Lecture 9 Olfaction (Chemical senses 2)

Transcription

1 Lecture 9 Olfaction (Chemical senses 2) All lecture material from the following links unless otherwise mentioned: 1. f 2. Research papers provided at the bottom of the slide Raghav Rajan Bio 354 Neurobiology 2 February 04th

2 From earlier classes...!! Responses to natural scenes (Radhika) 2

3 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?) 3

4 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? 4

5 Nobel Prize in Physiology and Medicine 2004 Linda 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

6 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 6

7 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 7

8 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 8

9 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 9

10 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!! 10

11 Each OSN responds to many different odors Although each OSN expresses only one receptor subtype Responses of OSNs in the tiger salamander 11

12 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 12

13 Example responses with appropriate controls System works well 13

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15 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 15

16 Anatomy of the olfactory system Neurons expressing one receptor subtype project to one glomerulus in the olfactory bulb Retinotopy, tonotopy receptorotopy?! 16

17 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 17

18 Higher order projections of the olfactory system maybe two different pathways 18

19 Odor processing is fast odors can be reliably identified within 250ms For difficult tasks there is some controversy One view Another view Easy tasks fast and accurate Difficult tasks fast and inaccurate Easy tasks fast and accurate Difficult tasks slow and accurate Another view Easy and difficult tasks fast independent of accuracy

20 How is odor location information obtained? Odour localization task rats have to detect the source of an odour 20

21 One sniff is enough to locate an odour source 21

22 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) 22

23 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?) 23