Inhibitory circuitry in the ventral cochlear nucleus is probably mediated by glycine.

Intracellular recordings from brain slice preparations of the ventral cochlear nuclei (VCN) of mice have shown that both the major cell types, stellate and bushy cells, distinguishable by their responses to intracellularly injected current (Oertel, 1983; Wu and Oertel, 1984), receive late inhibitory as well as early excitatory inputs when the auditory nerve is stimulated electrically. When the extracellular Cl- concentration was lowered or when the intracellular Cl- was raised, the reversal potential of IPSPs became more positive; the reversal potentials were independent of the extracellular K+ concentration. Therefore, IPSPs result from increases in Cl- permeability. To determine whether either or both GABA or glycine might mediate the inhibition, the sensitivity of cells to bath-applied putative neurotransmitters was tested. All cells responded to applications of 0.1-10 mM GABA and glycine with large drops in input resistance; these drops were Cl- dependent. To determine which of these 2 substances was more likely to mediate the IPSPs, antagonists specific to GABA and glycine were tested for their ability to block the IPSPs. All IPSPs were eliminated by 1 microM strychnine, a blocker of glycine-mediated inhibition; they were not consistently blocked by 100 microM bicuculline or by 100 microM picrotoxin, blockers of GABA-mediated inhibition. These results indicate that the inhibition is likely to be mediated by glycine. A simple interpretation of the finding that IPSPs have latencies (1.2-4 msec) at least 2X as long as EPSPs (0.6-0.9 msec) is that cells in the VCN are excited monosynaptically by auditory nerve fibers, and that they are inhibited disynaptically through interneurons within the VCN. To test physiologically whether EPSPs and IPSPs are, respectively, monosynaptic and polysynaptic, 500-700 microM sodium pentobarbital was applied to the preparation. Pentobarbital raised the thresholds of all impaled cells and their synaptic inputs. EPSPs could be evoked in the presence of pentobarbital by raising the stimulus strength, as expected when thresholds are raised in a monosynaptic circuit; even if the thresholds of IPSPs were lower than those of EPSPs in normal saline, they were raised above those of EPSPs in the presence of pentobarbital. The finding that the thresholds of IPSPs are raised more than those of EPSPs supports the interpretation that IPSPs are mediated through a polysynaptic pathway, and this may explain why inhibition has been detected inconsistently in vivo.