Publication Type:Journal Article
Source:J Neurosci, Volume 33, Issue 25, p.10324-39 (2013)
Keywords:Aging, Algorithms, Animals, Antimetabolites, Behavior, Animal, Blotting, Western, Bromodeoxyuridine, Cell Movement, Dendrites, Immunohistochemistry, Male, Membrane Potentials, Memory, Short-Term, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurogenesis, Olfactory Bulb, Patch-Clamp Techniques, Sensory Thresholds, Smell, Stereotaxic Techniques, Tenascin
Neuronal precursors produced in the subventricular zone throughout an animal's life migrate tangentially along the rostral migratory stream and, once in the olfactory bulb (OB), turn to migrate radially to the bulbar layers, where they differentiate into interneurons. Despite extensive investigations, it has remained largely unknown whether the same molecular mechanisms control OB neurogenesis during early postnatal development and in adulthood. In this study, we show that the extracellular matrix glycoprotein tenascin-R (TNR) is produced in the granule cell layer of the OB and that its expression increases during postnatal development. Time-lapse video imaging and morphological analyses revealed that a lack of TNR decreases the radial migration of neuronal precursors in the adult, but not in the developing OB. A lack of TNR also reduces spine development of newborn neurons in adult mice. To understand the functional consequences of a lack of TNR, we performed electrophysiological and behavioral studies on young and adult mice. Electrophysiological recordings showed that mitral cells, the target cells of newly generated interneurons, receive reduced spontaneous and evoked inhibitory activity in adult, but not young, TNR knock-out mice. Moreover, the synchronized activity of mitral cells was decreased in the OB of adult TNR knock-out mice. Behavioral studies revealed that the lower numbers of newborn interneurons in the adult OB induce alterations in short-term odor memory. Our results indicate that TNR modulates adult but not developmental neurogenesis in the OB and also highlight that the regulation of OB neurogenesis can vary during an animal's lifetime.