Eur J Neurosci. 2014 Dec;40(11):3591-607.

Sensory-specific modulation of adult neurogenesis in sensory structures is associated with the type of stem cell present in the neurogenic niche of the zebrafish brain.

Benjamin W. Lindsey1, Sabrina Di Donato2, Jan Kaslin1 and Vincent Tropepe2

  1. Australian Regenerative Medicine Institute, Monash University Clayton Campus, Clayton, Vic., Australia
  2. Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada

 

Abstract

Teleost fishes retain populations of adult stem/progenitor cells within multiple primary sensory processing structures of the mature brain. Though it has commonly been thought that their ability to give rise to adult-born neurons is mainly associated with continuous growth throughout life, whether a relationship exists between the processing function of these structures and the addition of new neurons remains unexplored. We investigated the ultrastructural organisation and modality-specific neurogenic plasticity of niches located in chemosensory (olfactory bulb, vagal lobe) and visual processing (periventricular grey zone, torus longitudinalis) structures of the adult zebrafish (Danio rerio) brain. Transmission electron microscopy showed that the cytoarchitecture of sensory niches includes many of the same cellular morphologies described in forebrain niches. We demonstrate that cells with a radial-glial phenotype are present in chemosensory niches, while the niche of the caudal tectum contains putative neuroepithelial-like cells instead. This was supported by immunohistochemical evidence showing an absence of glial markers, including glial fibrillary acidic protein, glutamine synthetase, and S100β in the tectum. By exposing animals to sensory assays we further illustrate that stem/progenitor cells and their neuronal progeny within sensory structures respond to modality-specific stimulation at distinct stages in the process of adult neurogenesis – chemosensory niches at the level of neuronal survival and visual niches in the size of the stem/progenitor population. Our data suggest that the adult brain has the capacity for sensory-specific modulation of adult neurogenesis and that this property may be associated with the type of stem cell present in the niche.

© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

KEYWORDS: Danio rerio; adult neural stem cells; adult neurogenesis; neurogenic plasticity; sensory enrichment/deprivation

PMID: 25231569

 

 

 

Supplement:

Relatively discrete populations of adult neural stem cells (ANSCs) reside in specialized neurogenic niches in the vertebrate brain endowed with the potential to give rise to newborn adult neurons. The presence of adult neurogenesis has revolutionized our understanding of brain function. We now know, for example, that adult neurogenesis in the songbird brain can modulate song production (Barnea and Pravosudov, 2011), while in the rodent brain adult neurogenesis regulates spatial learning and memory (Vadodaria and Jessberger, 2014) or olfactory discrimination (Gheusi and Lledo, 2014). Nonetheless, the functional significance of adult neurogenesis and the behaviour of their parent stem cells remain enigmatic in most other structures where ANSCs persist.

A hallmark of adult neurogenesis is its ability to be modulated by internal and external forms of stimuli – known as neurogenic plasticity. Neurogenesis is positively or negatively regulated at multiple stages in the process of adult neurogenesis in response to a number of factors such as signalling pathways, hormonal changes, environmental enrichment, or behavioural context (Kempermann, 2011).

The adult zebrafish has swum to the forefront of vertebrate models in recent years, as a champion of both adult neurogenesis and regeneration. Graced with a vast number of adult stem cell niches across the mature zebrafish brain in sensory and non-sensory structures, this freshwater teleost offers an exceptional experimental system to study ANSC plasticity, function, and regulation (Than-Trong and Bally-Cuif, 2015).

In our study, to better understand the behaviour of ANSCs and their progeny in adult neurogenic niches located within primary sensory processing centres of the brain, and to be able to make predictions regarding their function we asked two questions: First, do changes in sensory stimuli only modulate adult neurogenesis in the corresponding sensory-specific niche that processes the modality? Second, at what stage in the process of neurogenesis do changes in ambient stimuli impose an effect on the cellular population and might this be related to the type of ANSC within the niche?

 

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Figure 1. Top: Schematic showing the two different sensory modalities manipulated in the study (chemosensory, left; vision, right) and the sensory structures in the adult brain responsible for processing this information and in which the adult neurogenic niches reside that were investigated. Bottom: Stages in the process of adult neurogenesis that were examined following exposure of adult zebrafish to either chemosensory-specific or vision-specific assays. Tel, telencephalon; Ce, cerebellum, SC, spinal cord.

 

To examine how the brain is shaped by sensory experiences in adulthood in neurogenic niches residing in sensory structures, we developed novel modality-specific sensory assays (Fig. 1). By testing zebrafish in sensory assays compared with control (ambient) conditions, and using antibodies and transmission electron microscopy to identify proliferative ANSCs and populations of newly derived neurons, we were able to draw conclusions concerning the innate plasticity of distinct stem cell populations and their offspring. To target neurogenic niches situated in chemosensory processing structures of the brain, including the olfactory bulb (smell) and vagal lobe (taste), zebrafish were exposed to a chemosensory-induced novelty assay over 7-day consisting of a mixture of amino acids, bile salts and food extracts. Conversely, to investigate how restricted visual input may perturb ANSC populations located in the major visual processing centre of the brain, the optic tectum, animals were exposed to only a single wavelength of light for 7-days (green or blue). Following exposure to chemosensory or visual assays, zebrafish were examined at the cellular level for changes in the population size of the initial ANSC pool, the number of differentiated neurons, and the number of differentiated neurons surviving over the long-term.

