Sequential development of synapses in dendritic domains during adult neurogenesis.

ABSTRACT

During the process of integration into brain circuits, new neurons develop both input and output synapses with their appropriate targets. The vast majority of neurons in the mammalian brain are generated before birth and integrate into immature circuits while these are being assembled. In contrast, adult-generated neurons face an additional challenge as they integrate into a mature, fully functional circuit. Here, we examined how synapses of a single neuronal type, the granule cell in the olfactory bulb, develop during their integration into the immature circuit of the newborn and the fully mature circuit of the adult rat. We used a genetic method to label pre and postsynaptic sites in granule neurons and observed a stereotypical development of synapses in specific dendritic domains. In adult-generated neurons, synapses appeared sequentially in different dendritic domains with glutamatergic input synapses that developed first at the proximal dendritic domain, followed several days later by the development of input-output synapses in the distal domain and additional input synapses in the basal domain. In contrast, for neurons generated in neonatal animals, input and input-output synapses appeared simultaneously in the proximal and distal domains, respectively, followed by the later appearance of input synapses to the basal domain. The sequential formation of synapses in adult-born neurons, with input synapses appearing before output synapses, may represent a cellular mechanism to minimize the disruption caused by the integration of new neurons into a mature circuit in the adult brain.