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Hippocampal ischemia causes deficits in local field potential and synaptic plasticity.

Wang S, Zhang J, Sheng T, Lu W, Miao D - J Biomed Res (2015)

Bottom Line: We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia.Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dampened at these two time points.These results suggest that i-LTP elevates the induction threshold of subsequent synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Bone and Stem Cells, Department of Human Anatomy.

ABSTRACT
The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation (i-LTP), points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-1-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory postsynaptic potentials (fEPSPs) on CA1 hippocampal neurons in peri-infarct regions of the endothelin-1-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dampened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synaptic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.

No MeSH data available.


Related in: MedlinePlus

Increased expression level of NR2B, CaMKII and p-CaMKII after ischemia.A: Absence of change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05, n = 4; CaMKII, 0.97±0.09, P>0.05, n = 4; p-CaMKII, 1.05±0.04, P>0.05, n = 4). B: At 12 hours after ischemia, a slight but not significant increase in the expression of NR2B and CaMKII was detected (NR2B, 1.13±0.26, P>0.05, n = 4; CaMKII, 1.17±0.14, P>0.05, n = 4). No increases of p-CaMKII was detected (0.94±0.07, P>0.05, n = 4). C: At 24 hours after ischemia, a significant increase in the NR2B, CaMKII and p-CaMKII was detected (NR2B, 1.65±0.20, P<0.05, n = 4; CaMKII, 1.16±0.13, P<0.05, n = 3; p-CaMKII, 1.62±0.31, P<0.05, n = 4). Data represents mean±SEM. Statistic differences were compared using one-way ANOVA. CON: control, h: hours.
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f03: Increased expression level of NR2B, CaMKII and p-CaMKII after ischemia.A: Absence of change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05, n = 4; CaMKII, 0.97±0.09, P>0.05, n = 4; p-CaMKII, 1.05±0.04, P>0.05, n = 4). B: At 12 hours after ischemia, a slight but not significant increase in the expression of NR2B and CaMKII was detected (NR2B, 1.13±0.26, P>0.05, n = 4; CaMKII, 1.17±0.14, P>0.05, n = 4). No increases of p-CaMKII was detected (0.94±0.07, P>0.05, n = 4). C: At 24 hours after ischemia, a significant increase in the NR2B, CaMKII and p-CaMKII was detected (NR2B, 1.65±0.20, P<0.05, n = 4; CaMKII, 1.16±0.13, P<0.05, n = 3; p-CaMKII, 1.62±0.31, P<0.05, n = 4). Data represents mean±SEM. Statistic differences were compared using one-way ANOVA. CON: control, h: hours.

Mentions: I-LTP is usually accompanied by biochemical changes in LTP-related signaling molecules. Following activation of NMDA receptor[18] and Ca2+ influx through the receptor channel, increased intracellular Ca2+/CaM activates CaMKII[19-21], which in turn activates downstreaming signaling molecules like Ras, PI3K[22-23] and PKCλ[24-25][26-29]. As a result, AMPA receptor is phosphorylated and incorporated into postsynaptic membrane[30] which underlies LTP of AMPA receptor-mediated synaptic currents. Therefore, the possible alterations in these LTP-related molecules may be reminiscent of pathological i-LTP. We thus employed Western blotting assays to examine the expression of NR2B, CaMKII and p-CaMKII at 6, 12 and 24 hours after ischemia. As shown in Fig. 3, there was no change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05; CaMKII, 0.97±0.09, P>0.05; p-CaMKII, 1.05±0.04, P>0.05, Fig. 3A). Twelve hours after ischemia, the expression of NR2B and CaMKII showed a slight but statistically insignificant increase when compared with control (NR2B, 1.13±0.26, P>0.05; CaMKII, 1.17±0.14, P>0.05, Fig. 3B), while at this time there was no increase of p-CaMKII (0.94±0.07, P>0.05, Fig. 2). However, at 24 hours after ischemia, the expression of NR2B, CaMKII and p-CaMKII increased significantly (NR2B, 1.65±0.20, P<0.05; CaMKII, 1.16±0.13, P<0.05; p-CaMKII, 1.62±0.31, P<0.05, Fig. 3C). These results indicate that ischemic attack can increase the expression of these i-LTP-associated molecules and indirectly demonstrate the occurrence of i-LTP.


Hippocampal ischemia causes deficits in local field potential and synaptic plasticity.

