Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.
Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.
复制标题
慢性神经元兴奋导致结构长期增强信号的双重化塑性。
DOI：
10.1016/j.celrep.2021.110153
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
and Murakoshi H
中科院分区：
文献类型：
--
作者：
Ueda HH;Nagasawa Y;Sato A;Onda M;and Murakoshi H
突触可塑性是突触电流和结构的长期变化。当神经元暴露于诱导异常神经元兴奋的信号时，它们增加了诱导长时程增强（LTP）的阈值，称为后可塑性。然而，结构性LTP（sLTP）的化生调节仍不清楚。我们研究了GABA A受体拮抗剂慢性神经元兴奋后，海马CA 1区神经元中谷氨酸释放/光活化（pa）CaMK II依赖性sLTP诱导。我们发现，神经元的兴奋减少谷氨酸uncaging-evoked的Ca 2+内流介导的含GluN 2B的NMDA受体和抑制sLTP的诱导。此外，使用paCaMKII的单棘光遗传学刺激指示CaMKII信号传导的抑制。虽然Ca 2+内流的抑制是蛋白质合成无关的，但paCaMK II诱导的sLTP抑制依赖于它。我们的研究结果表明，慢性神经元兴奋以两种独立的方式抑制sLTP（即，Ca 2+内流和CaMK II信号传导的双重抑制）。这种双重抑制机制可能有助于在易兴奋环境中提供强大的神经元保护。
Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of long-term potentiation (LTP), known as metaplasticity. However, the metaplastic regulation of structural LTP (sLTP) remains unclear. We investigate glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABAAreceptor antagonists. We find that the neuronal excitation decreases the glutamate uncaging-evoked Ca2+influx mediated by GluN2B-containing NMDA receptors and suppresses sLTP induction. In addition, single-spine optogenetic stimulation using paCaMKII indicates the suppression of CaMKII signaling. While the inhibition of Ca2+influx is protein synthesis independent, the paCaMKII-induced sLTP suppression depends on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., dual inhibition of Ca2+influx and CaMKII signaling). This dual inhibition mechanism may contribute to robust neuronal protection in excitable environments.