Scents and Sensibility: A Molecular Logic of Olfactory Perception (Nobel Lecture)

Axel, Richard

doi:10.1002/anie.200501726

Cited by 161 publications

(60 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32,33,59 Here, following earlier work, 24,27,29 we study a simplified model which captures the essential physics of the electron transfer process. We assume that there exist specific electronic states of the receptor that can be identified as a DA pair, with other levels well separated in energy.…”

Section: Model Of Olfactionmentioning

confidence: 99%

See 1 more Smart Citation

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Chęcińska

Pollock

Heaney

et al. 2015

The Journal of Chemical Physics

View full text Add to dashboard Cite

Motivated by a proposed olfactory mechanism based on a vibrationally-activated molecular switch, we study electron transport within a donor-acceptor pair that is coupled to a vibrational mode and embedded in a surrounding environment. We derive a polaron master equation with which we study the dynamics of both the electronic and vibrational degrees of freedom beyond previously employed semiclassical (MarcusJortner) rate analyses. We show: (i) that in the absence of explicit dissipation of the vibrational mode, the semiclassical approach is generally unable to capture the dynamics predicted by our master equation due to both its assumption of one-way (exponential) electron transfer from donor to acceptor and its neglect of the spectral details of the environment; (ii) that by additionally allowing strong dissipation to act on the odorant vibrational mode we can recover exponential electron transfer, though typically at a rate that differs from that given by the Marcus-Jortner expression; (iii) that the ability of the molecular switch to discriminate between the presence and absence of the odorant, and its sensitivity to the odorant vibrational frequency, are enhanced significantly in this strong dissipation regime, when compared to the case without mode dissipation; and (iv) that details of the environment absent from previous Marcus-Jortner analyses can also dramatically alter the sensitivity of the molecular switch, in particular allowing its frequency resolution to be improved. Our results thus demonstrate the constructive role dissipation can play in facilitating sensitive and selective operation in molecular switch devices, as well as the inadequacy of semiclassical rate equations in analysing such behaviour over a wide range of parameters.

show abstract

Section: Model Of Olfactionmentioning

confidence: 99%

“…[31][32][33][34][35] The prevailing theory, known as the lock-and-key model, explains how the odorant size and shape can provide discrimination in the receptor. 36 However, this theory does not give a straightforward explanation of why it a) These authors contributed equally to the work.…”

Section: Introductionmentioning

confidence: 99%

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Chęcińska

Pollock

Heaney

et al. 2015

The Journal of Chemical Physics

View full text Add to dashboard Cite

show abstract

“…O dorant binding to specialized receptors in the cilia of olfactory sensory neurons triggers an increase in intracellular cAMP (1)(2)(3)(4), which directly opens cyclic nucleotide-gated (CNG) channels (5). Calcium influx through CNG channels activates an atypical chloride current (6)(7)(8), leading to depolarization of the cell membrane.…”

mentioning

confidence: 99%

Interplay between PIP ₃ and calmodulin regulation of olfactory cyclic nucleotide-gated channels

