在体大鼠海马CA1区侧枝/联合纤维通路和TA通路的不同EPSP空间整合特性

在麻醉Wistar大鼠上,结合脑室给药,应用双电极刺激技术刺激海马独立的两条侧枝／联合纤维通路、TA通路,并在CA1区放射层记录兴奋性突触后电位（EPSP）,对海马CA1区锥体细胞近、远端树突EPSP的空间整合进行了初步探讨。结果表明,海马CA1区锥体细胞近、远端树突的空间整合都是亚线性的;近端树突的空间整合不受期望值大小的影响,但远端树突的空间整合随期望值增加而减小（更趋于亚线性）。此外,荷包牡丹碱没有影响EPSP的空间整合;但瞬时A型钾通道（IAK^＋）的拮抗剂氨基吡啶-4却使得近端树突的空间整合趋于线性发展。本研究表明,海马CA1锥体细胞近、远端树突不同的被动、主动特征使它们具有了不同的空间整合特性。由于近端树突接受海马内部侧枝／联合纤维投射的信息,远端树突通过TA通路接受内嗅皮层投射的信息,由此提示,CA1区锥体细胞对来自海马内部和直接来自皮层的信息输入采用了不同的整合方式。     

家兔外膝体背核中继细胞的被动电缆特性

在离体脑片上测定了２４个家兔外膝体中继细胞的被动膜特性。它们的静息电位为－６２．７±４．１ｍＶ（ＳＤ）;膜输入阻抗为３０．４±１１．２ＭΩ。运用Ｒａｌｌ的线性电缆模型,计算出这些神经元树突的电紧张长度（Ｌ）为０．７９±０．１３;电压衰减因数（Ｈ）为回．３３±０．１１。说明家兔外膝体中继细胞是电学紧密的,树突远端的电位可扩散到胞体,幅度仅衰减２５％左右。     

刺激鲫鱼小脑腹外侧区诱发的Mauthner细胞兴奋性突触后电位

实验采用微电极胞内记录技术探查鲫鱼Mauthner细胞(M-细胞)对小脑刺激的电反应特征。电刺激鲫鱼小脑腹外侧部,可在双侧M-细胞胞体、腹侧树突和外侧树突近端记录到一种复合性兴奋性突触后电位(小脑诱发性EPSP)。小脑诱发性EPSP潜伏期较短(0.63±0.09 ms),持续时间较长(5.49±1.13 ms),幅度分级和刺激频率依从等特征。以较高强度刺激小脑常引起M-细胞顺向激活。多点胞内连续穿刺实验显示小脑诱发性EPSP起源于腹侧树突远端。实验结果提示,小脑-M-细胞通路可能包含一组长短不等的神经元链,它们根据链的短或长,由近及远依次投射在腹侧树突远端。     

酸中毒和ASIC1a在复发性癫痫引起的树突棘重塑中的作用

复发性癫痫诱导慢性树突棘重塑对癫痫发生、终止和长期认知变化很关键,但是调控树突棘重塑的机制并不十分清楚。研究表明,癫痫发作时细胞外[H+]i增加导致组织酸中毒,激活酸敏感离子通道(acid-sensing ion channels,ASICs),引起慢性树突棘重塑。现总结酸中毒和酸敏感离子通道亚型ASIC1a在复发性癫痫引起的树突棘重塑中的作用,重点分析了酸中毒过程的时空变化对痫样放电和树突棘重塑可能的影响,以及酸中毒与ASIC1a在兴奋性和抑制性神经元的功能表达之间的关系,认为ASIC1a可能通过不同机制介导酸中毒在癫痫发生和持续阶段对树突棘的影响。未来研究需要进一步探索癫痫引起的慢性神经元结构和功能改变,阐明酸中毒和ASIC1a在癫痫及其引起的树突棘缺失中的作用。     

超极化激活环核苷酸门控阳离子通道(HCN)研究进展

HCN是超极化激活环核苷酸门控阳离子通道,其激活后产生If/Ih电流,能被ZD7288和Cs+特异性阻断.该通道有4个亚型,具有稳定细胞膜电位、参与心脏和神经节律调节、参与树突整合,以及调节神经递质释放等生理功能.近期实验中发现豚鼠膀胱ICC上存在Ih电流,其功能特点值得进一步研究和探讨.     

线性整合放电模型的相干共振

研究了神经递质以随机点序列释放和电压门控离子通道噪声共同作用下,线性整合放电模型的相干共振现象。基于分形布朗运动和改进的欧拉方法,得到了神经元膜电压分布和神经元放电峰峰间隔的信噪比。结果表明,神经元放电的峰峰间隔是神经递质的达到强度、离子通道噪声强度的非单调函数。适当的神经递质到达强度和离子通道噪声强度使峰峰间隔的信噪比出现最大值,即出现相干共振现象。     

海马锥体神经元树突中电压依赖性钾通道研究进展

海马锥体神经元树突上分布着多种电压依赖性钾离子通道,但这些通道在胞体和树突不同部位的分布密度以及在突触电活动中的功能意义各不相同。倒传递动作电位（b-AP）和兴奋性突触后电位（EPSP）是树突中常见的功能电信号。本文简要介绍了近年来海马锥体神经元树突上这些钾离子通道及其电活动的生理和病理学研究成果。     

