Olfactory system
Functional organization and involvement in neurodegenerative disease
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GLOSSARY
The olfactory system has several unique features in terms of mechanisms of sensory transduction, relay, and central processing of information and provides a typical example of functional plasticity.1–5 Olfactory deficits are frequently found in neurodegenerative disorders, particularly Parkinson disease (PD) and Alzheimer disease (AD). The neuropathologic substrate of olfactory dysfunction in neurodegenerative disorders is incompletely elucidated and likely reflects degenerative changes at multiple levels of the olfactory system, including the olfactory epithelium, olfactory bulb, primary olfactory cortices, and their secondary targets.6,7 These issues have been extensively reviewed1–7 and only some salient points are emphasized here.
PHYSIOLOGY OF ODOR PERCEPTION
Olfactory receptor cells and sensory transduction.
The olfactory sensory neurons form clusters interposed among patches of respiratory neuroepithelium.1 These neurons are bipolar cells with a dendritic end containing 3–50 cilia that project into the overlying mucus; their unmyelinated axons form bundles that project through the cribriform plate and synapse in the olfactory bulb.1,2 Odorants bind to guanine nucleotide binding (G) protein–coupled receptors located in the cilia of the olfactory receptor neuron. There are about 400 types of receptors expressed in human olfactory neurons and an individual olfactory sensory neuron typically responds to more than one odorant type.1,5 The first step in olfactory signal transduction is the activation of the Gαolf, which stimulates adenylyl cyclase 3 and production of cyclic adenosyl monophosphate (figure). This triggers opening of a cyclic nucleotide–gated channel allowing calcium (Ca2+) influx and depolarization; subsequent opening of Ca2+ activated chloride (Cl−) channels elicits Cl− efflux that amplifies the depolarization of the sensory neuron.1 The olfactory receptor neurons have several unique features: they can regenerate; serve both as odorant-selective receptor cells and first-order neurons; and are directly exposed to the external environment, thus providing a primary route for invasion into the brain by viruses or toxins.5 …
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