Brady

Rich

Martens

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the odorant sensitivity of olfactory sensory neurons by inhibiting activation of cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the intracellular face of excised patches, PIP3 has been shown to inhibit activation of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3. Using chimeric channels and a deletion mutant, we determined that residues 61-90 within the N terminus of CNGA2 are necessary for PIP3 regulation, and a biochemical ''pulldown'' assay suggests that PIP3 directly binds this region. The N terminus of CNGA2 contains a previously identified calcium-calmodulin (Ca 2؉ ͞CaM)-binding domain (residues 68 -81) that mediates Ca 2؉ ͞CaM inhibition of homomeric CNGA2 channels but is functionally silent in heteromeric channels. We discovered, however, that this region is required for PIP3 regulation of both homomeric and heteromeric channels. Furthermore, PIP3 occluded the action of Ca 2؉ ͞CaM on both homomeric and heteromeric channels, in part by blocking Ca 2؉ ͞CaM binding. Our results establish the importance of the CNGA2 N terminus for PIP3 inhibition of olfactory CNG channels and suggest that PIP3 inhibits channel activation by disrupting an autoexcitatory interaction between the N and C termini of adjacent subunits. By dramatically suppressing channel currents, PIP3 may generate a shift in odorant sensitivity that does not require prior channel activity.lipid signaling ͉ olfaction ͉ phosphatidylinositide ͉ sensory adaptation O dorant binding to specialized receptors in the cilia of olfactory sensory neurons triggers an increase in intracellular cAMP (1-4), which directly opens cyclic nucleotide-gated (CNG) channels (5). Calcium influx through CNG channels activates an atypical chloride current (6-8), leading to depolarization of the cell membrane. The elevated calcium also causes rapid adaptation to odorants by triggering a calcium-calmodulin (Ca 2ϩ ͞CaM)-dependent decrease in the sensitivity of CNG channels to cAMP (9). Recent evidence suggests that phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ) also decreases the sensitivity of olfactory CNG channels and reduces the response of olfactory sensory neurons to complex odors, but the mechanism has yet to be elucidated (10, 11).Ca 2ϩ ͞CaM inhibits homomeric CNGA2 channel activation by binding to a Baa-like motif in the N terminus (12-14), thereby disrupting an autostimulatory interaction with the C terminus of an adjacent subunit (15-17). Deletion of the Ca 2ϩ ͞CaM-binding domain (amino acids 68-81) in CNGA2 produces channels that are resistant to inhibition by Ca 2ϩ ͞CaM and exhibit dramatically reduced sensitivity to cyclic nucleotides due to the loss of the autostimulatory interaction. Native olfactory CNG channels are tetrameric assemblies of three different pore-forming subunits, C...

show abstract

“…Olfactory information is encoded with numerous types of chemical substances, called odorants (Polak & Baliguet 1978). Odorants are captured by olfactory receptor neurons in the olfactory (nasal) epithelium, and those neurons that express the same odorant receptor genes project to specific glomeruli in the olfactory bulb, situated in most rostral region of the telencephalon (reviewed in Axel 2005). In the olfactory bulb, several types of projection neurons and interneurons elaborate highly ordered neuronal circuits, which play essential roles in processing odorant information (reviewed in Greer 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Two types of projection neurons, mitral and tufted cells, receive olfactory receptor innervations, and extend axons to several regions in the telencephalon, such as the olfactory cortex, olfactory tubercle, anterior olfactory nucleus, entorhinal cortex and several nuclei of the amygdala, where the odor information is further processed or stored (Zou et al 2001). Thus, the vertebrate olfactory system comprises several neuronal components of the peripheral and central nervous system, and each constituent plays pivotal roles in perception, transduction and integration of the olfactory information (reviewed in Axel 2005;Wilson & Mainen 2006;Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Role of a transcription factor Pax6 in the developing vertebrate olfactory system

2007

View full text Add to dashboard Cite

The olfactory system is responsible for capturing and processing odorant information, which significantly influences a variety of behaviors in animals. The vertebrate olfactory system consists of several neuronal components including the olfactory epithelium, olfactory bulb and olfactory cortex, which originate from distinct embryonic tissues. The transcription factor Pax6 is strongly expressed in the embryonic and postnatal olfactory systems, and regulates neuronal specification, migration and differentiation. Here we review classical and recent studies focusing on the role of Pax6 in the developing olfactory system, and highlight the cellular and molecular mechanisms underlying the highly coordinated developmental processes of the vertebrate olfactory system.

show abstract

Scents and Sensibility: A Molecular Logic of Olfactory Perception (Nobel Lecture)

Cited by 161 publications

References 63 publications

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Interplay between PIP ₃ and calmodulin regulation of olfactory cyclic nucleotide-gated channels

Role of a transcription factor Pax6 in the developing vertebrate olfactory system

Contact Info

Product

Resources

About

Scents and Sensibility: A Molecular Logic of Olfactory Perception (Nobel Lecture)

Cited by 161 publications

References 63 publications

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Interplay between PIP 3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels

Role of a transcription factor Pax6 in the developing vertebrate olfactory system

Contact Info

Product

Resources

About

Interplay between PIP ₃ and calmodulin regulation of olfactory cyclic nucleotide-gated channels