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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    • "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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    • "To retrieve information over this higher anatomical level, the structures of interest must be either entirely imaged or reconstructed from serially sectioned material. Recent advances in light microscopy and in molecular and genetic manipulations have greatly extended the possibility of imaging large volumes of both fixed and live neural tissue at cellular resolution, enabling the visualization of complex 3D objects such as neuronal or vascular networks (Mizrahi, 2007; Lu et al., 2009; Tsai et al., 2009; Wilt et al., 2009; Khairy and Keller, 2011). These imaging techniques represent a pivotal innovation for multiple neuroanatomical fields ranging from the definition of comprehensive maps anti-goat biotinylated secondary antibody for 1 h (1:250; Vector Laboratories, Burlingame, CA, USA), rinsed, and incubated in avidin–biotin complex (1:400; Vector Laboratories). "
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    ABSTRACT: Current advances in imaging techniques have extended the possibility of visualizing small structures within large volumes of both fixed and live specimens without sectioning. These techniques have contributed valuable information to study neuronal plasticity in the adult brain. However, technical limits still hamper the use of these approaches to investigate neurogenic regions located far from the ventricular surface such as parenchymal neurogenic niches, or the scattered neuroblasts induced by brain lesions. Here, we present a method to combine confocal laser scanning microscopy (CLSM) and serial section reconstruction in order to reconstruct large volumes of brain tissue at cellular resolution. In this method a series of thick sections are imaged with CLSM and the resulting stacks of images are registered and 3D reconstructed. This approach is based on existing freeware software and can be performed on ordinary laboratory personal computers. By using this technique we have investigated the morphology and spatial organization of a group of doublecortin (DCX)+ neuroblasts located in the lateral striatum of the late post-natal guinea pig. The 3D study unraveled a complex network of long and poorly ramified cell processes, often fascicled and mostly oriented along the internal capsule fiber bundles. These data support CLSM serial section reconstruction as a reliable alternative to the whole mount approaches to analyze cyto-architectural features of adult germinative niches.
    Frontiers in Neuroscience 05/2011; 5:70. DOI:10.3389/fnins.2011.00070 · 3.66 Impact Factor
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