Molecular layer inhibitory interneurons provide feedforward and lateral 1 inhibition in the dorsal cochlear nucleus

26 27 28 In the outer layers of the dorsal cochlear nucleus, a cerebellum-like structure in the 29 auditory brainstem, multimodal sensory inputs drive parallel fibers to excite both principal 30 (fusiform) cells and inhibitory cartwheel cells. Cartwheel cells, in turn, inhibit fusiform 31 cells and other cartwheel cells. At the microcircuit level, it is unknown how these circuit 32 components interact to modulate the activity of fusiform cells and thereby shape the 33 processing of auditory information. Using a variety of approaches in mouse brainstem 34 slices, we investigated the synaptic connectivity and synaptic strength among parallel 35 fibers, cartwheel cells, and fusiform cells. In paired recordings of spontaneous and evoked 36 activity, we found little overlap in parallel fiber input to neighboring neurons, and 37 activation of multiple parallel fibers was required to evoke or alter action potential firing in 38 cartwheel and fusiform cells. Thus, neighboring neurons likely respond best to distinct 39 subsets of sensory inputs. In contrast, there was significant overlap in inhibitory input to 40 neighboring neurons. In recordings from synaptically coupled pairs, cartwheel cells had a 41 high probability of synapsing onto nearby fusiform cells or other nearby cartwheel cells. 42 Moreover, single cartwheel cells strongly inhibited spontaneous firing in single fusiform 43 cells. These synaptic relationships suggest that the set of parallel fibers activated by a 44 particular sensory stimulus determines whether cartwheel cells provide feedforward or 45 lateral inhibition to their postsynaptic targets. 46 47 48