While it is not considered very important in humans compared to other senses, the olfactory and gustatory systems play a powerful role in influencing the behavior of animals including ourselves. Think about the fantastically strong emotional memories tied to smells— the olfactory system when robustly stimulated can have much influence over the formation of olfactory tied memories through its direct connectivity to the limbic and memory systems of the brain. We’ll learn a bit about this connectivity later.
* Odorants bind to specific receptors on olfactory receptor neurons (ORNs) found in the dorsal epithelium of the nose
* ORNs project to the ipsilateral olfactory bulb, which in turn sends projections **directly to the cerebral cortex**, including the pyriform cortex, amygdala, and entorhinal cortex in the temporal lobe
* Pyriform and entorhinal cortex and amygdala is part of archicortex– phylogenetically older (and more simply layered) than the neocortex (6 layers)
* Pyriform cortex relays information via the thalamus to the associational cortex to initiate motor, visceral, and emotional reactions to olfactory stimuli
* Many species have a specialized structure that recognizes species-specific odorants called pheromones that play important roles in innate social, reproductive, and parenting behaviors
* The vomeronasal organ (VNO) projects to the accessory olfactory bulb, which in turn projects to the hypothalamus
* The VNO is absent or not very prominent in primates (including humans) and there is debate as to whether humans detect pheromones
* In animals a lesion in the main olfactory projection leaves reproductive behaviors intact, however lesions of the VNO projection severely compromises sexual selection and dominance hierarchies
rudimentary VNO found in 8% of adults. And VNO projects to special region of ob called accessory olfactory bulb which is also largely absent in primates.
mating, aggression behaviors etc
loss of sex discrimination and male male aggression in mice without TRP2
TRP2/TRPC2: Transient receptor potential cation channel, subfamily C, member 2. Not expressed in humans
Stowers, L.; Holy, T. E.; Meister, M.; Dulac, C.; Koentges, G. (2002). "Loss of sex discrimination and male-male aggression in mice deficient for TRP2". Science 295 (5559): 1493–1500. Bibcode:2002Sci...295.1493S. doi:10.1126/science.1069259.
* Female rodents (mice) grouped together synchronize their estrous cycle upon exposure to pheromones in male mouse urine (‘Whitten effect’). This depends on pheromone receptors and VNO—>AOB connectivity.
* Myth: women who live in close proximity synchronize their menstrual cycle (the ‘McClintock effect’, after McClintock, Nature 1971). The current scientific evidence for this effect in human is not strong.
* However there’s some evidence for odorants working as pheromone-like molecules to influence behaviors (attraction, fear) mediated by the main olfactory system
myth of mcclintock effect. statistical issues with these studies, no one has reported human estrous cycle synchrony over more than 6-9 months as indeed the original study was on college women at wellsey over the period of one academic calendar year. Windshield wiper, coupled oscillator analogy. Just out of phase.
But other animals…
And olfactory cues that aren’t necessarily odorless certainly can affect our behavior and pheromone like molecules may act through our olfactory system
> Different works have shown that odor-cued memories are more emotional than memories triggered by visual or verbal cues
from one website:
Pheromones are naturally occurring odorless substances the fertile body excretes externally, conveying an airborne signal that provides information to, and triggers responses from, the opposite sex of the same species.
oxford dictionary doesn’t include the word ‘odorless’.
wikipedia: A pheromone (from Ancient Greek φέρω phero "to bear" and hormone, from Ancient Greek ὁρμή "impetus") is a secreted or excreted chemical factor that triggers a social response in members of the same species.
>the adult human VNO, in different studies, has been reviewed as non-functional as it contains few neurons and has no sensory function where no cells were shown to express olfactory marker protein, have synaptic contacts or have evidence for a nerve connecting to/from the VNO
VNO is vestigial in humans: VRs and TrpC2 are pseudogenes
myth: women who live in close proximity synchronize their menstrual cycle (the McClintock effect, McClintock, Nature 1971)
However there’s some evidence for pheromone like molecules and behaviors (attraction, fear) mediated by the main olfactory system
whitten effect: exposure of grouped female mice to phermones in male mouse urine synchronizes their estrous cycle. The pheromones in male urine are dependent on male sex hormones like testosterone.
>The normal estrus cycle of a laboratory mouse is 4-6 days in length
vandenburgh effect: early estrous cycle induction in prepubertal female mice exposed to urine from dominant male
lee-boot effect: suppression or prolongation of estrous cycle in female mice (and other rodents) when mice housed in groups and isolated from other males
bruce effect: female mouse pregnancy termination from exposure to scent of unfamiliar male
>Latent toxoplasmosis, a lifelong infection with the protozoan Toxoplasma gondii, has cumulative effects on the behaviour of hosts, including humans. The most impressive effect of toxoplasmosis is the "fatal attraction phenomenon," the conversion of innate fear of cat odour into attraction to cat odour in infected rodents.
>human and rodents diverged ∼75 million years ago, whereas mouse and rat diverged ∼12-24 million years ago[Waterston et al. 2002; Rat Sequencing Project Consortium 2004]
-human has equal genetic distance from both rodents
-human has been evolving from human/rodent common ancestor at slower rearrangement rate and thus has a more ancestral genome
>Rat Closer to Human?
>rearrangement differences between the two rodents suggest that, except for the small inversions, overall, the rat genome might have a structure on a large scale closer to the human genome than the mouse genome.
>lacking the extra interchromosomal changes of mouse (Table 3), many rat fragments are closer to human.
