Proliferation of external globus pallidus-subthalamic nucleus synapses following degeneration of midbrain dopamine neurons
Journal of Neuroscience. 2012-10-03; 32(40): 13718-13728
DOI: 10.1523/JNEUROSCI.5750-11.2012
Lire sur PubMed
1. J Neurosci. 2012 Oct 3;32(40):13718-28. doi: 10.1523/JNEUROSCI.5750-11.2012.
Proliferation of external globus pallidus-subthalamic nucleus synapses following
degeneration of midbrain dopamine neurons.
Fan KY(1), Baufreton J, Surmeier DJ, Chan CS, Bevan MD.
Author information:
(1)Northwestern University, Physiology, Feinberg School of Medicine, Chicago,
Illinois 60611, USA.
The symptoms of Parkinson’s disease (PD) are related to changes in the frequency
and pattern of activity in the reciprocally connected GABAergic external globus
pallidus (GPe) and glutamatergic subthalamic nucleus (STN). In idiopathic and
experimental PD, the GPe and STN exhibit hypoactivity and hyperactivity,
respectively, and abnormal synchronous rhythmic burst firing. Following lesion of
midbrain dopamine neurons, abnormal STN activity emerges slowly and intensifies
gradually until it stabilizes after 2-3 weeks. Alterations in cellular/network
properties may therefore underlie the expression of abnormal firing. Because the
GPe powerfully regulates the frequency, pattern, and synchronization of STN
activity, electrophysiological, molecular, and anatomical measures of GPe-STN
transmission were compared in the STN of control and 6-hydroxydopamine-lesioned
rats and mice. Following dopamine depletion: (1) the frequency (but not the
amplitude) of mIPSCs increased by ∼70%; (2) the amplitude of evoked IPSCs and
isoguvacine-evoked current increased by ∼60% and ∼70%, respectively; (3) mRNA
encoding α1, β2, and γ2 GABA(A) receptor subunits increased by 15-30%; (4) the
density of postsynaptic gephyrin and γ2 subunit coimmunoreactive structures
increased by ∼40%, whereas the density of vesicular GABA transporter and bassoon
coimmunoreactive axon terminals was unchanged; and (5) the number of
ultrastructurally defined synapses per GPe-STN axon terminal doubled with no
alteration in terminal/synapse size or target preference. Thus, loss of dopamine
leads, through an increase in the number of synaptic connections per GPe-STN axon
terminal, to substantial strengthening of the GPe-STN pathway. This adaptation
may oppose hyperactivity but could also contribute to abnormal firing patterns in
the parkinsonian STN.
DOI: 10.1523/JNEUROSCI.5750-11.2012
PMCID: PMC3475197
PMID: 23035084 [Indexed for MEDLINE]