The lateral superior olivary nucleus (LSO) is an auditory relay centre within the brain stem that encodes interaural level differences for sound localization by integrating GABA/glycinergic input from the contralateral ear via the medial nucleus of the trapezoid body (MNTB), and glutamatergic input from the ipsilateral ear via the ventral cochlear nucleus (VCN). To study the development of the circuits that contribute to the establishment of sound localization, the heterosynaptic modulation mediated by glutamate released from VCN terminals and group II metabotropic glutamate receptor (mGluR) expressed on MNTB inhibitory terminals was investigated using whole-cell patch-clamp techniques. At postnatal day-4-8 (P4-8), repetitive stimulation of the VCN-LSO excitatory afferents caused significant inhibition of MNTB-LSO inhibitory postsynaptic currents (IPSCs) in amplitude with an increase of its coefficient of variation and changed the paired-pulse ratio. These effects were antagonized by LY341495, an mGluR2/3 antagonist. Thus, the suppression of MNTB-LSO synaptic responses induced by repetitive stimulation applied to the VCN-LSO glutamatergic afferent is presumably due to an activation of mGluR2/3 existing on MNTB-LSO presynaptic terminals. The suppression rate of MNTB-LSO IPSCs by DCG IV, an mGluR2/3 agonist, decreased with development and became negligible by the third week after birth. The immunohistochemical staining of mGluR2/3 in the LSO was also less apparent at P18 compared with that at P4. We suggest that mGluR-mediated heterosynaptic modulation of MNTB-LSO GABAergic/glycinergic transmission might contribute to the development of appropriate adult auditory circuits.

During the development of the rat hippocampus, both gamma-aminobutyric acid (GABA)(B) autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABA(A) receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABA(A) receptor-mediated responses, the interactions between GABA(B) autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABA(A) receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABA(B) receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABA(B) receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.