Distribution of GABABRs in auditory brainstem nuclei. (A) Diagram of a coronal section through the brainstem showing a simplified representation of the circuits formed by neurons of the auditory nuclei, dorsal and ventral cochlear nuclei (DCN, VCN), lateral and medial superior olive (LSO, MSO), and medial nucleus of the trapezoid body (MNTB). Excitatory (glutamatergic) and inhibitory (glycinergic) projections are represented by red and blue lines, respectively. GABABRs have been identified on large axosomatic terminals on spherical bushy cells (SBC) and globular bushy cells (GBC) in the VCN and on MNTB principal cells (PC), referred to as endbulbs of Held (BH) and calyces of Held (CH), respectively, as well as on principal neurons in the LSO and MSO and their excitatory and inhibitory boutons. Dashed lines indicate ascending projections of brainstem neurons passing through the lateral lemniscus (LL) to the inferior colliculus (IC). The inset (asterisk) on the left of the section shows a detail of the inhibitory synapse formed by the axon of an MNTB PC on the soma of an LSO neuron. At mature LSO synapses, presynaptic GABABRs control glycine release by inhibiting VGCC (green), whereas at immature synapses, somatic GABABRs additionally regulate postsynaptic excitability by activating GIRK channels (red). See sections 4.1 and 4.2 for details. (B) Schematic representation of selected synaptic connections between excitatory (red) and inhibitory (blue) neurons in the DCN (adapted from (87). GABABRs have been found in pre- and postsynaptic compartments of DCN neurons, where they control glutamate release and short-term synaptic plasticity or neuronal excitability. Presynaptic receptors are localized in auditory nerve endings on basal dendrites of glutamatergic fusiform cells (FC) and in glutamatergic terminals of axons of granule cells (GrC), parallel fibers, innervating apical dendrites of both fusiform cells and glycinergic cartwheel cells (CwC). The subcellular distribution of postsynaptic GABABRs expressed by fusiform and cartwheel cells shows a dendrosomatic gradient, with receptor density reaching highest values in the distal parts of apical dendrites (dark green). AC – auditory cortex, IC – inferior colliculus, LL – lateral lemniscus, SOC – superior olivary complex, TvC – tuberculoventral cell, D-stellate – a subtype of inhibitory neuron in VCN.