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The cyclic AMP signaling pathway in the rodent main olfactory system

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Abstract

Odor perception begins with the detection of odorant molecules by the main olfactory epithelium located in the nasal cavity. Odorant molecules bind to and activate a large family of G-protein-coupled odorant receptors and trigger a cAMP-mediated transduction cascade that converts the chemical stimulus into an electrical signal transmitted to the brain. Morever, odorant receptors and cAMP signaling plays a relevant role in olfactory sensory neuron development and axonal targeting to the olfactory bulb. This review will first explore the physiological response of olfactory sensory neurons to odorants and then analyze the different components of cAMP signaling and their different roles in odorant detection and olfactory sensory neuron development.

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Abbreviations

ACIII:

Adenylyl cyclase type III

CaM:

Calmodulin

CNG:

Cyclic nucleotide-gated

GPCR:

G-protein-coupled receptors

KO:

Knockout

MOE:

Main olfactory epithelium

NCKX:

K+-dependent Na+/Ca2+ exchanger

OMP:

Olfactory marker protein

OSN:

Olfactory sensory neuron

OR:

Odorant receptor

PDE:

Phosphodiesterase

TMEM16:

Transmembrane protein of unknown function number 16

References

  • Antolin S, Reisert J, Matthews HR (2010) Olfactory response termination involves Ca2+-ATPase in vertebrate olfactory receptor neuron cilia. J Gen Physiol 135:367–378

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bakalyar HA, Reed RR (1990) Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250:1403–1406

    CAS  PubMed  Google Scholar 

  • Balasubramanian S, Lynch JW, Barry PH (1996) Calcium-dependent modulation of the agonist affinity of the mammalian olfactory cyclic nucleotide-gated channel by calmodulin and a novel endogenous factor. J Membr Biol 152:13–23

    CAS  PubMed  Google Scholar 

  • Barnea G, O’Donnell S, Mancia F, Sun X, Nemes A, Mendelsohn M, Axel R (2004) Odorant receptors on axon termini in the brain. Science 304:1468

    CAS  PubMed  Google Scholar 

  • Belluscio L, Gold GH, Nemes A, Axel R (1998) Mice deficient in G(olf) are anosmic. Neuron 20:69–81

    CAS  PubMed  Google Scholar 

  • Bhandawat V, Reisert J, Yau K-W (2010) Signaling by olfactory receptor neurons near threshold. Proc Natl Acad Sci USA 107:18682–18687

    CAS  PubMed  Google Scholar 

  • Billig GM, Pál B, Fidzinski P, Jentsch TJ (2011) Ca2+-activated Cl− currents are dispensable for olfaction. Nat Neurosci 14:763–769

    CAS  PubMed  Google Scholar 

  • Biskup C, Kusch SE, Nache V, Schwede F, Lehmann F, Hagen V, Benndorf K (2007) Relating ligand binding to activation gating in CNGA2 channels. Nature 446:440–443

    CAS  PubMed  Google Scholar 

  • Boccaccio A, Lagostena L, Hagen V, Menini A (2006) Fast adaptation in mouse olfactory sensory neurons does not require the activity of phosphodiesterase. J Gen Physiol 128:171–184

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boccaccio A, Menini A (2007) Temporal development of cyclic nucleotide-gated and Ca2+ -activated Cl- currents in isolated mouse olfactory sensory neurons. J Neurophysiol 98:153–160

    CAS  PubMed  Google Scholar 

  • Boekhoff I, Kroner C, Breer H (1996) Second-messenger signalling in olfactory cilia. Cell Signal 8:167–171

    CAS  PubMed  Google Scholar 

  • Borisy FF, Ronnett GV, Cunningham AM, Juilfs D, Beavo J, Snyder SH (1992) Calcium/calmodulin-activated phosphodiesterase expressed in olfactory receptor neurons. J Neurosci 12:915–923

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bönigk W, Bradley J, Müller F, Sesti F, Boekhoff I, Ronnett GV, Kaupp UB, Frings S (1999) The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits. J Neurosci 19:5332–5347

    PubMed  PubMed Central  Google Scholar 

  • Bradley J, Bönigk W, Yau K-W, Frings S (2004) Calmodulin permanently associates with rat olfactory CNG channels under native conditions. Nat Neurosci 7:705–710

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bradley J, Li J, Davidson N, Lester HA, Zinn K (1994) Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci U S A 91:8890–8894

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bradley J, Reuter D, Frings S (2001) Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits. Science 294:2176–2178

    CAS  PubMed  Google Scholar 

  • Brunet LJ, Gold GH, Ngai J (1996) General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17:681–693

    CAS  PubMed  Google Scholar 

  • Brunner JD, Lim NK, Schenck S, Duerst A, Dutzler R (2014) X-ray structure of a calcium-activated TMEM16 lipid scramblase. Nature 516:207–212

    CAS  PubMed  Google Scholar 

  • Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65:175–187

    CAS  Google Scholar 

  • Buiakova OI, Baker H, Scott JW, Farbman A, Kream R, Grillo M, Franzen L, Richman M, Davis LM, Abbondanzo S, Stewart CL, Margolis FL (1996) Olfactory marker protein (OMP) gene deletion causes altered physiological activity of olfactory sensory neurons. Proc Natl Acad Sci U S A 93:9858–9863

