Enhancement of Odor-Induced Activity in the Canine Brain by Zinc Nanoparticles: A Functional MRI Study in Fully Unrestrained Conscious Dogs.

Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected.

[1]  Thomas S. Denney,et al.  Anterior–posterior dissociation of the default mode network in dogs , 2015, Brain Structure and Function.

[2]  T. Denney,et al.  Functional MRI of the Olfactory System in Conscious Dogs , 2014, PloS one.

[3]  Michiyo Azuma,et al.  Changes in Cerebral Blood Flow during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity: A Multi-Channel Near-Infrared Spectroscopic Study , 2013, PloS one.

[4]  M. Kadohisa,et al.  Effects of odor on emotion, with implications , 2013, Front. Syst. Neurosci..

[5]  Fuqiang Xu,et al.  Lateral Entorhinal Modulation of Piriform Cortical Activity and Fine Odor Discrimination , 2013, The Journal of Neuroscience.

[6]  N. Sobel,et al.  An odor is not worth a thousand words: from multidimensional odors to unidimensional odor objects. , 2013, Annual review of psychology.

[7]  K. Noguchi,et al.  An improved bioluminescence‐based signaling assay for odor sensing with a yeast expressing a chimeric olfactory receptor , 2012, Biotechnology and bioengineering.

[8]  Andrew P. Horsfield,et al.  The Swipe Card Model of Odorant Recognition , 2012, Sensors.

[9]  O. Pustovyy,et al.  Olfactory responses to explosives associated odorants are enhanced by zinc nanoparticles. , 2012, Talanta.

[10]  N. Sobel,et al.  Neural activity at the human olfactory epithelium reflects olfactory perception , 2011, Nature Neuroscience.

[11]  M. Persuy,et al.  Relationship between Homo-oligomerization of a Mammalian Olfactory Receptor and Its Activation State Demonstrated by Bioluminescence Resonance Energy Transfer* , 2011, The Journal of Biological Chemistry.

[12]  E. Benarroch Olfactory system , 2010, Neurology.

[13]  E. Morrison,et al.  Odorant Response Kinetics from Cultured Mouse Olfactory Epithelium at Different Ages in vitro , 2010, Cells Tissues Organs.

[14]  U. Habel,et al.  Involvement of the human ventrolateral thalamus in olfaction , 2010, Journal of Neurology.

[15]  V. Vodyanoy Zinc nanoparticles interact with olfactory receptor neurons , 2010, BioMetals.

[16]  N. Sobel,et al.  Odorant concentration dependence in electroolfactograms recorded from the human olfactory epithelium. , 2009, Journal of neurophysiology.

[17]  N. Sobel,et al.  Spared and Impaired Olfactory Abilities after Thalamic Lesions , 2009, The Journal of Neuroscience.

[18]  Oleg Pustovyy,et al.  Enhancement of odorant-induced responses in olfactory receptor neurons by zinc nanoparticles. , 2009, Chemical senses.

[19]  R. Hall Olfactory Receptor Interactions with Other Receptors , 2009, Annals of the New York Academy of Sciences.

[20]  J. Giraldo,et al.  On the fitting of binding data when receptor dimerization is suspected , 2008, British journal of pharmacology.

[21]  Michael Leon,et al.  Chemotopic odorant coding in a mammalian olfactory system , 2007, The Journal of comparative neurology.

[22]  G. Shepherd Smell images and the flavour system in the human brain , 2006, Nature.

[23]  Donald A Wilson,et al.  Separate encoding of identity and similarity of complex familiar odors in piriform cortex , 2006, Proceedings of the National Academy of Sciences.

[24]  J. Suarez,et al.  Naturalistic quantification of canine olfactory sensitivity , 2006 .

[25]  J. Sarvey,et al.  Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion , 2006, Experimental Neurology.

[26]  David H. Zald,et al.  On the scent of human olfactory orbitofrontal cortex: Meta-analysis and comparison to non-human primates , 2005, Brain Research Reviews.

[27]  C. Zelano,et al.  Humans as an Animal Model for Systems-Level Organization of Olfaction , 2005, Neuron.

[28]  W. Gale,et al.  Novel Metal Clusters Isolated from Blood Are Lethal to Cancer Cells , 2005, Cells Tissues Organs.

[29]  N. Bye,et al.  Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration , 2005, Brain Research Reviews.

[30]  T. Hummel,et al.  Recording of the human electro-olfactogram , 2004, Physiology & Behavior.

[31]  Anna Boccaccio,et al.  Olfaction: from odorant molecules to the olfactory cortex. , 2004, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[32]  A. Owen,et al.  Anterior prefrontal cortex: insights into function from anatomy and neuroimaging , 2004, Nature Reviews Neuroscience.

[33]  T. Jacob,et al.  Evidence for peripheral plasticity in human odour response , 2004, The Journal of physiology.

[34]  A. Engel,et al.  Biophysics (communication arising): Is rhodopsin dimeric in native retinal rods? , 2003, Nature.

[35]  J. Henriksson,et al.  Transport and subcellular distribution of intranasally administered zinc in the olfactory system of rats and pikes. , 2003, Toxicology.

[36]  Á. Miklósi,et al.  When dogs seem to lose their nose: an investigation on the use of visual and olfactory cues in communicative context between dog and owner , 2003 .

[37]  J. M Boyett-Anderson,et al.  Functional brain imaging of olfactory processing in monkeys , 2003, NeuroImage.

[38]  H. Breer,et al.  Olfactory receptors: molecular basis for recognition and discrimination of odors , 2003, Analytical and bioanalytical chemistry.

