The emergence of coherent local field potentials (LFPs) in the beta (15-30 Hz) and gamma (35-100 Hz) frequency bands has been associated with attention, sensorimotor integration, and other active information processing states within and among brain regions. Beta/gamma coherence is broadly associated with action potential synchronization, which in turn has been hypothesized to define and delimit neural assemblies, and further to enable multiple assemblies of neurons within a population to synchronize within each assembly (but not among different assemblies) so that these multiple assemblies can compete to determine the systems output. The olfactory system has a strong and complex complement of LFP oscillations. Several different frequency bands are routinely observed, and are associated with particular behavioral tasks or states, such as acute sensory activity, resting alertness, and respiratory phases. Some oscillations coexist in the same structure; others appear to give way to one another. Some are local; others mediate interareal coupling either via LFP coherence or via subtler spike-field coherence in which periodic activity in the OB shapes the timing of action potentials in a limited assembly of neurons in a follower structure. Moreover, the olfactory system juxtaposes bottom-up network dynamics resulting from afferent stimulation with top-down dynamics arising from behavioral state factors, both affecting sensory information exported from olfactory bulb. Overall, the olfactory system is a particularly rich fied in which to study the biophysics and ethological utility of these neuronal dynamical systems in concert and within experimentally accessible tissues. This project will establish a robust, mechanistic, biophysically-based model of oscillations and synchronization in the mammalian olfactory system. The PIs will combine multichannel unit and LFP recordings from awake/behaving rats and from acute slices of the mouse OB using planar multielectrode array, and use the results to shape the expansion of an existing, biophysically detailed model of the early olfactory system. They will determine the extent to which the OB forms competing assemblies of gamma-coupled neurons and study beta oscillations as an interregional coupling mechanism with piriform cortex (PC) that supersedes these local gamma-coupled assemblies. Additional, less well-established OB interactions with olfactory tubercle and orbitofrontal cortex during odor sampling and response decisions also will be studied. Integrating these datasets into a common Hodgkin/Huxley-based network model will explicate the construction and utility of these systemwide dynamics based on their underlying cellular and network mechanisms. The proposed work takes a fairly well-characterized network and, via computational modeling, combines studies across different levels of analysis to build a mechanistic model of a complex dynamical system. The results will enable a deeper understanding of the dynamical flexibility of cortical circuits at many levels of analysis. Behavior provides tight control over oscillatory staes and cognitive processes associated with them, enabling explication of intact functional circuits. Slice electrophysiology and computational modeling will provide greater detail on the mechanistic, synaptic, neuromodulatory, and dynamical principles involved in generating and switching among these multiple states. The collaboration will benefit students at both institutions by integrating them into an interdisciplinary framework encompassing computational and experimental approaches, exposing students from diverse backgrounds to new research techniques and interdisciplinary and computational approaches to neuroscience. Close collaboration of the two investigators will transfer knowledge and methods across laboratories. Both laboratories actively train undergraduates in research and include them on many publications, and both laboratories actively recruit and train female and minority scientists in STEM fields. PI Kay has initiated participation in Project Exploration, an outreach program that provides access to science and scientists to underrepresented minority children and girls, and PI Cleland participates in the Leadership Alliance and Cornell Biology Scholars program for underrepresented minority and first-in-family students, and has published papers with undergraduate coauthors enrolled in these programs.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Sullivan, Susan L
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University of Chicago
Schools of Arts and Sciences
United States
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Kay, Leslie M (2017) How brains create the world: The dynamical legacy of Walter J Freeman in olfactory system physiology. Chaos Complex Lett 11:41-47
Li, Guoshi; Cleland, Thomas A (2017) A coupled-oscillator model of olfactory bulb gamma oscillations. PLoS Comput Biol 13:e1005760
Frederick, Donald E; Brown, Austin; Tacopina, Stephanie et al. (2017) Task-Dependent Behavioral Dynamics Make the Case for Temporal Integration in Multiple Strategies during Odor Processing. J Neurosci 37:4416-4426
McIntyre, Alexa B R; Cleland, Thomas A (2016) Biophysical constraints on lateral inhibition in the olfactory bulb. J Neurophysiol 115:2937-49
Osinski, Boles?aw L; Kay, Leslie M (2016) Granule cell excitability regulates gamma and beta oscillations in a model of the olfactory bulb dendrodendritic microcircuit. J Neurophysiol 116:522-39
Corcoran, Kevin A; Frick, Brendan J; Radulovic, Jelena et al. (2016) Analysis of coherent activity between retrosplenial cortex, hippocampus, thalamus, and anterior cingulate cortex during retrieval of recent and remote context fear memory. Neurobiol Learn Mem 127:93-101
Frederick, Donald E; Brown, Austin; Brim, Elizabeth et al. (2016) Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing. J Neurosci 36:7750-67
Kay, Leslie M (2015) Olfactory system oscillations across phyla. Curr Opin Neurobiol 31:141-7