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Cellular mechanisms underlying burst firing in substantia nigra dopamine neurons

Blythe, S.N., Wokosin, D., Atherton, J.F. and Bevan, M.D. (2009) Cellular mechanisms underlying burst firing in substantia nigra dopamine neurons. The Journal of Neuroscience, 29 (49). pp. 15531-15541. ISSN 0270-6474

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Burst firing of substantia nigra dopamine (SN DA) neurons is believed to represent an important teaching signal that instructs synaptic plasticity and associative learning. However, the mechanisms through which synaptic excitation overcomes the limiting effects of somatic Ca2+-dependent K+ current to generate burst firing are controversial. Modeling studies suggest that synaptic excitation sufficiently amplifies oscillatory dendritic Ca2+ and Na+ channel currents to lead to the initiation of high-frequency firing in SN DA neuron dendrites. To test this model, visually guided compartment-specific patch-clamp recording and ion channel manipulation were applied to rodent SN DA neurons in vitro.

As suggested previously, the axon of SN DA neurons was typically found to originate from a large-diameter dendrite that was proximal to the soma. However, in contrast to the predictions of the model, (1) somatic current injection generated firing that was similar in frequency and form to burst firing in vivo, (2) the efficacy of glutamatergic excitation was inversely related to the distance of excitation from the axon, (3) pharmacological blockade or genetic deletion of Ca2+ channels did not prevent high-frequency firing, (4) action potential bursts were invariably detected first at sites that were proximal to the axon, and (5) pharmacological blockade of Na+ channels in the vicinity of the axon/soma but not dendritic excitation impaired burst firing. Together, these data suggest that SN DA neurons integrate their synaptic input in a more conventional manner than was hypothesized previously.

Item Type: Article
Copyright, Publisher and Additional Information: © 2009 Society for Neuroscience. Reproduced in accordance with the publisher's self-archiving policy.
Keywords: Coupled-Oscillator Model; Pars-Compacta Neurons; Action-Potentials; In-Vitro; Extracellular Electrophysiology; Synaptic Plasticity; Parkinsons-Disease; Pyramidal Neurons; Midbrain; RAT
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 07 Jan 2010 10:28
Last Modified: 09 Jun 2014 03:45
Published Version: http://dx.doi.org/10.1523/JNEUROSCI.2961-09.2009
Status: Published
Publisher: Society for Neuroscience
Refereed: Yes
Identification Number: 10.1523/JNEUROSCI.2961-09.2009
URI: http://eprints.whiterose.ac.uk/id/eprint/10266

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