Response of olfactory axons to loss of synaptic targets in the adult mouse.
Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-d-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by 3 weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by 8 weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets.
BC 208, Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA.
Yona
Y
Ardiles
Rafael
R
de la Puente
Rafael
R
Toledo
Ceylan
C
Isgor
Kathleen
K
Guthrie
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D017403:In Situ Hybridization / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology* / Q000187:drug effects; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000187:drug effects; D018035:Receptors, Odorant / Q000235:genetics; D013266:Stilbamidines; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018690:Excitatory Amino Acid Agonists; D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D018035:Receptors, Odorant; D013266:Stilbamidines; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside