?Sensory cortex decomposes complex inputs into feature-based components, and distributes their representation over populations of neurons. In special cases this distribution is very clear--for instance the visual and auditory system respectively map retinal image and acoustic frequency along a spatial dimension within cortex. In general, however, rich sensory scenes are a mixture of features, and it remains unclear how the cortex mingles and segregates aspects of a complex sensory representation across neural populations. Olfactory stimuli are extraordinarily complex, with distinct odors comprised from a mixture of compounds. The circuitry in olfactory cortex is equally intricate, with populations of neurons coupling to one another with seemingly random rules, and receiving similarly random projections from lower centers. The combination of these two facts obfuscates the organization of odor representation. Our proposal leverages advances in experimental circuit identification and manipulation, as well as theoretical frameworks for large-scale cortical networks, to establish principles for the distribution of odor identity and concentration coding across olfactory cortex. Specifically, we aim to establish the following links between olfactory circuitry and odor coding: 1 )There exists a graded distribution of specific inhibitory sub-circuits along the rostral-caudal axis of the olfactory cortex. 2) The rostral-caudal distribution of inhibition interacts with Hebbian plasticity mechanisms so as to shape the odor selectivity of cells along the rostral-caudal axis. These advances will provide much needed insights into how cortical structures represent and process distinct aspects of an odor scene.

Public Health Relevance

In the brain, neural activity is controlled by inhibitory neurons that release the neurotransmitter, GABA. This proposal investigates the circuit mechanisms of inhibition in the olfactory cortex. The regulation of inhibition is essential for both normal cortical function and the prevention of pathological conditions such as epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC015139-02
Application #
9098686
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sullivan, Susan L
Project Start
2015-08-01
Project End
2018-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Large, Adam M; Vogler, Nathan W; Canto-Bustos, Martha et al. (2018) Differential inhibition of pyramidal cells and inhibitory interneurons along the rostrocaudal axis of anterior piriform cortex. Proc Natl Acad Sci U S A 115:E8067-E8076
Rosenbaum, Robert; Smith, Matthew A; Kohn, Adam et al. (2017) The spatial structure of correlated neuronal variability. Nat Neurosci 20:107-114
Doiron, Brent; Litwin-Kumar, Ashok; Rosenbaum, Robert et al. (2016) The mechanics of state-dependent neural correlations. Nat Neurosci 19:383-93
Large, Adam M; Kunz, Nicholas A; Mielo, Samantha L et al. (2016) Inhibition by Somatostatin Interneurons in Olfactory Cortex. Front Neural Circuits 10:62
Litwin-Kumar, Ashok; Rosenbaum, Robert; Doiron, Brent (2016) Inhibitory stabilization and visual coding in cortical circuits with multiple interneuron subtypes. J Neurophysiol 115:1399-409
Large, Adam M; Vogler, Nathan W; Mielo, Samantha et al. (2016) Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex. Proc Natl Acad Sci U S A 113:2276-81
Ocker, Gabriel Koch; Litwin-Kumar, Ashok; Doiron, Brent (2015) Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses. PLoS Comput Biol 11:e1004458