[Abstract Title]. - Society for Neuroscience

Topic: D.15.a. Transmitters and neuromodulation
Support: Fondation de France
NIH-NINDS Grant NS041280
CNRS
NIH-NINDS Grant NS040705
Title: Impact of chronic dopamine depletion on GABAergic transmission in the subthalamic
nucleus
Authors: *J. M. BAUFRETON 1 , A. RETAILLEAU 1 , E. KIRKHAM 2 , M. D. BEVAN 2 ;
1 Inst. des Neurosciences, Univ. Bordeaux 2, Bordeaux, France; 2 Dept. of Physiol., Northwestern
Univ., Chicago, IL
Abstract: The activity patterns of subthalamic nucleus (STN) neurons, which are intimately
related to normal movement and abnormal movement in idiopathic/experimental Parkinson‟s
disease (PD), are regulated by GABAergic inhibition from the reciprocally connected globus
pallidus (GP). Pathological hypoactivity of the GP may contribute the high rate of STN activity
in PD, whereas abnormal patterns of GP input may contribute to emergent, correlated, rhythmic
bursting STN activity in PD. Dopaminergic regulation of STN neuronal excitability is mediated,
in part, by presynaptic D2/3 dopamine receptors, which reduce activity-dependent synaptic
depression at GABAergic GP-STN synapses through a reduction in the initial probability of
transmitter release. Chronic depletion of dopamine has also been reported to lead to an increase
in whole-cell GABAA current in STN neurons. We therefore utilized patch clamp recording to
test the hypothesis that chronic depletion of dopamine leads to a profound alteration in the
magnitude and pattern of GP-STN synaptic transmission.
Young rats (17- to 24-days old) were first dopamine-depleted through unilateral stereotaxic
injection of 6-hydroxydopamine in the medial forebrain bundle or substantia nigra. The degree of
dopamine depletion was assessed using a forelimb use asymmetry test 6-13 days after surgery
and immunocytochemistry for tyrosine hydroxylase. Spontaneous and electrically evoked
GABAA receptor-mediated synaptic currents were then recorded 7-14 days after surgery from
slices ipsilateral and contralateral to lesions of midbrain dopamine neurons and age-matched
control animals.
Dopamine depletion increased the frequency but had no effect on the conductance or kinetics of
miniature GABAergic transmission recorded in the presence of tetrodotoxin. Electrically evoked
synaptic transmission also exhibited more profound synaptic depression following dopamine
depletion. Together these and other recently published data suggest that dopamine depletion
increases the initial probability of GABA release and/or number of GP-STN synapses. The
effect(s) of dopamine neuron degeneration on GP-STN transmission may therefore increase the
capability of the GP to pattern pathological STN activity in PD.
Disclosures: J.M. Baufreton, None; A. Retailleau, None; E. Kirkham, None; M.D. Bevan,
None.