Center for Brain and Behavior, Department of Neurobiology and Ethology, Haifa University, Haifa, Israel.
PLoS One. 2006 Dec 27;1(1):e138. doi: 10.1371/journal.pone.0000138.
The formation of enduring internal representation of sensory information demands, in many cases, convergence in time and space of two different stimuli. The first conveys the sensory input, mediated via fast neurotransmission. The second conveys the meaning of the input, hypothesized to be mediated via slow neurotransmission. We tested the biochemical conditions and feasibility for fast (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated Protein Kinase signaling pathways, crucial in several forms of synaptic plasticity, and recorded its effects upon synaptic transmission. We detected differing kinetics of ERK2 activation and synaptic strength changes in the CA1 for low and high doses of neurotransmitters in hippocampal slices. Moreover, when weak fast and slow inputs are given together, they converge on ERK2, but not on p38 or JNK, and induce strong short-term synaptic depression. Surprisingly, pharmacological analysis revealed that a probable site of such convergence is the NMDA receptor itself, suggesting it serves as a detector and integrator of fast and slow neurotransmission in the mature mammalian brain, as revealed by ERK2 activation and synaptic function.
持久的感觉信息内部表示的形成，在许多情况下，需要两种不同刺激在时间和空间上的汇聚。第一种刺激传递感觉输入，通过快速神经传递介导。第二种刺激传递输入的意义，假设通过慢速神经传递介导。我们测试了快速（NMDA）和慢速（多巴胺）神经传递汇聚到丝裂原活化蛋白激酶信号通路的生化条件和可行性，该通路在几种形式的突触可塑性中至关重要，并记录了其对突触传递的影响。我们在海马切片中检测到 CA1 中 ERK2 激活和突触强度变化的不同动力学，对于低剂量和高剂量的神经递质。此外，当给予弱的快速和慢速输入时，它们汇聚到 ERK2，但不会汇聚到 p38 或 JNK，并且诱导强烈的短期突触抑制。令人惊讶的是，药理学分析表明，这种汇聚的一个可能位点是 NMDA 受体本身，这表明它在成熟的哺乳动物大脑中充当快速和慢速神经传递的探测器和整合器，如 ERK2 激活和突触功能所揭示的那样。
