D 2 -like dopamine receptor-mediated modulation of activity-dependent plasticity at GABAergic synapses in the subthalamic nucleus

Jérôme Baufreton, Mark D. Bevan
The Journal of Physiology. 2008-04-14; 586(8): 2121-2142
DOI: 10.1113/jphysiol.2008.151118

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1. J Physiol. 2008 Apr 15;586(8):2121-42. doi: 10.1113/jphysiol.2008.151118. Epub
2008 Feb 21.

D2-like dopamine receptor-mediated modulation of activity-dependent plasticity at
GABAergic synapses in the subthalamic nucleus.

Baufreton J(1), Bevan MD.

Author information:
(1)Northwestern University, Department of Physiology, Feinberg School of
Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA.

Comment in
J Physiol. 2008 Apr 15;586(8):2033.

Reciprocally connected glutamatergic subthalamic nucleus (STN) and GABAergic
external globus pallidus (GP) neurons normally exhibit weakly correlated,
irregular activity but following the depletion of dopamine in Parkinson’s disease
they express more highly correlated, rhythmic bursting activity. Patch clamp
recording was used to test the hypothesis that dopaminergic modulation reduces
the capability of GABAergic inputs to pattern ‘pathological’ activity in STN
neurons. Electrically evoked GABA(A) receptor-mediated IPSCs exhibited
activity-dependent plasticity in STN neurons, i.e. IPSCs evoked at frequencies
between 1 and 50 Hz exhibited depression that increased with the frequency of
activity. Dopamine, the D(2)-like dopamine receptor agonist quinpirole and
external media containing a low [Ca(2+)] reduced both the magnitude of IPSCs
evoked at 1-50 Hz and synaptic depression at 10-50 Hz. Dopamine/quinpirole also
reduced the frequency but not the amplitude of miniature IPSCs recorded in the
presence of tetrodotoxin. D(1)-like and D(4) agonists were ineffective and D(2/3)
but not D4 receptor antagonists reversed the effects of dopamine or quinpirole.
Together these data suggest that presynaptic D(2/3) dopamine receptors modulate
the short-term dynamics of GABAergic transmission in the STN by lowering the
initial probability of transmitter release. Simulated GABA(A) receptor-mediated
synaptic conductances representative of control or modulated transmission were
then generated in STN neurons using the dynamic clamp technique.
Dopamine-modulated transmission was less effective at resetting autonomous
activity or generating rebound burst firing than control transmission. The data
therefore support the conclusion that dopamine acting at presynaptic D(2)-like
receptors reduces the propensity for GABAergic transmission to generate
correlated, bursting activity in STN neurons.

DOI: 10.1113/jphysiol.2008.151118
PMCID: PMC2465193
PMID: 18292127 [Indexed for MEDLINE]

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