Chemical Senses: Olfaction
Our research group studies olfaction – the sense of smell.
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 spiny
lobsters and rodents.
Research in our group centers around two primary
projects that are linked, ultimately, to odor coding. Our
longest-running project, funded by the National Institute on Deafness
and Other Communication 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.
Our 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, modulate 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
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.
Bobkov, YV and Ache, BW. 2003. Calcium sensitivity of a sodium-activated nonselective cation channel in lobster olfactory receptor neurons. J. Neurophysiol. 90:2928-2940.
Zhainazarov, A.B., Spehr, M., Wetzel, C.H., Hatt, H., and Ache, B.W. 2004. Modulation of the olfactory CNG channel by PtdIns (3,4,5)P3. J. Memb. Biol. 201:51-57.
Bobkov, Y.V. and Ache, B.W. 2005. Pharmacological properties and functional role of a TRP-related ion channel in lobster olfactory receptor neurons. J. Neurophysiol. 93:1327-1380.
Ache, B.W. and Young, J.M. 2005. Olfaction: diverse species, conserved principles. Neuron 48:417-430.
McClintock, T.S., Ache, B. W., Derby, C.D. 2006. Lobster olfactory genomics. Integr. Comp. Biol. 46: 940-947.
Bobkov, Y.V. and Ache B.W. 2007. Block by amiloride derivatives of odor-evoked discharge in lobster olfactory receptor neurons through action on a presumptive TRP channel. Chem. Senses32:149-159.
Bobkov, Y.V. and Ache, B.W. 2007. Intrinsically bursting olfactory receptor neurons. J. Neurophysiol. 97:1052-1057.