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carey RM, Verhagen JV, Wesson DW, Pírez N, Wachowiak M (2009) Temporal structure of receptor neuron input to the olfactory bulb imaged in behaving rats. J Neurophysiol 101:1073–1088

    PubMed  Google Scholar 

  • Chen C, Nakamura T, Koutalos Y (1999) Cyclic AMP diffusion coefficient in frog olfactory cilia. Biophys J 76:2861–2867

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen TY, Yau KW (1994) Direct modulation by Ca2+–calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. Nature 368:545–548

    CAS  PubMed  Google Scholar 

  • Chen X, Xia Z, Storm DR (2012) Stimulation of electro-olfactogram responses in the main olfactory epithelia by airflow depends on the type 3 adenylyl cyclase. J Neurosci 32:15769–15778

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cherry JA, Davis RL (1995) A mouse homolog of dunce, a gene important for learning and memory in Drosophila, is preferentially expressed in olfactory receptor neurons. J Neurobiol 28:102–113

    CAS  PubMed  Google Scholar 

  • Chesler AT, Zou DJ, Le Pichon CE, Peterlin ZA, Matthews GA, Pei X, Miller MC, Firestein S (2007) A G protein/cAMP signal cascade is required for axonal convergence into olfactory glomeruli. Proc Natl Acad Sci USA 104:1039–1044

    CAS  PubMed  Google Scholar 

  • Connelly T, Yu Y, Grosmaitre X, Wang J, Santarelli LC, Savigner A, Qiao X, Wang Z, Storm DR, Ma M (2015) G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons. Proc Natl Acad Sci U S A 112:590–595

    CAS  PubMed  Google Scholar 

  • Cygnar KD, Zhao H (2009) Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons. Nat Neurosci 12:454–462

    CAS  PubMed  PubMed Central  Google Scholar 

  • Czesnik D, Schild D, Kuduz J, Manzini I (2007) Cannabinoid action in the olfactory epithelium. Proc Natl Acad Sci USA 104:2967–2972

    CAS  PubMed  Google Scholar 

  • Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbühler K, Ye W, Qi L, Chen T, Craik CS, Jan YN, Minor DL, Cheng Y, Jan LY (2017) Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature 552:426–429

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dibattista M, Al Koborssy D, Genovese F, Reisert J (2021) The functional relevance of olfactory marker protein in the vertebrate olfactory system: A never-ending story. Cell Tissue Res

  • Dibattista M, Pifferi S, Boccaccio A, Menini A, Reisert J (2017) The long tale of the calcium activated Cl- channels in olfactory transduction. Channels (Austin) 11:399–414

    Google Scholar 

  • Dibattista M, Reisert J (2016) The odorant receptor-dependent role of olfactory marker protein in olfactory receptor neurons. J Neurosci 36:2995–3006

    CAS  PubMed  PubMed Central  Google Scholar 

  • Douguet D, Honoré E (2019) Mammalian mechanoelectrical transduction: structure and function of force-gated ion channels. Cell 179:340–354

    CAS  PubMed  Google Scholar 

  • Dubacq C, Jamet S, Trembleau A (2009) Evidence for developmentally regulated local translation of odorant receptor mRNAs in the axons of olfactory sensory neurons. J Neurosci 29:10184–10190

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dzeja C, Hagen V, Kaupp UB, Frings S (1999) Ca2+ permeation in cyclic nucleotide-gated channels. EMBO J 18:131–144

    CAS  PubMed  PubMed Central  Google Scholar 

  • Falzone ME, Malvezzi M, Lee B-C, Accardi A (2018) Known structures and unknown mechanisms of TMEM16 scramblases and channels. J Gen Physiol 150:933–947

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feinstein P, Mombaerts P (2004) A contextual model for axonal sorting into glomeruli in the mouse olfactory system. Cell 117:817–831

    CAS  PubMed  Google Scholar 

  • Firestein S, Picco C, Menini A (1993) The relation between stimulus and response in olfactory receptor cells of the tiger salamander. J Physiol 468:1–10

    CAS  PubMed  PubMed Central  Google Scholar 

  • Firestein S, Shepherd GM, Werblin FS (1990) Time course of the membrane current underlying sensory transduction in salamander olfactory receptor neurones. J Physiol 430:135–158

    CAS  PubMed  PubMed Central  Google Scholar 

  • Firestein S, Werblin F (1989) Odor-induced membrane currents in vertebrate-olfactory receptor neurons. Science 244:79–82

    CAS  PubMed  Google Scholar 

  • Firestein S, Zufall F, Shepherd GM (1991) Single odor-sensitive channels in olfactory receptor neurons are also gated by cyclic nucleotides. J Neurosci 11:3565–3572

    CAS  PubMed  PubMed Central  Google Scholar 

  • Flannery RJ, French DA, Kleene SJ (2006) Clustering of cyclic-nucleotide-gated channels in olfactory cilia. Biophys J 91:179–188

