GABAB Receptor Activation Modulates GABAA Receptor-Mediated Inhibition in Chicken Nucleus Magnocellularis Neurons

Abstract

Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl− channels [GABAA receptors (GABAARs)] and G protein-coupled receptors (GABAB receptors). The net effect of GABAAR-mediated input to NM is inhibitory, although depolarizing. Several studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance, we have found evidence for a second mechanism. We investigated modulation of GABAAR-mediated responses by GABABRs using whole cell recording techniques. Bath-applied baclofen, a GABABR agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432 , a potent and selective GABABR antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABAAR agonist muscimol, suggesting a presynaptic mechanism for the GABABR-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABABR activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABABRs function as autoreceptors, regulating synaptic strength of GABAAR-mediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.