Neurotrophins are not required for normal embryonic development of olfactory neurons.
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Neurons of the vertebrate olfactory epithelium (OE) regenerate continuously throughout life. The capacity of these neurons to regenerate and make new and precise synaptic connections in the olfactory bulb provides a useful model to study factors that may control or mediate neuronal regeneration. Expression and in vitro studies have suggested potential roles for the neurotrophins in the olfactory system. To directly examine whether neurotrophins are required for olfactory neuron development, we characterized in vivo the role of the neurotrophins in the primary olfactory system. For this, we generated mutant mice for TrkA, TrkB, TrkC, and also for BDNF and NT3 together with P2-IRES-tau-LacZ trangenic mice. Histochemical staining for beta-galactosidase at birth allowed in vivo analysis of the P2 subpopulation of olfactory neurons as well as their projections to the olfactory bulb. Our data indicate that Trk signaling is not required for normal embryonic development of the olfactory system. (+info)
Rhinotopy is disrupted during the re-innervation of the olfactory bulb that follows transection of the olfactory nerve.
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Re-innervation of the olfactory bulb was investigated after transection of the olfactory nerve using monoclonal antibody RB-8 to assess whether rhinotopy of the primary olfactory projection is restored. In normal animals RB-8 heavily stains the axons, and their terminals, that project from the ventrolateral olfactory epithelium onto glomeruli of the ventrolateral bulb (termed RB-8(+)). In contrast, axons from dorsomedial epithelium are unlabeled (RB-8(-)) and normally terminate in the dorsomedial bulb. Sprague-Dawley rats underwent unilateral olfactory nerve transection and survived for 6 weeks prior to perfusion, sectioning and immunostaining with RB-8. Nerve lesion does not shift the position of the boundary between RB-8(+) and RB-8(-) regions of the epithelium. However, following transection and bulb re-innervation, the distribution of RB-8(+) and RB-8(-) axons is markedly abnormal. First, in all 10 experimental animals RB-8(-) axons displace RB-8(+) axons from anterior glomeruli. Furthermore, the usual target of the RB-8(-) fibers, i.e. the dorsomedial bulb at more posterior levels of the bulb, remains denervated, judging by the lack of staining with antibodies that label axons derived from all epithelial zones. Finally, RB-8(+) fibers invade foreign territory in the dorsolateral bulb on the lesioned side in some cases. The shifts in terminal territory in the bulb after transection contrast with the restoration of the normal zonal patterning of the projection after recovery from methyl bromide lesion, but is consistent with reports of mistargeting by a receptor-defined subset of neurons after transection. (+info)
The development of the olfactory mucosa in the mouse: electron microscopy.
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The development of the olfactory epithelium from the 10th day of gestation of postnatal life has been examined electron miscroscopically in the mouse. At 10 days' gestation the epithelium is already differentiated into dark and pale cells, the former representing embryonic stem cells and the latter the developing receptors. Axons are also visible at this stage. At 11 days the first signs of dendrite formation appear, and at 12 days spheroidal terminal swellings containing numerous microtubules are present at the apices of receptor dendrites. Centriole clusters also appear in the receptor cell bodies and dendrites. From the 12th to the 16th day of gestation a few cilia are formed on the receptor endings. Final steps in the maturation of differentiating receptors begin on the 17th day of gestation, when membranous organelles and lysosomes increase greatly in numbers. However, immature receptors can still be found in the base of the epithelium in postnatal life. Supporting cells are first recognizable on the 17th day of gestation, derived apparently from the remaining stem cells. At the same time differentiated basal cells and glands of Bowman begin to appear. In the early develoment of the olfactory nerve bundles the axons have large and varying diameters, but later on axonal sizes are progressively reduced and the adult size range is achieved at about 18 days of gestation. The significance of these findings is discussed. (+info)
Membrane bistability in olfactory bulb mitral cells.
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Whole-cell patch-clamp recordings were used to investigate the electrophysiological properties of mitral cells in rat main olfactory bulb brain slice preparations. The majority of mitral cells are bistable. These cells spontaneously alternate between two membrane potentials, separated by approximately 10 mV: a relatively depolarized potential (upstate), which is perithreshold for spike generation, and a relatively hyperpolarized potential (downstate), in which spikes do not occur. Bistability occurs spontaneously in the absence of ionotropic excitatory or inhibitory synaptic inputs. Bistability is voltage dependent; transition from the downstate to the upstate is a regenerative event activated by brief depolarization. A brief hyperpolarization can switch the membrane potential from the upstate to the downstate. In response to olfactory nerve (ON) stimulation, mitral cells in the upstate are more likely to fire an action potential than are those in the downstate. ON stimulation can switch the membrane potential from the downstate to the upstate, producing a prolonged and amplified depolarization in response to a brief synaptic input. We conclude that bistability is an intrinsic property of mitral cells that is a major determinant of their responses to ON input. (+info)
Convergence of olfactory inputs from both antennae in the brain of the honeybee.
