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Editor | Long-term synaptic potentiation (LTP) is considered to be one of the cellular and molecular basis of learning and memory [1,2].
The most classic LTP research model is the synaptic connection (Shaffer collateral-CA1) in which the hippocampal Shaffer collateral branches project to CA1 pyramidal neurons.
Tonic stimulation of Schaeffer's collateral fibers can induce CA1 neurons to produce long-term synaptic signal enhancement, namely LTP.
The main molecular event is the increase in the expression and function of AMPA-type glutamate receptors in the postsynaptic membrane, thereby mediating "enhanced" synaptic transmission.
In the past, a large number of studies have shown that the subunit GluA1 (also known as GluR1) of the AMPA-type glutamate receptor is essential for the expression of LTP [3].
Recently, Shi Yun from Nanjing University and Chen Zhang from Capital Medical University published a research paper entitled The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65 in PNAS, revealing the long-term potentiation of hippocampal CA1 pyramidal neurons (LTP) important molecular mechanism.
In this study, the authors developed a single neuron gene knockout and replacement method based on CRISPR/Cas9.
It was found that when the endogenous AMPA receptor subunits GluA1, GluA2 and GluA3 were knocked out in CA1 neurons, the expression of GluA1 could rescue LTP, while the expression of GluA1 (GluA1△ATD) truncated by ATD (amino-terminal domain) could not.
LTP, indicating that the ATD of GluA1 plays a key role in LTP.Through immunoprecipitation and protein profiling, the authors found that GluA1 interacts with the cell adhesion molecule neuroplastin-65 (Np65) through ATD.
Np65 is highly expressed in hippocampal CA1 neurons and co-localizes with GluA1 in dendrites and dendritic spines.
Knockout of Neuroplastin using CRISPR/Cas9 resulted in significant impairment of AMPA receptor-mediated synaptic transmission, as well as impaired maintenance of LTP (Figure 1).
In neurons knocked out of Neuroplastin, overexpression of Np65 can rescue AMPA receptor-mediated synaptic transmission and LTP, while overexpression of Neuroplastin, another splicing form of Np55, cannot save LTP.
In addition, the authors also found that GluA2(Q)-mediated LTP does not depend on its ATD and Np65.
In summary, the study revealed that GluA1 interacts with Np65 and mediates synaptic transmission and the maintenance of LTP.
The innovative findings of this study are mainly as follows: First, the author found that the induction and maintenance of LTP are relatively independent processes, and previous studies often cannot distinguish between the two.
Second, it was known in the past that the maintenance of late LTP (a few hours or more) requires the participation of transcription and translation.
The maintenance mechanism of early LTP (within 1 hour) is not clear.
This article clearly reveals that the maintenance of early LTP requires the interaction of GluA1 and Np65.
Third, previous studies of LTP mainly focused on intracellular signaling molecules, but the author of this article found that synaptic cleft adhesion molecules play an important role in LTP.
Figure 1: Np65 deletion leads to the down-regulation of AMPA receptors in the postsynaptic membrane and the inability of LTP to maintain the Nanjing University doctoral student Jiang Chaohua, the first author of this article, and Wei Mengping, associate professor of Capital Medical University, as the co-first author, Shi Yun of Nanjing University and Capital Medical University University professor Zhang Chen is the corresponding author of the article.
Link to the original text: https:// Plate maker: Notes for reprinting on the eleventh [Non-original article] The copyright of this article belongs to the author of the article.
Reprinting without permission is prohibited, and the author owns all legal rights.
Rights, offenders must be investigated.
References 1.
Bliss, TV, and Lomo, T.
(1973).
Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path.
J Physiol 232, 331-356.
2.
Huganir, RL , and Nicoll, RA (2013).
AMPARs and synaptic plasticity: the last 25 years.
Neuron 80, 704-717.
3.
Diering, GH, and Huganir, RL (2018).
The AMPA Receptor Code of Synaptic Plasticity.
