Cross-talk pattern between GABAA- and glycine-receptors in CNS neurons is shaped by their relative expression levels

Abstract

GABA_A receptors (GABA_ARs) and glycine receptors (GlyRs) are two principal inhibitory chloride ion channels in the central nervous system. The two receptors do not function independently but cross-talk to each other, i.e., the activation of one receptor would inhibit the other. This cross-talk is present in different patterns across various regions in the central nervous system; however, the factor that determines these patterns is not understood. Here, we show that the pattern of cross-talk between the two receptors is shaped by their relative expression level in a neuron: a higher expression level correlates with louder talk. In line with a tendency of decrease in expression level of GlyRs and increase in expression level of GABA_ARs from the spinal cord, the brainstem to the neocortex, GlyRs talked much louder (i.e. produced greater inhibition) than GABA_ARs (one-way pattern) in spinal cord neurons, about equally loud as GABA_ARs (symmetric pattern) in inferior colliculus neurons and less loud (i.e. less inhibition) than GABA_ARs (asymmetric pattern) in auditory cortex neurons. Overexpression of GlyRs in inferior colliculus neurons produced an asymmetric pattern that should otherwise have been observed in spinal cord neurons. These expression level-dependent patterns of cross-talk between the two receptors may suggest how the central nervous system uses an alternative mechanism to maintain a delicate level of inhibition through adjusting the proportion of the two receptors in a neuron along its pathway.

Keywords: Cross-talk; Glycine receptor; Patch-clamp; γ-Aminobutyric acid type A receptor.