BIPN140 Lecture 15: The Chemical Senses

1. Olfactory System 2. Olfactory Receptors & Transduction Mechanism

Su (FA16)

Three Stages of Information Processing

(Afferent)

external or internal

(Efferent)

external or internal Olfaction

 The sensory system that mediates the detection of volatile chemicals (airborne molecules) in the environment.  Evolutionarily, olfaction is considered to the “most primitive” sense; the only sensory modality that bypasses the thalamus (no thalamic relay) and sends input directly to the cortex.  Functions for most animals: (1) Critical for survival: identify food/prey, mating partners, and foes/predators. (2) Modulating foraging/feeding behavior, social interactions, reproduction and defensive responses (aggression).  For humans, important for quality of life (evaluating the quality of food, influencing mood and emotion, influencing social interactions and reproduction).  Odorant: a pure volatile compound that can be detected by the olfactory system  Odor: the property of a substance that activates the olfactory system; usually consists of multiple odorants, e.g. coffee odor, flower odor, food odor, etc.

Odor space is boundless and dimensionless

. Vision: wavelength; Hearing: frequency

. Number of pure odorants is unknown.

. Which two odorants are more similar to one another?

 Olfactory system does not function like a gas chromatography-mass spectrometry (GCMS) machine. Structural similarity between two odorants does not predict perceptual similarity.  Olfactory system does not care about the structure of odorants but the “hedonic value” or “valence” of the odor (pleasant/attractive v.s. unpleasant/aversive). (Goldstein, Sensation and Perception, 8th edition) The Nobel Prize in Physiology or Medicine 2004 was awarded jointly to Richard Axel and Linda Buck "for their discoveries of odorant receptors and the organization of the olfactory system"

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/odorant_high_eng.jpg

Odorant Receptor Proteins (Fig. 15.9)  Richard Axel & Linda Buck: cloning of rodent olfactory receptor genes (7-TM GPCR) in 1991; awarded a Nobel Prize in 2004.  A large family of GPCRs. In mammals, odorant receptors are the largest known single gene family, representing 3-5% of the genome. Out of ~950 human Or genes, ~400 are transcribed. Out of ~1500 mouse Or genes, ~1200 are transcribed.  Insects in general have a much smaller Or repertoire (<100 genes in general). Insect odorant receptors are not GPCRs, but likely to be ligand-gated non-selective cation channels.  One ORN expresses only one type of Or gene. For humans, there are ~400 different types of ORNs, each type has ~30,000 neurons. Molecular Mechanisms of Olfactory Transduction (Fig. 15.11)  Olfactory transduction: conversion of chemical stimuli into electrical neuronal signal (odorant + receptor => transduction current => action potential). Taking place at cilia.  Activation of an odorant receptor

(GPCR) by odorant => Golf (belongs to Gs family) => activation of adenylyl cyclase III (ACIII) to increase cAMP level => cAMP opens cAMP-gated nonselctive cation channel (CNG channel) => Na+ and Ca2+ influx (depolarization) => Ca2+ opens a Ca2+-gated chloride channel (Anoctamin 2, Ano2) => Cl- efflux to further depolarize ORN.  NKCC1, a Na+K+2Cl- co-transporter, is expressed at ORNs to elevate intracellular Cl- concentration + 2+  Na /Ca exchanger (NCKX4): remove (remember: NKCC1 is also expressed 2+ Ca from ORNs to return to basal level; in immature neurons so that activation important for the termination of olfactory of GABA-A is depolarizing). response

Structure and Function of the Olfactory Epithelium (Fig. 15. 7)  Olfactory epithelium: the sheet of neurons and supporting cells that lines roughly half of the surface of the nasal cavity (the other half: respiratory epithelium).  Olfactory receptor neurons (ORNs): olfactory cilia (olfactory receptor & transduction components, primary site for olfactory transduction) + cell body (surrounded by the supporting cells) + unmyelinated axons  ORNs are exceptionally exposed to airborne pollutants, microorganisms and environmental toxins.  Solutions: Bowman’s gland: secret mucus to (1) protect cells in the 1. mucus: physical barrier + rich in olfactory epithelium (2) control the ionic environment of the immunoglobulins olfactory epithelium 2. supporting cells: enzymes to break down organic chemicals 3. macrophages in the nasal mucosa 4. regeneration of ORNs (6-8 weeks for rodents), depending on basal cells. Organization of the Human Olfactory System (Fig. 15.1)

Olfactory receptor neurons (ORNs): found in the olfactory epithelium; detect odorants; activation of ORNs => action potentials => ORN axons send information to the olfactory bulb => pyriform cortex Olfactory learning (olfactory cortex) and other forebrain areas.

