Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999 Gustatory and Olfactory Outmessaging

In theory it would be possible to insert artificial flavors onto the lingual surface, or to release artificial scents into the nasal epithelium. However, human taste buds have a lifetime of ~10 days, requiring constant repositioning of resident chemical emission devices. Human olfactory receptors are located at the back of the nose (Fig. 8.11), covered by a sheet of mucus, adding signal time delays and dispersion (due to finite and differential molecular diffusion rates) to high-frequency olfactory messages. Additionally, frequent large-volume chemical emissions from individual nanorobots is not feasible due to scaling factors (Section

In this case it appears more efficient to stimulate the gustatory and olfactory nerves directly. This minimizes power consumption, reduces the required volume of chemical releases by many orders of magnitude, and permits rapid multiplexing of numerous distinct synthetic sensory signals.

A. Gustatory Outmessaging -- There are ~12,000 taste buds innervated by nerve fibers that lose their myelin sheaths as they pass through the basement membrane. Large fibers end on two or more bud cells, with the endings of small fibers invaginating the receptor cell membrane. The large taste fibers from the anterior twothirds of the tongue branch from the lingual nerve to form a slender nerve, the chorda tympani, which traverses the eardrum as part of the facial (7th cranial) nerve en route to the medulla. The afferent fibers from the posterior third of the tongue collect in the lingual branch of the glossopharyngeal (9th cranial) nerve, through the petrosal ganglia and into the medulla. Since taste buds have a response repertoire of only five known distinct sensations (sweet, sour, bitter, salt, and umami*), nanorobots seeking to artificially provoke these sensations may proceed to the chorda tympani or petrosal ganglia with the objective of triggering a higher-level confluent signal on each of a handful of distinct ganglial positions corresponding to the five primary stimuli plus a small set of mixed-sensitivity combinations. Proper identification of the nerve bundles carrying information on each of the five primary stimuli may require a brief training session or prior connectivity mapping (Chapter 25). Note also that natural taste response time is diffusion-limited to ~1 sec (~1 Hz, ~1 bit/sec), and it is not yet known whether the natural conscious brain can be educated to process multiplexed high-frequency (up to 10-100 Hz, or ~10-100 bits/sec) artificially-stimulated taste signals.

* Umami, a complex "meaty" or "savory" tastiness factor, was first identified as the fifth taste by a Japanese scientist, Professor Ikeda, at the University of Tokyo.3030-3034 Umami is specifically associated with monosodium glutamate (MSG),3035 sodium inosinate, and sodium guanylate. Specific taste bud receptors (e.g., mGluR4) for umami have been discovered.3033,3034

B. Olfactory Outmessaging -- Humans have up to 50 million olfactory sensors spaced an average ~3 microns apart in the olfactory epithelium (~2.5 cm2/nostril) located in the upper part of the nasal cavities on the surface of the superior conchae and upper part of the septum (see Figure 8.11). Each sensor protrudes a long and extremely thin olfactory nerve fiber. These fibers are grouped into ~20 filaments in each nasal cavity, and the filaments pass through the cribriform plate of the ethmoid bone into the olfactory bulb (the terminus of the olfactory (1st cranial) nerve) in the forebrain in the cranial cavity. The nasal epithelium also contains a few bare nerve endings from fibers of the trigeminal (5th cranial) nerve. The responses of olfactory receptor neurons are rarely specific to only one odor; the majority of cells respond to a broad range of substances.3433

The olfactory nerve fibers enter the olfactory bulb to end in a series of intricate basketlike synaptic terminations or antenna-shaped dendritic clusters called glomeruli. Each olfactory glomerulus receives impulses from about 26,000 receptors and sends them on through 24 mitral cells and 68 tufted cells, thus showing a high degree of neural convergence.

The number of such glomeruli (~1000) may approximate the number of nonmultiplexed distinct olfactory sensations available to man. Humans can identify over 10,000 structurally distinct odorant ligands807 -- some have claimed as many as 400,000 discernible odors3134,3135 -- but this does not imply an equally large repertoire of odorant receptors, because structurally related odorants may bind to the same receptor molecules.1120 Indeed, individual neurons respond strongly to closely related groups of odorants and weakly or not at all to many others.807 Sensory neurons with similar ligand specificities project to common glomeruli. The family of 7TD membrane proteins, which is localized to the olfactory cilia and shares homology with the superfamily of neurotransmitters and neuropeptide 7TD receptors,808 constitutes an extremely large multigene family likely to encode odorant receptors that transduce intracellular signals by interacting with cellular transmembrane G proteins which then activate second messenger systems inside the cell. This family of putative odorant receptors could constitute one of the largest gene families in the genome, with perhaps as many as 500-1000 genes,809 approximately one receptor type for each glomerulus.

If each glomerulus may be treated as the locus for a single unique olfactory sensation, this may provide an essentially clear output channel for a neurostimulatory nanodevice. Such a device could trigger action potentials in a single glomerulus producing a perception of a rapidly pulsing (possibly up to ~10-100 Hz, or ~10-100 bits/sec) rare scent. Such signals would no longer be diffusion limited (to ~1 Hz, ~1 bit/sec) as is the case with natural olfaction, and rapid adaptation caused by receptor saturation would also be eliminated for these signals since the signals are inserted at the glomeruli and don't pass through the sensory receptors at all. A thousand coordinated nanorobots positioned one at each glomerulus could provide complete olfactory sensation control and the potential for massive multiplexing. As with taste messaging, it is unknown whether the natural conscious brain can be trained to process such multiplexed high-frequency smell signals. In 1998, studies of the human olfactory (combinatorial) code were in progress.3207


Last updated on 19 February 2003