Synaptic release of dopamine in the subthalamic nucleus

Stephanie J. Cragg, Jerome Baufreton, Yi Xue, J. Paul Bolam, Mark D. Bevan
Eur J Neurosci. 2004-10-01; 20(7): 1788-1802
DOI: 10.1111/j.1460-9568.2004.03629.x

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1. Eur J Neurosci. 2004 Oct;20(7):1788-802.

Synaptic release of dopamine in the subthalamic nucleus.

Cragg SJ(1), Baufreton J, Xue Y, Bolam JP, Bevan MD.

Author information:
(1)Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.

The direct modulation of subthalamic nucleus (STN) neurons by dopamine (DA)
neurons of the substantia nigra (SN) is controversial owing to the thick caliber
and low density of DA axons in the STN. The abnormal activity of the STN in
Parkinson’s disease (PD), which is central to the appearance of symptoms, is
therefore thought to result from the loss of DA in the striatum. We carried out
three experiments in rats to explore the function of DA in the STN: (i) light and
electron microscopic analysis of tyrosine hydroxylase (TH)-, dopamine
beta-hydroxylase (DbetaH)- and DA-immunoreactive structures to determine whether
DA axons form synapses; (ii) fast-scan cyclic voltammetry (FCV) to determine
whether DA axons release DA; and (iii) patch clamp recording to determine whether
DA, at a concentration similar to that detected by FCV, can modulate activity and
synaptic transmission/integration. TH- and DA-immunoreactive axons mostly formed
symmetric synapses. Because DbetaH-immunoreactive axons were rare and formed
asymmetric synapses, they comprised the minority of TH-immunoreactive synapses.
Voltammetry demonstrated that DA release was sufficient for the activation of
receptors and abolished by blockade of voltage-dependent Na+ channels or removal
of extracellular Ca2+. The lifetime and concentration of extracellular DA was
increased by blockade of the DA transporter. Dopamine application depolarized STN
neurons, increased their frequency of activity and reduced the impact of
gamma-aminobutyric acid (GABA)-ergic inputs. These findings suggest that SN DA
neurons directly modulate the activity of STN neurons and their loss may
contribute to the abnormal activity of STN neurons in PD.

DOI: 10.1111/j.1460-9568.2004.03629.x
PMID: 15380000 [Indexed for MEDLINE]

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