Differential Regulation of NMDA Receptor-Mediated Transmission by SK Channels Underlies Dorsal-Ventral Differences in Dynamics of Schaffer Collateral Synaptic Function
Differential Regulation of NMDA Receptor-Mediated Transmission by SK Channels Underlies Dorsal-Ventral Differences in Dynamics of Schaffer Collateral Synaptic Function
复制标题
SK 通道对 NMDA 受体介导的传递的不同调控是沙弗侧突触功能动态背腹差异的基础
DOI：
10.1523/jneurosci.3196-16.2017
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发表时间：
2017-02-15
影响因子：
5.3
通讯作者：
O'Dell, Thomas J.
中科院分区：
文献类型：
--
作者：
Babiec, Walter E.;Jami, Shekib A.;O'Dell, Thomas J.
行为学、生理学和解剖学证据表明，海马体的背侧区和腹侧区在认知中具有不同的作用。这些区域的独特功能如何可能取决于突触和神经元功能的差异，这些差异来自背侧和腹侧CA 1锥体细胞所表现出的显著不同的基因表达谱，目前尚不清楚。为了开始解决这个问题，我们研究了小鼠海马背侧和腹侧Schaffer侧支（SC）突触的突触传递和可塑性差异的机制。我们发现，虽然基础的突触传递是相似的，SC突触在背侧和腹侧海马表现出显着不同的反应θ频率模式的刺激。与背侧海马相反，θ频率刺激不能引起突触后复合体尖峰爆发，也不能诱导腹侧SC突触的LTP。此外，EPSP-锋电位耦合，一个强烈影响突触的信息传递的过程，在腹侧锥体细胞中较弱。我们的研究结果表明，所有这些突触后功能的差异是由于增强激活的SK型K+通道，抑制NMDAR依赖的EPSP放大腹侧SC突触。与此一致，SK通道的SK 3亚基的mRNA水平在腹侧CA 1锥体细胞中显著更高。总之，我们的研究结果表明，背腹侧差异SK通道调节NMDAR激活有深远的影响，在SC突触的信息的传输，处理和存储，因此可能有助于背侧和腹侧海马在不同的行为中的不同作用。
Behavioral, physiological, and anatomical evidence indicates that the dorsal and ventral zones of the hippocampus have distinct roles in cognition. How the unique functions of these zones might depend on differences in synaptic and neuronal function arising from the strikingly different gene expression profiles exhibited by dorsal and ventral CA1 pyramidal cells is unclear. To begin to address this question, we investigated the mechanisms underlying differences in synaptic transmission and plasticity at dorsal and ventral Schaffer collateral (SC) synapses in the mouse hippocampus. We find that, although basal synaptic transmission is similar, SC synapses in the dorsal and ventral hippocampus exhibit markedly different responses to theta frequency patterns of stimulation. In contrast to dorsal hippocampus, theta frequency stimulation fails to elicit postsynaptic complex-spike bursting and does not induce LTP at ventral SC synapses. Moreover, EPSP-spike coupling, a process that strongly influences information transfer at synapses, is weaker in ventral pyramidal cells. Our results indicate that all these differences in postsynaptic function are due to an enhanced activation of SK-type K+ channels that suppresses NMDAR-dependent EPSP amplification at ventral SC synapses. Consistent with this, mRNA levels for the SK3 subunit of SK channels are significantly higher in ventral CA1 pyramidal cells. Together, our findings indicate that a dorsal-ventral difference in SK channel regulation of NMDAR activation has a profound effect on the transmission, processing, and storage of information at SC synapses and thus likely contributes to the distinct roles of the dorsal and ventral hippocampus in different behaviors.