Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development

Abstract

Sensory experience is necessary for normal cortical development. This has been shown by sensory deprivation and pharmacological perturbation of the cortex. Because these manipulations affect the cortical network as a whole, the role of postsynaptic cellular properties during experience-dependent development is unclear. Here we addressed the developmental role of somatodendritic excitability, which enables postsynaptic spike timing–dependent forms of plasticity, in rat somatosensory cortex. We used short interfering RNA (siRNA)-based knockdown of Na+ channels to suppress the somatodendritic excitability of small numbers of layer 2/3 pyramidal neurons in the barrel cortex, without altering the ascending sensory pathway. In vivo recordings from siRNA-expressing cells revealed that this manipulation interfered with the normal developmental strengthening of sensory responses. The sensory responsiveness of neighboring cortical neurons was unchanged, indicating that the cortical network was unchanged. We conclude that somatodendritic excitability of the postsynaptic neuron is needed for the regulation of synaptic strength in the developing sensory cortex.

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Figure 1: Na+ channel knockdown by lentivirus-based siRNA expression.
Figure 2: Numerical simulation of the electrical behavior of a cortical pyramidal cell with reduced Na+ conductance.
Figure 3: Evaluation of Nav1.1–1.3 knockdown by in vitro electrophysiology and western blotting.
Figure 4: Action potential–evoked dendritic Ca2+ transients are diminished in Nav1.1–1.3 knockdown neurons.
Figure 5: Nav1.1–1.3 knockdown reduces sensory responses.
Figure 6: Reduced sePSPs in Nav1.1–1.3 knockdown cells are due to postsynaptic development effects.
Figure 7: Effect of Nav1.1–1.3 knockdown on layer 2/3 spinogenesis and synaptogenesis.

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Acknowledgements

We thank P.H. Seeburg for long-term support; C. Grosskurth, S. Gruenewald, M. Kaiser and J. Müller for technical assistance; and R. Bruno, T. Celikel, D. Haydon-Wallace, M. Häusser, T. Margrie, M. Mehta, B. Sakmann and P.H. Seeburg for comments on the manuscript. This work was supported by the Max Planck Society.

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Correspondence to Pavel Osten.

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Supplementary information

Supplementary Fig. 1

Correlation between AP amplitude and AP threshold in Nav1.1-1.3 knockdown layer 2/3 pyramidal neurons in vitro. (PDF 510 kb)

Supplementary Fig. 2

Nav1.1–1.3 knock-down reduces sensory-evoked responses. (PDF 527 kb)

Supplementary Fig. 3

Correlation between sePSP amplitude and number of infected Nav1.1–1.3 knockdown cells in vivo. (PDF 417 kb)

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Komai, S., Licznerski, P., Cetin, A. et al. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development. Nat Neurosci 9, 1125–1133 (2006). https://doi.org/10.1038/nn1752

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