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Chemosensory Disorders and Nutrition
Published in Alan R. Hirsch, Nutrition and Sensation, 2023
Carl M. Wahlstrom, Alan R. Hirsch, Bradley W. Whitman
The area on the cortex where olfaction is localized, that is, the primary olfactory cortex, includes the prepiriform area, the periamygdaloid area, and the entorhinal area. The piriform cortex and the amygdala are the primary olfactory cortex, while the insula and orbitofrontal cortex are secondary olfactory cortex association areas (Doty, Bromley, Moberg, and Hummel 1997). Afferent projections to the primary olfactory cortex include the mitral cells, which enter the lateral olfactory tract and synapse in the prepiriform cortex (lateral olfactory gyrus) and the corticomedial part of the amygdala. Efferent projections from the primary olfactory cortex extend to the entorhinal cortex, the basal and lateral amygdaloid nuclei, the lateral preoptic area of the hypothalamus, the nucleus of the diagonal band of Broca, the medial forebrain bundle, the dorsal medial nucleus and submedial nucleus of the thalamus, and the nucleus accumbens.
Chemosensation
Published in Emily Crews Splane, Neil E. Rowland, Anaya Mitra, Psychology of Eating, 2019
Emily Crews Splane, Neil E. Rowland, Anaya Mitra
Although only about 400 receptor types are expressed in the human nose, there are about 40 million olfactory receptor neurons; it follows that each type of GPCR occurs, on average, in thousands of olfactory receptor neurons. Mice have somewhat more (1,000) receptor types than humans. The receptor neurons send axonal projections to the olfactory bulb where they converge onto about 1,000 ball-like structures (on each side of the nasal cavity, in mice) called glomeruli. Although randomly distributed across the olfactory epithelium, each GPCR type converges on one and only one glomerulus to form a two-dimensional “olfactory map” on the olfactory bulb (Mori & Sakano, 2011). It is assumed that a similar convergence occurs in humans. Glomeruli are relay stations: They collect incoming signals from olfactory nerves and transmit them to the dendrites of mitral cells that are located in the main olfactory bulb. Axons of mitral cells then send action potentials to the brain via the olfactory tracts.
Richard Axel (b. 1946) and Linda Buck (b. 1947)
Published in Andrew P. Wickens, Key Thinkers in Neuroscience, 2018
Following the mapping of the olfactory epithelium, Buck and her colleagues turned their attention to the olfactory bulb – an anatomically complex brain structure that contains a specialised type of neuron called a “mitral cell”, which has a triangular shape, named after its resemblance to a bishop’s mitre. In the human olfactory bulb, there are about 50,000 mitral cells and each receives input from about 2500 bipolar cell axons originating from the nasal epithelium. Interestingly, the mitral cells are also bundled together in spherical clumps (in essence a dense accumulation of cells, synapses and dendrites) known as olfactory glomeruli – of which there are about 2000 in the human olfactory bulb. Using probes that recognised a single odorant receptor gene, Buck found that each glomerulus receives information from just one kind of olfactory receptor. It was also apparent that each odor presented to the nose activated a different pattern of glomeruli. Put another way, by analysing the different sets of activated glomeruli, one could, in theory, decode the identity of the odor. Again, this work was being paralleled by researchers in Axel’s laboratory, who published similar findings for the rats in 1994.
Investigational drugs for the treatment of olfactory dysfunction
Published in Expert Opinion on Investigational Drugs, 2022
Arianna Di Stadio, Cinzia Severini, Andrea Colizza, Marco De Vincentiis, Ignazio La Mantia
The neuroepithelium is connected through the axons of the ORN to the olfactory bulb, which contains glomerulus, mitral cells and tufted relay neurons. The axons converge in the glomerulus to form the first cranial nerve (olfactory nerve). The glomerulus is connected by synapses to the mitral cells; the latter together with the tufted relay neurons forms the olfactory tract. This structure bifurcates in the medial and lateral olfactory stria (y inverted-shaped). The olfactory stimulus is conducted through these structures up to the piriform cortex, the periamygdaloid cortex, the olfactory tuberculosis and the anterior olfactory nucleus. The primary olfactory cortex is formed by the medial and lateral olfactory stria and the anterior perforated substance. The lateral olfactory stria is extended posteriorly giving origin to the entorhinal area which, together with the uncus, forms the secondary olfactory cortex, also known as the orbitofrontal cortex (Figure 2). This area is straightly related to memory. The primary cortex is responsible for the active perception of the sense of smell, while the secondary one is the portion where the smell perception is integrated with emotions and memory.
Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies
Published in Expert Opinion on Drug Delivery, 2018
Gina Li, Nicolas Bonamici, Mahua Dey, Maciej S. Lesniak, Irina V. Balyasnikova
The nasal epithelium is innervated by the olfactory nerves, which can be utilized by cell-based therapies to rapidly gain access to the brain after IND across the cribriform plate and into mitral cells of the olfactory bulbs. From the olfactory bulbs, afferent neurons carry olfactory signals to the olfactory tract, piriform cortex, amygdala, and hypothalamus. Specialized myelinating glia (olfactory ensheathing cells) form cerebrospinal fluid (CSF)-filled cavities along the olfactory nerves, which are thought to play a role in extracellular trafficking into the brain after IND [12]. The majority of studies on IND found that the delivery of agents occurred within a short time period (5–30 min), suggesting the roles of extracellular transport and bulk flow mechanisms [13–17]. From the olfactory bulb, stem cells can either migrate directly into the frontal lobe or to caudal portions of the brain via CSF flow [18]. The olfactory pathways have been shown to be a large component of IND therapy, with our lab and others showing that stem cells delivered intranasally can be visualized in the olfactory bulb and frontal lobe with MRI [13,19]. As the olfactory epithelium is significantly larger in mouse, it is likely that this pathway plays a larger role in cell migration in the murine model than in humans.
New insight into brain disease therapy: nanomedicines-crossing blood–brain barrier and extracellular space for drug delivery
Published in Expert Opinion on Drug Delivery, 2022
Ziqi Gu, Haishu Chen, Han Zhao, Wanting Yang, Yilan Song, Xiang Li, Yang Wang, Dan Du, Haikang Liao, Wenhao Pan, Xi Li, Yajuan Gao, Hongbin Han, Zhiqian Tong
It has found that sublingual levodopa has been implemented in PD patients [175]. Intranasal administration has been noted as a method for noninvasive delivery of a drug to the brain by bypassing the BBB via the ‘nose-to-brain’ route, the olfactory pathway (Figure 6(e)). The therapeutic drugs are sprayed into the nasal cavity diffuses through the olfactory sensory nerve and olfactory glomeruli via passive or active transport mechanisms. It then reaches brain tissues via projection neurons, tufted or mitral cells [176]. However, these two pathways are limited by the small amount of curative medicine that can successfully reach the brain tissue, relative to the amount administered [177].