Cutsuridis Vassilis, Poirazi Panayiota
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Vassilika Vouton 71110, Heraklion, Crete, Greece.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Vassilika Vouton 71110, Heraklion, Crete, Greece.
Neurobiol Learn Mem. 2015 Apr;120:69-83. doi: 10.1016/j.nlm.2015.02.002. Epub 2015 Feb 24.
A recent experimental study (Mizuseki, Sirota, Pastalkova, & Buzsaki, 2009) has shown that the temporal delays between population activities in successive entorhinal and hippocampal anatomical stages are longer (about 70-80ms) than expected from axon conduction velocities and passive synaptic integration of feed-forward excitatory inputs. We investigate via computer simulations the mechanisms that give rise to such long temporal delays in the hippocampus structures. A model of the dentate gyrus (DG), CA3 and CA1 microcircuits is presented that uses biophysical representations of the major cell types including granule cells, CA3 and CA1 pyramidal cells (PCs) and six types of interneurons: basket cells (BCs), axo-axonic cells (AACs), bistratified cells (BSCs), oriens lacunosum-moleculare cells (OLMs), mossy cells (MCs) and hilar perforant path associated cells (HC). Inputs to the network came from the entorhinal cortex (EC) (layers 2 and 3) and the medial septum (MS). The model simulates accurately the timing of firing of different hippocampal cells with respect to the theta rhythm. The model shows that the experimentally reported long temporal delays in the DG, CA3 and CA1 hippocampal regions are due to theta modulated somatic and axonic inhibition. The model further predicts that the phase at which the CA1 PCs fire with respect to the theta rhythm is determined primarily by their increased dendritic excitability caused by the decrease of the axial resistance and the A-type K(+) conductance along their dendritic trunk. The model predicted latencies by which the DG, CA3 and CA1 principal cells fire are inline with the experimental evidence. Finally, the model proposes functional roles for the different inhibitory interneurons in the retrieval of the memory pattern by the DG, CA3 and CA1 networks. The model makes a number of predictions, which can be tested experimentally, thus leading to a better understanding of the biophysical computations in the hippocampus.
最近的一项实验研究（水関、西田、帕斯塔科娃和布扎克，2009年）表明，在连续的内嗅皮层和海马解剖阶段，群体活动之间的时间延迟（约70 - 80毫秒）比根据轴突传导速度和前馈兴奋性输入的被动突触整合所预期的要长。我们通过计算机模拟研究了在海马结构中产生这种长时间延迟的机制。提出了一个齿状回（DG）、CA3和CA1微电路模型，该模型使用了主要细胞类型的生物物理表示，包括颗粒细胞、CA3和CA1锥体细胞（PCs）以及六种中间神经元：篮状细胞（BCs）、轴-轴突细胞（AACs）、双分层细胞（BSCs）、腔隙-分子层细胞（OLMs）、苔藓细胞（MCs）和门区穿通路径相关细胞（HC）。网络的输入来自内嗅皮层（EC）（第2和3层）和内侧隔区（MS）。该模型准确模拟了不同海马细胞相对于θ节律的放电时间。该模型表明，实验报道的DG、CA3和CA1海马区域的长时间延迟是由于θ调制的体细胞和轴突抑制。该模型进一步预测，CA1锥体细胞相对于θ节律放电的相位主要由其树突兴奋性增加所决定，这种增加是由沿其树突干的轴向电阻和A型钾离子电导的降低引起的。该模型预测的DG、CA3和CA1主要细胞放电的潜伏期与实验证据一致。最后，该模型提出了不同抑制性中间神经元在DG、CA3和CA1网络检索记忆模式中的功能作用。该模型做出了许多可以通过实验进行测试的预测，从而有助于更好地理解海马体中的生物物理计算。