Neuron 100, 314 -329.
The most classic LTP research model is the synaptic connection (Shaffer collateral-CA1) in which the hippocampal Shaffer collateral branches project to CA1 pyramidal neurons.
Tonic stimulation of Schaeffer's collateral fibers can induce CA1 neurons to produce long-term synaptic signal enhancement, namely LTP.
The main molecular event is the increase in the expression and function of AMPA-type glutamate receptors in the postsynaptic membrane, thereby mediating "enhanced" synaptic transmission.
In the past, a large number of studies have shown that the subunit GluA1 (also known as GluR1) of the AMPA-type glutamate receptor is essential for the expression of LTP [3].
Recently, Shi Yun from Nanjing University and Chen Zhang from Capital Medical University published a research paper entitled The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65 in PNAS, revealing the long-term potentiation of hippocampal CA1 pyramidal neurons (LTP) important molecular mechanism.
In this study, the authors developed a single neuron gene knockout and replacement method based on CRISPR/Cas9.
It was found that when the endogenous AMPA receptor subunits GluA1, GluA2 and GluA3 were knocked out in CA1 neurons, the expression of GluA1 could rescue LTP, while the expression of GluA1 (GluA1△ATD) truncated by ATD (amino-terminal domain) could not.
LTP, indicating that the ATD of GluA1 plays a key role in LTP.Through immunoprecipitation and protein profiling, the authors found that GluA1 interacts with the cell adhesion molecule neuroplastin-65 (Np65) through ATD.
Np65 is highly expressed in hippocampal CA1 neurons and co-localizes with GluA1 in dendrites and dendritic spines.
Knockout of Neuroplastin using CRISPR/Cas9 resulted in significant impairment of AMPA receptor-mediated synaptic transmission, as well as impaired maintenance of LTP (Figure 1).
In neurons knocked out of Neuroplastin, overexpression of Np65 can rescue AMPA receptor-mediated synaptic transmission and LTP, while overexpression of Neuroplastin, another splicing form of Np55, cannot save LTP.
In addition, the authors also found that GluA2(Q)-mediated LTP does not depend on its ATD and Np65.
In summary, the study revealed that GluA1 interacts with Np65 and mediates synaptic transmission and the maintenance of LTP.
The innovative findings of this study are mainly as follows: First, the author found that the induction and maintenance of LTP are relatively independent processes, and previous studies often cannot distinguish between the two.
Second, it was known in the past that the maintenance of late LTP (a few hours or more) requires the participation of transcription and translation.
The maintenance mechanism of early LTP (within 1 hour) is not clear.
This article clearly reveals that the maintenance of early LTP requires the interaction of GluA1 and Np65.
Third, previous studies of LTP mainly focused on intracellular signaling molecules, but the author of this article found that synaptic cleft adhesion molecules play an important role in LTP.
Figure 1: Np65 deletion leads to the down-regulation of AMPA receptors in the postsynaptic membrane and the inability of LTP to maintain the Nanjing University doctoral student Jiang Chaohua, the first author of this article, and Wei Mengping, associate professor of Capital Medical University, as the co-first author, Shi Yun of Nanjing University and Capital Medical University University professor Zhang Chen is the corresponding author of the article.
Link to the original text: https:// Plate maker: Notes for reprinting on the eleventh [Non-original article] The copyright of this article belongs to the author of the article.
Reprinting without permission is prohibited, and the author owns all legal rights.
Rights, offenders must be investigated.
References 1.
Bliss, TV, and Lomo, T.
(1973).
Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path.
J Physiol 232, 331-356.
2.
Huganir, RL , and Nicoll, RA (2013).
AMPARs and synaptic plasticity: the last 25 years.
Neuron 80, 704-717.
3.
Diering, GH, and Huganir, RL (2018).
The AMPA Receptor Code of Synaptic Plasticity.
Neuron 100, 314 -329.
