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Non-synaptic inhibition between grouped neurons in an olfactory circuit (2012)

C. Y. Su ; K. Menuz ; J. Reisert ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 492(7427): 66-71. doi: 10.1038/nature11712.

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Publication Date: 2012-11-23

Description: Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Chih-Ying -- Menuz, Karen -- Reisert, Johannes -- Carlson, John R -- DC009613/DC/NIDCD NIH HHS/ -- F32 DC011242/DC/NIDCD NIH HHS/ -- F32DC011242/DC/NIDCD NIH HHS/ -- R01 DC004729/DC/NIDCD NIH HHS/ -- R01 DC009613/DC/NIDCD NIH HHS/ -- R01 DC011697/DC/NIDCD NIH HHS/ -- England -- Nature. 2012 Dec 6;492(7427):66-71. doi: 10.1038/nature11712. Epub 2012 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23172146" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Anopheles gambiae/drug effects/physiology ; Carbon Dioxide/pharmacology ; Dose-Response Relationship, Drug ; Drosophila melanogaster/cytology/drug effects/physiology ; Female ; Neural Inhibition/drug effects/*physiology ; Olfactory Pathways/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*metabolism ; Sensilla/cytology/drug effects/innervation/physiology ; Smell/drug effects/physiology ; *Synapses ; Synaptic Transmission/drug effects

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

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TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists (2007)

K. Menuz ; R. M. Stroud ; R. A. Nicoll ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 318(5851): 815-7. doi: 10.1126/science.1146317.

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Publication Date: 2007-11-03

Description: Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Menuz, Karen -- Stroud, Robert M -- Nicoll, Roger A -- Hays, Franklin A -- GM078754/GM/NIGMS NIH HHS/ -- P50 GM73210/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):815-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975069" target="_blank"〉PubMed〈/a〉

Keywords: 6-Cyano-7-nitroquinoxaline-2,3-dione/chemistry/*pharmacology ; Animals ; Benzodiazepines/pharmacology ; Binding, Competitive ; Cell Line ; Cerebellum/cytology ; Crystallography, X-Ray ; *Drug Partial Agonism ; Hippocampus/cytology ; Humans ; In Vitro Techniques ; Interneurons/drug effects ; Mice ; Models, Molecular ; Patch-Clamp Techniques ; Protein Conformation ; Protein Subunits/*physiology ; Pyramidal Cells/drug effects/metabolism ; Quinoxalines/pharmacology ; Receptors, AMPA/*agonists/*antagonists & inhibitors ; Structure-Activity Relationship ; Synaptic Transmission/drug effects ; Trichlormethiazide/pharmacology

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics