lecture 9 – olfaction (chemical senses 2)raghav/pdfs/neurobiology2/lecture9_olfaction.… · 3...

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Lecture 9 – Olfaction (Chemical senses 2)

Raghav RajanBio 354 – Neurobiology 2

February 04th 2015

All lecture material from the following links unless otherwise mentioned:1.http://wws.weizmann.ac.il/neurobiology/labs/ulanovsky/sites/neurobiology.labs.ulanovsky/files/uploads/kandel_ch32_smell_taste.pdf2. Research papers provided at the bottom of the slide

http://wws.weizmann.ac.il/neurobiology/labs/ulanovsky/sites/neurobiology.labs.ulanovsky/files/uploads/kandel_ch32_smell_taste.pdf

http://wws.weizmann.ac.il/neurobiology/labs/ulanovsky/sites/neurobiology.labs.ulanovsky/files/uploads/kandel_ch32_smell_taste.pdf

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From earlier classes ...!!

● Responses to natural scenes (Radhika)

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Chemical senses – olfaction and gustation

● Chemicals in the external enviroment are being sensed

● How does a chemical signal get transduced into an electrical signal?

● How are the different features of olfactory stimuli represented in the brain?

– Basic attributes● What is the smell?● Where is it coming from?● How strong is it?● Timing

– Higher order attributes● Odor based recognition of individuals, objects (a form of what?)

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Structure of the external olfactory system – the nose

● Olfactory epithelium on the roof of the nasal cavity

● Olfactory epithelium has OSNs – olfactory sensory neurons

● How do OSNs detect odorant molecules?

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Nobel Prize in Physiology and Medicine 2004Linda Buck and Richard Axel

● Linda Buck was a postdoc in Richard Axel's lab

● Nobel prize awarded “for their discoveries of odorant receptors and the organisation of the olfactory system”

● Linda Buck and Richard Axel – A novel multigene family may encode odorant receptors: A molecular basis for odor recognition (Cell. 1991 - http://phy.ucsf.edu/neurograd/files/ns200_fa13/091013_buck_axel.pdf)

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/

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Background information available to Buck and Axel

● Cilia are required for olfactory transduction

● Odor exposure results in increase in cAMP concentration

● And depolarisation potentially through a cyclic-nucleotide gated channel

http://phy.ucsf.edu/neurograd/files/ns200_fa13/091013_buck_axel.pdf

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Their key assumptions to guide their search for odorant receptors

● Transduction through GPCRs (7 transmembrane G-Protein Coupled Receptors)

● Should belong to a multi-gene family so that they can detect diverse odorants

● Expression should be restricted to olfactory epithelium


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Experimental strategy and results

● Used primers targeting conserved trans-membrane regions of GPCRs

● Used PCR to amplify c-DNA from rat olfactory epithelium

● Then used restriction enzymes with the following logic

– If this is a multigene family, after cutting

– Σ(Molecular weight of parts) > Σ(Molecular weight of original PCR product)

● Found 18 PCR products

● Variable trans-membrane domain, may be for binding different ligands


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Olfactory signal transduction cascade

● In the rat, there are about 1000 receptor subtypes

● Golf – G protein specific to OSNs

● Adenylyl cyclase III

● There are also suggestions of other membrane molecules acting as receptors – receptor guanylyl cyclases

● Other signal transduction cascades too

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Each odorant receptor is expressed in one zone of the epithelium

● Mouse olfactory epithelium – in-situ hybridisation with probes of different odorant receptors

● OMP – olfactory marker protein expressed in all sensory neurons

● Each OR is expressed in one zone

● Within that zone, distribution is random

● Each OSN expresses only one receptor subtype!!

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Each OSN responds to many different odors

● Although each OSN expresses only one receptor subtype

● Responses of OSNs in the tiger salamander

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A more comprehensive response profile of OSNs

● Drosophila

● Different ORs expressed in one ORN where the normal receptor was deleted

● Electrophysiological responses recorded and compared with recordings from wild-type ORNs expressing known ORs

http://ac.els-cdn.com/S0092867404004982/1-s2.0-S0092867404004982-main.pdf?_tid=3be57fc6-a918-11e4-a6ae-00000aab0f27&acdnat=1422688407_d7ec8807681f36c70edd529330976aa0

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Example responses with appropriate controls

● System works well


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Odor Identity represented by combinatorial code across OSNs

● Each receptor neuron expresses one receptor sub-type and responds to multiple odorants

● Individual odorants evoke responses in multiple receptors

● Information from the olfactory epithelium – combinatorial code among all OSNs


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Anatomy of the olfactory system

● Neurons expressing one receptor subtype project to one glomerulus in the olfactory bulb

● Retinotopy, tonotopy – receptorotopy?!http://web.mit.edu/7.31/restricted/pdfs/Mori-review.pdf

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Excitation/Inhibition – circuitry in the olfactory

bulb● One receptor sub-type

projects to only two glomeruli in the olfactory bulb

● Lateral inhibition – believed to sharpen receptive fields of individual mitral/tufted cells

http://web.mit.edu/7.31/restricted/pdfs/Mori-review.pdf

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Higher order projections of the olfactory system – maybe two different pathways

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Odor processing is fast – odors can be reliably identified within 250ms

● For difficult tasks there is some controversy

– One view● Easy tasks – fast and accurate● Difficult tasks – fast and inaccurate

– Another view● Easy tasks – fast and accurate● Difficult tasks – slow and accurate

– Another view● Easy and difficult tasks – fast independent of accuracy

http://www.chaos.gwdg.de/~michael/teaching/UchidaMainenNN03.pdfhttp://www.sciencedirect.com/science/article/pii/S0896627304007536

http://www.sciencedirect.com/science/article/pii/S0896627306005538http://www.sciencedirect.com/science/article/pii/S0896627313001682

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How is odor location information obtained?

● Odour localization task – rats have to detect the source of an odour

http://www.iiserpune.ac.in/~raghav/pdfs/Rajan_Science2006.pdf

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One sniff is enough to locate an odour source


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Odor localization requires two nostrils

● A number of different controls

● Odor discrimination

● A purely olfactory stimulant that does not stimulate the trigeminal system (therefore not an irritant)


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Chemical senses – olfaction and gustation

● Chemicals in the external enviroment are being sensed

● How does a chemical signal get transduced into an electrical signal?

● How are the different features of olfactory stimuli represented in the brain?

– Basic attributes● Identity – one sniff – cominatorial representation that evolves over time and

space● Where is it coming from – one sniff – stereo cues – maybe different

pathways?● How strong is it – intensity – unclear – maybe strength of activation of

individual OSNs● Timing – respiration cycle – phase locked firing

– Higher order attributes● Odor based recognition of individuals, objects (a form of what?)

lecture 9 – olfaction (chemical senses 2)raghav/pdfs/neurobiology2/lecture9_olfaction.… · 3...

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