Formation of Precise Connections in the Olfactory Bulb Occurs in the Absence of Odorant-Evoked Neuronal Activity

Lin, David M.; Wang, Fan; Lowe, Graeme; Gold, Geoffrey H.; Axel, Richard; Ngai, John; Brunet, Lisa J.

doi:10.1016/s0896-6273(00)81139-3

Cited by 195 publications

(193 citation statements)

References 57 publications

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“…26 In general, deprivation commenced in postnatal/adult animals, when all the connections between the OE and the OB have already been established. Nevertheless, similar changes have been observed when odor-evoked signaling was genetically eliminated, before connections are established, for example in mice lacking either functional olfactory cyclic nucleotidegated channels 54 (Table 1), G (olf) , the major G protein a subunit in olfactory receptors 55 or OMP, the olfactory marker protein, which takes part in odor perception 56 (Table 1). Furthermore, some peripheral olfactory projections are affected in mice deficient for a cyclic nucleotidegated channel subunit, suggesting that the pathfinding of these axons is in part influenced by odorant-dependent activity.…”

Section: Mutual Influences Between Oe and Obmentioning

confidence: 68%

“…46 No hypertrophic changes in non-deprived laminae of the OBs were observed, suggesting that no compensatory changes occur after olfactory deprivation. 46 Interestingly, blocking odor transduction by either naris closure or by genetically engineering the loss of receptors or channels, does not affect the convergence of OSN axons in the OB 54,55 (Table 1). Moreover, the restoration of the projection from the OE after genetic ablation suggests that the positional cues involved in the formation of the olfactory projection might persist in the OB throughout the entire life of the animal.…”

Section: Mutual Influences Between Oe and Obmentioning

confidence: 99%

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The olfactory bulb as an independent developmental domain

López‐Mascaraque

Castro

2002

Cell Death Differ

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The olfactory system is a good model to study the mechanisms underlying guidance of growing axons to their appropriate targets. The formation of the olfactory bulb involves differentiation of several populations of cells and the initiation of the central projections, all under the temporal and spatial patterns of gene expression. Moreover, the nature of interactions between the olfactory epithelium, olfactory bulb and olfactory cortex at early developmental stages is currently of great interest. To explore these questions more fully, the present review aims to correlate recent data from different developmental studies, to gain insight into the mechanisms involved in the specification and development of the olfactory system. From our studies in the pax6 mutant mice (Sey Neu /Sey Neu ), it was concluded that the initial establishment of the olfactory bulb central projections is able to proceed independently of the olfactory sensory axons from the olfactory epithelium. The challenge that now remains is to consider the validity of the olfactory bulb as an independent development domain. In the course of evaluating these ideas, we will review the orchestra of molecular cues involved in the formation of the projection from the OB to the olfactory cortex.

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Section: Mutual Influences Between Oe and Obmentioning

confidence: 68%

Section: Mutual Influences Between Oe and Obmentioning

confidence: 99%

The olfactory bulb as an independent developmental domain

López‐Mascaraque

Castro

2002

Cell Death Differ

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“…The olfactory signal transduction components could play a similar role in signaling from OR protein to OR genes in the nucleus. Genetic disruption of the CNGA2-channel subunit responsible for ORmediated Ca 2ϩ ion influx does not lead to miswiring that might be expected if multiple receptors are expressed in each cell (28), although second messengers further upstream in the signaling pathway could mediate the feedback signal. Interestingly, glomerular disorganization is reported in mice deficient for the olfactory-specific adenylyl cyclase, ACIII (29).…”

Section: Discussionmentioning

confidence: 99%

A feedback mechanism regulates monoallelic odorant receptor expression

Lewcock

Reed

2004

Proc. Natl. Acad. Sci. U.S.A.

