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Modulation of GABA A ‐ergic synaptic currents by GABA B ‐ergic presynaptic inputs in mouse locus coeruleus neurons
Author(s) -
Jin Xin,
Cui Ningren,
Zhong Weiwei,
Oginsky Max,
Zhang Shuang,
Jiang Chun
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.903.4
Subject(s) - inhibitory postsynaptic potential , gabab receptor , baclofen , neuroscience , hyperpolarization (physics) , excitatory postsynaptic potential , chemistry , locus coeruleus , postsynaptic potential , postsynaptic current , neurotransmission , gabaa receptor , biophysics , biology , receptor , central nervous system , biochemistry , agonist , organic chemistry , nuclear magnetic resonance spectroscopy
Norepinephrinergic neurons in the locus coeruleus (LC) play an important role in neuromodulation of a variety of neurons. These cells are modulated by both GABA A ‐ergic and GABA B ‐ergic synaptic inputs. The GABA A ‐ergic input produces inhibition of LC neurons. However, the GABA B effect remains controversial. Through GIRK channels, activation of the GABA B ‐ergic receptors in post‐synaptic neurons leads to hyperpolarization and an inhibition of spontaneous firing activity, whereas the presynaptic GABA B ‐ergic modulation can be inhibitory or excitatory depending on the primary neurotransmitter targeted. To reveal the GABA B ‐ergic modulation, we studied LC neurons in mouse brain slices. In whole‐cell current clamp, an exposure to 5 μM baclofen produced hyperpolarization, accompanied with ~20% decrease in input resistance and ~30% inhibition of firing activity. The same baclofen treatment, in contrast, produced significant depolarization with increased input resistance when 1 mM GDP‐β‐S was added to the pipette solution, suggesting a disinhibiton of the LC neurons by presynaptic GABA B ‐ergic input. Therefore, the modulation of the GABA A ‐ergic post‐synaptic currents by presynaptic GABA B receptors was studied in voltage clamp. The frequency, but not the amplitude, of GABA A ‐ergic miniature post‐synaptic currents was strongly inhibited by 5 μM baclofen and augmented by 20 μM phaclofen, respectively. These results thus suggest that activation of GABA B receptors produces postsynaptic inhibition, whereas the presynaptic GABA B modulation seems to serve for a feedback control of the GABA release from presynaptic terminals.