Odor information is encoded by selective activation of olfactory receptors and mapped topographically to glomeruli in the olfactory bulb. Our broad, long term objective is to understand dendritic and synaptic signaling mechanisms in the bulb that transform this mapped input into odor-encoding spike patterns in output neurons - the mitral cells and tufted cells. We focus on the tufted cells, a major class of principal neurons in the olfactory bulb that has been mostly ignored. Tufted cells differ from mitral cells in their cortical projections, dendritic fields, spike frequencies, and lateral inhibitory tuning of molecular receptive ranges. Our working hypothesis is that sensory processing in the olfactory bulb is split into parallel pathways by sub-circuits containing the tufted cells and mitral cells. We will test this theory by analyzing and contrasting the spike timing and synchronization of tufted cells relative to mitral cells, by mapping out the spatial structure of local interneuron circuits that link to tufted cells and mitral cells, and by determining biophysical and synaptic mechanisms of spike synchrony. We will also analyze the intrabulbar projections of tufted cells to granule cells linking mirror symmetric glomerular maps, and test a specific model for the role of the neuropeptide cholecytokinin as a co-transmitter or modulator in these projections. Our work will yield new insights into differential coding and dynamic inhibitory mechanisms regulating rhythmic spike activity in a sensory system. Our experimental approaches include a combination of patch-clamp electrophysiology and optical recording or stimulation in slice preparations in a rodent model.

Public Health Relevance

This work address a major gap in our knowledge of connectivity and synaptic physiology of circuits in the olfactory bulb that process sensory information. It has broad significance for understanding the synchronization and dynamics of brain circuits,.and is relevant to improving our understanding of pathologies in the coordination of neuronal networks, such as epilepsy and dementia. We also take pioneering steps in developing a new cellular model for analyzing a peptide signal transduction pathway that is involved in oncogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004208-10
Application #
8299397
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2001-08-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2012
Total Cost
$315,211
Indirect Cost
$111,568
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Mainland, Joel D; Lundström, Johan N; Reisert, Johannes et al. (2014) From molecule to mind: an integrative perspective on odor intensity. Trends Neurosci 37:443-54
Cruz, Georgina; Lowe, Graeme (2013) Neural coding of binary mixtures in a structurally related odorant pair. Sci Rep 3:1220
Ma, Jie; Dankulich-Nagrudny, Luba; Lowe, Graeme (2013) Cholecystokinin: an excitatory modulator of mitral/tufted cells in the mouse olfactory bulb. PLoS One 8:e64170
Ma, J; Lowe, G (2010) Correlated firing in tufted cells of mouse olfactory bulb. Neuroscience 169:1715-38
McQuade, Lindsey E; Ma, Jie; Lowe, Graeme et al. (2010) Visualization of nitric oxide production in the mouse main olfactory bulb by a cell-trappable copper(II) fluorescent probe. Proc Natl Acad Sci U S A 107:8525-30
Lowe, G; Buerk, D G; Ma, J et al. (2008) Tonic and stimulus-evoked nitric oxide production in the mouse olfactory bulb. Neuroscience 153:842-50
Ma, J; Lowe, G (2007) Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb. Neuroscience 144:1094-108
Ma, Jie; Lowe, Graeme (2004) Action potential backpropagation and multiglomerular signaling in the rat vomeronasal system. J Neurosci 24:9341-52
Lowe, Graeme (2003) Flash photolysis reveals a diversity of ionotropic glutamate receptors on the mitral cell somatodendritic membrane. J Neurophysiol 90:1737-46
Lowe, Graeme (2002) Inhibition of backpropagating action potentials in mitral cell secondary dendrites. J Neurophysiol 88:64-85