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First published online December 1, 2006
Journal of Experimental Biology 209, 4821-4827 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02567
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Plasticity and stability in neuronal output via changes in intrinsic excitability: it's what's inside that counts

David J. Schulz

Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA


Figure 1
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Fig. 1. Examples of plasticity in intrinsic neuronal excitability. (A) Diagram illustrating the concept of potentiation of intrinsic excitability. The circles represent two different neurons connected by an excitatory synapse (triangle). In the case of potentiation of excitability, one form of plasticity in intrinsic properties of neurons, activity in the pre-synaptic neuron potentiates the connection with the post-synaptic neuron. This potentiation is the result of an increase in the overall excitability of the post-synaptic neuron independent of changes in synaptic strength. One possible mechanism for this change in excitability is a decrease in action potential threshold. The result of this increased excitability is an increase in the input-output function of the postsynaptic cell: more spikes are elicited post-synaptically for the same amount of pre-synaptic input. This results in a de facto increase in synaptic strength mediated by changes in the intrinsic excitability of the post-synaptic neuron. Examples of this kind of plasticity have recently been published (Cudmore and Turrigiano, 2004Go; Li et al., 2004Go; Xu et al., 2005Go). (B) Diagram illustrating the concept of compensatory changes in excitability leading to conserved neuronal output. In this case, the post-synaptic neuron maintains a constant level of spiking activity as a result of compensatory decreases in excitability triggered by increased pre-synaptic activity. The outcome is a constantly maintained level of spiking activity in the post-synaptic cell, which could be the result of an increased action potential threshold, for example. For examples of this kind of plasticity, see recent publications (Aptowicz et al., 2004Go; Brickley et al., 2001Go; van Welie et al., 2004Go).

 

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Fig. 2. Visually driven regulation of intrinsic neuronal excitability in Xenopus tectal neurons improves stimulus detection in vivo. (A) Tectal neurons from tadpoles exposed to a visual stimulation protocol show increased excitability in response to injected depolarizing current. Left: input-output relationships in response to square pulse depolarizations of varying amplitudes. Neurons from visually stimulated animals (open triangles; N=25) show significantly more spiking activity in response to injected current than do controls (filled circles; N=20). Right: representative recordings from these neurons showing the differences in response to current injection. (B) Increases in the excitability of tectal neurons are the result of changes in voltage-dependent Na+ currents. Na+ currents (left) but not K+ currents (right) show a significant increase in peak amplitude in visually stimulated animals. An increase in these Na+ currents, which are depolarizing and excitatory, would account for the increase in excitability seen in visually stimulated tadpoles. Open symbols represent recordings from visually stimulated neurons (N=46), and closed symbols are controls (N=25). K+ currents: trans, transient; sust, sustained; Ca2+ currents: I-plateau. (C) Increased excitability of tectal neurons improves visual stimulus detection in semi-intact tadpoles. Recordings of visually evoked field potentials were made from the tectum in control and stimulated tadpoles. The recordings shown represent five trials from a control cell, and five trials recorded from a cell in a tadpole previously subjected to the visual stimulation protocol. The neuron from the visually stimulated animal fires more action potentials than the control in response to a subsequently presented light stimulus (open arrow), indicating that the sensitivity to visual stimuli is increased in tadpoles with previous visual stimulation experience. Figure adapted from Aizenman et al. (Aizenman et al., 2003Go) and reproduced with permission.

 

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Fig. 3. Variable membrane conductance and ion channel expression in single lateral pyloric (LP) neurons of the crab stomatogastric ganglion. (A) Two LP neurons from two different animals show robust conservation of output. (B) Two-electrode voltage clamp measures of three K+ conductances (IKd=delayed rectifier, IK[Ca]=calcium-activated K+, IA=fast-transient A-type) in LP neurons from nine different animals reveals that neurons with functionally similar outputs show highly variable levels of membrane conductances. (C) Quantitative PCR measures of expression of three K+ channels that carry the conductances measured in Fig. 3B (shab [IKd], BK-KCa [IK[Ca]], shal [IA]) in the same LP neurons. The same level of variability exists at the level of gene expression and membrane conductance. These data combined with correlations between measured membrane conductance and ion channel expression in LP neurons of the crab (D) demonstrate that this variability is biologically meaningful and not the result of `noise' in either the voltage clamp recordings or the quantitative analyses of gene expression. These data suggest that these neurons continually adjust their intrinsic properties via activity-dependent processes in order to maintain consistent functional output. Figure adapted from Schulz et al. (Schulz et al., 2006Go) and reproduced with permission. LP recordings courtesy of J.-M. Goaillard.

 





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