Genetic Increases in Olfactory Bulb BDNF Do Not Enhance Survival of Adult-Born Granule Cells

Abstract

Adult-born neurons produced in the dentate gyrus subgranular zone (SGZ) develop as excitatory hippocampal granule cells (GCs), while those from the subventricular zone (SVZ) migrate to the olfactory bulb (OB), where most develop as GABAergic olfactory GCs. Both types of neurons express TrkB as they mature. Normally ~50% of new olfactory GCs survive, but survival declines if sensory drive is reduced. Increases in endogenous brain-derived neurotrophic factor (BDNF) in hippocampus, particularly with wheel running, enhance dentate GC survival. Whether survival of new olfactory GCs is impacted by augmenting BDNF in the OB, where they mature and integrate, is not known. Here, we determined if increasing OB BDNF expression enhances survival of new GCs, and if it counters their loss under conditions of reduced sensory activity. Neurogenesis was assessed under normal conditions, and following unilateral naris occlusion, in mice overexpressing BDNF in the granule cell layer (GCL). OB BDNF levels were significantly higher in transgenic mice compared to controls, and this was maintained following sensory deprivation. Bromodeoxyuridine (BrdU) cell birth dating showed that at 12–14 days post-BrdU, numbers of new GCs did not differ between genotypes, indicating normal recruitment to the OB. At later intervals, transgenic and control mice showed levels of GC loss in deprived and nondeprived animals that were indistinguishable, as was the incidence of apoptotic cells in the GCL. These results demonstrate that, in contrast to new dentate GCs, elevations in endogenous BDNF do not enhance survival of adult-born olfactory GCs.

Distinct Effects of BDNF and NT-3 on the Dendrites and Presynaptic Boutons of Developing Olfactory Bulb GABAergic Interneurons In Vitro

“…BDNF has also been shown to promote the dendritic growth of mitral and tufted OB neurons in vitro (Imamura and Greer 2009), and this neurotrophin alters the morphology and number of spines on granule neurons (Matsutani and Yamamoto 2004;McDole et al 2015). However, BDNF does not significantly enhance the survival of adult generated granule neurons in the OB (McDole et al 2020). As opposed to its growth-promoting effects, during development, pro-BDNF and BDNF can influence axon and spine pruning, two mechanisms that refine and stabilize neuronal connections (An et al 2008;Johnson et al 2007;Orefice et al 2016Orefice et al , 2013Singh et al 2008;Choo et al 2017).…”