Synapse formation in the mouse olfactory bulb. I. Quantitative studies.

A quantitative study of synapse formation in the mouse olfactory bulb has been carried out using serial sections. Volumetric synaptic density as well as absolute number of synapses per olfactory bulb for eight distinct synaptic types have been determined at 15 different ages, from the beginning of synapse formation at embryonic day 14 (E14) to postnatal day 44 (P44). Synapses are first found in appreciable numbers at E15 when both axo-dendritic and a few dendro-dendritic synapses occur in the presumptive glomerular layer. Initial synapse formation correlates closely with the reorientation of mitral cells from a primitive tangenital to a definitive radial direction. Synapse formation by mitral cell dendrites occurs after mitral cell axons have grown into the future olfactory cortical areas, either simultaneous with or before synapse formation by these axons. Virtually all synaptic types detected in adults have been found on the day of birth, consistent with the idea that olfaction is an important sensory modality for newborn mice. Volumeric density of a given synaptic type generally increases 50--100 times during development while the absolute number increases about 1,000 times. Synapses in glomeruli develop more precociously than those in the time of origin and differentiation of the principal postsynaptic elements of these two divisions (mitral cells and internal granule cells). Correlation of the time of synapse formation of various synaptic types with their putative excitary or inhibitory role determined in adult studies suggests that excitatory synapses generally form somewhat earlier, although throughout nearly all of synaptic development, both excitatory and inhibitory synapses are present. Reciprocal dendro-dendritic synapses in the external plexiform layer appear to have a special mode of formation. It is suggested that a granule-to-mitral dendro-dendritic synapse only forms next to an already existing mitral-to-granule synapse on the same gemmule.