Whether it be the aroma of our morning coffee or the scent of a lover, the sense of smell is a critical feature of our daily life. The long-term objective of our research is to understand how olfactory information is processed in the mammalian brain. To address this question, we study the properties of neuronal circuits and synapses in the olfactory bulb and olfactory cortex, which are the first sites in the brain where olfactory information is processed. Our unifying hypothesis is that understanding the synaptic mechanisms of olfactory circuits is critical for revealing how the brain encodes our sense of smell. The experiments proposed employ patch-clamp recording techniques to study the functional properties of olfactory circuits in vivo and in vitro.
Specific Aim 1 proposes to characterize the fundamental mechanisms governing odor representations in the piriform cortex. We hypothesize that odor-evoked excitatory input to cortical pyramidal cells in vivo reflects both direct sensory input from the olfactory bulb and associational (recurrent) connections between cortical pyramidal cells.
Specific Aim 2 proposes to investigate the role of local inhibitory circuits that shape activity in piriform cortex. We hypothesize that distinct types of dynamic feedback circuits govern recurrent inhibition and are differentially recruited by physiologically relevant patterns of pyramidal cell activity.
Specific Aim 3 proposes to investigate the role of long-range feedback connections from piriform cortex to the olfactory bulb. We hypothesize that excitatory projections from pyramidal cells regulate the initial stages of odor coding in the olfactory bulb. These experiments will provide new insight into the synaptic mechanisms of neural circuits underlying olfaction in the brain.

Public Health Relevance

The sense of smell is an 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004682-13
Application #
8465859
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2000-12-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
13
Fiscal Year
2013
Total Cost
$296,668
Indirect Cost
$94,793
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Sturgill, James F; Isaacson, Jeffry S (2015) Somatostatin cells regulate sensory response fidelity via subtractive inhibition in olfactory cortex. Nat Neurosci 18:531-5
Kato, Hiroyuki K; Gillet, Shea N; Isaacson, Jeffry S (2015) Flexible Sensory Representations in Auditory Cortex Driven by Behavioral Relevance. Neuron 88:1027-39
Boyd, Alison M; Kato, Hiroyuki K; Komiyama, Takaki et al. (2015) Broadcasting of cortical activity to the olfactory bulb. Cell Rep 10:1032-9
Stokes, Caleb C A; Teeter, Corinne M; Isaacson, Jeffry S (2014) Single dendrite-targeting interneurons generate branch-specific inhibition. Front Neural Circuits 8:139
Kato, Hiroyuki K; Gillet, Shea N; Peters, Andrew J et al. (2013) Parvalbumin-expressing interneurons linearly control olfactory bulb output. Neuron 80:1218-31
Boyd, Alison M; Sturgill, James F; Poo, Cindy et al. (2012) Cortical feedback control of olfactory bulb circuits. Neuron 76:1161-74
Kato, Hiroyuki K; Chu, Monica W; Isaacson, Jeffry S et al. (2012) Dynamic sensory representations in the olfactory bulb: modulation by wakefulness and experience. Neuron 76:962-75
Poo, Cindy; Isaacson, Jeffry S (2011) A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex. Neuron 72:41-8
Isaacson, Jeffry S; Scanziani, Massimo (2011) How inhibition shapes cortical activity. Neuron 72:231-43
Yuan, Qi; Isaacson, Jeffry S; Scanziani, Massimo (2011) Linking neuronal ensembles by associative synaptic plasticity. PLoS One 6:e20486

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