Modulation of GABA A ‐ergic synaptic currents by GABA B ‐ergic presynaptic inputs in mouse locus coeruleus neurons

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.