Olfactory stimulus can elicit a variety of physiological responses. Innate Aroma of food: salivating olfactory behavior & and increased gastric aggression motility. Olfactory memory Reproduction Noxious smell: gagging or vomiting. Pheromone: reproduction and endocrine function.

Olfactory information processing: convergent evolution

. One receptor from a large gene family . Glomerular structure . Multiple higher brain targets

(Su et al., Cell, 2009) Odorant Receptor Neuron Selectivity (Fig. 15.12) odorant

(Malnic et al., Cell, 1999)

 Combinatorial code: each ORN recognizes multiple odorants and one odorant is recognized by multiple ORN types. Odor identity is likely encoded by the activation pattern of ORNs.

Anosmia (Box. 15A)  Anosmia: inability to perceive odor or impaired olfactory function.

 Peripheral: damage to olfactory epithelium or genetic mutations (e.g. genes important for olfactory transduction). Chronic sinus infection, inflammation or exposure to toxins may lead to anosmia.

 Zinc salts (e.g. zinc gluconate, commonly used in homeopathic cold remedies) cause significant cellular damage to the olfactory epithelium.

 Central: damage to brain regions important for olfactory information processing. Alzheimer’s disease, aging or traumatic head injury can all cause anosmia.

 Affecting quality of life and the ability to avoid spoiled food, toxic chemicals & smoke. May also reduce appetite leading to weight loss and malnutrition.

Many primary sensory cells are grouped together

Olfactory Sensilla Pheromone Sensilla Humidity Sensilla Auditory Scolopidia

(Su et al, Nature, 2012) (based on Thistle et al, Neuron, 2012)

Taste Sensilla Taste Buds

(Kim & Wang, (Bechstedt & Howard, Current Biology, 2016) Current Biology, 2008)

(Weiss et al, Neuron, 2011) (Yarmolinsky et al, Cell, 2009)

Fly olfaction

sensillum Antenna Maxillary palp

(Su et al., Cell, 2009) A detailed map of fly ORNs

basiconic coeloconic

trichoid

ab11 ab12

(de Bruyne et al, Neuron, 2001; Couto et al, Current Biology, 2005; Benton et al, Cell, 2009; Kwon et al, Current Biology, 2010)

Activation of one ORN inhibits its neighbor

2-hep (37 Hz)

(34 Hz)

(Or85b-rpr)

(Su et al., Nature, 2012) Communication between grouped ORNs is bidirectional

Does lateral inhibition require central processing?

? Olfactory computation without a synapse

Conventional means of neuronal communication

Chemical Synapse Gap Junction Communication without a synapse

(Shanbhag et al, International Journal of Insect Morphology and Embryology, 1999) (Shanbhag et al, Arthropod Structure & Development, 2000)

Ephaptic coupling

Electrical interactions that arise from the close apposition of neuronal processes from two or a few neurons. (Jefferys, Physiol Reviews, 1995)

(Vermeulen and Rospars, Eur Biophys J, 2004) Model: ephaptic coupling

(Adapted from Vermeulen and Rospars, Eur Biophys J, 2004)

Why are fly ORNs compartmentalized?

 Communication by sharing the same environment

 Each sensillum type as a processing unit in olfactory computation

 What is the functional output of those processing units? Do they process information about odor identity and/or the valence of the odor?

 What is the functional impact of those processing units on olfactory behavior?

(Couto et al, Current Biology, 2005) Ephaptic interaction is asymmetrical: A > B

3D reconstruction of a labeled ORN and its neighbor

1 µm 3D reconstruction of a labeled ORN and its neighbor

1 µm

Large-spiked neuron has large soma than their

(Angela Tsang, Ben Damasco and Renny Ng ) Fig. 1. Lateral inhibition of ORNs

Fig. 4. Lateral inhibition does not require synapses. Fig. 5. Lateral inhibition in a sensillum modulates behavior.