathy et al, 2009). It is exclusively expressed in the sensory neuron and regulates serotonin-mediated synaptic plasticity through the regulation of CREB (Rajasethupathy et al, 2009). In addition to these miRNAs, several miRNAs are reported to be highly enriched in the brain (Sempere et al, 2004), but their roles in synaptic plasticity, learning, and memory are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory

Sim¹,

Lim²,

Kim³

et al. 2016

J. Neurosci.

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MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory

Sim¹,

Lim²,

Kim³

et al. 2016

J. Neurosci.

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Neur1 and Neur2 are required for hippocampus‐dependent spatial memory and synaptic plasticity

et al. 2020

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Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus-dependent memory, whereas the role of Neur2 remains largely unknown. Here, we aimed to elucidate the respective roles of Neur1 and Neur2 in hippocampus-dependent memory using three lines of genetically modified mice: Neur1 knockout , Neur2 knockout , and Neur1 and Neur2 double knockout (D-KO). Our results showed that spatial memory was impaired when both Neur1 and Neur2 were deleted, but not in the individual knockout of either Neur1 or Neur2. In addition, basal synaptic properties estimated by input-output relationships and paired-pulse facilitation did not change, but a form of long-term potentiation that requires protein synthesis was specifically impaired in the D-KO mice. These results collectively suggest that Neur1 and Neur2 are crucially involved in hippocampusdependent spatial memory and synaptic plasticity.

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Enriched environment ameliorates chronic temporal lobe epilepsy‐induced behavioral hyperexcitability and restores synaptic plasticity in CA3–CA1 synapses in male Wistar rats

Salaka

Nair

Annamalai

et al. 2021

J of Neuroscience Research

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Temporal lobe epilepsy (TLE) is the most common form of focal epilepsies.Pharmacoresistance and comorbidities pose significant challenges to its treatment necessitating the development of non-pharmacological approaches. In an earlier study, exposure to enriched environment (EE) reduced seizure frequency and duration and ameliorated chronic epilepsy-induced depression in rats. However, the cellular basis of beneficial effects of EE remains unknown. Accordingly, in the current study, we evaluated the effects of EE in chronic epilepsy-induced changes in behavioral hyperexcitability, synaptic transmission, synaptophysin (SYN), and calbindin (CB) expression, hippocampal subfield volumes and cell density in male Wistar rats.Epilepsy was induced by lithium-pilocarpine-induced status epilepticus. Chronic epilepsy resulted in behavioral hyperexcitability, decreased basal synaptic transmission, increased paired-pulse facilitation ratio, decreased hippocampal subfields volumes. Moreover, epileptic rats showed decreased synaptophysin and CB expression in the hippocampus. Six weeks post-SE, epileptic rats were exposed to EE for 2 weeks, 6 hr/ day. EE significantly reduced the behavioral hyperexcitability and restored basal synaptic transmission correlating with increased expression of SYN and CB. Our results reaffirm the beneficial effects of EE on behavior in chronic epilepsy and establishes some of the putative cellular mechanisms. Since drug resistance and comorbidities are a major concern in TLE, we propose EE as a potent non-pharmacological treatment modality to mitigate these changes in chronic epilepsy.

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Calcium-Permeable AMPA Receptors Mediate the Induction of the Protein Kinase A-Dependent Component of Long-Term Potentiation in the Hippocampus

Cited by 84 publications

References 36 publications

The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory

The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory

Neur1 and Neur2 are required for hippocampus‐dependent spatial memory and synaptic plasticity

Enriched environment ameliorates chronic temporal lobe epilepsy‐induced behavioral hyperexcitability and restores synaptic plasticity in CA3–CA1 synapses in male Wistar rats

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