Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (P r ), and large quantal size (Q). However, high P r also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low P r . For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased P r . These changes in N and P r were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activitydependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences.homeostasis | release probability | cochlear nucleus S ynapses must be able to transmit information reliably over a range of activity levels. A critical factor in regulating this fidelity is the probability of neurotransmitter release (P r ). If P r is too high, synapses may have high fidelity at low rates of activity, but they would strongly depress at high rates, which could reduce postsynaptic spiking. If P r is too low, failure to release neurotransmitter could reduce fidelity.Activity can influence synaptic properties through multiple mechanisms. One mechanism, homeostatic synaptic scaling, is an activity-dependent regulation of quantal size (Q) (1-3), which has recently been reported to occur in vivo (4, 5). One limitation is that changes in Q do not change the degree of synaptic depression. Furthermore, increases in Q could be limited by receptor number or density. In dissociated hippocampal cell cultures, activity-dependent changes in P r have been observed (6-8). However, it is not known whether such changes in P r occur in vivo in the intact brain. In addition, it is not clear how modulation of P r could prevent depression without also causing large changes in the magnitude of the excitatory postsynaptic current (EPSC).Fidelity is critical for auditory nerve (AN) synapses onto bushy cells (BCs) in the anteroventr...

Auditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages in the ventral cochlear nucleus (VCN). Remarkably, to date only a single subtype of inhibitory neuron has been documented in the VCN, a projection neuron termed the D-stellate cell. With the use of a transgenic mouse line, optical clearing and imaging techniques, combined with electrophysiological tools, we revealed a population of glycinergic cells in the VCN distinct from the D-stellate cell. These multipolar glycinergic cells were smaller in soma size and dendritic area, but over 10-fold more numerous than D-stellate cells. They were activated by AN and T-stellate cells, and made local inhibitory synaptic contacts on principal cells of the VCN. Given their abundance, combined with their narrow dendritic fields and axonal projections, it is likely that these neurons, here termed L-stellate cells, play a significant role in frequency-specific processing of acoustic signals.

12Auditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages 13 in the ventral cochlear nucleus (VCN). Remarkably, to date only a single subtype of inhibitory 14 neuron has been documented in the VCN, a projection neuron termed the D-stellate cell. With 15 the use of a transgenic mouse line, optical clearing and imaging techniques, combined with 16 electrophysiological tools, we revealed a population of glycinergic cells in the VCN distinct from 17 the D-stellate cell. These novel multipolar glycinergic cells were smaller in soma size and 18 dendritic area, but over 10-fold more numerous than D-stellate cells. They were activated by 19 auditory nerve fibers and T-stellate cells, and made local inhibitory synaptic contacts on 20 principal cells of the VCN. Given their abundance, combined with their narrow dendritic fields 21 and axonal projections, it is likely that these neurons, here termed L-stellate cells, play a 22 significant role in frequency-specific processing of acoustic signals. 23Axon-dendritic arbors of cell types 132