The ability to identify an odor is crucial for avoiding predators, obtaining food or finding a mate. The concerted activity of distributed ensembles of neurons in piriform cortex (aPCx) is thought to lead directly to the formation of an odor percept however the coding strategies used to represent different features of an odor stimulus, like odor identity and odor intensity, remain poorly understood. aPCx consists of a heterogeneous population of neurons that likely serve distinct roles in shaping odor representations and/or conveying this information to downstream target areas. Little is known about how they actually do so as most investigations into cortical odor coding were agnostic to cell type or target projection. Moreover, most previous studies were performed in anesthetized animals, where both the cells' functions and consequent cortical representations may be dra- matically altered. The objective here is to understand how different features of an odor stimulus are repre- sented in diverse populations of aPCx neurons, and elucidate the underlying neural circuit mechanisms that shape these representations. The approach used will be to record odor-evoked spiking in large ensembles of functionally identified aPCx neurons in awake mice. The central hypothesis is that independent coding strate- gies are used to represent odor identity and odor intensity, and that different types of aPCx cells play distinct roles in shaping these representations. The rationale for these studies is that determining how odors are repre- sented in aPCx of an awake, behaving animal is crucial for understanding olfactory system function. To this end the following three aims are proposed:
Aim 1 : To determine how piriform cortex simultaneously rep- resents odor identity and odor intensity. Preliminary studies suggest that odor identity is encoded in distrib- uted ensembles of aPCx neurons, and these ensembles are largely concentration-invariant (i.e. a spatial iden- tity code); and odor intensity is encoded by the synchrony of the ensembles activity (i.e. a temporal intensity code).
Aim 2 : To determine odor responses in diverse subtypes of aPCx neurons, defined genetically, by laminar organization or by distinct projection targets. In vivo optogenetic tagging will be used to identify responses in defined subtypes of neurons. Odor responses in different subtypes of neurons are predicted to reflect their specific roles in shaping the ensemble or the feature of the odor stimulus most relevant for different target regions.
Aim 3 : To determine how recurrent circuitry shapes cortical odor representations. Output from principal neurons will be unilaterally blocked, permitting simultaneous bilateral recordings of control and ?feedforward? circuits. Preliminary data suggest recurrent circuits dramatically shape the size, timecourse and gain of odor responses in aPCx. This proposal is innovative because it deploys novel tools and methods to re- cord odor-evoked activity in large populations of neurons in awake animals and ascribe distinct response prop- erties to identified cortical circuit elements. This contribution is significant because it will provide deep insight into how odors are represented in piriform cortex through understanding underlying circuit mechanisms.

Public Health Relevance

The sense of smell is important factor that contributes to our quality of life. This research seeks to understand the fundamental features governing how the sense of smell is processed in the brain. Moreover, piriform cortex is a highly epileptogenic brain region, where epilepsy results from imbalances between neural excitation and neural inhibition. This research examines how excitatory and inhibitory circuits in piriform cortex interact to produce a balanced, ?normalized? output, and disruptions to these circuits are expected to lend insight into the development, expression and progression of epilepsy.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Sullivan, Susan L
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Duke University
Schools of Medicine
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Bolding, Kevin A; Franks, Kevin M (2018) Recurrent cortical circuits implement concentration-invariant odor coding. Science 361:
Bolding, Kevin A; Franks, Kevin M (2017) Complementary codes for odor identity and intensity in olfactory cortex. Elife 6:
Roland, Benjamin; Deneux, Thomas; Franks, Kevin M et al. (2017) Odor identity coding by distributed ensembles of neurons in the mouse olfactory cortex. Elife 6: