Ultrastructure of Inputs to the Granule Cell Domain of the Dorsal Cochlear Nucleus

The granule cell domain of the cochlear nucleus (GCD) receives input from multimodal brain regions including the second cervical spinal ganglion, the spinal trigeminal nucleus, the cuneate nucleus, and the lateral reticular nucleus. Most of the input are in the form of large mossy fibers and small boutons containing round synaptic vesicles and forming asymmetric synapses. A smaller number of inputs arise from the lateral reticular nucleus and the spinal trigeminal nucleus that contain pleomorphic synaptic vesicles implying inhibitory action. This circumstance positions the GCD for integrating polysensory excitatory and inhibitory inputs at the earliest stages of auditory processing, which suggests a role for segregating sound streams. The structural substrate for such a function is naturally elaborate. Mossy fibers from these different origins are large, multilobed endings that form synaptic glomeruli with postsynaptic targets that include granule cells, unipolar brush cells, cartwheel cells, and chestnut cells, which in turn project to principal cells in the dorsal cochlear nucleus (DCN). Numerous synapses contribute to the integration of the different modalities, but the organization of these synapses is still not well understood. We investigated this issue by labelling the presynaptic endings of different somatosensory inputs using biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin, and studying their post-synaptic relationships in the GCD. The anterogradely-labeled endings and associated targets were visualized by light and electron microscopy. Following computer-aided, three-dimensional reconstructions, we found that unipolar brush cells are the main target of the C2 DRG and cuneate nucleus. Mossy fibers from the spinal trigeminal nucleus project to Golgi cells, an inhibitory neuron. In contrast, inhibitory boutons originated from the lateral reticular nucleus. These results reveal that somatosensory integration in the granule cell domain is achieved by distinctive synaptic wiring and specialized chemical signaling.