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fletcher RB, Das D, Gadye L, Street KN, Baudhuin A, Wagner A, Cole MB, Flores Q, Choi YG, Yosef N, Purdom E, Dudoit S, Risso D, Ngai J (2017) Deconstructing olfactory stem cell trajectories at single-cell resolution. Cell Stem Cell 20:817-830.e8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frings S (2009) Chloride-based Signal Amplification in Olfactory Sensory Neurons. In: Alvarez-Leefmans FJ, Delpire E (eds) Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. From Molecules to Diseases . Academic Press, New York , pp 409–420

    Google Scholar 

  • Frings S, Lindemann B (1990) Single unit recording from olfactory cilia. Biophys J 57:1091–1094

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frings S, Reuter D, Kleene SJ (2000) Neuronal Ca2+ -activated Cl- channels–homing in on an elusive channel species. Prog Neurobiol 60:247–289

    CAS  PubMed  Google Scholar 

  • Frings S, Seifert R, Godde M, Kaupp UB (1995) Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels. Neuron 15:169–179

    CAS  PubMed  Google Scholar 

  • Gesteland RC, Sigwart CD (1977) Olfactory receptor units–a mammalian preparation. Brain Res 133:144–149

    CAS  PubMed  Google Scholar 

  • Getchell TV (1977) Analysis of intracellular recordings from salamander olfactory epithelium. Brain Res 123:275–286

    CAS  PubMed  Google Scholar 

  • Ghosh S, Larson SD, Hefzi H, Marnoy Z, Cutforth T, Dokka K, Baldwin KK (2011) Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons. Nature 472:217–220

    CAS  PubMed  Google Scholar 

  • Graziadei PP, Graziadei GA (1979) Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. J Neurocytol 8:1–18

    CAS  PubMed  Google Scholar 

  • Grosmaitre X, Santarelli LC, Tan J, Luo M, Ma M (2007) Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors. Nat Neurosci 10:348–354

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grosmaitre X, Vassalli A, Mombaerts P, Shepherd GM, Ma M (2006) Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice. Proc Natl Acad Sci USA 103:1970–1975

    CAS  PubMed  Google Scholar 

  • Gu J, Zhang QY, Genter MB, Lipinskas TW, Negishi M, Nebert DW, Ding X (1998) Purification and characterization of heterologously expressed mouse CYP2A5 and CYP2G1: role in metabolic activation of acetaminophen and 2,6-dichlorobenzonitrile in mouse olfactory mucosal microsomes. J Pharmacol Exp Ther 285:1287–1295

    CAS  PubMed  Google Scholar 

  • Hanchate NK, Kondoh K, Lu Z, Kuang D, Ye X, Qiu X, Pachter L, Trapnell C, Buck LB (2015) Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis. Science 350:1251–1255

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hayoz S, Jia C, Hegg C (2012) Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium. BMC Neurosci 13:53

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hengl T, Kaneko H, Dauner K, Vocke K, Frings S, Möhrlen F (2010) Molecular components of signal amplification in olfactory sensory cilia. Proc Natl Acad Sci USA 107:6052–6057

    CAS  PubMed  Google Scholar 

  • Henriques T, Agostinelli E, Hernandez-Clavijo A, Maurya DK, Rock JR, Harfe BD, Menini A, Pifferi S (2019) TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium. J Gen Physiol 151:954–966

    CAS  PubMed  PubMed Central  Google Scholar 

  • Humphrey JD, Dufresne ER, Schwartz MA (2014) Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 15:802–812

    CAS  PubMed  PubMed Central  Google Scholar 

  • Imai T, Suzuki M, Sakano H (2006) Odorant receptor-derived cAMP signals direct axonal targeting. Science 314:657–661

    CAS  PubMed  Google Scholar 

  • Inoue N, Nishizumi H, Naritsuka H, Kiyonari H, Sakano H (2018) Sema7A/PlxnCl signaling triggers activity-dependent olfactory synapse formation. Nat Commun 9: 1842. https://doi.org/10.1038/s41467-018-04239-z

  • Iwata R, Kiyonari H, Imai T (2017) Mechanosensory-based phase coding of odor identity in the olfactory bulb. Neuron 96:1139-1152.e7

    CAS  PubMed  Google Scholar 

  • Jones DT, Reed RR (1989) Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science 244:790–795

    CAS  PubMed  Google Scholar 

  • Juilfs DM, Fülle HJ, Zhao AZ, Houslay MD, Garbers DL, Beavo JA (1997) A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway. Proc Natl Acad Sci USA 94:3388–3395

    CAS  PubMed  Google Scholar 

  • Jung A, Lischka FW, Engel J, Schild D (1994) Sodium/calcium exchanger in olfactory receptor neurones of Xenopus laevis. NeuroReport 5:1741–1744

    CAS  PubMed  Google Scholar 

  • Jung J, Nam JH, Park HW, Oh U, Yoon J-H, Lee MG (2013) Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin. Proc Natl Acad Sci USA 110:360–365

    CAS  PubMed  Google Scholar 

  • Kaneko H, Nakamura T, Lindemann B (2001) Noninvasive measurement of chloride concentration in rat olfactory receptor cells with use of a fluorescent dye. Am J Physiol, Cell Physiol 280:C1387-1393

    CAS  Google Scholar 

  • Kaneko H, Putzier I, Frings S, Kaupp UB, Gensch T (2004) Chloride accumulation in mammalian olfactory sensory neurons. J Neurosci 24:7931–7938

