Animals acquire information about the environment through their sensory systems. The first sensory stages play a critical role by formatting the representation of this information in an efficient manner that facilitates easy and flexible extraction by downstream areas. Some of the proposed computations in sensory areas of the brain include gain control, decorrelation, orthogonalization, redundancy reduction, and temporal coding. A diverse population of inhibitory interneurons in local brain areas is believed to play a crucial role in these computations. The mammalian olfactory system has multiple features, which make this system uniquely suited to test these ideas: the relative structural simplicity compared to other sensory systems, high relevance of olfaction to animal behavior, availability of modern genetic tools, and the combination of both sensory and state-dependent activity in a single network. Recent efforts of Koulakov and Rinberg groups helped to overcome some obstacles, which slowed down the progress in the field, such as experimental difficulties in controlling olfactory stimuli and insufficient connection between theory and experiment. Capitalizing on the advantages of the system and utilizing recently developed theoretical framework, new optogenetic methods for stimulus control, and multineuron recordings, we propose a collaborative project to test the basic principles of sensory processing in this system. We will investigate an emergence and a role of the temporal code in the representation of odorants in the OB, by studying the role of the interaction of the principal neurons of the olfactory bulb, mitral and tufted cells (MTCs), with the most abundant class of inhibitory interneurons, granule cells (GCs). We will test our recently proposed theory for the MTC-GC network called the Sparse Incomplete Representations (SIR) model. According to the SIR model, GCs form representations of odorants, while MTCs transmit to higher processing centers the errors of these representations. The SIR model predicts that, due to the balance between excitatory odorant-driven inputs from glomeruli and the inhibition from GCs, olfactory code carried by the MTCs becomes combinatorially and temporarily sparse. In the combinatorial form of sparseness, a small fraction of MTCs that receive excitatory inputs yield noticeable responses to odorants that persist through the sniff cycle. In the temporal sparseness, MTCs respond to odorants during a small temporal window within the sniff cycle. Complex temporal patterns of responses will be predicted and tested within this project. Both temporal and combinatorial sparseness are predicted to be dependent on the inputs from cortex, giving the olfactory code an enormous potential flexibility. To test the detailed predictions of the SIR model we propose the following specific aims (SAs): SA1: To investigate diversity of sparse temporal representations of odorants by the MTCs of the OB. Here we will investigate the temporal patterns of responses predicted by the SIR model and compare them with experimental data. We will also study the plasticity of the temporal code carried by the MTCs. SA 2: To investigate the temporal discreteness of sparse representations of odorants by the MTCs of the OB. Here we will study the synchronization of the transient events in MTC firing with ?-frequency oscillations and study the implications for the temporal coding in the OB. SA3: To study the context and state dependence of the sparse representations in the OB. In this Aim we will investigate how the olfactory code carried by the MTCs can be modified dynamically to better fit a particular task. Intellectual merit: Our project will help elucidate the general principles of information processing. We will demonstrate how sensory representations can be dynamically tuned to reflect particular tasks faced by the organism. We will show how networks can adapt to better detect novel features in the environment and disregard familiar ones. We will show how spatial information can be converted into temporal representations by the use of inhibitory interneurons. Broader impacts: The award will provide a unique cross-disciplinary environment for training of young neuroscientists. We expect that two postdoctoral fellows, specializing in theoretical and in experimental approaches, will receive training through this award. Undergraduate students at NYU and CSHL will be involved in the project as summer interns or as senior thesis writers. We will strive to involve minority graduate and undergraduate students, who will be recruited through dedicated programs at each institution. Health implications for the broader society: About 1-2% of people in North America experience a smell disorder. Since our sense of smell helps us enjoy life, may serve as a warning system alerting us of danger, such as spoiled food, fire, or a gas leak, and may be a sign of other health problems, any loss in the sense of smell can negatively affect our quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC014366-01
Application #
8837253
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Sullivan, Susan L
Project Start
2014-06-01
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$395,795
Indirect Cost
$100,080
Name
New York University
Department
Physiology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016