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Plasticity of Voltage-Gated Ion Channels in Pyramidal Cell Dendrites S Remy1,2, H Beck1 and Y Yaari3,4

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Plasticity of Voltage-Gated Ion Channels in Pyramidal Cell Dendrites S Remy1,2, H Beck1 and Y Yaari3,4 Available online at www.sciencedirect.com Plasticity of voltage-gated ion channels in pyramidal cell dendrites S Remy1,2, H Beck1 and Y Yaari3,4 Dendrites of pyramidal neurons integrate multiple synaptic particularly interesting compartments where local inputs and transform them into axonal action potential output. changes in intrinsic excitability can occur. Indeed, in This fundamental process is controlled by a variety of dendritic some paradigms, intrinsic neuronal and synaptic plasticity channels. The properties of dendritic ion channels are not static can be induced simultaneously in the same compartment but can be modified by neuronal activity. Activity-dependent [3,4]. changes in the density, localization, or biophysical properties of dendritic voltage-gated channels can persistently alter the Pyramidal neurons integrate synaptic inputs that are integration of synaptic inputs. Furthermore, dendritic intrinsic widely distributed across the extent of the dendritic plasticity can induce neuronal output mode transitions (e.g. arborization. The magnitude of the local voltage deflec- from regular spiking to burst firing). Recent advances in the field tion at the dendrite, and how it propagates to the action reviewed here represent an important step toward uncovering potential initiation zone at the axon initial segment and the principles of neuronal input/output transformations in the first node of Ranvier [5,6], is strongly determined by response to various patterns of brain activity. both the passive properties of the dendritic tree and the Addresses active dendritic conductances [7]. The pattern of axonal 1 Department of Epileptology, University of Bonn Medical Center, output also depends on the properties of local axonal D-53105 Bonn, Germany conductances that transduce the dendritic signals into 2 German Center for Neurodegenerative Diseases (DZNE), D-53127, axonal spiking. Accordingly, plastic changes in the Bonn, Germany density, localization, or biophysical properties of dendritic 3 Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, channels, can persistently alter neuronal integration and Jerusalem 91120, Israel induce neuronal output mode transitions (e.g. from 4 The Interdisciplinary Center for Neuronal Computation, the Hebrew regular spiking to burst firing). University, Jerusalem 91904, Israel Corresponding author: Yaari, Y ([email protected]) The active properties of dendrites and their plasticity have been particularly well studied in pyramidal cells. These dendrites express a plethora of voltage-dependent Current Opinion in Neurobiology 2010, 20:503–509 ionic conductances with a branch-specific expression pattern, conferring strongly nonlinear properties on den- This review comes from a themed issue on dritic subsegments. In particular, clustered and synchro- Signalling mechanisms Edited by Linda van Aelst and Pico Caroni nous excitatory synaptic inputs can trigger local, nonlinear ‘all or nothing’ depolarizations at some branches, referred Available online 4th August 2010 to as dendritic spikes [8]. These spikes propagate from 0959-4388/$ – see front matter their dendritic initiation site toward the axon, where they # 2010 Elsevier Ltd. All rights reserved. can trigger axonal spikes. In this way, the spatial and temporal synchrony of synaptic inputs strongly influence DOI 10.1016/j.conb.2010.06.006 neuronal spike output [9]. Here, we review the most recent advances regarding the Introduction intrinsic plasticity of pyramidal cell dendrites induced by physiological and pathophysiological stimuli and discuss Physiological and abnormal bouts of neuronal activity can its impact on neuronal integration and spike output mode. induce persistent changes in the expression level and/or biophysical properties of ionic channels in the dendritic and axosomatic membranes of hippocampal and cortical Distribution of voltage-gated ion channels in pyramidal neurons, thereby modifying their intrinsic pyramidal cell dendrites properties [1]. In rodents, such intrinsic neuronal Our knowledge about the distribution of voltage-gated plasticity occurs during learning or exposure to enriched ion channels in pyramidal cell dendrites stems mainly environment, as well as during sensory deprivation or from direct dendritic patch-clamp recordings and immu- status epilepticus [2]. It is also readily induced in vitro, nolocalization of their underlying subunits [10]. Cell- using stimulation patterns mimicking normal brain attached patch-clamp recordings and freeze-fracture elec- activity. As is the case of synaptic plasticity, neuronal tron microscopy have revealed