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  • Review Article
  • Published:

Plasticity of intrinsic neuronal properties in CNS disorders

Nature Reviews Neuroscience volume 9, pages 357–369 (2008)Cite this article

Key Points

  • In many chronic neurological disorders, manifold changes in intrinsic membrane properties have been associated with disease pathophysiology.

  • These changes are termed intrinsic plasticity and can affect neuronal dendrites, somata or axons.

  • Depending on the cellular compartment in which intrinsic plasticity occurs, local dendritic integration processes or global functional parameters, such as action-potential threshold or firing mode, are altered.

  • The underlying cellular mechanisms of intrinsic plasticity comprise altered expression, trafficking or modulation of dendritic, somatic and axonal voltage-gated ion channels.

  • In many cases, there is a striking similarity between the underlying molecular mechanisms mediating physiological forms intrinsic plasticity, and the intrinsic-plasticity mechanisms that are invoked in neurological disorders.

Abstract

The input–output relationship of neuronal networks depends both on their synaptic connectivity and on the intrinsic properties of their neuronal elements. In addition to altered synaptic properties, profound changes in intrinsic neuronal properties are observed in many CNS disorders. These changes reflect alterations in the functional properties of dendritic and somatic voltage- and Ca2+-gated ion channels. The molecular mechanisms underlying this intrinsic plasticity comprise the highly specific transcriptional or post-transcriptional regulation of ion-channel expression, trafficking and function. The studies reviewed here show that intrinsic plasticity, in conjunction with synaptic plasticity, can fundamentally alter the input–output properties of neuronal networks in CNS disorders.

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Figure 1: Ion channel distribution and signal processing in cortical neurons.
Figure 2: Regulation of dendritic ion channels by physiological activity and in CNS disorders.
Figure 3: Changes in intrinsic firing properties of CA1 neurons after status epilepticus.
Figure 4: Somatic and dendritic mechanisms controlling firing behaviour and spike ADPs in hippocampal CA1 pyramidal neurons.
Figure 5: Behaviour of regular-firing and spontaneously bursting neurons in relation to epileptiform population activity.

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Acknowledgements

We thank N. Spruston and W. Kath for contributing Fig. 1B and C. We thank T. Opitz and S. Remy for careful reading of the manuscript We thank the Transregional Program Project SFB-TR3 of the Deutsche Forschungsgemeinschaft, the German Bundesministerium für Bildung und Forschung (BMBF), the Israeli Ministry of Science and Technology (MOST), and the European Epilepsy Research Consortium EPICURE for generous support. Y.Y. was supported by the Henri and Erna Leir Chair for Research in Neurodegenerative Diseases.

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  1. Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Str. 25, Bonn, 53105, Germany

    Heinz Beck

  2. Department of Physiology, Institute of Medical Sciences, Hebrew University-Hadassah Faculty of Medicine, Jerusalem, 91120, Israel

    Yoel Yaari

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Glossary

Excitatory postsynaptic potential

(EPSP). The depolarizing voltage response of a postsynaptic neuron to an excitatory neurotransmitter released by afferent presynaptic terminals.

Long-term potentiation

(LTP). A lasting increase of synaptic transmission in response to strong, correlated input.

Dendritic spike

Regenerative spike in a dendrite that can be locally elicited by activation of excitatory synapses.

A-type K+ current

(IA). Voltage-dependent K+ current, activated by depolarization. It is characterized by a hyperpolarized voltage-dependent activation, with current activation at subthreshold voltages and rapid inactivation during prolonged depolarizations. In dendrites it is mediated primarily by Kv4.2 subunits.

H-current

(Ih). Slow, non-inactivating nonspecific cationic current that is tonically active at resting membrane potential and is further activated by hyperpolarization. It is mediated by HCN1–4 subunits.

Principal neurons

Excitatory neurons that make up the major fraction of CNS neurons. They are distinguished from inhibitory interneurons with respect to their synaptic input, their integrative properties and their synaptic output.

Dorsal root ganglion cell

Pseudo-unipolar neuron with an axon that separates into a peripheral and a central branch. Sensory information is conveyed along the peripheral and central axonal branches to relay neurons in the dorsal horn of the spinal cord.

T-type Ca2+ current

(ICa,T). Voltage-dependent Ca2+ current that activates at subthreshold voltages and inactivates rapidly during prolonged depolarization. Upon repolarization, channels close slowly (slow de-activation). It is mediated by Cav3.1–3.3 subunits.

Allodynia

An exaggerated response to a normally nonpainful stimulus.

Persistent Na+ current

(INaP). A fast voltage-dependent Na+ current that activates at subthreshold depolarizations but fails to inactivate. The molecular correlate of INaP is still intensively discussed.

M-current

(IM). A voltage-dependent K+ current that activates at subthreshold depolarizations but fails to inactivate. In brain neurons it is mediated primarily by KCNQ1 and KCNQ2 subunits (termed also Kv7.1 and Kv7.2 subunits).

Ictogenesis

The cellular and network processes that underlie the generation of an epileptic seizure.

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Beck, H., Yaari, Y. Plasticity of intrinsic neuronal properties in CNS disorders. Nat Rev Neurosci 9, 357–369 (2008). https://doi.org/10.1038/nrn2371

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