Cortical processing of sensory information plays a critical role in sensory discrimination, object recognition and memory. Cortical sensory processing has been shown to be highly dynamic, with past experience, current context and expectations shaping how the world is perceived on a moment by moment basis. Disorders of sensory processing constitute a major component of impairments induced by CNS disease and aging, as well as congenital disorders such as schizophrenia and autism. A largely overlooked aspect of odor processing is the role of top-down inputs in shaping olfactory cortical activity based on past-experience, expectation and context. Here we propose to explore the role of the lateral entorhinal cortex (LEC) in both odor processing and top-down control of piriform cortex (PCX ) and olfactory bulb. The LEC is both a component of the olfactory cortex (receives direct input from the olfactory bulb) and is a major component of the temporal lobe/limbic system memory circuitry as the primary afferent to the hippocampal formation. Importantly, the LEC also sends a strong projection back to the PCX and olfactory bulb - a pathway not well understood. There are three specific aims, each supported by new preliminary data, that test novel, specific hypotheses about the function of LEC in olfaction.
In Specific Aim 1 we will extend our initial work showing significantly more selective single-unit odor receptive fields in LEC compared to PCX. First we will use in vivo intracellular recording in anesthetized animals to allow odor RF characterization of identified LEC cell types, and second we will compare single-unit and ensemble odor evoked activity in the awake, freely moving LEC and PCX to novel and familiar odors. These data will be the first to characterize olfactory sensory physiology of this region of olfactory cortex, and test our hypothesis that odor coding becomes more precise, in an experience-dependent manner, in this neocortical component of the olfactory cortex.
In Aim 2, using optogenetic and reversible lesion techniques we will extend our preliminary data to test the hypothesis that LEC feedback to PCX functions in a highly cell specific manner to shape both PCX neuron odor RF's and temporal structure of PCX activity. This top-down influence may contribute to both perceptual acuity and odor memory as tested in Aim 3.
In Aim 3 we will extend our preliminary data in awake, freely moving animals performing odor discrimination tasks to test our hypothesis that LEC top-down input shapes odor acuity both by modulating ongoing PCX odor-evoked activity and by contributing to anticipatory PCX single-unit and ensemble activity, prior to odor onset.
Each Aim uses innovative concepts and techniques to test specific hypotheses regarding the role of a structure that serves not only as a component of the olfactory cortex, but also as a critical component of temporal lobe memory circuits.

Public Health Relevance

Disturbances of sensory processing and memory are associated with a variety of disorders across the lifespan. This proposal examines perceptual learning and experience-dependent plasticity within the olfactory system, a system uniquely challenged by many of these same disorders. Understanding how memories are stored or modulated could have a significant impact on treatment and prevention of these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC003906-16A1
Application #
8439070
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
1998-12-01
Project End
2018-02-28
Budget Start
2013-03-10
Budget End
2014-02-28
Support Year
16
Fiscal Year
2013
Total Cost
$341,963
Indirect Cost
$90,370
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Cohen, Yaniv; Wilson, Donald A; Barkai, Edi (2015) Differential modifications of synaptic weights during odor rule learning: dynamics of interaction between the piriform cortex with lower and higher brain areas. Cereb Cortex 25:180-91
Barnes, Dylan C; Wilson, Donald A (2014) Slow-wave sleep-imposed replay modulates both strength and precision of memory. J Neurosci 34:5134-42
Wilson, Donald A; Xu, Wenjin; Sadrian, Benjamin et al. (2014) Cortical odor processing in health and disease. Prog Brain Res 208:275-305
Sadrian, B; Lopez-Guzman, M; Wilson, D A et al. (2014) Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure. Neuroscience 280:204-19
Courtiol, Emmanuelle; Wilson, Donald A (2014) Thalamic olfaction: characterizing odor processing in the mediodorsal thalamus of the rat. J Neurophysiol 111:1274-85
Wesson, Daniel W; Morales-Corraliza, Jose; Mazzella, Matthew J et al. (2013) Chronic anti-murine Aýý immunization preserves odor guided behaviors in an Alzheimer's ýý-amyloidosis model. Behav Brain Res 237:96-102
Morales-Corraliza, Jose; Schmidt, Stephen D; Mazzella, Matthew J et al. (2013) Immunization targeting a minor plaque constituent clears *-amyloid and rescues behavioral deficits in an Alzheimer's disease mouse model. Neurobiol Aging 34:137-45
Chapuis, Julie; Cohen, Yaniv; He, Xiaobin et al. (2013) Lateral entorhinal modulation of piriform cortical activity and fine odor discrimination. J Neurosci 33:13449-59
Chapuis, Julie; Wilson, Donald A (2013) Cholinergic modulation of olfactory pattern separation. Neurosci Lett 545:50-3
Sadrian, Benjamin; Wilson, Donald A; Saito, Mariko (2013) Long-lasting neural circuit dysfunction following developmental ethanol exposure. Brain Sci 3:704-27

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