[39]  Doron Lancet,et al.  Towards an odor communication system , 2003, Comput. Biol. Chem..

[40]  G. Glover,et al.  Dissociated neural representations of intensity and valence in human olfaction , 2003, Nature Neuroscience.

[41]  A. Engel,et al.  Atomic-force microscopy: Rhodopsin dimers in native disc membranes , 2003, Nature.

[42]  P. Scott-Johnson,et al.  The electroolfactogram: A review of its history and uses , 2002, Microscopy research and technique.

[43]  James M. Johnston,et al.  Training and maintaining the performance of dogs (Canis familiaris) on an increasing number of odor discriminations in a controlled setting , 2002 .

[44]  I. Savic Brain Imaging Studies of the Functional Organization of Human Olfaction , 2002, Chemical senses.

[45]  M. Horning,et al.  Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms. , 2001, Journal of neurophysiology.

[46]  S. Firestein How the olfactory system makes sense of scents , 2001, Nature.

[47]  L. Haberly,et al.  Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. , 2001, Chemical senses.

[48]  L. J. Myers,et al.  The scientific foundation and efficacy of the use of canines as chemical detectors for explosives. , 2001, Talanta.

[49]  Bruce R. Rosen,et al.  Activation and Habituation in Olfaction—An fMRI Study , 2001, NeuroImage.

[50]  B. Gulyás,et al.  Olfactory Functions Are Mediated by Parallel and Hierarchical Processing , 2000, Neuron.

[51]  J. Pardo,et al.  Functional neuroimaging of the olfactory system in humans. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[52]  L. Paul Waggoner,et al.  Canine detection odor signatures for explosives , 1998, Other Conferences.

[53]  P. Skudlarski,et al.  Functional MR imaging of regional brain responses to pleasant and unpleasant odors. , 1998, AJNR. American journal of neuroradiology.

[54]  J. Pardo,et al.  Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[55]  S. Okada,et al.  Zinc transport in the rat olfactory system , 1997, Neuroscience Letters.

[56]  L. Turin,et al.  A spectroscopic mechanism for primary olfactory reception. , 1996, Chemical senses.

[57]  T. Hummel,et al.  Peripherally obtained electrophysiological responses to olfactory stimulation in man: electro-olfactograms exhibit a smaller degree of desensitization compared with subjective intensity estimates , 1996, Brain Research.

[58]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[59]  Gordon M. Shepherd,et al.  Discrimination of molecular signals by the olfactory receptor neuron , 1994, Neuron.

[60]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[61]  R. S. Hinks,et al.  Time course EPI of human brain function during task activation , 1992, Magnetic resonance in medicine.

[62]  F. Zufall,et al.  Analysis of single cyclic nucleotide-gated channels in olfactory receptor cells , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[63]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[64]  R. Doty,et al.  Human odor intensity perception: correlation with frog epithelial adenylate cyclase activity and transepithelial voltage response , 1990, Brain Research.

[65]  D. Passe,et al.  Behavioral determination of olfactory thresholds to amyl acetate in dogs , 1984, Neuroscience & Biobehavioral Reviews.

[66]  N. Nadi,et al.  Laminar Distribution of Putative Neurotransmitter Amino Acids and Ligand Binding Sites in the Dog Olfactory Bulb , 1980, Journal of neurochemistry.

[67]  S. Price,et al.  Anisole binding protein from dog olfactory epithelium , 1978 .

[68]  J. King,et al.  Studies on olfactory discrimination in dogs: (3) ability to detect human odour trace , 1964 .

[69]  Beckers Rf,et al.  Studies on oltactory discrimination in dogs. II. Discriminatory behavior in a free environment. , 1962 .

[70]  D. Ottoson,et al.  Sustained potentials evoked by olfactory stimulation. , 1954, Acta physiologica Scandinavica.

[71]  E. Pajot-Augy,et al.  Deciphering activation of olfactory receptors using heterologous expression in Saccharomyces cerevisiae and bioluminescence resonance energy transfer. , 2013, Methods in molecular biology.

[72]  Hadas Lapid,et al.  Recording odor-evoked response potentials at the human olfactory epithelium. , 2013, Chemical senses.

[73]  C. Crasto Olfactory Receptors , 2013, Methods in Molecular Biology.

[74]  C. F. Bush Olfactory receptor dimerization , 2008 .

[75]  Cat Nutrition Nutrient requirements of dogs and cats , 2006 .

[76]  Kei M. Igarashi,et al.  Odor maps in the dorsal and lateral surfaces of the rat olfactory bulb. , 2005, Chemical senses.

[77]  T. Valentinčič,et al.  The amplitude of the electroolfactogram in catfish correlates with the proportion of responding ORNs , 2000, Pflügers Archiv.

[78]  J. Steinfeld,et al.  Explosives detection: a challenge for physical chemistry. , 1998, Annual review of physical chemistry.

[79]  Jack L. Lancaster,et al.  Clustered pixels analysis for functional MRI activation studies of the human brain , 1995 .

[80]  D. Lancet,et al.  The molecular basis of odor recognition , 1987 .

[81]  J. Raymond [Cyclic AMP]. , 1972, La Nouvelle presse medicale.

[82]  J. King,et al.  Studies on oltactory discrimination in dogs. II. Discriminatory behavior in a free environment. , 1962, Journal of Comparative and Physiological Psychology.

[83]  D. Ottoson,et al.  Analysis of the electrical activity of the olfactory epithelium. , 1955, Acta physiologica Scandinavica. Supplementum.

[84]  A. Lundberg,et al.  The electrophysiology of the submaxillary gland of the cat. , 1955, Acta physiologica Scandinavica.