Barry W. Ache
(Ph.D. University of California, Santa Barbara, 1970)

Distinguished Professor of Zoology and Neuroscience and Director of the University of Florida Center for Smell and Taste

bwa@whitney.ufl.edu

Chemical Senses: Olfaction

Our research group studies olfaction. Natural odors are complex blends of chemicals that the brain discriminates by the unique pattern of neural activity each odor generates. We are trying to decipher the cellular and neural processes that give rise to these patterns in order to ultimately understand how the brain recognizes and discriminates odors. We investigate the sense of smell by studying animal models for olfaction as diverse as the spiny lobster and the mouse.

Current Projects

Research in our group centers around three primary projects linked, ultimately, to odor coding. Our longest-running project, funded by the National Institute on Deafness and Other Communicaiton Disorders, explores the cellular events by which odors activate lobster olfactory receptor cells. The general focus of this project is to understand the involvement of lipid signaling in olfactory transduction. Olfactory transduction is the process by which the receptor cell converts odor signals into the electrical signal the brain uses to process information. In particular, we are focusing on a family of ion channels, called trp channels that typically serve as the intracellular target of the phosphoinositide signaling pathway. Trp channels are increasingly implicated in chemosensory transduction, but the extent of their involvement in olfactory transduction is still unclear with the notable exception of the lobster. We are using lobster olfactory receptor cells as models to understand for the first time how trp channels can function in olfactory transduction. Much of what we know of trp channels in other systems comes from studying recombinant trp channels in non-native or heterologous cells. Our work to date has made the lobster olfactory trp channel one of the best characterized native trp channels. This work has the potential to contribute to a broader understanding of this functionally important class of ion channels as well as advance our understanding of the cellular mechanism of olfactory transduction.

A newer project, also funded by the National Institute on Deafness and other Communication Disorders, explores the role of phospholipid signaling in mammalian olfactory transduction. In particular, we are focusing on how a specialized group of membrane lipids, collectively known as 3-phosphoinositides, modulates the output of mammalian olfactory receptor cells, which they appear to do at least in part by targeting the well known olfactory cyclic nucleotide-gated ion channel. This project grew out of our work with lobster olfactory receptor cells that showed for the first time that 3-phosphoinositides are potentially important in olfactory transduction. Problems with any of the cellular events associated with olfactory receptor cell activation would disrupt normal input, and necessarily lead to olfactory impairment. Therefore, the more detailed understanding we have of these processes, the more effectively we can address the diminished quality of life that results from olfactory dysfunction. This project is an excellent example of the utility of marine biomedical research - how research on a marine animal can generate information of potential usefulness to understanding human health.

Our newest project, funded by the McDonnell Foundation in San Francisco, is being done in collaboration with scientists at Stanford University, the University of California Berkeley, and the Ohio State University. This project uses multi-electrode array recording to explore the central neural organization of the lobster olfactory pathway. The primary goal is to understand how the spatial and temporal properties of odor plumes shape the signal the brain uses to deciphers odors. Typically, olfactory scientists have focused on odor quality and quantity and have not considered the other two fundamental stimulus parameters - space and time - as potential coding variables. This project will be one of the first comprehensive, interdisciplinary efforts to explore the spatial and temporal components of the odor signal in natural stimulus settings.

Personnel

Our research group presently consists of:

Barry Ache, Distinguished Professor
Yuri Bobkov, Postdoctoral Associate
Betsy Corey, Postdoctoral Associate
Adeline Pezier, Postdoctoral Associate
Asylbek Zhainazarov, Research Associate Professor
Anna Liza Antonio, Laboratory Technician
Anna Mistretta-Bradley, Laboratory Technician

Our research program is centered in two locations. One laboratory is located at the Whitney Laboratory in St. Augustine, and the other at the McKnight Brain Institute on the main campus of the University in Gainesville.

Selected Publications

Bobkov, Y.V. and Ache, B.W. (2003) Calcium sensitivity of a sodium-activated nonselective cation channel in lobster olfactory receptor neurons. J. Neurophysiol. 90: 2928-2940.

Wachowiak, M. Cohen, L.B., and Ache, B. W. (2002) Presynaptic inhibition of olfactory receptor neurons in crustaceans. J. Microsc. Res. 58: 365-375.