Wang S, Zhang J, Sheng T, Lu W, Miao D - J Biomed Res (2015)

Increased expression level of NR2B, CaMKII and p-CaMKII after ischemia.A: Absence of change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05, n = 4; CaMKII, 0.97±0.09, P>0.05, n = 4; p-CaMKII, 1.05±0.04, P>0.05, n = 4). B: At 12 hours after ischemia, a slight but not significant increase in the expression of NR2B and CaMKII was detected (NR2B, 1.13±0.26, P>0.05, n = 4; CaMKII, 1.17±0.14, P>0.05, n = 4). No increases of p-CaMKII was detected (0.94±0.07, P>0.05, n = 4). C: At 24 hours after ischemia, a significant increase in the NR2B, CaMKII and p-CaMKII was detected (NR2B, 1.65±0.20, P<0.05, n = 4; CaMKII, 1.16±0.13, P<0.05, n = 3; p-CaMKII, 1.62±0.31, P<0.05, n = 4). Data represents mean±SEM. Statistic differences were compared using one-way ANOVA. CON: control, h: hours.
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Related In: Results  -  Collection

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f03: Increased expression level of NR2B, CaMKII and p-CaMKII after ischemia.A: Absence of change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05, n = 4; CaMKII, 0.97±0.09, P>0.05, n = 4; p-CaMKII, 1.05±0.04, P>0.05, n = 4). B: At 12 hours after ischemia, a slight but not significant increase in the expression of NR2B and CaMKII was detected (NR2B, 1.13±0.26, P>0.05, n = 4; CaMKII, 1.17±0.14, P>0.05, n = 4). No increases of p-CaMKII was detected (0.94±0.07, P>0.05, n = 4). C: At 24 hours after ischemia, a significant increase in the NR2B, CaMKII and p-CaMKII was detected (NR2B, 1.65±0.20, P<0.05, n = 4; CaMKII, 1.16±0.13, P<0.05, n = 3; p-CaMKII, 1.62±0.31, P<0.05, n = 4). Data represents mean±SEM. Statistic differences were compared using one-way ANOVA. CON: control, h: hours.
Mentions: I-LTP is usually accompanied by biochemical changes in LTP-related signaling molecules. Following activation of NMDA receptor[18] and Ca2+ influx through the receptor channel, increased intracellular Ca2+/CaM activates CaMKII[19-21], which in turn activates downstreaming signaling molecules like Ras, PI3K[22-23] and PKCλ[24-25][26-29]. As a result, AMPA receptor is phosphorylated and incorporated into postsynaptic membrane[30] which underlies LTP of AMPA receptor-mediated synaptic currents. Therefore, the possible alterations in these LTP-related molecules may be reminiscent of pathological i-LTP. We thus employed Western blotting assays to examine the expression of NR2B, CaMKII and p-CaMKII at 6, 12 and 24 hours after ischemia. As shown in Fig. 3, there was no change in these proteins at 6 hours after ischemia (NR2B, 0.97±0.18, P>0.05; CaMKII, 0.97±0.09, P>0.05; p-CaMKII, 1.05±0.04, P>0.05, Fig. 3A). Twelve hours after ischemia, the expression of NR2B and CaMKII showed a slight but statistically insignificant increase when compared with control (NR2B, 1.13±0.26, P>0.05; CaMKII, 1.17±0.14, P>0.05, Fig. 3B), while at this time there was no increase of p-CaMKII (0.94±0.07, P>0.05, Fig. 2). However, at 24 hours after ischemia, the expression of NR2B, CaMKII and p-CaMKII increased significantly (NR2B, 1.65±0.20, P<0.05; CaMKII, 1.16±0.13, P<0.05; p-CaMKII, 1.62±0.31, P<0.05, Fig. 3C). These results indicate that ischemic attack can increase the expression of these i-LTP-associated molecules and indirectly demonstrate the occurrence of i-LTP.

Bottom Line: We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia.Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dampened at these two time points.These results suggest that i-LTP elevates the induction threshold of subsequent synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Bone and Stem Cells, Department of Human Anatomy.

ABSTRACT
The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation (i-LTP), points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-1-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory postsynaptic potentials (fEPSPs) on CA1 hippocampal neurons in peri-infarct regions of the endothelin-1-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dampened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synaptic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.

No MeSH data available.


Related in: MedlinePlus