241

229

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In olfactory neurons, expression of a single odorant receptor (OR) from a repertoire of >1,000 genes is required for odor coding and axonal targeting. Here, we demonstrate a role for OR protein as an essential regulator in the establishment of monoallelic OR expression. An OR-promoter-driven reporter expresses in a receptor-like pattern but, unlike a native OR, is coexpressed with an additional OR allele. Expression of a functional OR from the identical promoter eliminates expression of other OR alleles. The presence of an untranslatable OR coding sequence in the mRNA is insufficient to exclude expression of a second OR. Together, these data identify the OR protein as a critical element in a feedback pathway that regulates OR selection.T he mammalian olfactory system detects odors with remarkable sensitivity while decoding the complex odorant stimuli present in the environment. Populations of olfactory neurons with similar response profiles generate patterned activity within the olfactory bulb (OB) and lead to the perception of a given odor. These cellular responses are defined by the selective expression of seven-transmembrane odorant receptor (OR) proteins (1).Each olfactory neuron expresses only one allele of an individual OR gene from Ͼ1,000 related genes dispersed throughout the genome, a process termed monoallelic expression (2-4). The neurons expressing a particular OR reside in one of multiple zones defined by their dorsal-medial to ventral-lateral position in the olfactory epithelium (OE) (5, 6). These OR expression zones contribute broad topographic organization for the axons of olfactory neurons as they target the OB (5,7,8). ORs also play an important role in olfactory axon pathfinding (9, 10). Neurons that express the same OR, while interspersed with neurons expressing other ORs in the epithelium, project axons that converge to a small number of stereotyped glomeruli in the OB (11, 12). A transgene comprised of proximal OR promoter sequences is in many cases sufficient to recapitulate normal expression (13,14), although the transgene integration site can significantly influence reporter expression. This variability has confounded the elucidation of the processes that contribute to monoallelic, zonal OR expression.The monoallelic expression of ORs is critical to the establishment of the functionally distinct neuronal populations required for odor discrimination and organization of axonal projections to the OB (15, 16). This highly regulated expression could be achieved through a probabilistic promoter selection mechanism that is independent of the production of functional OR protein (10). Alternatively, OR protein or mRNA could initiate a feedback signal that ensures monoallelic expression.To determine whether monoallelic OR expression depends on feedback regulation, we targeted an OR promoter-driven reporter to a defined, reproducible transgene insertion site amid a cluster of ORs. This approach alleviates transgenic variability while facilitating analysis of potential coexpression with adjacent ORs...

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“…Similar results were observed from cells from all ages of animals in this range. The olfactory bulb develops early, with mitral cell dendritic morphology at P7 being indistinguishable from adult (Lin et al, 2000). Mice were anesthetized (0.1% ketamine/0.1% xylazine; ϳ3 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

Tuft Calcium Spikes in Accessory Olfactory Bulb Mitral Cells

Urban

Castro²

2005

J. Neurosci.

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The mammalian accessory olfactory system is critical for the detection and identification of pheromones and the representation of complex stimuli including sex, genetic relatedness, and individual identity. Mitral cells, the principal cells of the accessory olfactory bulb (AOB), receive monosynaptic input from the sensory periphery and already show highly specific response properties, firing selectively for combinations of genetic markers and gender-specific cues. Vomeronasal sensory neuron axons form synapses onto distal tuft-like branches of mitral cell primary dendrites. We have studied dendritic excitability and synaptic integration in AOB mitral cell dendrites, and we show that dendrites of accessory olfactory bulb mitral cells support action potential propagation and can fire regenerative spike-like events that are likely to contribute to the integration of inputs to these cells. These tuft spikes may be important for the specificity of AOB mitral cell responses.

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Formation of Precise Connections in the Olfactory Bulb Occurs in the Absence of Odorant-Evoked Neuronal Activity

Cited by 195 publications

References 57 publications

The olfactory bulb as an independent developmental domain

The olfactory bulb as an independent developmental domain

A feedback mechanism regulates monoallelic odorant receptor expression

Tuft Calcium Spikes in Accessory Olfactory Bulb Mitral Cells

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