The Mammalian Interaural Time Difference Detection Circuit Is Differentially Controlled by GABAB Receptors during Development

Abstract

Throughout development GABA(B) receptors (GABA(B)Rs) are widely expressed in the mammalian brain. In mature auditory brainstem neurons, GABA(B)Rs are involved in the short-term regulation of the strength and dynamics of excitatory and inhibitory inputs, thus modulating sound analysis. During development, GABA(B)Rs also contribute to long-term changes in input strength. Using a combination of whole-cell patch-clamp recordings in acute brain slices and immunostainings in gerbils, we characterized developmental changes in GABA(B)R-mediated regulation of synaptic inputs to neurons in the medial superior olive (MSO), an auditory brainstem nucleus that analyzes interaural time differences (ITDs). Here, we show that, before hearing onset, GABA(B)R-mediated depression of transmitter release is much stronger for excitation than inhibition, whereas in mature animals GABA(B)Rs mainly control the inhibition. During the same developmental period, GABA(B)R immunoreactivity shifts from the dendritic to the somatic region of the MSO. Furthermore, only before hearing onset (postnatal day 12), stimulation of the fibers originating in the medial and the lateral nucleus of the trapezoid body (MNTB and LNTB) activates GABA(B)Rs on both the inhibitory and the excitatory inputs. After hearing onset, GAD65-positive endings devoid of glycine transporter reactivity suggest GABA release from sources other than the MNTB and LNTB. At this age, pharmacological increase of spontaneous synaptic release activates GABA(B)Rs only on the inhibitory inputs. This indicates not only a profound inhibitory effect of GABA(B)Rs on the major inputs to MSO neurons in neonatal animals but also a direct modulatory role of GABA(B)Rs for ITD analysis in the MSO of adult animals.