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kato A, Katada S, Touhara K (2008) Amino acids involved in conformational dynamics and G protein coupling of an odorant receptor: targeting gain-of-function mutation. J Neurochem 107:1261–1270

    CAS  PubMed  Google Scholar 

  • Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82:769–824

    CAS  PubMed  Google Scholar 

  • Kleene SJ (1993) Origin of the chloride current in olfactory transduction. Neuron 11:123–132

    CAS  PubMed  Google Scholar 

  • Kleene SJ (1994) Inhibition of olfactory cyclic nucleotide-activated current by calmodulin antagonists. Br J Pharmacol 111:469–472

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kleene SJ (1997) High-gain, low-noise amplification in olfactory transduction. Biophys J 73:1110–1117

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kleene SJ (1999) Both external and internal calcium reduce the sensitivity of the olfactory cyclic-nucleotide-gated channel to cAMP. J Neurophysiol 81:2675–2682

    CAS  PubMed  Google Scholar 

  • Kleene SJ (2008) The electrochemical basis of odor transduction in vertebrate olfactory cilia. Chem Senses 33:839–859

    CAS  PubMed  Google Scholar 

  • Kleene SJ, Gesteland RC (1991) Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 11:3624–3629

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kleene SJ, Pun RY (1996) Persistence of the olfactory receptor current in a wide variety of extracellular environments. J Neurophysiol 75:1386–1391

    CAS  PubMed  Google Scholar 

  • Kramer RH, Siegelbaum SA (1992) Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels in olfactory receptor neurons. Neuron 9:897–906

    CAS  PubMed  Google Scholar 

  • Kuhlmann K, Tschapek A, Wiese H, Eisenacher M, Meyer HE, Hatt HH, Oeljeklaus S, Warscheid B (2014) The membrane proteome of sensory cilia to the depth of olfactory receptors. Mol Cell Proteomics 13:1828–1843

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kurahashi T (1989) Activation by odorants of cation-selective permeabilities. J Physiol 419:177–192

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kurahashi T, Kaneko A (1993) Gating properties of the cAMP-gated channel in toad olfactory receptor cells. J Physiol 466:287–302

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kurahashi T, Kaneko A (1991) High density cAMP-gated channels at the ciliary membrane in the olfactory receptor cell. NeuroReport 2:5–8

    CAS  PubMed  Google Scholar 

  • Kurahashi T, Menini A (1997) Mechanism of odorant adaptation in the olfactory receptor cell. Nature 385:725–729

    CAS  PubMed  Google Scholar 

  • Kurahashi T, Shibuya T (1990) Ca2+-dependent adaptive properties in the solitary olfactory receptor cell of the newt. Brain Res 515:261–268

    CAS  PubMed  Google Scholar 

  • Kurahashi T, Yau KW (1993) Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells. Nature 363:71–74

    CAS  PubMed  Google Scholar 

  • Lacroix MC, Badonnel K, Meunier N, Tan F, Schlegel-Le Poupon C, Durieux D, Monnerie R, Baly C, Congar P, Salesse R, Caillol M (2008) Expression of insulin system in the olfactory epithelium: first approaches to its role and regulation. J Neuroendocrinol 20:1176–1190

    CAS  PubMed  Google Scholar 

  • Larsson HP, Kleene SJ, Lecar H (1997) Noise analysis of ion channels in non-space-clamped cables: estimates of channel parameters in olfactory cilia. Biophys J 72:1193–1203

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leinders-Zufall T, Ma M, Zufall F (1999) Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca2+/calmodulin kinase II. J Neurosci 19:RC19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leinders-Zufall T, Rand MN, Shepherd GM, Greer CA, Zufall F (1997) Calcium entry through cyclic nucleotide-gated channels in individual cilia of olfactory receptor cells: spatiotemporal dynamics. J Neurosci 17:4136–4148

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li F, Ponissery-Saidu S, Yee KK, Wang H, Chen M-L, Iguchi N, Zhang G, Jiang P, Reisert J, Huang L (2013) Heterotrimeric G protein subunit Gγ13 is critical to olfaction. J Neurosci 33:7975–7984

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Lester HA (1999) Single-channel kinetics of the rat olfactory cyclic nucleotide-gated channel expressed in Xenopus oocytes. Mol Pharmacol 55:883–893

    CAS  PubMed  Google Scholar 

  • Li RC, Lin CC, Ren X, Wu JS, Molday LL, Molday RS, Yau KWl, (2018) Ca2+-activated Cl current predominates in threshold response of mouse olfactory receptor neurons. Proc Natl Acad Sci USA 115:5570–5575

    CAS  PubMed  Google Scholar 

  • Lidow MS, Menco BP (1984) Observations on axonemes and membranes of olfactory and respiratory cilia in frogs and rats using tannic acid-supplemented fixation and photographic rotation. J Ultrastruct Res 86:18–30

    CAS  PubMed  Google Scholar 

  • Liman ER, Buck LB (1994) A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron 13:611–621

    CAS  PubMed  Google Scholar 

  • Liu M, Chen TY, Ahamed B, Li J, Yau KW (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266:1348–1354

