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Neuroscience

The physiological role of pre- and postsynaptic GABA(B) receptors in membrane excitability and synaptic transmission of neurons in the rat's dorsal cortex of the inferior colliculus.


PMID 19409201

Abstract

In the inferior colliculus (IC), GABAergic inhibition mediated by GABA(A) receptors has been shown to play a significant role in regulating physiological responses, but little is known about the physiological role of GABA(B) receptors in IC neurons. In the present study, we used whole-cell patch clamp recording in vitro to investigate the effects of activation of GABA(B) receptors on membrane excitability and synaptic transmission of neurons in the rat's dorsal cortex of the inferior colliculus (ICD). Repetitive stimulation of GABAergic inputs to ICD neurons at high frequencies could elicit a slow and long-lasting postsynaptic response, which was reversibly abolished by the GABA(B) receptor antagonist, CGP 35348. The results suggest that postsynaptic GABA(B) receptors can directly mediate inhibitory synaptic transmission in ICD. The role of postsynaptic GABA(B) receptors in regulation of membrane excitability was further investigated by application of the GABA(B) receptor agonist, baclofen. Baclofen hyperpolarized the cell, reduced the membrane input resistance and firing rate, increased the threshold for generating action potentials (APs), and decreased the amplitude of the AP and its associated after-hyperpolarization. The Ca2+-mediated rebound depolarization following hyperpolarization and the depolarization hump at the beginning of membrane depolarization were also suppressed by baclofen. In voltage clamp experiments, baclofen induced inward rectifying K+ current and reduced low- and high-threshold Ca2+ currents, which may account for the suppression of membrane excitability by postsynaptic GABA(B) receptors. Application of baclofen also reduced excitatory synaptic responses mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and inhibitory synaptic responses mediated by GABA(A) receptors. Baclofen increased the ratios of 2nd/1st excitatory and inhibitory postsynaptic currents to paired-pulse stimulation of the synaptic inputs. These results suggest that fast glutamatergic and GABAergic synaptic transmission in ICD can be modulated by presynaptic GABA(B) receptors.

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C5851
CGP 35348 hydrate, ≥97% (NMR), solid
C8H20NO4P · xH2O