Through repetitive experience, one can better detect or discriminate sensory stimuli. This form of learning, termed perceptual learning, fundamentally shapes the way our brains process sensory information. The precise loci and mechanisms underlying perceptual learning are still debated. We address mechanisms of olfactory perceptual learning, focusing on the olfactory bulb, the first olfactory center of the brain. In th olfactory bulb, newborn inhibitory neurons are continuously integrated throughout adulthood, providing a remarkable potential for plasticity. Our central hypotheses are that 1) olfactory perceptual learning improves odor discriminability by the ensemble activity of mitral cells, the principal neurons in the olfactory bulb, and that 2) adult-born inhibitory neurons show particularly adaptive plasticity and support mitral cell plasticity during learning. To address thee ideas, we will apply in vivo two-photon calcium imaging chronically in the olfactory bulb of awake mice undergoing various olfactory experience paradigms over days. This is combined with mouse genetics to specifically label mitral cells and adult-born inhibitory neurons and ablate adult neurogenesis. We recently developed a system to chronically image the activity of defined populations of neurons in the olfactory bulb of awake mice (Kato et al. Neuron 2012, Kato et al. Neuron 2013). The current proposal extends this approach to characterize the dynamics of odor representations in the olfactory bulb during one-week-long experience paradigms.
In Aim 1, we will characterize mitral cell responses to a pair of very similar odors during one-week-long experience in a passive exposure condition as well as several discrimination learning tasks. Our preliminary results suggest that discrimination learning enhances the discriminability of experienced odors by mitral cell ensemble activity.
In Aim 2, we will test whether adult neurogenesis is necessary for olfactory perceptual learning and mitral cell plasticity. We will use genetic strategies to block adult neurogenesis and examine the effect on discrimination learning tasks. Furthermore, neurogenesis ablation will be combined with mitral cell imaging to test whether mitral cell plasticity during olfactory experience is altered with neurogenesis ablation.
I Aim 3, we will evaluate the hypothesis that young adult-born inhibitory neurons show particularly pronounced and adaptive plasticity during olfactory experience. We will do this by directly imaging the activity of age-defined adult-born granule cells throughout the olfactory experience paradigms. These experiments combine cutting-edge technologies including chronic high-resolution two-photon imaging, behavioral tasks by head-fixed mice, and mouse genetics to label or ablate specific neuron types. They will reveal fine-scale circuit plasticity underlying perceptual learning and identify functional significance of adult neurogenesis.

Public Health Relevance

Dynamic and flexible processing of sensory information is essential for the well-being of animals in a changing environment and often impaired in neural disorders such as schizophrenia. We study neural mechanisms underlying olfactory perceptual learning, with a particular emphasis on adult neurogenesis within the olfactory bulb, the first olfactory center of the brain. The results will not only help us understand the functional significance of adult neurogenesis but also have implications in future treatments of learning disorders such as Alzheimer's disease and aging-related dementia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC014690-02
Application #
9091552
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2015-07-01
Project End
2020-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Mitani, Akinori; Dong, Mingyuan; Komiyama, Takaki (2018) Brain-Computer Interface with Inhibitory Neurons Reveals Subtype-Specific Strategies. Curr Biol 28:77-83.e4
Peters, Andrew J; Liu, Haixin; Komiyama, Takaki (2017) Learning in the Rodent Motor Cortex. Annu Rev Neurosci 40:77-97
McIntyre, Jeremy C; Thiebaud, Nicolas; McGann, John P et al. (2017) Neuromodulation in Chemosensory Pathways. Chem Senses 42:375-379
Chu, Monica W; Li, Wankun L; Komiyama, Takaki (2017) Lack of Pattern Separation in Sensory Inputs to the Olfactory Bulb during Perceptual Learning. eNeuro 4:
Hwang, Eun Jung; Dahlen, Jeffrey E; Mukundan, Madan et al. (2017) History-based action selection bias in posterior parietal cortex. Nat Commun 8:1242
Peters, Andrew J; Lee, Jun; Hedrick, Nathan G et al. (2017) Reorganization of corticospinal output during motor learning. Nat Neurosci 20:1133-1141
Makino, Hiroshi; Ren, Chi; Liu, Haixin et al. (2017) Transformation of Cortex-wide Emergent Properties during Motor Learning. Neuron 94:880-890.e8
Makino, Hiroshi; Hwang, Eun Jung; Hedrick, Nathan G et al. (2016) Circuit Mechanisms of Sensorimotor Learning. Neuron 92:705-721
Chu, Monica W; Li, Wankun L; Komiyama, Takaki (2016) Balancing the Robustness and Efficiency of Odor Representations during Learning. Neuron 92:174-186

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