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)
Type
Research Project (R01)
Project #
5R01DC004682-14
Application #
8664360
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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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
Stokes, Caleb C A; Isaacson, Jeffry S (2010) From dendrite to soma: dynamic routing of inhibition by complementary interneuron microcircuits in olfactory cortex. Neuron 67:452-65
Apicella, Alfonso; Yuan, Qi; Scanziani, Massimo et al. (2010) Pyramidal cells in piriform cortex receive convergent input from distinct olfactory bulb glomeruli. J Neurosci 30:14255-60
Isaacson, Jeffry S (2010) Odor representations in mammalian cortical circuits. Curr Opin Neurobiol 20:328-31
Yuan, Qi (2009) Theta bursts in the olfactory nerve paired with beta-adrenoceptor activation induce calcium elevation in mitral cells: a mechanism for odor preference learning in the neonate rat. Learn Mem 16:676-81
Darcy, Daniel P; Isaacson, Jeffry S (2009) L-type calcium channels govern calcium signaling in migrating newborn neurons in the postnatal olfactory bulb. J Neurosci 29:2510-8
Poo, Cindy; Isaacson, Jeffry S (2009) Odor representations in olfactory cortex: "sparse" coding, global inhibition, and oscillations. Neuron 62:850-61

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