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.
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.
"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. "
"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). "
[Show abstract][Hide abstract] 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
"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). "
[Show abstract][Hide abstract] 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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