Cortical neural circuits for odor perception – COCODE

Sensory perception and behavior critically depend on neurons and neural circuits to efficiently extract salient information from noisy sensory stimuli in the environment. However, the neural mechanisms that generate perception and behavior remain poorly understood. To address this fundamental question in neuroscience we study sensory processing in the mouse olfactory system. Olfaction represents a simple, tractable sensory system of outstanding ethological importance, and an ideal model to link neural circuit functions and behavior.
Odor perception is initiated by the binding of odorants to odorant receptors, expressed on olfactory sensory neurons in the olfactory epithelium. Olfactory sensory neurons project to the olfactory bulb, where odor exposure elicits stereotyped patterns of glomerular activity. Odor information encoded in patterns of glomerular activity must then be integrated at higher olfactory centers in the brain to generate unified odor objects, defined by olfactory perceptual features such as odor identity and intensity. The piriform cortex has been suggested to serve as such a site of integration. Information about odors is also encoded in the temporal structure of neural activity, and odor exposure elicits robust neural oscillations in the olfactory bulb and the piriform cortex. However, how odor information is encoded by the spatio-temporal patterns of activity in the piriform cortex, and how cortical odor representations control behaviors remains unknown.
Our long-term goal is to understand the neural circuit mechanisms underlying olfactory processing and behavior. The objectives of this application are to understand how odor identity and intensity are encoded in neural ensemble activity in the piriform cortex. Our working hypothesis is that odor identity is encoded in the spatial patterns of piriform activity, and that information about odor intensity is encoded in the latency of piriform odor responses. Our preliminary results indeed suggest that the spatial patterns of piriform odor responses are largely independent of odorant concentration, and we propose that parvalbumin (PV)-expressing interneurons in the piriform cortex play a central role in piriform signal normalization. We also hypothesize that PV cells are necessary for the generation of gamma oscillations and synchrony in the olfactory system, which in turn determines the latency of piriform odor responses.
Thus, the rationale for this project is to combine in vivo two-photon calcium imaging (Fleischmann lab) with multi-unit recordings in behaving animals (Benchenane lab) to decipher the spatio-temporal patterns of neural odor coding in the piriform cortex.

Task 1. We will use in vivo two-photon calcium imaging and computational approaches to quantitatively analyze information coding in large ensembles of piriform neurons in anesthetized mice. We predict that odor identity is encoded in the spatial patterns of piriform activity.
Task 2. We will record odor-evoked oscillations and multi-unit activity in the olfactory bulb and the piriform cortex, and we will determine the extent to which information about odor intensity can be encoded in the latency of piriform odor responses.
Task 3. We will silence piriform PV cells, using chemical genetics, to determine their functions in the generation of the spatio-temporal piriform odor response patterns.
Task 4. We will use a go/no go operant conditioning task in head-fixed mice to test odor discrimination accuracy across a range of odor intensities, and we will correlate neural representations of odor identity and intensity with discrimination accuracy.

The highly complimentary expertise of the two partner labs will allow us to determine the contribution of both spatial and temporal patterns of neural activity to the encoding of stimulus identity and intensity in the olfactory cortex. Achieving the tasks of this proposal will provide a mechanistic understanding of the neural correlates of behavior.