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A biophysical signature of network affiliation and sensory processing in mitral cells


One defining characteristic of the mammalian brain is its neuronal diversity1. For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists2,3,4,5. Although it is well known that such cellular properties vary considerably according to neuronal type, the substantial biophysical diversity of neurons of the same morphological class is typically averaged out and ignored. Here we show that the amplitude of hyperpolarization-evoked sag of membrane potential recorded in olfactory bulb mitral cells is an emergent, homotypic property of local networks and sensory information processing. Simultaneous whole-cell recordings from pairs of cells show that the amount of hyperpolarization-evoked sag potential and current (Ih)6 is stereotypic for mitral cells belonging to the same glomerular circuit. This is corroborated by a mosaic, glomerulus-based pattern of expression of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) subunit of the Ih channel. Furthermore, inter-glomerular differences in both membrane potential sag and HCN2 protein are diminished when sensory input to glomeruli is genetically and globally altered so that only one type of odorant receptor is universally expressed7. Population diversity in this intrinsic property therefore reflects differential expression between local mitral cell networks processing distinct odour-related information.

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Figure 1: Diversity of sag potential amplitude within and between mitral cell networks.
Figure 2: Glomerular expression of HCN2 in wild-type and OMP-IRES-tau-LacZ mice.
Figure 3: Glomerular expression of HCN2 and mitral cell sag in M71 monoclonal mice.
Figure 4: Population diversity reflects local network membership and sensory processing.


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We thank M. Velez-Fort for comments on the manuscript. E.A.R. is a recipient of a Sir Henry Wellcome Fellowship. This project was supported by the Oticon Foundation, the Danish Council for Independent Research and the Lundbeckfondation (K.A.), the Gulbenkian PhD Programme and Fundação para a Ciência e Tecnologia (D.P.), The Wellcome Trust (T.W.M.) and Medical Research Council MC_U1175975156 (B.P. and T.W.M.).

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K.A. and E.A.R. performed electrophysiological experiments. C.H. and J.H. carried out immunohistochemistry. D.P. performed morphological reconstructions and some initial electrophysiological experiments. B.P. and E.A.R. contributed to data analysis. A.F. generated the transgenic mouse line. K.A. and T.W.M. conceived the project and performed analysis. T.W.M. wrote the paper with input from all other authors.

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Correspondence to Troy W. Margrie.

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The authors declare no competing financial interests.

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Angelo, K., Rancz, E., Pimentel, D. et al. A biophysical signature of network affiliation and sensory processing in mitral cells. Nature 488, 375–378 (2012).

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