Abstract
Dopaminergic neurons of the substantia nigra pars compacta (SNc) exhibit functional heterogeneity that likely underpins their diverse roles in behavior. We examined how the functional diversity of identified dopaminergic neurons in vivo correlates with differences in somato-dendritic architecture and afferent synaptic organization. Stereological analysis of individually recorded and labeled dopaminergic neurons of rat SNc revealed that they received approximately 8,000 synaptic inputs, at least 30% of which were glutamatergic and 40–70% were GABAergic. The latter synapses were proportionally greater in number and denser on dendrites located in the substantia nigra pars reticulata (SNr) than on those located in SNc, revealing the existence of two synaptically distinct and region-specific subcellular domains. We also found that the relative extension of SNc neuron dendrites into the SNr dictated overall GABAergic innervation and predicted inhibition responses to aversive stimuli. We conclude that diverse wiring patterns determine the heterogeneous activities of midbrain dopaminergic neurons in vivo.
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Change history
05 March 2012
In the version of this article initially published online, the large arrowheads were undefined in Figure 3a; the Figure 3b legend stated that the proportion of GABAergic synapses made with dendrites located in the SNr was greater than that of GABAergic and glutamatergic synapses in the SNc, whereas it should have stated that it was greater than that of GABAergic synapses in SNc and glutamatergic synapses in the SNr; the Table 2 legend listed the number of neurons as five, contradicting the correct values given in the table itself; a spurious reference to a Figure 5i should have read Figure 5f; and the units on the y axis in Figure 5e were given as mm × 103 instead of mm. The errors have been corrected for the print, PDF and HTML versions of this article.
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Acknowledgements
We are grateful to M. West for providing critical comments during the development of the single-cell stereological protocol. We also thank E. Norman, C. Francis, K. Whitworth, B. Micklem, S. Fernández, J. Mpodozis and G. Marín for expert technical assistance, and C. Morales and M. Quispe for statistical analysis. This work was supported by the Medical Research Council (UK), Parkinson's UK (grant G-0601, to J.P.B., P.J.M. and M.A.U.), and the Comisión Nacional de Investigación Científica y Tecnológica (Fondecyt grant 11100433, Conicyt, Chile to P.H.).
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P.H. performed the juxtacellular labeling of some neurons, carried out most of the immunohistochemical procedures, electron microscopic analysis, neuronal reconstructions and stereological analysis, analyzed most of the anatomical and some of the physiological data, prepared the figures, and wrote the manuscript. M.T.C.B. recorded and juxtacellularly labeled most of the neurons that we used, and performed most of the physiological analysis. A.N. carried out neuronal reconstructions in half of the neurons. M.F. performed the light microscopic stereological analysis of immunolabeled varicosities. M.A.U. provided important feedback during the development of the project and gave critical comments during the writing of the manuscript. P.J.M. supervised and contributed to the recording and juxtacellular labeling of neurons and the project in general, and provided insightful comments during the writing of the manuscript. J.P.B. supervised the entire project, provided expertise in immunohistochemistry and tissue processing, helped with ultrastructural analysis, and provided critical and insightful comments during the writing of the manuscript.
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Henny, P., Brown, M., Northrop, A. et al. Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons. Nat Neurosci 15, 613–619 (2012). https://doi.org/10.1038/nn.3048
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DOI: https://doi.org/10.1038/nn.3048
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