Saraga Fernanda, Ng Leo, Skinner Frances K
Div. of Cell and Molecular Biology, Toronto Western Research Institute, Toronto Western Hospital, 399 Bathurst St., MP13-317, Toronto, Ontario M5T 2S8, Canada.
J Neurophysiol. 2006 Mar;95(3):1669-82. doi: 10.1152/jn.00662.2005. Epub 2005 Dec 7.
Gap junctions allow direct electrical communication between CNS neurons. From theoretical and modeling studies, it is well known that although gap junctions can act to synchronize network output, they can also give rise to many other dynamic patterns including antiphase and other phase-locked states. The particular network pattern that arises depends on cellular, intrinsic properties that affect firing frequencies as well as the strength and location of the gap junctions. Interneurons or GABAergic neurons in hippocampus are diverse in their cellular characteristics and have been shown to have active dendrites. Furthermore, parvalbumin-positive GABAergic neurons, also known as basket cells, can contact one another via gap junctions on their distal dendrites. Using two-cell network models, we explore how distal electrical connections affect network output. We build multi-compartment models of hippocampal basket cells using NEURON and endow them with varying amounts of active dendrites. Two-cell networks of these model cells as well as reduced versions are explored. The relationship between intrinsic frequency and the level of active dendrites allows us to define three regions based on what sort of network dynamics occur with distal gap junction coupling. Weak coupling theory is used to predict the delineation of these regions as well as examination of phase response curves and distal dendritic polarization levels. We find that a nonmonotonic dependence of network dynamic characteristics (phase lags) on gap junction conductance occurs. This suggests that distal electrical coupling and active dendrite levels can control how sensitive network dynamics are to gap junction modulation. With the extended geometry, gap junctions located at more distal locations must have larger conductances for pure synchrony to occur. Furthermore, based on simulations with heterogeneous networks, it may be that one requires active dendrites if phase-locking is to occur in networks formed with distal gap junctions.
缝隙连接允许中枢神经系统神经元之间进行直接电通信。从理论和建模研究可知，虽然缝隙连接可以使网络输出同步，但它们也能引发许多其他动态模式，包括反相和其他锁相状态。所出现的特定网络模式取决于影响放电频率的细胞内在特性以及缝隙连接的强度和位置。海马体中的中间神经元或γ-氨基丁酸能神经元在细胞特征上各不相同，并且已被证明具有活跃的树突。此外，小白蛋白阳性的γ-氨基丁酸能神经元，也被称为篮状细胞，可以通过其远端树突上的缝隙连接相互接触。我们使用双细胞网络模型来探究远端电连接如何影响网络输出。我们使用NEURON构建海马体篮状细胞的多室模型，并赋予它们不同数量的活跃树突。对这些模型细胞以及简化版本的双细胞网络进行了探究。内在频率与活跃树突水平之间的关系使我们能够根据远端缝隙连接耦合时出现的网络动力学类型定义三个区域。弱耦合理论用于预测这些区域的划分以及相位响应曲线和远端树突极化水平的检验。我们发现网络动态特征（相位滞后）对缝隙连接电导存在非单调依赖性。这表明远端电耦合和活跃树突水平可以控制网络动力学对缝隙连接调制的敏感程度。在扩展的几何结构中，位于更远端位置的缝隙连接必须具有更大的电导才能实现纯同步。此外，基于异质网络的模拟结果，在由远端缝隙连接形成的网络中，如果要发生锁相，可能需要活跃树突。