Spehr, M., Wetzel, C.H., Hatt, H., and Ache, B.W. (2002) 3-phosphoinositides modulate cyclic nucleotide signaling in olfactory receptor neurons. Neuron 33:731-739.

Ache, B.W. (2002) Crustaceans as animal models for olfactory research. In: Frontiers in Crustacean Neurobiology (Wiese, K., Ed.) . Springer-Verlag. Pp. 189-199.

Doolin. R.E. and Ache, B.W. (2002) A simple method for focally delivering multiple drugs or ligands to cells. J. Neurosci. Methods. 116:9-14.

Zhainazarov, A.B., Doolin, R.E., and Ache, B.W. (2001) Properties and functional role of a sodium-activated nonselective cation channel in lobster olfactory receptor neurons. In: Frontiers in Crustacean Neurobiology (Wiese, K., Ed.) Springer-Verlag.

Zhainazarov, A.B., Doolin, R.E., Herlihy, J-D., and Ache, B.W. (2001) Odor-stimulated phosphatidylinositol 3-kinase in lobster olfactory receptor cells. J. Neurophysiol. 85: 2537-2544.

Doolin, R.E., Zhainazarov, A.B., and Ache, B.W. (2001) An odorant-suppressed Cl conductance in lobster olfactory receptor cells. J. Comp. Physiol. 187:447-487.

Ache, B.W. and Restrepo, D. (2000) Olfactory Transduction. In: The Neurobiology of Taste and Smell, 2nd Ed. (Finger, T. et al., Eds.) Wiley-Liss, New York. Pp. 159-177.

Munger, S.D., Gleeson, R.A., Aldrich, H.C., Rust, N.C., Ache, B.W. and Greenberg, R.M. (2000) Characterization of a phosphoinositide-mediated odor transduction pathway reveals plasma membrane localization of an inositol 1,4,5-trisphosphate receptor in lobster olfactory receptor neurons. J. Biol. Chem. 275:20450-20457.

Reich, G., Boekhoff, I., Breer, H. and Ache, B.W. (1999). Calcium regulation of cyclic nucleotide signaling in lobster olfactory receptor neurons. J. Neurochem. 73: 147-152.

Zhainazarov, A. B. and Ache, B. W. (1999). Effects of phosphatidylinositol 4,5 bisphosphate and phosphatidylinositol 4-phosphate on a Na⁺-gated nonselective cation channel. J. Neuroscience 19: 2929-2937.

Zhainazarov, A.B., R.E. Doolin and B.W. Ache. (1998). Sodium-gated cation channel implicated in the activation of lobster olfactory receptor neurons. J. Neurophysiol. 79:1349-1359.

Wachowiak, D.M. and B. W. Ache. (1998). Multiple inhibitory pathways shape odor-evoked responses of lobster olfactory projection neurons. J. Comp. Physiol. A. 182:425-434.

Zhainazarov, A. B. and Ache, B. W. (1998). A Na⁺-gated nonselective cation channel from lobster olfactory projection neurons. J. Neurophysiol. 80: 3387-3391.

Zhainazarov, A.B. and B.W. Ache. (1998) A Na+-gated nonselective cation channel from lobster olfactory projection neurons. J. Neurophysiol 80:3387-3391.

Wachowiak, D.M. and B. W. Ache. (1997). Dual inhibitory pathways mediated by GABA- and histaminergic interneurons in the lobster olfactory lobe. J. Comp. Physiol. A 180:357-372.

Schmidt, M. and B.W. Ache. (1997). Immunocytochemical analysis of glomerular regionalization and neuronal diversity in the olfactory deutocerebrum of the spiny lobster. Cell Tiss. Res. 287:541-563.

Wachowiak, M., C.E. Diebel and B.W. Ache. (1997). Local interneurons define functionally distinct regions within lobster olfactory glomeruli. J. Exp. Biol. 200:989-1001.

Zhainazarov, A.B., M. Wachowiak, A. Boettcher, S. Elenes and B.W. Ache. (1997). Ionotropic GABA receptor from lobster olfactory projection neurons. J. Neurophysiol. 77:2235-2251.

Zhainazarov, A.B. and B.W. Ache. (1997). Gating and conduction properties of a sodium-activated cation channel from lobster olfactory receptor neurons. J. Memb. Biol. 156:173-190.