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Functional specificity of local synaptic connections in neocortical networks

Abstract

Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli1,2,3,4. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.

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Figure 1: Imaging functional properties of neurons in vivo and indentifying the same neurons in vitro.
Figure 2: Relating orientation and direction preference to connection probability among L2/3 pyramidal neurons.
Figure 3: Relationship between response correlation to natural movies and connection probability.
Figure 4: Relationship between similarity of visual responses and probability of finding unidirectionally and bidirectionally connected pairs.

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Acknowledgements

We thank T. Margrie for discussions about the project and the manuscript, and J. Vogelstein for the spike inference algorithm. This work was supported by the Wellcome Trust (T.D.M.-F.), the European Research Council (T.D.M.-F.), the European Molecular Biology Organisation (S.B.H.), the Medical Research Council and FP7 grant #243914 (K.A.B., P.J.S.), the Overseas Research Students Award Scheme and UCL studentship (H.K.).

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Contributions

H.K. and S.B.H. performed experiments and data analysis. H.K. developed image registration software using preliminary data obtained by S.B.H. and K.A.B., and programs for data analysis. B.P. developed image acquisition software and the program for extracting calcium transients. P.J.S. designed electrophysiology setup and software for acquisition and analysis. B.P., H.K., S.B.H. and T.D.M.-F. built experimental setups. H.K. and T.D.M.-F. wrote the paper.

Corresponding author

Correspondence to Thomas D. Mrsic-Flogel.

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The authors declare no competing financial interests.

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Ko, H., Hofer, S., Pichler, B. et al. Functional specificity of local synaptic connections in neocortical networks. Nature 473, 87–91 (2011). https://doi.org/10.1038/nature09880

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