Activity-Dependent Activation of Presynaptic Metabotropic Glutamate Receptors in Locus Coeruleus

• Published in: Journal of neurophysiology Vol. 83; no. 3; pp. 1141 - 1149
• Main Authors: Dube, G. R, Marshall, K. C
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01-03-2000
• Subjects: amino acids (excitatory); Aminobutyrates - pharmacology; Animals; Cycloleucine - analogs & derivatives; Cycloleucine - pharmacology; Electric Stimulation; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Feedback - drug effects; Feedback - physiology; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; Locus Coeruleus - drug effects; Locus Coeruleus - physiology; Male; Rats; Rats, Sprague-Dawley; Receptors, GABA-B - drug effects; Receptors, Metabotropic Glutamate - drug effects; Receptors, Metabotropic Glutamate - physiology; Receptors, Presynaptic - antagonists & inhibitors; Receptors, Presynaptic - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.2000.83.3.1141

Department of Cellular and Molecular Medicine, Faculty of Medicine,
University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
Dubé, G. R. and
K. C. Marshall.
Activity-Dependent Activation of Presynaptic Metabotropic
Glutamate Receptors in Locus Coeruleus. J. Neurophysiol. 83: 1141-1149, 2000. Synaptic activation of
metabotropic glutamate receptors (mGluRs) in the locus coeruleus (LC)
was investigated in adult rat brain slice preparations. Evoked
excitatory postsynaptic potentials (EPSPs) resulting from stimulation
of LC afferents were measured with current clamp from intracellularly
recorded LC neurons. In this preparation, mGluR agonists
(±)-1-aminocyclopentane- trans -1,3-dicarboxylic acid
( t -ACPD) and L(+)-2-amino-4-phosphonobutyric
acid (L-AP4) activate distinct presynaptic mGluRs,
resulting in an inhibition of EPSPs. When two stimuli were applied to
afferents at intervals >200 ms, the amplitude of the second [test
(T)] EPSP was identical in amplitude to the first [control(C)].
However, when a stimulation volley was delivered before T, the
amplitude of the latter EPSP was consistently smaller than C. The
activity-dependent depression (ADD) was dependent on the frequency and
duration of the train and the interval between the train and T. ADD was
potentiated in the presence of an excitatory amino acid (EAA) uptake
inhibitor L- trans -pyrrolidine-2,4-dicarboxylic acid
( t -PDC, 100 µM), changing the T/C ratio from 0.84 ± 0.05 (mean ± SE) in control to 0.69   ± 0.04 in
t- PDC ( n  = 9). In the presence of
t- PDC, the depolarizing response of LC neurons to
focally applied glutamate was also increased. Together, these results
suggest that accumulation of EAA after synaptic stimulation may be
responsible for ADD. To test if ADD is a result of the activation of
presynaptic mGluRs, the effect of selective mGluR antagonists on ADD
was assessed. In the presence of t -PDC, bath applied
(S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 500 µM), a mGluR
group III antagonist, significantly reversed the decrease in T/C ratio
after a train stimulation [from 0.66 ± 0.04 to 0.81 ± 0.02 (mean ± SE), n  = 5]. The T/C ratio in the
presence of MAP4 was not different from that measured in the absence of
a stimulation volley. Conversely, ethyl glutamic acid (EGLU, 500 µM),
a mGluR group II antagonist, failed to alter the T/C ratio. Together,
these results suggest that, in LC, group III presynaptic mGluR
activation provides a feedback mechanism by which excitatory synaptic
transmission can be negatively modulated during high-frequency synaptic
activity. Furthermore, this study provides functional differentiation
between presynaptic groups II and III mGluR in LC and suggests that the
group II mGluR may be involved in functions distinct from those of
group III mGluRs.