Babiec Walter E, Jami Shekib A, Guglietta Ryan, Chen Patrick B, O'Dell Thomas J
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
Molecular, Cellular, and Integrative Physiology Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, California 90095.
J Neurosci. 2017 Feb 15;37(7):1950-1964. doi: 10.1523/JNEUROSCI.3196-16.2017. Epub 2017 Jan 16.
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 θ frequency patterns of stimulation. In contrast to dorsal hippocampus, θ 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. Differences in short- and long-term plasticity at Schaffer collateral (SC) synapses in the dorsal and ventral hippocampus likely contribute importantly to the distinct roles of these regions in cognition and behavior. Although dorsal and ventral CA1 pyramidal cells exhibit markedly different gene expression profiles, how these differences influence plasticity at SC synapses is unclear. Here we report that increased mRNA levels for the SK3 subunit of SK-type K channels in ventral pyramidal cells is associated with an enhanced activation of SK channels that strongly suppresses NMDAR activation at ventral SC synapses. This leads to striking differences in multiple aspects of synaptic transmission at dorsal and ventral SC synapses and underlies the reduced ability of ventral SC synapses to undergo LTP.
行为学、生理学和解剖学证据表明，海马体的背侧和腹侧区域在认知中具有不同的作用。目前尚不清楚这些区域的独特功能如何依赖于背侧和腹侧CA1锥体神经元显著不同的基因表达谱所导致的突触和神经元功能差异。为了开始解决这个问题，我们研究了小鼠海马体中背侧和腹侧海马伞（Schaffer collateral，SC）突触传递和可塑性差异的潜在机制。我们发现，尽管基础突触传递相似，但背侧和腹侧海马体中的SC突触对θ频率刺激模式表现出明显不同的反应。与背侧海马体相反，θ频率刺激未能在腹侧SC突触处引发突触后复合峰发放，也不能诱导长时程增强（LTP）。此外，兴奋性突触后电位-动作电位（EPSP-spike）耦合（这一过程强烈影响突触处的信息传递）在腹侧锥体神经元中较弱。我们的结果表明，突触后功能的所有这些差异是由于SK型钾通道的激活增强，从而抑制了腹侧SC突触处依赖N-甲基-D-天冬氨酸受体（NMDAR）的EPSP放大。与此一致的是，腹侧CA1锥体神经元中SK通道的SK3亚基的mRNA水平显著更高。总之，我们的研究结果表明，SK通道对NMDAR激活的背腹差异对SC突触处的信息传递、处理和存储有深远影响，因此可能导致背侧和腹侧海马体在不同行为中发挥不同作用。背侧和腹侧海马体中SC突触的短期和长期可塑性差异可能对这些区域在认知和行为中的不同作用有重要贡献。尽管背侧和腹侧CA1锥体神经元表现出明显不同的基因表达谱，但这些差异如何影响SC突触的可塑性尚不清楚。在这里，我们报告腹侧锥体神经元中SK型钾通道的SK3亚基的mRNA水平增加，这与SK通道的激活增强有关，该激活强烈抑制腹侧SC突触处的NMDAR激活。这导致背侧和腹侧SC突触在突触传递的多个方面存在显著差异，并成为腹侧SC突触进行LTP能力降低的基础。