不同强度工频磁场对皮层神经元瞬时外向钾离子通道的影响

人们对电磁辐射越来越关注,但是工频磁场产生的生物效应并不确定.选用1、5、10 mT的工频磁场照射急性分离的小鼠皮层神经元(15 min),应用全细胞膜片钳技术离线记录瞬时外向钾通道电流,研究工频磁场对离子通道的影响.结果显示:工频磁场抑制通道的电流密度,并且1 mT、5 mT及10 mT工频磁场的抑制率分别为(63.0±2.2)%、(55.0±1.7)%和(38.0±1.8)%.工频磁场影响离子通道的激活和失活特性,半数激活电压和半数失活电压变小.不同强度工频磁场对离子通道产生的影响程度不同,其中1 mT工频磁场对通道电流的抑制率最大,5 mT工频磁场对通道的半数激活电压和半数失活电压影响最大,10 mT工频磁场增大了通道的失活斜率因子.研究结果表明,工频磁场影响了细胞膜上离子通道蛋白质构象的变化,进一步影响了离子通道的正常功能.     

味觉感受细胞离子通道和动作电位的建模与仿真

结合膜片钳测量的味觉感受细胞离子通道实验数据,提出了一个哺乳动物味觉感受细胞动作电位的数学模型.首先,建立了味觉感受细胞的电压门控Na＋通道和外向延迟整流K＋通道的模型,在此基础上建立了味觉感受细胞的单细胞计算模型.其次,仿真研究了味觉感受细胞在电刺激和酸味刺激下产生的动作电位,以及离子通道动力学特性对其的影响.该模型对于研究味觉感受细胞在味觉物质刺激下产生的动作电位及其离子通道的工作机制,以及味觉信息在外周神经的传递和信息编码具有指导意义。     

退化蛋白/上皮钠通道超家族成员的激活与调控机制

退化蛋白/上皮钠通道(DEG/ENaC)超家族是20世纪90年代发现的一类非电压依赖性的、阿米诺利敏感的钠离子选择性离子通道,其激活方式复杂多样,参与如囊肿性纤维化、焦虑及癫痫等多种生理病理过程,已成为多种疾病的潜在药物靶标。现就DEG/ENaC超家族成员的结构、特异激活方式以及交互激活与调控机制进行综述。     

Ion Channel Gradients in the Apical Tuft Region of CA1 Pyramidal Neurons

Dendritic ion channels play a critical role in shaping synaptic input and are fundamentally important for synaptic integration and plasticity. In the hippocampal region CA1, somato-dendritic gradients of AMPA receptors and the hyperpolarization-activated cation conductance (I_h) counteract the effects of dendritic filtering on the amplitude, time-course, and temporal integration of distal Schaffer collateral (SC) synaptic inputs within stratum radiatum (SR). While ion channel gradients in CA1 distal apical trunk dendrites within SR have been well characterized, little is known about the patterns of ion channel expression in the distal apical tuft dendrites within stratum lacunosum moleculare (SLM) that receive distinct input from the entorhinal cortex via perforant path (PP) axons. Here, we measured local ion channels densities within these distal apical tuft dendrites to determine if the somato-dendritic gradients of I_h and AMPA receptors extend into distal tuft dendrites. We also determined the densities of voltage-gated sodium channels and NMDA receptors. We found that the densities of AMPA receptors, I_h, and voltage-gated sodium channels are similar in tuft dendrites in SLM when compared with distal apical dendrites in SR, while the ratio of NMDA receptors to AMPA receptors increases in tuft dendrites relative to distal apical dendrites within SR. These data indicate that the somato-dendritic gradients of I_h and AMPA receptors in apical dendrites do not extend into the distal tuft, and the relative densities of voltage-gated sodium channels and NMDA receptors are poised to support nonlinear integration of correlated SC and PP input.     

How voltage-gated ion channels alter the functional properties of ganglion and amacrine cell dendrites

