Division of Engineering Science, University of Toronto Toronto, ON, Canada.
Front Comput Neurosci. 2012 May 24;6:30. doi: 10.3389/fncom.2012.00030. eCollection 2012.
Theta-frequency (4-12 Hz) rhythms in the hippocampus play important roles in learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare and radiatum junction (LM/RAD) are thought to contribute to hippocampal theta population activities by rhythmically pacing pyramidal cells with inhibitory postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at theta frequencies in vivo. To determine whether this could occur, we use biophysically based LM/RAD model cells and apply different cholinergic and synaptic inputs to simulate in vivo-like network environments. We assess spike reliabilities and spiking frequencies, identifying biophysical properties and network conditions that best promote reliable theta spiking. We find that synaptic background activities that feature large inhibitory, but not excitatory, fluctuations are essential. This suggests that strong inhibitory input to these cells is vital for them to be able to contribute to population theta activities. Furthermore, we find that Type I-like oscillator models produced by augmented persistent sodium currents (I(NaP)) or diminished A-type potassium currents (I(A)) enhance reliable spiking at lower theta frequencies. These Type I-like models are also the most responsive to large inhibitory fluctuations and can fire more reliably under such conditions. In previous work, we showed that I(NaP) and I(A) are largely responsible for establishing LM/RAD cells' subthreshold activities. Taken together with this study, we see that while both these currents are important for subthreshold theta fluctuations and reliable theta spiking, they contribute in different ways - I(NaP) to reliable theta spiking and subthreshold activity generation, and I(A) to subthreshold activities at theta frequencies. This suggests that linking subthreshold and suprathreshold activities should be done with consideration of both in vivo contexts and biophysical specifics.
海马体中的θ节律（4-12 Hz）在学习和记忆中发挥着重要作用。位于腔隙分子层和辐射层交界处（LM/RAD）的 CA1 中间神经元被认为通过抑制性突触后电位节律性地起搏锥体细胞，从而对海马体θ群体活动做出贡献。这意味着 LM/RAD 细胞需要在体内可靠地以θ频率发射。为了确定是否可以发生这种情况，我们使用基于生物物理的 LM/RAD 模型细胞，并应用不同的胆碱能和突触输入来模拟类似于体内的网络环境。我们评估了尖峰可靠性和尖峰频率，确定了最能促进可靠θ尖峰的生物物理特性和网络条件。我们发现，具有大的抑制性但不是兴奋性波动的突触背景活动是必不可少的。这表明，这些细胞的强抑制性输入对于它们能够为群体θ活动做出贡献是至关重要的。此外，我们发现，通过增强的持续钠电流（I(NaP)）或减弱的 A 型钾电流（I(A)）产生的 I 型样振荡器模型增强了在较低θ频率下可靠的尖峰放电。这些 I 型样模型对大的抑制性波动也最敏感，并且可以在这种情况下更可靠地发射。在以前的工作中，我们表明 I(NaP)和 I(A)在很大程度上负责建立 LM/RAD 细胞的亚阈值活动。与本研究一起，我们看到这两种电流对于亚阈值θ波动和可靠的θ尖峰放电都很重要，但它们的贡献方式不同——I(NaP)促进可靠的θ尖峰放电和亚阈值活动产生，而 I(A)则促进亚阈值θ频率活动。这表明，在考虑体内环境和生物物理细节的情况下，应该将亚阈值和超阈值活动联系起来。
