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Synaptically driven state transitions in distal dendrites of striatal spiny neurons

Nature Neuroscience volume 14, pages 881–888 (2011)Cite this article

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Abstract

Striatal spiny neurons (SPNs) associate a diverse array of cortically processed information to regulate action selection. But how this is done by SPNs is poorly understood. A key step in this process is the transition of SPNs from a hyperpolarized 'down state' to a sustained, depolarized 'up state'. These transitions are thought to reflect a sustained synaptic barrage, involving the coordination of hundreds of pyramidal neurons. Indeed, in mice, simulation of cortical input by glutamate uncaging on proximal dendritic spines produced potential changes in SPNs that tracked input time course. However, brief glutamate uncaging at spines on distal dendrites evoked somatic up states lasting hundreds of milliseconds. These regenerative events depended upon both NMDA receptors and voltage-dependent Ca2+ channels. Moreover, they were bidirectionally regulated by dopamine receptor signaling. This capacity not only changes our model of how up states are generated in SPNs, it also has fundamental implications for the associative process underlying action selection.

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Figure 1: State transitions can be triggered by local stimulation of distal dendrites.
Figure 2: State transitions generated by proximal and distal dendritic glutamate uncaging are independent of the somatic EPSP size and internal solution used in the recording electrode.
Figure 3: State transition generation is similar in dSPN and iSPNs.
Figure 4: State transition generation requires NMDA receptors and voltage-gated Ca2+ channels.
Figure 5: NMDA acts at distal dendritic synapses to enable state transition generation.
Figure 6: Neuron modeling supports synergistic action of NMDA receptors and T- and R-type Ca2+ channels in up-state generation and maintenance.
Figure 7: Up-state duration is modulated by dopamine and adenosine receptor signaling.

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Acknowledgements

The US National Institutes of Health (NS 034696, MH074866), the Picower Foundation and CHDI Foundation supported this work. We thank J. Dempster, K. Saporito, N. Schwarz, S. Ulrich and D. Wokosin for technical assistance.

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  1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

    Joshua L Plotkin, Michelle Day & D James Surmeier

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Contributions

J.L.P. conducted experiments and data analysis; M.D. conducted the experiments in cortical pyramidal neurons and provided technical assistance with uncaging; D.J.S. supervised the project; and D.J.S. and J.L.P. designed the experiments and prepared the manuscript.

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Correspondence to D James Surmeier.

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Plotkin, J., Day, M. & Surmeier, D. Synaptically driven state transitions in distal dendrites of striatal spiny neurons. Nat Neurosci 14, 881–888 (2011). https://doi.org/10.1038/nn.2848

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