The results of our study indicate that adult neurogenic niches positioned within primary sensory processing structures of the zebrafish brain are modulated in a modality-specific manner, but at different stages in the process of adult neurogenesis (Fig. 2). Each sensory assay elicited a change in the stem cell niches only where the associated modality was processed. Thus, chemosensory enrichment altered niches of the olfactory bulb and vagal lobe while no change was observed in visual centre of the optic tectum (Fig. 2A-B). Similarly, visual deprivation showed no change in chemosensory niches, such as the vagal lobe (taste), but produced a direct response in the cycling stem cell population in the optic tectum with green light (Fig. 2C-E). Our data suggest that in line with the structure-specific role of new granule cells in the mammalian hippocampus for learning and memory (Garthe et al., 2009; Stone et al., 2011), ANSCs maintained into adulthood in sensory structures of the adult zebrafish brain could also be required to assist in sensory processing of the specific modality, and that these populations are enhanced or pruned depending on the degree of sensory input.

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Figure 2. Differences in neurogenic plasticity on distinct cellular populations during the process of adult neurogenesis following exposure to chemosensory (left) or visual (right) assays. Left: (A) Exposure to chemosensory assays increased the number of surviving adult-born neurons in neurogenic niches located in the olfactory bulb (OB) and vagal lobe (LX), but not the caudal domain of the periventricular grey zone (PGZ) of the optic tectum. (B-B’’) Representative image of a newborn neuron co-labelled with the proliferative marker BrdU and neuronal marker HuCD in chemosensory niches (white arrow). Right: (C) Visual exposure to green light only (but not blue) reduced the number of proliferating BrdU-positive adult neural stem cells (ANSCs) compared with full spectrum (FS) light. (D-E) Representative image depicting the change in the population size of BrdU-positive ANSCs in the PGZ with exposure to full spectrum light compared to a single wavelength of green light.

 

Interestingly, our findings further highlight that the cellular population undergoing neurogenic plasticity along the lineage from a stem cell to a viable adult-born neuron varies according to the phenotype of the initial ANSC population. Transmission electron microscopy revealed that chemosensory niches were defined by radial-glial (RG) stem/progenitor cells, while the visual niche was composed of neuroepithelial-like (NE) stem/progenitor cells. Accordingly, chemosensory niches displayed neurogenic plasticity with a significant increase in the resulting number of surviving adult neurons (Fig. 2A), whereas the NE stem/progenitor population itself in the visual niche of the optic tectum was significantly reduced with a restricted visual spectrum (Fig. 2C). Whether the ANSC phenotype of neurogenic niches can broadly be a predictor of neurogenic plasticity remains to be confirmed, however testing this notion with appropriate assays in niches of the zebrafish forebrain characterized by these two different stem cell populations would provide an excellent follow-up study.

Novel experiences shape our brain by modulating the degree of neurogenesis, and this is a highly conserved trait from fish to man. Identifying how unique contexts can cellularly and molecularly regulate neurogenesis in the adult central nervous system will undoubtedly provide a significant scientific step forward in understanding the relationship between experience, brain plasticity, and behaviour. Uncovering the control of lineage-specific adult neural stem cell plasticity will additionally have exciting implications for future therapeutical approaches to neurodegeneration and regenerative cell therapies.

Copyright 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd

 

REFERENCES

Barnea, A. & Pravosudov, V. (2011) Birds as a model to study adult neurogenesis: bridging evolutionary, comparative and neuroethological approaches. Eur. J. Neurosci., 34, 884-907.

Garthe, A., Behr, J. & Kempermann, G. (2009) Adult-generated hippocampal neurons allow the flexible use of spatial precise learning strategies. PLoS ONE, 4, e5464.

Gheusi, G. & Lledo, P.M. (2014) Adult neurogenesis in the olfactory system shapes odor memory and perception. Prog. Brain Res., 208, 157-175.

Kempermann, G. (2011) Seven principles in the regulation of adult neurogenesis. Eur. J. Neurosci., 33, 1018-1024.

Stone, S.S.D., Teixeira, C.M., Zaslavsky, K., Wheeler, A.L., Martinez-Canabal, A., Wang, A.H., Sakaguchi, M., Lozano, A.M. & Frankland, P.W. (2011) Hippocampus, 21, 1348-1362.

Than-Trong, E. & Bally-Cuif, L. (2015) Radial glial and neural progenitors in the adult zebrafish central nervous system. Glia, 63, 1406-1428.

Vadodaria, K.C. & Jessberger, S. (2014) Functional neurogenesis in the hippocampus: then and now. Front. Neurosci., 8, 1-3.

 

 

 

 

 

 

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