Whether it be the aroma of our morning coffee or the scent of a lover, the sense of smell is a critical feature of 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 important for revealing how the brain encodes our sense of smell. The experiments proposed employ an in vitro brain slice preparation of the rat anterior piriform cortex. We also use a novel slice preparation in which the olfactory bulb remains attached to the cortex. Piriform cortex pyramidal cells and interneurons will be visualized using infrared differential interference optics. We will study these cells using whole-cell patch clamp recording and imaging of intracellular calcium concentration.
Specific Aim 1 proposes to characterize the fundamental mechanisms governing the transfer of sensory information from the olfactory bulb to the cortex. We hypothesize that individual mitral cells can make strong connections onto piriform pyramidal cells and that the synaptic integration of relatively few mitral cell inputs underlies feature detection in piriform cortex.
Specific Aim 2 proposes to investigate the role of local inhibitory circuits in shaping synaptic integration in piriform cortex. We hypothesize that feedforward and feedback inhibitory interneurons regulate synaptic integration and spike output during physiologically relevant patterns of olfactory bulb input.
Specific Aim 3 proposes to investigate population coding using imaging of cell activity in olfactory bulb-piriform cortex slices. We hypothesize that temporal and spatial patterns of pyramidal cell activity can encode information regarding the timing and localization of olfactory input in the olfactory bulb.These experiments will provide new insight into the synaptic mechanisms underlying olfaction in the brain.

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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Davis, Barry
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University of California San Diego
Schools of Medicine
La Jolla
United States
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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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