    CAS  PubMed  Google Scholar 

  • Lowe G, Gold GH (1991) The spatial distributions of odorant sensitivity and odorant-induced currents in salamander olfactory receptor cells. J Physiol 442:147–168

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lowe G, Gold GH (1993) Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells. Nature 366:283–286

    CAS  PubMed  Google Scholar 

  • Lowe G, Nakamura T, Gold GH (1989) Adenylate cyclase mediates olfactory transduction for a wide variety of odorants. Proc Natl Acad Sci U S A 86:5641–5645

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lynch JW, Lindemann B (1994) Cyclic nucleotide-gated channels of rat olfactory receptor cells: divalent cations control the sensitivity to cAMP. J Gen Physiol 103:87–106

    CAS  PubMed  Google Scholar 

  • Ma M, Chen WR, Shepherd GM (1999) Electrophysiological characterization of rat and mouse olfactory receptor neurons from an intact epithelial preparation. J Neurosci Methods 92:31–40

    CAS  PubMed  Google Scholar 

  • Macrides F, Chorover SL (1972) Olfactory bulb units: activity correlated with inhalation cycles and odor quality. Science 175:84–87

    CAS  PubMed  Google Scholar 

  • Malnic B, Gonzalez-Kristeller DC, Gutiyama LM (2010) Odorant Receptors. In: Menini A (ed) The Neurobiology of Olfaction. CRC Press/Taylor & Francis, Boca Raton (FL)

    Google Scholar 

  • Malnic B, Hirono J, Sato T, Buck LB (1999) Combinatorial receptor codes for odors. Cell 96:713–723

    CAS  PubMed  Google Scholar 

  • Margolis FL (1972) A brain protein unique to the olfactory bulb. Proc Natl Acad Sci U S A 69:1221–1224

    CAS  PubMed  PubMed Central  Google Scholar 

  • Margrie TW, Schaefer AT (2003) Theta oscillation coupled spike latencies yield computational vigour in a mammalian sensory system. J Physiol 546:363–374

    CAS  PubMed  Google Scholar 

  • Matsuzaki O, Bakin RE, Cai X, Menco BP, Ronnet GV (1999) Localization of the olfactory cyclic nucleotide-gated channel subunit 1 in normal, embryonic and regenerating olfactory epithelium. Neuroscience 94:131–140

    CAS  PubMed  Google Scholar 

  • Menco BP (1980) Qualitative and quantitative freeze-fracture studies on olfactory and nasal respiratory epithelial surfaces of frog, ox, rat, and dog. II. Cell apices, cilia, and microvilli. Cell Tissue Res 211:5–29

    CAS  PubMed  Google Scholar 

  • Menco BP (1997) Ultrastructural aspects of olfactory signaling. Chem Senses 22:295–311

    CAS  PubMed  Google Scholar 

  • Menco BP, Bruch RC, Dau B, Danho W (1992) Ultrastructural localization of olfactory transduction components: the G protein subunit Golf alpha and type III adenylyl cyclase. Neuron 8:441–453

    CAS  PubMed  Google Scholar 

  • Menini A (1999) Calcium signalling and regulation in olfactory neurons. Curr Opin Neurobiol 9:419–426

    CAS  PubMed  Google Scholar 

  • Michalakis S, Reisert J, Geiger H, Wetzel C, Zong X, Bradley J, Spehr M, Hüttl S, Gerstner A, Pfeifer A, Hatt H, Yau KW, Biel M (2006) Loss of CNGB1 protein leads to olfactory dysfunction and subciliary cyclic nucleotide-gated channel trapping. J Biol Chem 281:35156–35166

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278

    CAS  PubMed  Google Scholar 

  • Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R (1996) Visualizing an olfactory sensory map. Cell 87:675–686

    CAS  PubMed  Google Scholar 

  • Mori K, Sakano H (2011) How is the olfactory map formed and interpreted in the mammalian brain? Annu Rev Neurosci 34:467–499

    CAS  PubMed  Google Scholar 

  • Munger SD, Lane AP, Zhong H, Leinders-Zufall T, Yau KW, Zufall F, Reed RR (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science 294:2172–2175

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nache V, Schulz E, Zimmer T, Kusch J, Biskup C, Koopmann R, Hagen V, Benndorf K (2005) Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative. J Physiol 569:91–102

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nache V, Wongsamitkul N, Kusch J, Zimmer T, Schwede F, Benndorf K (2016) Deciphering the function of the CNGB1b subunit in olfactory CNG channels. Sci Rep 6:29378

    PubMed  PubMed Central  Google Scholar 

  • Nache V, Zimmer T, Wongsamitkul N, Schmauder R, Kusch J, Reinhardt L, Bönigk W, Seifert R, Biskup C, Schwede F, Benndorf K (2012) Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels. Sci Signal 5:ra48. https://doi.org/10.1126/scisignal.2003110

  • Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444

    CAS  PubMed  Google Scholar 

  • Nakamura T, Kaneko H, Nishida N (1997) Direct measurement of the chloride concentration in newt olfactory receptors with the fluorescent probe. Neurosci Lett 237:5–8

