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 neurons in slices of the rat olfactory bulb-the first site in the brain where olfactory information is processed. While fast synaptic transmission in the brain is typically mediated by neurotransmitters released from axon nerve endings, dendritic transmitter release is thought to play an important role in the olfactory bulb. Glutamate released from principal mitral cell dendrites excites the dendrites of local interneurons, granule cells, which in turn release gamma-aminobutyric acid (GABA) back onto mitral dendrites. This dendrodendritic circuit underlies self- and lateral inhibition of mitral cells and has been suggested to play a critical role in odor discrimination and resolution in the olfactory bulb. The major goal of this research proposal is to elucidate the synaptic mechanisms governing dendrodendritic inhibition between mitral and granule cells in the olfactory bulb.
The specific aims focus on characterizing the fundamental properties of transmission between the two cell types, as well as the role of GABAB receptors and activity-dependent plasticity in modulating dendritic signaling. Mitral and granule neurons are visualized with infrared differential interference optics (IR-DIC) and studied using patch-clamp recording techniques.
Specific Aim I proposes to establish the basic quantal mechanisms governing the strength of dendritic transmission between synaptically coupled pairs of mitral and granule cells.
Specific Aim 2 proposes to investigate the role of GABAB receptors in dendrodendritic inhibition. We hypothesize that metabotropic GABAB receptors play an important role in modulating dendritic interactions between mitral and granule cells.
Specific Aim 3 proposes to investigate synaptic plasticity at dendrodendritic synapses. We hypothesize that excitatory dendritic inputs to granule cells express activity-dependent long-term potentiation and depression. These experiments will provide new insight into the synaptic mechanisms underlying dendrodendritic transmission, which is of critical importance in the processing of olfactory information in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004682-04
Application #
6755984
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
2001-07-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$223,308
Indirect Cost
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
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
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

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