Olfactory disturbance induced by deafferentation of serotonergic fibers in the olfactory bulb

doi:10.1016/0306-4522(94)90396-4

Neuroscience

Volume 61, Issue 4, August 1994, Pages 733-738

https://doi.org/10.1016/0306-4522(94)90396-4 Get rights and content

Abstract

The serotonergic neurons of the brain stem project widely throughout the central nervous system, and the olfactory bulb is one of the major forebrain targets of the ascending serotonin pathway.^13,16 According to physiological studies,^3,5 neurons of the olfactory bulb were found to reduce their spontaneous discharge rates by electrophoretically applied serotonin. However, roles of the bulbar serotonin in the sense of smell remain unanswered. In the present study, using 5,7-dihydroxytryptamine, a specific neurotoxin for serotonin, we found that the conditioned rats who learned to avoid a repellent by olfaction lost ability of discrimination by deafferentation of the bulbar serotonergic fibers. Such olfactory dysfunction did not occur in the early stage (three days after injection of the toxin) when the serotonergic fibers disappeared in the bulb, but developed a few weeks later. Interestingly, histological examination revealed marked shrinkage of the bulbar glomerulus which is a major termination site of the bulbopetal serotonergic fibers, and also a synaptic site of olfactory receptor cells and bulbar output neurons. The results indicate that depletion of the serotonergic fibers in the olfactory bulb causes glomerular atrophy and olfactory disturbance in the rat.

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Despite age-related deficits in smell and sleep, no age-related changes are apparent in the proportion of cells that are able to synthesise serotonin in the medial raphe nuclei.60 Nevertheless, one study61 reported smell loss in rats within a few weeks after lesioning serotonergic projections to the olfactory bulb with the serotonergic neurotoxin 5,7-DHT. Noradrenergic fibres were spared but glomerular dopaminergic neurons were not, and the olfactory receptor cell population was markedly reduced, reflecting atrophy within the granule and the internal and external plexiform layers.
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Our study aimed to determine whether the short latency afferent inhibition (SAI) response could be associated with the severity of olfactory dysfunction in PD patients.
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Many neurons of the olfactory system, particularly those within the microglia-rich olfactory bulb, have high metabolic activity and reduced antioxidant capacity, making them susceptible to impairment of mitochondrial function, oxidative stress, and excitotoxicity. The observation that toxic damage to serotonergic neurons that enter the bulb produces anosmia and marked atrophy of all layers of the bulb strongly suggests that 5-HT input is essential for maintaining the integrity of the bulb and, in particular, dopaminergic neurons (Moriizumi et al., 1994; Tsukatani et al., 1995). Drugs that inhibit the 5-HT transporter are known to induce microglial activation and damage to dopaminergic neurons within the substantia nigra (Macgillivray et al., 2011).
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For this purpose, after direct visualization of the LOT, we made sharp transections on the LOT at different levels between the olfactory bulb and the middle cerebral artery. After removal of the olfactory bulb contralateral to the injured LOT, olfactory function was examined in the LOT-transected rats by their olfactory ability to discriminate between the smell of water and cycloheximide solution, a strong repellent for rodents (Fukushima et al., 2002; Moriizumi et al., 1994; Sakamoto et al., 2010). An anterograde neuronal tracing method was employed to confirm completeness of LOT transection and to exclude incomplete LOT-transected animals.
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Olfactory disturbance induced by deafferentation of serotonergic fibers in the olfactory bulb

Abstract

Neuroscience

Devl Brain Res.

Neuroscience

Trends Neurosci.

Brain Res.

Neurosci. Lett.

Transneuronal regulation of tyrosine hydroxylase expression in olfactory bulb of mouse and rat

J. Neurosci.

Response of individual olfactory nerve cells to microelectrophoretically administered chemical substances

Pflügers Arch. ges. Physiol.

The use of neurotoxic dihydroxytryptamines as tools for morphological studies and localized lesioning of central indolamine neurons

Z. Zellforsch. mikrosk. Anal.

Analysis of individual rabbit olfactory bulb neuron responses to the microelectrophoresis of acetylcholine, norepinephrine and serotonin synergists and antagonists

J. Pharmac. exp. Ther.