    CAS  PubMed  Google Scholar 

  • Nakashima A, Ihara N, Shigeta M, Kiyonari H, Ikegaya Y, Takeuchi H (2019) Structured spike series specify gene expression patterns for olfactory circuit formation. Science 365: eaaw5030. https://doi.org/10.1126/science.aaw5030

  • Nakashima A, Takeuchi H, Imai T, Saito H, Kiyonari H, Abe T, Chen M, Weinstein LS, Yu CR, Storm DR, Nishizumi H, Sakano H (2013) Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell 154:1314–1325

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nakashima N, Nakashima K, Taura A, Takaku-Nakashima A, Ohmori H, Takano M (2020) Olfactory marker protein directly buffers cAMP to avoid depolarization-induced silencing of olfactory receptor neurons. Nat Commun 11:2188. https://doi.org/10.1038/s41467-020-15917-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nickell WT, Kleene NK, Gesteland RC, Kleene SJ (2006) Neuronal chloride accumulation in olfactory epithelium of mice lacking NKCC1. J Neurophysiol 95:2003–2006

    CAS  PubMed  Google Scholar 

  • Nickell WT, Kleene NK, Kleene SJ (2007) Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium. J Physiol 583:1005–1020

    CAS  PubMed  PubMed Central  Google Scholar 

  • Noé J, Tareilus E, Boekhoff I, Breer H (1997) Sodium/calcium exchanger in rat olfactory neurons. Neurochem Int 30:523–531

    PubMed  Google Scholar 

  • Paulino C, Kalienkova V, Lam AKM, Neldner Y, Dutzler R (2017a) Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM. Nature 552:421–425

    CAS  PubMed  Google Scholar 

  • Paulino C, Neldner Y, Lam AK, Kalienkova V, Brunner JD, Schenck S, Dutzler R (2017b) Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A. Elife 6:e26232. https://doi.org/10.7554/eLife.26232

    Article  PubMed  PubMed Central  Google Scholar 

  • Pedemonte N, Galietta LJV (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459

    CAS  Google Scholar 

  • Peterlin Z, Firestein S, Rogers ME (2014) The state of the art of odorant receptor deorphanization: a report from the orphanage. J Gen Physiol 143:527–542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pietra G, Dibattista M, Menini A, Reisert J, Boccaccio A (2016) The Ca2+-activated Cl- channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons. J Gen Physiol 148:293–311

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pietrobon M, Zamparo I, Maritan M, Franchi SA, Pozzan T, Lodovichi C (2011) Interplay among cGMP, cAMP, and Ca2+ in living olfactory sensory neurons in vitro and in vivo. J Neurosci 31:8395–8405

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pifferi S, Boccaccio A, Menini A (2006a) Cyclic nucleotide-gated ion channels in sensory transduction. FEBS Lett 580:2853–2859

    CAS  PubMed  Google Scholar 

  • Pifferi S, Cenedese V, Menini A (2012) Anoctamin 2/TMEM16B: a calcium-activated chloride channel in olfactory transduction. Exp Physiol 97:193–199

    CAS  PubMed  Google Scholar 

  • Pifferi S, Dibattista M, Menini A (2009a) TMEM16B induces chloride currents activated by calcium in mammalian cells. Pflugers Arch 458:1023–1038

    CAS  PubMed  Google Scholar 

  • Pifferi S, Dibattista M, Sagheddu C, Boccaccio A, Al Qteishat A, Ghirardi F, Tirindelli R, Menini A (2009b) Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2. J Physiol 587:4265–4279

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pifferi S, Menini A, Kurahashi T (2010) Signal transduction in vertebrate olfactory cilia. In: Menini A (ed) The Neurobiology of Olfaction. CRC Press/Taylor & Francis, Boca Raton (FL), pp 203–224

    Google Scholar 

  • Pifferi S, Pascarella G, Boccaccio A, Mazzatenta A, Gustincich S, Menini A, Zucchelli S (2006b) Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction. Proc Natl Acad Sci USA 103:12929–12934

    CAS  PubMed  Google Scholar 

  • Ponissery Saidu S, Stephan AB, Talaga AK, Zhao H, Reisert J (2013) Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2. J Gen Physiol 141:691–703

    PubMed  PubMed Central  Google Scholar 

  • Rasche S, Toetter B, Adler J, Tschapek A, Doerner JF, Kurtenbach S, Hatt H, Meyer H, Warscheid B, Neuhaus EM (2010) Tmem16b is specifically expressed in the cilia of olfactory sensory neurons. Chem Senses 35:239–245

    CAS  PubMed  Google Scholar 

  • Rebrik TI, Botchkina I, Arshavsky VY, Craft CM, Korenbrot JI (2012) CNG-modulin: a novel Ca-dependent modulator of ligand sensitivity in cone photoreceptor cGMP-gated ion channels. J Neurosci 32:3142–3153

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J (2010) Origin of basal activity in mammalian olfactory receptor neurons. J Gen Physiol 136:529–540

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Bauer PJ, Yau K-W, Frings S (2003) The Ca-activated Cl channel and its control in rat olfactory receptor neurons. J Gen Physiol 122:349–363

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Lai J, Yau K-W, Bradley J (2005) Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons. Neuron 45:553–561

