Gating of NMDA receptor-mediated hippocampal spike timing-dependent potentiation by mGluR5.
Gating of NMDA receptor-mediated hippocampal spike timing-dependent potentiation by mGluR5.
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DOI：
10.1016/j.neuropharm.2012.05.021
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发表时间：
2012-09
影响因子：
4.7
通讯作者：
Paulsen O
中科院分区：
文献类型：
--
作者：
Kwag J;Paulsen O
海马长时程增强（LTP）被认为对学习和记忆很重要。在实验中，精确定时的突触前和突触后尖峰配对在10毫秒的时间窗口内可以诱导时间依赖性LTP（tLTP），但诱导tLTP的要求随着发育而变化：在年轻的啮齿动物中，单个突触后尖峰足以诱导tLTP，而突触后爆发放电似乎是成年人所必需的。然而，海马神经元在体内显示θ调制的单峰活动，也在老年海马。在这里，我们调查的条件下，单锋配对诱导tLTP在旧的CA 3-CA 1突触。我们发现，当突触后神经元膜去极化且配对频率超过1.4Hz时，单个突触前和突触后棘波配对可在老年海马中诱导tLTP。尖峰频率的要求是突触后的，因为只要突触后尖峰频率超过104 Hz，tLTP仍然可以用1 Hz的突触前刺激诱导，这表明在较老的CA 3-CA 1突触中成功诱导tLTP需要突触后θ频率活动。NMDA受体拮抗剂和选择性mGluR 5阻断剂MPEP和MTEP阻断了tLTP的诱导，而DHPG激活mGluR 1和mGluR 5则缓解了tLTP诱导所需的突触后尖峰频率。这些结果表明，激活的mGluR 5在单穗配对在旧的CA 3-CA 1突触门NMDA受体依赖性tLTP。在海马CA 3-CA 1区，单棘波配对可诱导tLTP。LTP诱导需要突触后去极化和突触后峰电位频率>4 Hz。LTP诱导需要NMDA受体，并由mGluR 5门控。
Hippocampal long-term potentiation (LTP) is believed to be important for learning and memory. Experimentally, the pairing of precisely timed pre- and postsynaptic spikes within a time window of ∼10 ms can induce timing-dependent LTP (tLTP), but the requirements for induction of tLTP change with development: in young rodents single postsynaptic spikes are sufficient to induce tLTP, whereas postsynaptic burst firing appears to be required in the adult. However, hippocampal neurons in vivo show theta-modulated single spike activities also in older hippocampus. Here we investigated the conditions for single spike pairing to induce tLTP at older CA3–CA1 synapses. We found that the pairing of single pre- and postsynaptic spikes could induce tLTP in older hippocampus when the postsynaptic neuronal membrane was depolarized and the pairing frequency exceeded ∼4 Hz. The spike frequency requirement is postsynaptic, as tLTP could still be induced with presynaptic stimulation at 1 Hz as long as the postsynaptic spike frequency exceeded ∼4 Hz, suggesting that postsynaptic theta-frequency activity is required for the successful induction of tLTP at older CA3–CA1 synapses. The induction of tLTP was blocked by an NMDA receptor antagonist and by the selective mGluR5 blockers, MPEP and MTEP, whereas activation of mGluR1 and mGluR5 by DHPG relieved the postsynaptic spike frequency requirement for tLTP induction. These results suggest that activation of mGluR5 during single-spike pairing at older CA3–CA1 synapses gates NMDA receptor-dependent tLTP. ► Single-spike pairing can induce tLTP at older hippocampal CA3–CA1 synapses. ► tLTP induction requires postsynaptic depolarization and postsynaptic spike rate >4 Hz. ► tLTP induction requires NMDA receptors and is gated by mGluR5.
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DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
影响因子：
3.4
作者：
Clement, J. P.;Randall, A. D.;Brown, J. T.
通讯作者：
Brown, J. T.
影响因子：
4.7
作者：
Bortolotto, ZA;Collett, VJ;Collingridge, GL
通讯作者：
Collingridge, GL
影响因子：
25
作者：
Carlson, G;Wang, Y;Alger, BE
通讯作者：
Alger, BE
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T