Distribution and Function of HCN Channels in the Apical Dendritic Tuft of Neocortical Pyramidal Neurons
Distribution and Function of HCN Channels in the Apical Dendritic Tuft of Neocortical Pyramidal Neurons
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DOI：
10.1523/jneurosci.2813-14.2015
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发表时间：
2015-01-21
影响因子：
5.3
通讯作者：
Williams, Stephen R.
中科院分区：
文献类型：
--
作者：
Harnett, Mark T.;Magee, Jeffrey C.;Williams, Stephen R.
顶丛是新皮层锥体神经元树突树中最远的区域。尽管其远端位置，第5层锥体神经元的顶端树突簇接收大量兴奋性突触驱动，并在行为过程中积极处理皮质皮质输入。然而，电压激活的离子通道调节簇状树突突触整合的特性还没有得到彻底的研究。在这里，我们使用电生理和光学方法来研究大鼠第5 B层锥体神经元中超极化激活的环核苷酸门控非选择性阳离子（HCN）通道的亚细胞分布和功能。由外向外的补丁记录表明，合奏HCN通道活动的幅度和属性是均匀的补丁从远端顶端树突状干和簇网站。同时顶端树突簇和躯干全细胞电流钳记录显示，HCN通道的药理学阻断降低了电压区室化，增强了顶端树突簇和躯干再生活性的产生和传播。此外，多位点双光子谷氨酸释放表明，HCN通道控制的幅度和持续时间的突触诱发的再生活动的远端顶端树突簇。相反，在近端顶端树突干和体细胞记录网站，HCN通道的封锁降低兴奋性。动态钳实验表明，这些隔室特定的行动的HCN通道受到严重影响的高密度的HCN通道在远端顶端树突状乔木的本地和分布式的影响。因此，HCN通道的性质和亚细胞分布模式被调谐以调节5B层锥体神经元中整合隔室之间的相互作用。
The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons.