A Critical Period for Activity-Dependent Synaptic Development during Olfactory Bulb Adult Neurogenesis

Abstract

New neurons integrate in large numbers into the mature olfactory bulb circuit throughout life. The factors controlling the synaptic development of adult-born neurons and their connectivity remain essentially unknown. We examined the role of activity-dependent mechanisms in the synaptic development of adult-born neurons by genetic labeling of synapses while manipulating sensory input or cell-intrinsic excitability. Sensory deprivation induced marked changes in the density of input and output synapses during the period when new neurons develop most of their synapses. In contrast, when sensory deprivation started after synaptic formation was complete, input synapses increased in one domain without detectable changes in the other dendritic domains. We then investigated the effects of genetically raising the intrinsic excitability of new neurons on their synaptic development by delivering a voltage-gated sodium channel that triggers long depolarizations. Surprisingly, genetically increasing excitability did not affect synaptic development but rescued the changes in glutamatergic input synapses caused by sensory deprivation. These experiments show that, during adult neurogenesis in the olfactory bulb, synaptic plasticity is primarily restricted to an early period during the maturation of new neurons when they are still forming synapses. The addition of cells endowed with such an initial short-lived flexibility and long-term stability may enable the processing of information by the olfactory bulb to be both versatile and reliable in the face of changing behavioral demands.

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

“…Spine density in the proximal compartment of adult-born GCs peaks at 15-30 d before further pruning at 90 dpi (29). Moreover, impairing NMDA receptors decreases the proximal spine density but sensory deprivation distinctly alters proximal and basal domains (22,31). Collectively, these data indicate that sensory experience strongly influences the direction and location of structural synaptic plasticity.…”

“…Developmental analysis of apical spine density in adult-born GCs has shown a progressive increase at 15-30 dpi followed by a slight decrease and stabilization at 50-90 d (28)(29)(30). Olfactory deprivation between 15 and 30 dpi strongly reduces apical spine density (22), whereas passive odorant exposure has no significant effect on spine density (29) but decreases spine turnover (8). We also confirmed that neither odor exposure nor odor learning affects apical spine density and maturation, suggesting that apical spine turnover, rather than the total number of spines, is impacted by sensory experience.…”

“…We next asked whether the observed compartment-specific changes in spine density were differentially associated with alterations in excitatory and inhibitory synaptic inputs. To selectively quantify adult-born GC glutamatergic inputs, PSD95, a postsynaptic scaffolding protein of glutamatergic synapses, was visualized using lentiviral expression of PSD95 fused to GFP (7,8,(20)(21)(22). PSD95-GFP + puncta were observed mainly in spine heads and, to a lesser degree, in the dendritic shafts ( Fig.…”

GluN2B-Containing NMDA Receptors Promote Wiring of Adult-Born Neurons into Olfactory Bulb Circuits

“…Tissue processing and analysis of PSD-95GFP ϩ clusters was performed as previously described (Kelsch et al, 2009). Confocal image stacks were acquired using a Zeiss LSM700 (63ϫ oil-immersion objective) (512 ϫ 512 pixel with pixel size of 0.196 ϫ 0.196 m), and with z-step 0.25 m (80 -150 sections).…”

“…Adult-born GCs are generated in the subventricular zone (SVZ) and migrate to the OB where they form synaptic connections during a narrow time window (Carleton et al, 2003;Whitman and Greer, 2007;Kelsch et al, 2008). Only during this period of synaptic development, sensory deprivation changes the synaptic organization of glutamatergic synapses and increases cell death of adult-born GCs (Yamaguchi and Mori, 2005;Kelsch et al, 2009).…”