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Electrical activities of the olfactory neurones in the brain of the honeybee were investigated. Odorous stimuli were given to each antenna separately or to both simultaneously. The inputs from the antennae affected both the impulse frequency and the latency of the olfactory interneurones in the protocerebrum. The predominant response was to the stimulation of the ipsilateral antenna. Input from the contralateral antenna produced mainly excitatory effects, although a few inputs gave inhibitory effects. No particular relationships between the loci of the units in the brain and the types of responses produced were found. Most of the units were located in the protocerebral lobe and in the central commissure. The units in the deutocerebrum responded only to the stimulation of the ipsilateral antenna, and the magnitude of response and the latency were not different with respect to unilateral or bilateral stimulation of the antennae. Differences in latency between unilateral and bilateral stimulation were observed in some of the units in the protocerebrum. Neural models which explain these phenomena are postulated. (+info)
The lin-11 LIM homeobox gene specifies olfactory and chemosensory neuron fates in C. elegans.
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Chemosensory neuron diversity in C. elegans arises from the action of transcription factors that specify different aspects of sensory neuron fate. In the AWB and AWA olfactory neurons, the LIM homeobox gene lim-4 and the nuclear hormone receptor gene odr-7 are required to confer AWB and AWA-specific characteristics respectively, and to repress an AWC olfactory neuron-like default fate. Here, we show that AWA neuron fate is also regulated by a member of the LIM homeobox gene family, lin-11. lin-11 regulates AWA olfactory neuron differentiation by initiating expression of odr-7, which then autoregulates to maintain expression. lin-11 also regulates the fate of the ASG chemosensory neurons, which are the lineal sisters of the AWA neurons. We show that lin-11 is expressed dynamically in the AWA and ASG neurons, and that misexpression of lin-11 is sufficient to promote an ASG, but not an AWA fate, in a subset of neuron types. Our results suggest that differential temporal regulation of lin-11, presumably together with its interaction with asymmetrically segregated factors, results in the generation of the distinct AWA and ASG sensory neuron types. We propose that a LIM code may be an important contributor to the generation of functional diversity in a subset of olfactory and chemosensory neurons in C. elegans. (+info)
Ephaptic interactions in the mammalian olfactory system.
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Ephaptic coupling refers to interactions between neurons mediated by current flow through the extracellular space. Ephaptic interactions between axons are considered negligible, because of the relatively large extracellular space and the layers of myelin that separate most axons. By contrast, olfactory nerve axons are unmyelinated and arranged in tightly packed bundles, features that may enhance ephaptic coupling. We tested the hypothesis that ephaptic interactions occur in the mammalian olfactory nerve with the use of a computational approach. Numerical solutions of models of axon fascicles show that significant ephaptic interactions occur for a range of physiologically relevant parameters. An action potential in a single axon can evoke action potentials in all other axons in the fascicle. Ephaptic interactions can also lead to synchronized firing of independently stimulated axons. Our findings suggest that ephaptic interactions may be significant determinants of the olfactory code and that such interactions may occur in other, similarly organized axonal or dendritic bundles. (+info)
Volumetric and horseradish peroxidase tracing analysis of rat olfactory bulb following reversible olfactory nerve lesions.
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Olfactory receptor neurons can regenerate from basal stem cells. Receptor neuron lesion causes degenerative changes in the olfactory bulb followed by regeneration as new olfactory receptor axons innervate the olfactory bulb. To our knowledge, parametric analyses of morphometric changes in the olfactory bulb during degeneration and regeneration do not exist except in abstract form. To better characterize olfactory bulb response, we performed morphometric analysis in rats following reversible olfactory nerve lesion with diethyldithiocarbamate. We also performed anterograde tracing of the olfactory nerve with wheatgerm agglutinin linked to horseradish peroxidase. Results of morphometry and tracing were complementary. The glomerular layer and external plexiform layer showed shrinkage of 45 and 26%, respectively, at 9 days. No significant shrinkage occurred in any other layer. Individual glomeruli shrank by 40-50% at 3 and 9 days following lesion. These data show that degenerative changes occur both in the glomeruli and transneuronally in the external plexiform layer. Olfactory nerve regeneration (identified by WGA-HRP transport) paralleled volumetric recovery. Recovery occurred first in ventral and lateral glomeruli between 9 and 16 days followed by recovery in medial and dorsal glomeruli. These data indicate substantial transynaptic degeneration in the olfactory bulb and a heretofore unrecognized gradient in olfactory nerve regeneration that can be used to systematically study recovery of a cortical structure. (+info)