The ability to detect and discriminate between thousands of different odorants begins with olfactory stimuli activating ensembles of receptor neurons that send axonal projections terminating in neuropil regions called glomeruli located on the surface of the olfactory bulb. Mitral/tufted neurons are the primary output neurons of the olfactory bulb, and have primary apical dendrites that extend into the glomerular tufts that are innervated by the olfactory receptor axon terminals. Different odorants activate spatially distinct patterns of glomeruli across the surface of the olfactory bulb. This input organization has been characterized for a wide range of odorants and concentrations. However, mitral/tufted neuron responses are shaped by two layers of inhibitory and excitatory interneurons, a complex arrangement that allows for many possible functions of the bulb. Here, we propose to simultaneously use calcium dyes loaded into sensory axons to examine the input to the bulb, and target the novel fast fluorescent protein voltage sensor ArcLight mitral/tufted neurons to examine the output. These experiments would be the first to simultaneously examine the spatio-temporal patterns of both the input and output of the olfactory bulb.

Public Health Relevance

Current understanding of how different brain regions process sensory information is limited, in part because it has been difficult for current recording techniques to compare the inputs and outputs of a brain structure. The proposed experiments will allow for simultaneous comparison of the input and output of the olfactory bulb. This will allow us to measure the spatio-temporal transfer function of the olfactory bulb, and improve our understanding of olfactory processing, deficits of which have been implicated in several diseases including Alzheimer's.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DC012981-03
Application #
8893941
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Rivera-Rentas, Alberto L
Project Start
2013-09-01
Project End
2016-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
Sepehri Rad, Masoud; Choi, Yunsook; Cohen, Lawrence B et al. (2017) Voltage and Calcium Imaging of Brain Activity. Biophys J 113:2160-2167
Storace, Douglas A; Cohen, Lawrence B (2017) Measuring the olfactory bulb input-output transformation reveals a contribution to the perception of odorant concentration invariance. Nat Commun 8:81
Storace, Douglas; Sepehri Rad, Masoud; Kang, BokEum et al. (2016) Toward Better Genetically Encoded Sensors of Membrane Potential. Trends Neurosci 39:277-289
Storace, Douglas A; Braubach, Oliver R; Jin, Lei et al. (2015) Monitoring brain activity with protein voltage and calcium sensors. Sci Rep 5:10212
Storace, Douglas; Rad, Masoud Sepehri; Han, Zhou et al. (2015) Genetically Encoded Protein Sensors of Membrane Potential. Adv Exp Med Biol 859:493-509
EscabĂ­, Monty A; Read, Heather L; Viventi, Jonathan et al. (2014) A high-density, high-channel count, multiplexed ?ECoG array for auditory-cortex recordings. J Neurophysiol 112:1566-83