Plasticity of voltage-gated ion channels in pyramidal cell dendrites

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Dendrites of pyramidal neurons integrate multiple synaptic inputs and transform them into axonal action potential output. This fundamental process is controlled by a variety of dendritic channels. The properties of dendritic ion channels are not static but can be modified by neuronal activity. Activity-dependent changes in the density, localization, or biophysical properties of dendritic voltage-gated channels can persistently alter the integration of synaptic inputs. Furthermore, dendritic intrinsic plasticity can induce neuronal output mode transitions (e.g. from regular spiking to burst firing). Recent advances in the field reviewed here represent an important step toward uncovering the principles of neuronal input/output transformations in response to various patterns of brain activity.

Introduction

Physiological and abnormal bouts of neuronal activity can induce persistent changes in the expression level and/or biophysical properties of ionic channels in the dendritic and axosomatic membranes of hippocampal and cortical pyramidal neurons, thereby modifying their intrinsic properties [1]. In rodents, such intrinsic neuronal plasticity occurs during learning or exposure to enriched environment, as well as during sensory deprivation or status epilepticus [2]. It is also readily induced in vitro, using stimulation patterns mimicking normal brain activity. As is the case of synaptic plasticity, neuronal dendrites or dendritic subsegments are emerging as particularly interesting compartments where local changes in intrinsic excitability can occur. Indeed, in some paradigms, intrinsic neuronal and synaptic plasticity can be induced simultaneously in the same compartment [3, 4].

Pyramidal neurons integrate synaptic inputs that are widely distributed across the extent of the dendritic arborization. The magnitude of the local voltage deflection at the dendrite, and how it propagates to the action potential initiation zone at the axon initial segment and the first node of Ranvier [5, 6], is strongly determined by both the passive properties of the dendritic tree and the active dendritic conductances [7]. The pattern of axonal output also depends on the properties of local axonal conductances that transduce the dendritic signals into axonal spiking. Accordingly, plastic changes in the density, localization, or biophysical properties of dendritic channels, can persistently alter neuronal integration and induce neuronal output mode transitions (e.g. from regular spiking to burst firing).

The active properties of dendrites and their plasticity have been particularly well studied in pyramidal cells. These dendrites express a plethora of voltage-dependent ionic conductances with a branch-specific expression pattern, conferring strongly nonlinear properties on dendritic subsegments. In particular, clustered and synchronous excitatory synaptic inputs can trigger local, nonlinear ‘all or nothing’ depolarizations at some branches, referred to as dendritic spikes [8]. These spikes propagate from their dendritic initiation site toward the axon, where they can trigger axonal spikes. In this way, the spatial and temporal synchrony of synaptic inputs strongly influence neuronal spike output [9].

Here, we review the most recent advances regarding the intrinsic plasticity of pyramidal cell dendrites induced by physiological and pathophysiological stimuli and discuss its impact on neuronal integration and spike output mode.

Section snippets

Distribution of voltage-gated ion channels in pyramidal cell dendrites

Our knowledge about the distribution of voltage-gated ion channels in pyramidal cell dendrites stems mainly from direct dendritic patch-clamp recordings and immunolocalization of their underlying subunits [10]. Cell-attached patch-clamp recordings and freeze-fracture electron microscopy have revealed a more or less uniform voltage-gated Na+ channel density in the apical trunk of pyramidal neurons [11, 12], which is sufficient for generating dendritic Na+ spikes [13]. Several voltage-gated Ca2+

Nonlinear integration in pyramidal cell dendrites

Voltage-gated channels in dendrites of pyramidal neurons play an important role in both the processing of synaptic inputs and the storage of information. One important function of dendritic ion channels is regulating the integration of subthreshold synaptic potentials (EPSPs and IPSPs) and their influence on membrane potential at the site of action potential initiation (see [7] for a detailed review). In addition, dendritic voltage-gated channels are important in the generation of dendritic

Plasticity of dendritic branch strength

Can the excitability of individual dendritic branches be adjusted by excitatory synaptic activity, and if so, what does it imply for the conversion of synaptic input to spike output? Stimulation patterns used to induce long-term potentiation (LTP) of EPSPs have been shown also to induce specific changes in the properties of voltage-gated ion channels expressed on main apical CA1 dendrites. For instance, dendritic A-type currents were shown to be persistently downregulated, resulting in

Contribution of dendritic conductances to intrinsic burst firing

Extracellular single-unit recordings in vivo have shown that neocortical and hippocampal neurons fire in a solitary spike mode or in a burst mode [32]. However, the contribution of intrinsic factors to burst firing in CA1, CA3, subicular, and cortical pyramidal cells has been examined thoroughly only in slice preparations in vitro. Both dendritic and axosomatic conductances have been shown to be promote burst firing in these neurons [2]. These conductances control, by different mechanisms, the

Plasticity of dendritic conductances contributing to intrinsic burst firing

The molecular mechanisms underlying the emergence of Ca2+-dependent bursting in CA1 pyramidal cells following pilocarpine-induced SE has been intensively investigated [38, 39]. An upregulation of a Ni2+ sensitive T-type current in the apical dendrites was previously implicated in this phenomenon [40]. Recently, Becker et al. demonstrated a transient transcriptional upregulation of the Ni2+ sensitive T-type Ca2+ channel subunit Cav3.2 beginning within a few days after SE. Mice with genetic

Concluding remarks

The recent discoveries reviewed here represent a step further toward understanding the role dendrites play in the transformation of synaptic input into neuronal output in pyramidal cells. As we learn more about the function of small diameter dendritic branches, we move toward the goal of defining rules for the input/output integration in these principal neurons. It seems possible that at some point we may be able to predict under which conditions a neuron will fire single action potentials or

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

Supported by the German-Israel Foundation (GIF), the Deutsche Forschungsgemeinschaft SFB TR3, NGFNplus, the Ministry for Innovation, Science, Research and Technology of Nordrhein-Westfalen and the Henri J. and Erna D. Leir Chair for Research in Neurodegenerative Diseases.

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