>In terms of chromosome morphology (and possibly the genome size as well), rat is also between mouse and human.
Humans have 23 pairs of chromosomes, while rats have 21 and mice have 20.
>all three organisms to be related to each other by about 280 large regions of sequence similarity - called "syntenic blocks" - distributed in varying patterns across the organisms' chromosomes.
> 50 chromosomal rearrangements occurred in each of the rodent lines after divergence from their common ancestor
>number of chromosomal rearrangements, as well as other types of genome changes, was found to be much lower in the primate lineage, indicating that evolutionary change has occurred at a faster rate in rodents than in primates.
---
## Olfactory receptors
* Discovered by Linda Buck and Richard Axel. Shared nobel prize in 2004
* They found that olfactory receptors comprise a large GPCR gene family (~1000 olfactory receptors)
red arrows indicate intron locations of splice sites in other animals. Mammalian genes for ORs lack introns.
largest single known gene family in all mammals. Representing 3-5% of genome. Perhaps 60% of these 950 OR genes are not transcribed in humans and chimps rendering them pseudogenes, vs 15-20% in mice and dogs.
: sequence of DNA containing a promoter and transcription initiation site, but due to sequence changes the DNA cannot be transcribed into a stable mRNA or the transcript cannot be translated into a protein
* Binding of odorant to receptor activates a Gα (Called G-olf) that in turn activates adenylyl cyclase
* cAMP gates a Na+/Ca2+ cation channel. Calcium rushes in and activates a Cl- channel. Chloride normally high in-low out in olfactory neurons and thus Cl- leaving also depolarizes cell
These afferent fibers all end in the nucleus of the solitary tract (NST) in the medulla. From there the information flows mainly to the thalamus and then to the gustatory cortex.
pathways
* afferents from tongue and epiglottis to gustatory nucleus (in medulla next to 4th ventricle, part of solitary nuclear complex) and then to VPM
* from taste bud to solitary nuclear complex and then to VPM
* Solitary nuclear complext to nucleus ambiguous to salivary glands
From the VPM projections reach the gustatory cortex: anterior insular cortex and frontal operculum.
Information derived from different areas of the tongue is spatially segregated in the n. of the solitary tract, the thalamus, and the cortex. (Still true?)
<figure><img src="figs/Neuroscience5e-Fig-15.18-1R_495eb15.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 15.18</figcaption></figure>
Types of papillae:
Circumvallatepapillae
Foliatepapillae
Fungiformpapillae
---
## Structure of a taste bud
<figure><img src="figs/Neuroscience5e-Fig-15.18-2R_ae72520.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 15.18</figcaption></figure>
Note:
---
## Tastes
<figure><img src="figs/Neuroscience5e-Fig-15.19-0_41ee554.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 15.19</figcaption></figure>
Note:
Composite fMRI image showing different locations of activation in insular cortex to each of these tastes.
---
## Taste receptors
* 5 distinct classes of taste receptors
* Salty and sour generally transduced by ions (Na+ or H+) that open channels
* This depolarizes neuron, that then leads to opening of voltage gated Na+ channels
* This depolarizes neuron more and leads to opening of voltage gated Ca2+ channels
* Leads to the release of serotonin
Note:
---
## Taste receptors
* Sweet and Unami receptors are GPCRs that share a subunit called T1R3
* T1R3 is paired with T1R2 for sweet and T1R1 for amino acids
* T1R1 and T1R2 are expressed in non-overlapping neurons
* T1R2/3 activation leads to activation of PLC, increases IP3 and opens Ca2+channels (TRPM5). Ca2+ channel opening depolarizes cell
* Bitter taste receptors (T2R) have 30 subtypes. Multiple members are expressed in same neurons but not in same neurons as the others. These use a specific Gα called gustucin
<figure><img src="figs/Neuroscience5e-Fig-15.22-0_copy_8088d1f.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 15.22</figcaption></figure>
sweet a.a. and bitter receptors are expressed in diff subsets of taste cells.
gene from the TRPM5 channel is inactivated in ko mice and behavioral responses measured with taste preference test. Mouse gets two drinking spouts (one with water and one with tastant and relative frequency of licking is measured).
pleasant tastes (sugar and umami), incr concentration gives incr response. For bitter there is decr response.
KO the PLCB2 (phospholipase) and responses are eliminated to sweet, umami, and bitter but rescuing expression only in T2R expressing cells recovers just the bitter taste response to wildtype levels.
* Sour receptor is expressed in every taste bud but isn’t in the same neurons as other receptors
* An experiment to show that T1R2 is a sweet receptor and PKD2L1 is a sour receptor
* Taste pathways remain segregated in the cortex (Zuker lab imaging?)
---
## Putting the bitter receptor into sweet receptor neurons will cause mice to be attracted to bitter!
<div><img src="figs/image16_190e843.png" height="300px"><figcaption>Based on Fig. 5 from Zhang et al., Cell 2003</figcaption></div>
Note:
Based on/adapted from Fig. 5 from Zhang et al., Cell 2003
<div><img src="figs/ScreenShot2016-02-22at4.43.22PM_712d13b.png" height="400px"><figcaption>[Video 1 from Peng et al., Nature 2015](https://www.nature.com/articles/nature15763#supplementary-information)</figcaption></div>
The orbital frontal cortex (OFC) receives inputs from vision, olfaction, and touch, as shown. It is the first area where signals from the taste and smell systems meet. (info based on E. T. Rolls (2000). The orbitofrontal cortex and reward. Cerebral Cortex, 10, 284-294, Fig. 2.)