a more or less uniform dendrites or dendritic subsegments are emerging as voltage-gated Na+ channel density in the apical trunk of www.sciencedirect.com Current Opinion in Neurobiology 2010, 20:503–509 504 Signalling mechanisms pyramidal neurons [11,12], which is sufficient for gener- inputs and the storage of information. One important ating dendritic Na+ spikes [13]. Several voltage-gated function of dendritic ion channels is regulating the integ- Ca2+ channel types have also been observed in these ration of subthreshold synaptic potentials (EPSPs and dendrites, including the low voltage-gated T-type and IPSPs) and their influence on membrane potential at the the high voltage-gated L-type, P/Q-type, N-type and site of action potential initiation (see [7] for a detailed R-type Ca2+ channels [11,14]. In CA1 pyramidal neurons, review). In addition, dendritic voltage-gated channels are the densities of T-type and R-type Ca2+ channels appear important in the generation of dendritic spikes, regen- to be highest in the distal dendrites, whereas L-type and erative events initiated by strong, correlated synaptic N-type channels are more abundant in the proximal inputs. Direct dendritic patch-clamp recordings from dendritic regions [11,14–16]. Among several functions, hippocampal and layer 5 neocortical pyramidal cells have activation of dendritic Ca2+ channels provides additional confirmed that the main apical dendrites are capable of depolarization to excitatory postsynaptic potentials generating dendritic spikes mediated by voltage-gated (EPSPs) and links dendritic signal integration to intra- Na+ channels, Ca2+ channels and NMDA receptor chan- cellular signaling cascades. Another group of channels nels and curtailed by transient A-type K+ channels present at higher densities on the distal main apical [9,13,23,24]. dendrites in both neocortical layer V and CA1 pyramidal neurons are the hyperpolarization-activated channels Two recent technological improvements, namely, i) the (HCN) [17,18]. These channels are partially activated use of gradient-scanning confocal microscopy to visually at resting potential, generating an inward current, Ih. aid dendritic patch-clamp recordings [22 ,25 ], and ii) the Deactivation of Ih reduces EPSPs duration, while its introduction of two-photon glutamate uncaging, have now activation reduces the duration of inhibitory post synaptic allowed to probe the integrative properties of even the potentials (IPSPs). Therefore, this current strongly smallest dendrites of the brain at unprecedented detail affects the temporal summation of synaptic signals. [9,26]. Using these techniques, the excitability of small The somatodendritic gradient and biophysical properties diameter branches, such as basal dendrites, radial oblique of HCN channels reduce the location dependence of branches, and apical tufts, has recently been successfully synaptic integration for a wide range of spatiotemporal examined. These studies have shown that small diameter input patterns [19]. Another prominent group of dendritic dendritic branches possess voltage-gated conductances channels, the A-type K+ channels, underlie a rapidly that support the generation and propagation of local den- + activating and inactivating K current (IA). They are also dritic spikes. Nevian et al. were the first to establish dual expressed with an increasing somatodendritic gradient in somatic and dendritic patch-clamp recordings from basal CA1 pyramidal neurons [23], whereas layer V pyramidal dendrites of layer V pyramidal cells [22]. They found that neurons show a uniform somatodendritic distribution these dendrites possess the ionic machinery to generate [20,21]. In the former neurons, the several-fold higher fast Na+ spikes and NMDA receptor-mediated spikes, but density of these channels at the distal part of the main lack Ca2+ spikes. Subsequently this technique was success- apical dendrites compared to the soma, is thought to fully used on apical tuft dendritic branches [25]. These function as a neuronal ‘shock absorber’, limiting the branches were also capable of triggering Na+ and NMDA spread of backpropagating action potentials into the den- receptor-mediated spikes, whereas Ca2+ spikes seemed to dritic tree and curtailing dendritic spikes [9,21]. The originate from a distinct initiation zone several hundred density of sustained K+ current components along the micrometers away from the soma. The authors proposed a somatodendritic axis remains relatively constant. unifying view of integration in layer 5 pyramidal cells, in which all fine dendrites, basal and tuft, integrate inputs Much is known about the identity and general distri- locally through recruitment of NMDA receptor-mediated bution patterns of voltage-gated ion channels in the main dendritic spikes, whereas fixed integration zones exist for apical trunk of different classes
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