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

Abstract

The production of new neurons in the olfactory bulb (OB) through adulthood is a major mechanism of structural and functional plasticity underlying learning-induced circuit remodeling. The recruitment of adult-born OB neurons depends not only on sensory input but also on the context in which the olfactory stimulus is received. Among the multiple steps of adult neurogenesis, the integration and survival of adult-born neurons are both strongly influenced by olfactory learning. Conversely, optogenetic stimulation of adultborn neurons has been shown to specifically improve olfactory learning and long-term memory. However, the nature of the circuit and the synaptic mechanisms underlying this reciprocal influence are not yet known. Here, we showed that olfactory learning increases the spine density in a region-restricted manner along the dendritic tree of adult-born granule cells (GCs). Anatomical and electrophysiological analysis of adult-born GCs showed that olfactory learning promotes a remodeling of both excitatory and inhibitory inputs selectively in the deep dendritic domain. Circuit mapping revealed that the malleable dendritic portion of adult-born neurons receives excitatory inputs mostly from the regions of the olfactory cortex that project back to the OB. Finally, selective optogenetic stimulation of olfactory cortical projections to the OB showed that learning strengthens these inputs onto adult-born GCs. We conclude that learning promotes input-specific synaptic plasticity in adult-born neurons, which reinforces the top-down influence from the olfactory cortex to early stages of olfactory information processing.sensory systems | inhibitory circuits | piriform cortex | cortico-bulbar projections | glutamate

Development and Refinement of Functional Properties of Adult-Born Neurons

“…However, a more recent study using epifluorescence and multiphoton calcium imaging suggested that abGC maturation may instead follow an opposite trend, with broader tuning curves observed in putative mature cells (older than 4 weeks, labeled in the Crhr1 Cre line) than in younger cells (between 3 and 4 weeks old, labeled in the Dlx5/6 Cre line) (Quast et al, 2017). Despite the advantages of such genetic strategies for widespread labeling, it is still unclear whether they target cell populations equivalent to those labeled by the extensively validated, nucleotide-based (Gratzner, 1982; Yamaguchi and Mori, 2005) or lentiviral labeling methods (Kopel et al, 2009; Lepousez et al, 2014). In addition, genetic methods necessarily rely on studying populations of neurons at different time points, which precludes the characterization of the developmental process in individual adult-born cells and is likely to be particularly important in light of the extensive heterogeneity reported among granule cells (Naritsuka et al, 2009; Orona et al, 1983).…”

BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo

“…Activity plays a role in maintaining normal GC dendritic morphology in the adult bulb, and the activity-dependent nature of BDNF release makes this an attractive candidate factor for facilitating GC spine maturation and maintenance in response to environmental sensory cues (Kelsch et al, 2009; Dahlen et al, 2011). Recent demonstrations of GC spine remodeling with olfactory learning also suggest parallels to BDNF-mediated synaptic plasticity in this context (Tanaka et al, 2008, Vigers et al, 2012; Lepousez et al, 2014; Zagrebelsky and Korte, 2014). Taken together, the demonstrations that BDNF enrichment can increase GC spine density, while inhibition of TrkB signaling can reduce it, point to a role for endogenous BDNF signaling in modulating GC dendritic connectivity in vivo (Bergami et al, 2013).…”

“…Increased spine density in GC apical, proximal, and basal dendrites raises the possibility that in TgBDNF mice, excess BDNF may modify inputs from multiple TrkB-expressing neuronal populations that terminate on different portions of the dendritic tree. Spine plasticity within the proximal dendrite, targeted by excitatory afferents from olfactory cortex, occurs with olfactory learning, producing increased spine density in this domain and in basal dendrites on adult-born GCs (Lepousez et al, 2014). GC over-expression of BDNF may alter spine density in these compartments by remodeling cortical input, although piriform cortex itself expresses BDNF in both normal and TgBDNF mice, with potential anterograde effects on spine plasticity.…”

La plasticité hors du commun du système olfactif

“…Au-delà de leur nombre, la morphologie des nouveaux neurones peut être façonnée par l'apprentissage (Daroles et al, 2016, Lepousez et al, 2014 afin d'améliorer les performances olfactives.…”