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Matthews HR (1998) Na+-dependent Ca2+ extrusion governs response recovery in frog olfactory receptor cells. J Gen Physiol 112:529–535

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Matthews HR (1999) Adaptation of the odour-induced response in frog olfactory receptor cells. J Physiol 519(3):801–813

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Matthews HR (2001a) Simultaneous recording of receptor current and intraciliary Ca2+ concentration in salamander olfactory receptor cells. J Physiol 535:637–645

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Matthews HR (2001b) Response properties of isolated mouse olfactory receptor cells. J Physiol 530:113–122

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reisert J, Reingruber J (2019) Ca2+-activated Cl- current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons. Proc Natl Acad Sci USA 116:1053–1058

    CAS  PubMed  Google Scholar 

  • Reisert J, Yau K-W, Margolis FL (2007) Olfactory marker protein modulates the cAMP kinetics of the odour-induced response in cilia of mouse olfactory receptor neurons. J Physiol 585:731–740

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ressler KJ, Sullivan SL, Buck LB (1993) A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell 73:597–609

    CAS  PubMed  Google Scholar 

  • Reuter D, Zierold K, Schröder WH, Frings S (1998) A depolarizing chloride current contributes to chemoelectrical transduction in olfactory sensory neurons in situ. J Neurosci 18:6623–6630

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rospars J-P, Lansky P, Chaput M, Duchamp-Viret P (2008) Competitive and noncompetitive odorant interactions in the early neural coding of odorant mixtures. J Neurosci 28:2659–2666

    CAS  PubMed  PubMed Central  Google Scholar 

  • Royet JP, Souchier C, Jourdan F, Ploye H (1988) Morphometric study of the glomerular population in the mouse olfactory bulb: numerical density and size distribution along the rostrocaudal axis. J Comp Neurol 270:559–568

    CAS  PubMed  Google Scholar 

  • Sagheddu C, Boccaccio A, Dibattista M, Montani G, Tirindelli R, Menini A (2010) Calcium concentration jumps reveal dynamic ion selectivity of calcium-activated chloride currents in mouse olfactory sensory neurons and TMEM16b-transfected HEK 293T cells. J Physiol 588:4189–4204

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sailani MR, Jingga I, MirMazlomi SH, Bitarafan F, Bernstein JA, Snyder MP, Garshasbi M (2017) Isolated Congenital Anosmia and CNGA2 Mutation. Sci Rep 7:2667. https://doi.org/10.1038/s41598-017-02947-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakano H (2010) Neural map formation in the mouse olfactory system. Neuron 67:530–542

    CAS  PubMed  Google Scholar 

  • Sautter A, Zong X, Hofmann F, Biel M (1998) An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit expressed in olfactory neurons. Proc Natl Acad Sci USA 95:4696–4701

    CAS  PubMed  Google Scholar 

  • Schild D, Restrepo D (1998) Transduction mechanisms in vertebrate olfactory receptor cells. Physiol Rev 78:429–466

    CAS  PubMed  Google Scholar 

  • Serizawa S, Miyamichi K, Takeuchi H, Yamagishi Y, Suzuki M, Sakano H (2006) A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting. Cell 127:1057–1069

    CAS  PubMed  Google Scholar 

  • Sobel EC, Tank DW (1993) Timing of odor stimulation does not alter patterning of olfactory bulb unit activity in freely breathing rats. J Neurophysiol 69:1331–1337

    CAS  PubMed  Google Scholar 

  • Song Y, Cygnar KD, Sagdullaev B, Valley M, Hirsh S, Stephan A, Reisert J, Zhao H (2008) Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation. Neuron 58:374–386

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stephan AB, Shum EY, Hirsh S, Cygnar KD, Reisert J, Zhao H (2009) ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification. Proc Natl Acad Sci USA 106:11776–11781

    CAS  PubMed  Google Scholar 

  • Stephan AB, Tobochnik S, Dibattista M, Wall CM, Reisert J, Zhao H (2011) The Na+/Ca2+ exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response. Nat Neurosci 15:131–137

    PubMed  PubMed Central  Google Scholar 

  • Stohr H, Heisig JB, Benz PM, Schoberl S, Milenkovic VM, Strauss O, Aartsen WM, Wijnholds J, Weber BHF, Schulz HL (2009) TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals. J Neurosci 29:6809–6818

    PubMed  PubMed Central  Google Scholar 

  • Suzuki Y, Takeda M, Farbman AI (1996) Supporting cells as phagocytes in the olfactory epithelium after bulbectomy. J Comp Neurol 376:509–517

    CAS  PubMed  Google Scholar 

  • Takeuchi H, Kurahashi T (2008) Distribution, amplification, and summation of cyclic nucleotide sensitivities within single olfactory sensory cilia. J Neurosci 28:766–775

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takeuchi H, Kurahashi T (2018) Second messenger molecules have a limited spread in olfactory cilia. J Gen Physiol 150:1647–1659

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takeuchi H, Kurahashi T (2002) Photolysis of caged cyclic AMP in the ciliary cytoplasm of the newt olfactory receptor cell. J Physiol 541:825–833

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tien J, Peters CJ, Wong XM, Cheng T, Jan YN, Jan LY, Yang H (2014) A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity. Elife 3:e02772. https://doi.org/10.7554/eLife.02772

