Mizrahi, A. Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb. Nature Neurosci. 10, 444-452

Department of Neurobiology, Institue for Life Sciences and the Interdisciplinary Center for Neural Computation, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
Nature Neuroscience (Impact Factor: 16.1). 05/2007; 10(4):444-52. DOI: 10.1038/nn1875
Source: PubMed


The mammalian brain maintains few developmental niches where neurogenesis persists into adulthood. One niche is located in the olfactory system where the olfactory bulb continuously receives functional interneurons. In vivo two-photon microscopy of lentivirus-labeled newborn neurons was used to directly image their development and maintenance in the olfactory bulb. Time-lapse imaging of newborn neurons over several days showed that dendritic formation is highly dynamic with distinct differences between spiny neurons and non-spiny neurons. Once incorporated into the network, adult-born neurons maintain significant levels of structural dynamics. This structural plasticity is local, cumulative and sustained in neurons several months after their integration. Thus, I provide a new experimental system for directly studying the pool of regenerating neurons in the intact mammalian brain and suggest that regenerating neurons form a cellular substrate for continuous wiring plasticity in the olfactory bulb.

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    • "Sensory deprivation leads to decreases in the density of dendritic spines (Keck et al., 2011) and branch tips (Chen et al., 2011) along with reductions in axonal bouton density (Marik et al., 2010; Chen et al., 2011; Keck et al., 2011) in inhibitory cortical neurons, which contrasts with concomitant elevations in spine turnover (Keck et al., 2008) or axonal growth (Yamahachi et al., 2009; Marik et al., 2010) in neighboring pyramidal cells. In the OB, activitydependent alterations in the structure of postnatally generated interneurons (Saghatelyan et al., 2005; Mizrahi, 2007; Livneh et al., 2009) contrast not only with the lack of such changes in the resident developmentally generated GABAergic population (Saghatelyan et al., 2005) but also with the striking structural stability of mitral/tufted cell dendrites (Mizrahi and Katz, 2003). Therefore, our data reveal a novel form of plasticity in OB dopaminergic cells, which, like many other forms of structural plasticity in inhibitory interneurons, takes the opposite form to changes observed in excitatory cells. "
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    ABSTRACT: The axon initial segment (AIS) is a specialized structure near the start of the axon that is a site of neuronal plasticity. Changes in activity levels in vitro and in vivo can produce structural AIS changes in excitatory cells that have been linked to alterations in excitability, but these effects have never been described in inhibitory interneurons. In the mammalian olfactory bulb (OB), dopaminergic interneurons are particularly plastic, undergoing constitutive turnover throughout life and regulating tyrosine hydroxylase expression in an activity-dependent manner. Here we used dissociated cultures of rat and mouse OB to show that a subset of bulbar dopaminergic neurons possess an AIS and that these AIS-positive cells are morphologically and functionally distinct from their AIS-negative counterparts. Under baseline conditions, OB dopaminergic AISs were short and located distally along the axon but, in response to chronic 24 h depolarization, lengthened and relocated proximally toward the soma. These activity-dependent changes were in the opposite direction to both those we saw in non-GABAergic OB neurons and those reported previously for excitatory cell types. Inverted AIS plasticity in OB dopaminergic cells was bidirectional, involved all major components of the structure, was dependent on the activity of L-type CaV1 calcium channels but not on the activity of the calcium-activated phosphatase calcineurin, and was opposed by the actions of cyclin-dependent kinase 5. Such distinct forms of AIS plasticity in inhibitory interneurons and excitatory projection neurons may allow considerable flexibility when neuronal networks must adapt to perturbations in their ongoing activity. Copyright © 2015 Chand et al.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2015; 35(4):1573-90. DOI:10.1523/JNEUROSCI.3515-14.2015 · 6.34 Impact Factor
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    • "These results show that the spontaneous firing characteristics and the basic odor response profiles of adult-born neurons eventually mature to become similar to those of resident neurons. These results build upon and seem to support earlier morphological and biophysical characteristics of adult-born neurons along development (Carleton et al., 2003; Grubb et al., 2008; Mizrahi, 2007). Thus, at least under normal conditions in which animals are not behaviorally challenged with novel sensory stimuli in their environment, adult-born neurons seem to mature to become similar to resident neurons (but see below). "
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    ABSTRACT: The adult mammalian brain is continuously supplied with adult-born neurons in the olfactory bulb (OB) and hippocampus, where they are thought to be important for circuit coding and plasticity. However, direct evidence for the actual involvement of these neurons in neural processing is still lacking. We recorded the spiking activity of adult-born periglomerular neurons in the mouse OB in vivo using two-photon-targeted patch recordings. We show that odor responsiveness reaches a peak during neuronal development and then recedes at maturity. Sensory enrichment during development enhances the selectivity of adult-born neurons after maturation, without affecting neighboring resident neurons. Thus, in the OB circuit, adult-born neurons functionally integrate into the circuit, where they acquire distinct response profiles in an experience-dependent manner. The constant flow of these sensitive neurons into the circuit provides it with a mechanism of long-term plasticity, wherein new neurons mature to process odor information based on past demands.
    Neuron 02/2014; 81(5). DOI:10.1016/j.neuron.2014.01.007 · 15.05 Impact Factor
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    • "This hypothesis implies that comparisons of adult OB and DG functions with neuronal functions of young neurons during neurodevelopment may lead to useful insights. Adult born neurons in the OB undergo structural plasticity throughout their maturation and integration into OB circuits (Mizrahi, 2007). Reducing OB circuit activity lowers dendritic complexity and dendritic spine number (Dahlen et al., 2011). "
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    ABSTRACT: Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus of the hippocampus and the olfactory bulb, suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and olfactory bulb, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially valid selective contexts.
    Frontiers in Neuroanatomy 07/2013; 7(21). DOI:10.3389/fnana.2013.00021 · 3.54 Impact Factor
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