Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex

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Abstract

The thalamus provides fundamental input to the neocortex. This input activates inhibitory interneurons more strongly than excitatory neurons, triggering powerful feedforward inhibition. We studied the mechanisms of this selective neuronal activation using a mouse somatosensory thalamocortical preparation. Notably, the greater responsiveness of inhibitory interneurons was not caused by their distinctive intrinsic properties but was instead produced by synaptic mechanisms. Axons from the thalamus made stronger and more frequent excitatory connections onto inhibitory interneurons than onto excitatory cells. Furthermore, circuit dynamics allowed feedforward inhibition to suppress responses in excitatory cells more effectively than in interneurons. Thalamocortical excitatory currents rose quickly in interneurons, allowing them to fire action potentials before significant feedforward inhibition emerged. In contrast, thalamocortical excitatory currents rose slowly in excitatory cells, overlapping with feedforward inhibitory currents that suppress action potentials. These results demonstrate the importance of selective synaptic targeting and precise timing in the initial stages of neocortical processing.

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Figure 1: In paired FS-RS cell recordings, thalamocortical responses were strongest in FS cells, but intrinsic excitability was greatest in RS cells.
Figure 2: Excitatory and inhibitory conductances evoked by thalamocortical stimulation were larger in FS than in RS cells.
Figure 3: Strengths of individual thalamic cell connections, and the number of thalamic cells making connections, were greater for FS than for RS cells.
Figure 4: A cell-type difference in Ge-Gi kinetics allowed inhibition to be most effective in RS cells.

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Acknowledgements

We thank our colleagues A. Agmon, O. Ahmed, C. Aizenman, J.-M. Edeline, E. Fanselow, A. Gray, S.-C. Lee, M. Long, R. Metherate, K. Pratt, K. Richardson, B. Rudy and H. Swadlow for their helpful comments about this work; S. Patrick for technical assistance; and Z. Huang for providing G42 mice. Our research was supported by grants from the US National Institutes of Health, the US National Science Foundation and the Brown University Brain Science Program.

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Correspondence to Barry W Connors.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

GFP expression in FS cells of the G42 mouse line. (PDF 856 kb)

Supplementary Fig. 2

Mean intrinsic properties, reversal potentials and synaptic conductances recorded during the experiments and applied in the models. (PDF 127 kb)

Supplementary Fig. 3

The influence of Ge kinetics on functional inhibition depends on inhibitory driving force. (PDF 110 kb)

Supplementary Fig. 4

Effects of input resistance (Rin) on time-course of PSPs. (PDF 127 kb)

Supplementary Methods (PDF 88 kb)

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