Effects of noradrenaline and serotonin depletions on the neuronal activity of globus pallidus and substantia nigra pars reticulata in experimental parkinsonism
Neuroscience. 2012-01-01; 202: 424-433
DOI: 10.1016/j.neuroscience.2011.11.024
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1. Neuroscience. 2012 Jan 27;202:424-33. doi: 10.1016/j.neuroscience.2011.11.024.
Epub 2011 Nov 25.
Effects of noradrenaline and serotonin depletions on the neuronal activity of
globus pallidus and substantia nigra pars reticulata in experimental
parkinsonism.
Delaville C(1), Navailles S, Benazzouz A.
Author information:
(1)Université Bordeaux Segalen, Centre National de la Recherche Scientifique
(CNRS UMR 5293), Neurodegenerative Diseases Institute, 146 rue Léo-Saignat,
33076 Bordeaux Cedex, France.
Parkinson’s disease (PD) is characterized by a degeneration of dopaminergic
neurons and also by a degradation of noradrenergic neurons from the locus
coeruleus and serotonergic neurons from the dorsal raphe. However, the effect of
these depletions on the neuronal activity of basal ganglia nuclei is still
unknown. By using extracellular single-unit recordings, we have addressed this
question by testing the effects of selective depletions of noradrenaline (NA)
(with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4)) and
serotonin (5-HT) (with 4-chloro-l-phenylalanine (pCPA)) on the neuronal activity
of globus pallidus (GP) and substantia nigra pars reticulata (SNr) neurons in
the 6-hydroxydopamine (6-OHDA) rat model of PD and sham-lesioned rats. We showed
that 6-OHDA-induced dopamine (DA) depletion resulted in an increased number of
GP and SNr neurons discharging in a bursty and irregular manner, confirming
previous studies. These pattern changes were region-dependently influenced by
additional monoamine depletion. Although the number of irregular and bursty
neurons in 6-OHDA rats tended to decrease in the GP after NA depletion, it did
not change after pCPA treatment in both GP and SNr. Furthermore, a significant
interaction between DA and 5-HT depletions was observed on the firing rate of
SNr neurons. By themselves, NA depletion did not change GP or SNr neuronal
activity, whereas 5-HT depletion decreased the firing rate and increased the
proportion of bursty and irregular neurons in both brain regions, suggesting
that 5-HT, but not NA, plays a major role in the modulation of both the firing
rate and patterns of GP and SNr neurons. Finally, our data suggest that, in
addition to the primary role of DA in the control of basal ganglia activity, NA
and 5-HT depletion also contribute to the dysregulation of the basal ganglia in
PD by changes to neuronal firing patterns.
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuroscience.2011.11.024
PMID: 22138505 [Indexed for MEDLINE]