Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex

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Feedforward inhibitory GABAergic transmission is critical for mature cortical circuit function; in the neonate, however, GABA is depolarizing and believed to have a different role. Here we show that the GABAA receptor–mediated conductance is depolarizing in excitatory (stellate) cells in neonatal (postnatal day [P]3–5) layer IV barrel cortex, but GABAergic transmission at this age is not engaged by thalamocortical input in the feedforward circuit and has no detectable circuit function. However, recruitment occurs at P6–7 as a result of coordinated increases in thalamic drive to fast-spiking interneurons, fast-spiking interneuron–stellate cell connectivity and hyperpolarization of the GABAA receptor–mediated response. Thus, GABAergic circuits are not engaged by thalamocortical input in the neonate, but are poised for a remarkably coordinated development of feedforward inhibition at the end of the first postnatal week, which has profound effects on circuit function at this critical time in development.

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Figure 1: Reversal potential for GABAA receptor–mediated currents recorded in stellate cells becomes more hyperpolarized during the first postnatal week.
Figure 2: Blockade of GABAA receptor–mediated transmission does not affect thalamocortical-evoked responses in stellate cells at P3–5.
Figure 3: Blockade of GABAA receptors affects thalamocortical-evoked responses in stellate cells at P7–9.
Figure 4: GABAA receptor–mediated transmission is only weakly and unreliably activated by the thalamocortical input in the neonate, but strongly activated by P7–9.
Figure 5: Characterization of cell types in layer IV barrel cortex in the first postnatal week.
Figure 6: Fast spiking interneurons mediate a major component of feedforward inhibition in layer IV at P7–9.
Figure 7: Thalamic input to fast spiking interneurons increases with age relative to the input to stellate cells.
Figure 8: Fast spiking interneuron to stellate cell connection probability and strength is low at P3–5, but increases at the end of the first postnatal week.


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We are grateful to K. Roche, K. Pelkey and J. Diamond for comments on the manuscript, and to C. McBain for comments on the work and providing access to the GIN mice. We thank Z. Molnar for the use of his drawing of the thalamocortical slice. This work was supported by the Wellcome Trust and the National Institute of Neurological Disorders and Stroke Intramural Program.

Author information

M.I.D. conducted, designed and analyzed the majority of experiments. M.C.A. conducted some of the electrophysiolgy experiments, performed all the imaging and contributed to experimental design and analysis. J.T.R.I. supervised the project, wrote the manuscript and contributed to the experimental design and analysis.

Correspondence to John T R Isaac.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Non-FS interneurons are distinct from fast-spiking interneurons and are inhibitory. (PDF 97 kb)

Supplementary Fig. 2

Non-FS interneurons receive a weak thalamic input compared with simultaneously recorded stellate cells or with fast-spiking interneurons at the same developmental stage (all at P7–9). (PDF 81 kb)

Supplementary Fig. 3

Electrophysiological properties of fast-spiking interneurons and stellate cells at different ages between P3 and P9. (PDF 108 kb)

Supplementary Methods (PDF 85 kb)

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