In humans, the sense of smell contributes significantly to our quality of life. Odors are strong cues for evoking memories of past events and olfaction plays an important role in our perception of flavor. However, the mechanisms underlying the processing and encoding of olfactory information in the brain are not clear. To address this question, we study the properties of neuronal circuits formed by excitatory and inhibitory neurons in the rodent olfactory bulb, a site where olfactory information is initially encoded in the brain. We also examine the properties of circuits in the primary olfactory (piriform) cortex, the next major level at which olfactory information is processed. Our long term goal is to understand how neural circuits ultimately give rise to sensory perception The experiments proposed employ optical and electrophysiological techniques to determine the response properties of identified neuronal populations in both the olfactory bulbs and cortex.
Specific Aim 1 proposes the use of chronic, in vivo two-photon recording of activity from identified principal cells and inhibitory interneurons in the olfactory bulb of awake, head-fixed mice. We will use this approach to determine how associative learning modifies odor representations in behaving mice. We hypothesize that local interneurons play an important role in learning-related changes in olfactory bulb activity.
Specific Aim 2 proposes to investigate how particular subtypes of GABAergic inhibitory interneurons modulate odor coding in piriform cortex. We combine optogenetics, brain slice and in vivo electrophysiological recordings to reveal the operations by which distinct interneuron classes govern odor-evoked activity of cortical principal cells.Together, these experiments will show how local inhibitory interneurons in the olfactory bulb and cortex regulate sensory information processing in the brain.
We propose examining how the interplay between excitatory and inhibitory neurons in brain circuits contribute to sensory perception. Dysfunction in the balance of excitation and inhibition we study could contribute to major cognitive disorders such as schizophrenia and autism.
| Kato, Hiroyuki K; Asinof, Samuel K; Isaacson, Jeffry S (2017) Network-Level Control of Frequency Tuning in Auditory Cortex. Neuron 95:412-423.e4 |
| Gillet, Shea N; Kato, Hiroyuki K; Justen, Marissa A et al. (2017) Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation. Front Neural Circuits 11:112 |
| Kato, Hiroyuki K; Gillet, Shea N; Isaacson, Jeffry S (2015) Flexible Sensory Representations in Auditory Cortex Driven by Behavioral Relevance. Neuron 88:1027-1039 |
| Sturgill, James F; Isaacson, Jeffry S (2015) Somatostatin cells regulate sensory response fidelity via subtractive inhibition in olfactory cortex. Nat Neurosci 18:531-5 |
| 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 |
| Isaacson, Jeffry S; Scanziani, Massimo (2011) How inhibition shapes cortical activity. Neuron 72:231-43 |
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