The present study compares the structure and function of retinal ganglion and amacrine cell dendrites. Although a superficial similarity exists between amacrine and ganglion cell dendrites, a comparison between the branching pattern of the two cell types reveals differences which can only be appreciated at the microscopic level. Whereas decremental branching is found in ganglion cells, a form of non-decremental or "trunk branching" is observed in amacrine cell dendrites. Physiological differences are also observed in amacrine vs ganglion cells in which many amacrine cells generate dendritic impulses which can be readily distinguished from those of the soma, while separate dendritic impulses in ganglion cell dendrites have not been reported. Despite these differences, both amacrine and ganglion cell dendrites appear to contain voltage-gated ion channels, including TTX-sensitive sodium channels. One way to account for separate dendritic impulses in amacrine cells is to have a higher density of sodium channels and we generally find in modeling studies that a dendritic sodium channel density that is more than about 50% of that in the soma is required for excitatory, synaptic currents to give rise to local dendritic spike activity. Under these conditions, impulses can be generated in the dendrites and propagate for some distance along the dendritic tree. When the soma generates impulse activity in amacrine cells, it can activate, antidromically, the entire dendritic tree. Although ganglion cell dendrites do not appear to generate independent impulses, the presence of voltage-gated ion channels in these structures appears to be important for their function. Modeling studies demonstrate that when dendrites lack voltage-gated ion channels, impulse activity evoked by current applied to the cell body is generated at rates that are much higher than those observed physiologically. However, by placing ion channels in the dendrites at a reduced density compared to those of amacrine cells, the firing rate of ganglion cells becomes more physiological and the relationship between frequency and current (F/I relationship) can be precisely matched with physiological data. Recent studies have demonstrated the presence of T-type calcium channels in ganglion cells and our analysis suggests that they are found in higher density in the dendrites compared to the soma. This is the first voltage-gated ion channel which appears more localized to the dendrites than other cell copartments and this difference alone cries for an interpretation. The presence of a significant T-type calcium channel density in the dendrites can influence their integrative properties in several important ways. First, excitatory synaptic currents can be augmented by the activation of T-type calcium channels, although this is more likely to occur for transient rather than sustained synaptic currents because T-type currents show strong inactivation properties. In addition, T-type calcium channels may serve to limit the electrical load which dendrites impose on the spike initiation process and thus enhance the speed with which impulses can be triggered by the impulse generation site. This role whill enhance the safety factor for impulses traveling in the orthograde direction.     

A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons

The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the HCN1 gene, which we find encodes a major component of the hyperpolarization-activated inward current (Ih) and is an important determinant of dendritic integration in hippocampal CA1 pyramidal cells. Deletion of HCN1 from forebrain neurons enhances hippocampal-dependent learning and memory, augments the power of theta oscillations, and enhances long-term potentiation (LTP) at the direct perforant path input to the distal dendrites of CA1 pyramidal neurons, but has little effect on LTP at the more proximal Schaffer collateral inputs. We suggest that HCN1 channels constrain learning and memory by regulating dendritic integration of distal synaptic inputs to pyramidal cells.     

Plasticity of dendritic function

The various properties of neuronal dendrites--their morphology, active membrane and synaptic properties--all play important roles in determining the functional capabilities of central nervous system neurons. Because of their fundamental involvement in both synaptic integration and synaptic plasticity, the active dendritic properties are important for both neuronal information processing and storage. The active properties of dendrites are determined by the densities of voltage-gated ion channels located within the dendrites in addition to the biophysical characteristics of those channels. The real power of this system resides in the level of plasticity that is provided by the many forms of channel modulation known to exist in neurons. Indeed, voltage gated ion channel modulation shapes the active properties of neuronal dendrites to specific conditions, thus tailoring the functional role of the single neuron within its circuit.     

RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1.     

Specific Sorting and Post-Golgi Trafficking of Dendritic Potassium Channels in Living Neurons

Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific subcompartments. However, the molecular mechanisms that control ion channel localization in distinct dendritic subcompartments are largely unknown. Here, we developed a quantitative live cell imaging method to analyze protein sorting and post-Golgi vesicular trafficking. We focused on two dendritic voltage-gated potassium channels that exhibit distinct localizations: Kv2.1 in proximal dendrites and Kv4.2 in distal dendrites. Our results show that Kv2.1 and Kv4.2 channels are sorted into two distinct populations of vesicles at the Golgi apparatus. The targeting of Kv2.1 and Kv4.2 vesicles occurred by distinct mechanisms as evidenced by their requirement for specific peptide motifs, cytoskeletal elements, and motor proteins. By live cell and super-resolution imaging, we identified a novel trafficking machinery important for the localization of Kv2.1 channels. Particularly, we identified non-muscle myosin II as an important factor in Kv2.1 trafficking. These findings reveal that the sorting of ion channels at the Golgi apparatus and their subsequent trafficking by unique molecular mechanisms are crucial for their specific localizations within dendrites.     

Plasticity of dendritic excitability

Dendrites are equipped with a plethora of voltage-gated ion channels that greatly enrich the computational and storage capacity of neurons. The excitability of dendrites and dendritic function display plasticity under diverse circumstances such as neuromodulation, adaptation, learning and memory, trauma, or disorders. This adaptability arises from alterations in the biophysical properties or the expression levels of voltage-gated ion channels-induced by the activity of neurotransmitters, neuromodulators, and second-messenger cascades. In this review we discuss how this plasticity of dendritic excitability could alter information transfer and processing within dendrites, neurons, and neural networks under physiological and pathological conditions.     

A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells

Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca²⁺ signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca²⁺] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage–activated Ca²⁺ channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination.     

Motoneuron dendrites: role in synaptic integration.

Dendrites constitute over 80 per cent of the receptive surface area in cat motoneurons. Calculations based on matched electrical and gemoetrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on the dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties.     

The Subcellular Distribution of T-Type Ca2+ Channels in Interneurons of the Lateral Geniculate Nucleus

Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca²⁺-spikes and possibly by backpropagating action potentials. Ca²⁺-spikes in INs are predominantly mediated by T-type Ca²⁺-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling.