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  • Review Article
  • Published:

The other side of the engram: experience-driven changes in neuronal intrinsic excitability

Nature Reviews Neuroscience volume 4, pages 885–900 (2003)Cite this article

Key Points

  • In addition to synaptic plasticity, which confers neurons with the ability to modify the strength of individual synapses, nerve cells also possess forms of intrinsic plasticity (changes in intrinsic excitability), which affect largest ensembles of synapses and might affect the whole cell. This form of plasticity might endow neurons with an additional capacity to store information.

  • Different learning tasks induce changes in intrinsic excitability in several vertebrate and invertebrate species. In many cases, these changes manifest as reductions in spike threshold, spike accommodation and amplitude of burst-evoked afterhyperpolarization, all of which point to the modulation of K+ channels as one potential underlying mechanism.

  • Forms of experience-dependent plasticity other than learning also elicit intrinsic plasticity, which share similar mechanisms as learning-mediated plastic changes. These forms of experience include adaptive and maladaptive states, such as seizures.

  • Studies in cell culture and brain slices have shown that it is possible to study intrinsic excitability in vitro. These studies have pointed to a series of K+, Ca2+ and Na+ conductances as possible molecular substrates of the plastic changes.

  • The signal transduction cascades mediating the conductance changes that seem to be crucial for intrinsic plasticity remain unknown for most model systems. Ca2+/calmodulin-dependent protein kinase II and other kinases, the action of G-proteins, and the release of intracellular Ca2+ have been proposed, but the definitive experiments remain to be reported.

  • Many changes remain to be answered in this nascent field. What is the relationship between intrinsic and synaptic plasticities, particularly in cases when both phenomena seem to co-exist? What is the duration of intrinsic plasticity? Does it really function to encode information? If so, what kind of memories could it store? These and many other issues should generate as much attention of intrinsic excitability changes as there has been on synaptic plasticity.

Abstract

Modern theories of memory storage have largely focused on persistent, experience-dependent changes in synaptic function such as long-term potentiation and depression. But in addition to these synaptic changes, certain learning tasks produce enduring changes in the intrinsic excitability of neurons by changing the function of voltage-gated ion channels, a change that can produce broader, even neuron-wide changes in synaptic throughput. We will consider the evidence for persistent changes in intrinsic neuronal excitability — what we will call intrinsic plasticity — that is produced by training in behaving animals and by artificial patterns of activation in brain slices and neuronal cultures. These intrinsic changes might function as part of the engram itself, or as a related phenomenon such as a trigger for the consolidation or adaptive generalization of memories.

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Figure 1: Input-specificity and candidate memory storage mechanisms.
Figure 2: Intrinsic plasticity evoked by associative eyelid conditioning.
Figure 3: Intrinsic plasticity evoked by brief synaptic stimulation in the deep cerebellar nuclei.
Figure 4: Intrinsic plasticity in neocortical pyramidal cells produces an improvement in the temporal precision and reliability of throughput.

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Acknowledgements

Thanks to H. Nishiyama, A. Sdrulla and J. H. Shin for helpful suggestions. This work was supported by the USPHS and the Develbiss Fund.

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  1. Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Wei Zhang & David J. Linden

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Correspondence to David J. Linden.

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FURTHER INFORMATION

Encyclopedia of Life Sciences

long-term depression and depotentiation

long-term potentiation

Glossary

SYNAPTIC STRENGTH

The amplitude of the postsynaptic potential that is evoked by a single shock to a population of axons.

ASSOCIATIVITY

The property of long-term potentiation (LTP) whereby weak stimulation of a synaptic input, which will not elicit an increase in synaptic strength, can lead to the onset of LTP if strong stimulation is simultaneously applied to an independent input to the same postsynaptic cell.

INPUT SPECIFICITY

The property of long-term potentiation whereby strong synaptic stimulation only elicits an increase in synaptic strength at the activated pathway, leaving every other input unaffected.

THROUGHPUT

The probability of a single synapse evoking an action potential.

STATOCYST

Organ that mediates balance in many invertebrates. It consists of a fluid-filled sac that contains statoliths (minute calcareous particles) that stimulate sensory cells and help indicate position when the animal moves.

PNEUMOSTOME

A small opening in the mantle of gastropods through which air passes.

HABITUATION

The cessation of a response upon repeated presentations of a stimulus.

SENSITIZATION

The unspecific augmentation of a behavioural response to a stimulus after the animal has been exposed to an injurious stimulus.

INPUT RESISTANCE

The voltage change that is elicited by the injection of current into a cell, divided by the amount of current injected.

GLABELLA

The smooth area between the eyebrows just above the nose.

AFTERHYPERPOLARIZATION

The membrane hyperpolarization that follows the occurrence of an action potential.

OPERANT CONDITIONING

Form of conditioning in which the subject learns from the consequences of its actions, thereby modifying its behaviour.

ACCOMMODATION

The cessation of spike firing despite constant depolarization above firing threshold.

INWARD PLATEAU CURRENT

A current that inactivates slowly, resulting in a sustained depolarization.

DELAYED OUTWARD-RECTIFIER K+ CURRENT

A slowly activating and very slowly inactivating voltage-gated K+ conductance that preferentially passes K+ out of the cell.

REFRACTORY PERIOD

The period after a spike during which a neuron cannot fire a new action potential.

MACROPATCHES

Giant membrane patches that are commonly obtained to study membrane currents of cells that are too large to record with conventional patch-clamp methods.

CURRENT–VOLTAGE RELATION

A plot of the changes in ionic current as a function of membrane voltage.

POPULATION SPIKE

The summated action potential of the postsynaptic neurons that respond to a given stimulus as recorded with an extracellular electrode.

SCHAFFER COLLATERALS

Axons of the CA3 pyramidal cells of the hippocampus that form synapses with the apical dendrites of CA1 neurons.

THETA BURSTS

Rhythmic neural activity with a frequency of 4–8 Hz.

DYNAMIC CLAMPING

Recording configuration in which the current that is injected into the cell mimics a specific pattern of synaptic activation.

METAPLASTICITY

Term that has been coined to refer to the higher-order plasticity of synaptic plasticity. In other words, how synaptic activity or other stimuli modify the properties of synaptic plasticity itself.

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Zhang, W., Linden, D. The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat Rev Neurosci 4, 885–900 (2003). https://doi.org/10.1038/nrn1248

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