    Article  CAS  PubMed Central  Google Scholar 

  • Tirindelli R, Dibattista M, Pifferi S, Menini A (2009) From pheromones to behavior. Physiol Rev 89:921–956

    CAS  PubMed  Google Scholar 

  • Trotier D (1986) A patch-clamp analysis of membrane currents in salamander olfactory receptor cells. Pflugers Arch 407:589–595

    CAS  PubMed  Google Scholar 

  • Trotier D, MacLeod P (1983) Intracellular recordings from salamander olfactory receptor cells. Brain Res 268:225–237

    CAS  PubMed  Google Scholar 

  • Trudeau MC, Zagotta WN (2003) Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. J Biol Chem 278:18705–18708

    CAS  PubMed  Google Scholar 

  • Vassar R, Ngai J, Axel R (1993) Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74:309–318

    CAS  PubMed  Google Scholar 

  • Vocke K, Dauner K, Hahn A, Ulbrich A, Broecker J, Keller S, Frings S, Möhrlen F (2013) Calmodulin-dependent activation and inactivation of anoctamin calcium-gated chloride channels. J Gen Physiol 142:381–404

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vogalis F, Hegg CC, Lucero MT (2005) Ionic conductances in sustentacular cells of the mouse olfactory epithelium. J Physiol 562:785–799

    CAS  PubMed  Google Scholar 

  • Waldeck C, Vocke K, Ungerer N, Frings S, Möhrlen F (2009) Activation and desensitization of the olfactory cAMP-gated transduction channel: identification of functional modules. J Gen Physiol 134:397–408

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wayman GA, Impey S, Storm DR (1995) Ca2+ inhibition of type III adenylyl cyclase in vivo. J Biol Chem 270:21480–21486

    CAS  PubMed  Google Scholar 

  • Wei J, Wayman G, Storm DR (1996) Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. J Biol Chem 271:24231–24235

    CAS  PubMed  Google Scholar 

  • Weitz D, Zoche M, Müller F, Beyermann M, Körschen HG, Kaupp UB, Koch KW (1998) Calmodulin controls the rod photoreceptor CNG channel through an unconventional binding site in the N-terminus of the beta-subunit. EMBO J 17:2273–2284

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wingler LM, Lefkowitz RJ (2020) Conformational basis of G protein-coupled receptor signaling versatility. Trends Cell Biol 30:736–747

    CAS  PubMed  Google Scholar 

  • Wong ST, Trinh K, Hacker B, Chan GC, Lowe G, Gaggar A, Xia Z, Gold GH, Storm DR (2000) Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27:487–497

    CAS  PubMed  Google Scholar 

  • Yan C, Zhao AZ, Bentley JK, Loughney K, Ferguson K, Beavo JA (1995) Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons. Proc Natl Acad Sci USA 92:9677–9681

    CAS  PubMed  Google Scholar 

  • Yang T, Colecraft HM (2016) Calmodulin regulation of TMEM16A and 16B Ca2+-activated chloride channels. Channels (Austin) 10:38–44

    Google Scholar 

  • Yang T, Hendrickson WA, Colecraft HM (2014) Preassociated apocalmodulin mediates Ca2+-dependent sensitization of activation and inactivation of TMEM16A/16B Ca2+-gated Cl- channels. Proc Natl Acad Sci U S A 111:18213–18218

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zak JD, Grimaud J, Li RC, Lin CC, Murthy VN (2018) Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons. Sci Rep 8:10600. https://doi.org/10.1038/s41598-018-28855-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamparo I, Francia S, Franchi SA, Redolfi N, Costanzi E, Kerstens A, Fukutani Y, Battistutta R, Polverino de Laureto P, Munck S, De Strooper B, Matsunami H, Lodovichi C (2019) Axonal odorant receptors mediate axon targeting. Cell Rep 29:4334-4348.e7. https://doi.org/10.1016/j.celrep.2019.11.099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zapiec B, Mombaerts P (2015) Multiplex assessment of the positions of odorant receptor-specific glomeruli in the mouse olfactory bulb by serial two-photon tomography. Proc Natl Acad Sci USA 112:E5873-5882

    CAS  PubMed  Google Scholar 

  • Zhainazarov AB, Ache BW (1995) Odor-induced currents in Xenopus olfactory receptor cells measured with perforated-patch recording. J Neurophysiol 74:479–483

    CAS  PubMed  Google Scholar 

  • Zheng J, Zagotta WN (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 42:411–421

    CAS  PubMed  Google Scholar 

  • Zufall F, Shepherd GM, Firestein S (1991) Inhibition of the olfactory cyclic nucleotide gated ion channel by intracellular calcium. Proc Biol Sci 246:225–230

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Biophysics, National Research Council (CNR), Genova, Italy

    Anna Boccaccio

  2. Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy

    Anna Menini & Simone Pifferi

  3. Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy

    Simone Pifferi

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  1. Anna Boccaccio
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Boccaccio, A., Menini, A. & Pifferi, S. The cyclic AMP signaling pathway in the rodent main olfactory system. Cell Tissue Res 383, 429–443 (2021). https://doi.org/10.1007/s00441-020-03391-7

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