However, the reduced transmitter release in these mice caused longer AP delays, and a decreased timing precision of postsynaptic APs. These differences were not caused by changes in the passive membrane properties nor in the intrinsic firing properties of MNTB cells, which were unchanged (Figure S2). We also investigated Robo3 cKO mice at a near-adult age (P90– P110), to verify the possibility that some of the synaptic deficits might be remedied over much INCB018424 research buy longer developmental periods. We found that EPSC

amplitudes were still significantly smaller in Robo3 cKO mice (8.9 ± 2.2 nA; n = 19) as compared to control mice (21.5 ± 2.5 nA, n = 18; p < 0.001; Figures 7E and 7F). Multiple inputs were, however, seldomly observed in Robo3 cKO and control mice (2 out of n = 18 and 0 out of n = 19 recordings, respectively). Interestingly, the paired-pulse ratio, and the EPSC rise

and decay times were unchanged (Figure 7F; p > 0.05). These findings suggest that the reduced release probability, and reduced release synchronicity found in young Robo3 cKO mice (Figures 3 and 5) recovered with further development, whereas the total synaptic strength remained significantly smaller. The latter finding might suggest that the size of the fast-releasable pool (FRP) remains reduced in Robo3 cKO mice up Imatinib datasheet to adulthood. We have shown that genetic deletion of Robo3, a manipulation which forced the commissural calyx of Held axons to make synapses on the wrong (ipsilateral) brain side, strongly impairs the developmental maturation of presynaptic function. In order to investigate whether this effect of Robo3 deletion is specific to mislocalized

commissural synapses, or else, whether it represents a more general adaptive plasticity of the auditory network, we finally measured inhibitory postsynaptic currents (IPSCs) at the MNTB to LSO synapse. Measuring IPSCs in LSO neurons at P10-P12 did not show obvious defects in inhibitory synaptic transmission (Figure 8). Several inhibitory synaptic inputs were detected upon gradual increase of the stimulation strength in both genotypes (Figure 8C; Kim and Kandler, 2003). The difference between successive stable amplitude levels in plots of IPSC amplitudes versus stimulus strength (Figures 8A and 8B) was taken as IPSC input amplitude. The IPSC new input amplitudes varied largely within each cell, but were not different between Robo3 cKO and control mice on average (Figures 8C and 8D). Similarly, the rise time and decay time of the IPSCs were not different between the two genotypes (Figure 8E), indicating that there were no obvious changes in the synchronicity of transmitter release and the postsynaptic receptor kinetics, respectively. Therefore, the functional development of the MNTB to LSO synapse, a non-crossed inhibitory connection downstream of the commissural calyx of Held synapse, was unchanged in Robo3 cKO mice.