The Journal of Neuroscience, January 15, 2003, 23(2):442-452
Bidirectional Modulation of GABA Release by Presynaptic Glutamate
Receptor 5 Kainate Receptors in the Basolateral Amygdala
Maria F. M.
Braga1,
Vassiliki
Aroniadou-Anderjaska1,
Jianwu
Xie2, and
He
Li1
Departments of 1 Psychiatry and
2 Pathology, Uniformed Services University of the Health
Sciences, Bethesda, Maryland 20814
The activation of kainate receptors modulates GABAergic
synaptic transmission, but the mechanisms are currently a matter of intense debate. In the basolateral amygdala (BLA), the glutamate receptor 5 (GluR5) subunit of kainate receptors is heavily expressed, and GluR5 antagonists block a novel form of synaptic plasticity; yet
little is known about the role of GluR5-containing kainate receptors in
the physiology of the amygdala. Here we show that GluR5 agonists
bidirectionally modulate the strength of synaptic transmission from
GABAergic interneurons to pyramidal cells in a concentration-dependent
manner. Low concentrations of
(RS)-S-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA) (0.3 µM) or glutamate (5 µM) reduced
the number of failures of GABAergic synaptic transmission and enhanced
the frequency of miniature IPSCs (mIPSCs). High concentrations of ATPA
(10 µM) or glutamate (200 µM) increased the
number of synaptic failures and reduced the frequency of mIPSCs. The
facilitation or suppression of GABAergic transmission by the GluR5
agonists did not require activation of voltage-gated calcium channels
or presynaptic GABAB receptors. It was also found that
extracellular, endogenous glutamate tonically reduces the rate of
failures of GABAergic transmission. These results suggest that the
terminals of GABAergic neurons in the BLA carry two subtypes of
GluR5-containing kainate receptors, which have different agonist
affinities and activate opposing mechanisms of action. The
GluR5-mediated, bidirectional modulation of GABA release by glutamate
in the BLA may play an important role in the regulation of synaptic
plasticity and neuronal excitability in this structure, under normal
and pathological conditions.
Key words:
GluR5; presynaptic kainate receptors; glutamate
diffusion; GABA release; inhibitory synaptic transmission; amygdala
Copyright © 2003 Society for Neuroscience 0270-6474/03/232442-11$05.00/0
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