Complex odor recognition by the main olfactory system
(collaboration with Dr. Emily Gibson, CU Anschutz Bioengineering). We are testing the hypothesis that tiling of fast oscillatory response of mitral cells along the phase of the slower q oscillations, conveys odor information critical for odor discrimination and learning and we will determine whether different types of information are carried at different frequency bandwidths (b vs. low or high g). In addition, we are studying the modulation of olfactory bulb activity by noradrenergic innervation from the locus coreuleus and the involvement of basolateral amygdala in olfactory decision making (BLA is studied in collaboration with Dr. Molly Huntsman, School of Pharmacy, CU Anschutz). We use combined high density Neuropixels recording, spatially patterned closed loop optogenetic stimulation and two photon imaging. Supported by NIH NIDCD R01DC000566, Restrepo (PI), Gibson (Co-PI) |
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Controlled neuronal firing in vivo using two-photon spatially shaped optogenetics
(collaboration with Drs. Emily Gibson, CU Anschutz Bioengineering, Juliet Gopinath, CU Boulder, and Victor Bright). We are deploying a fiber-coupled two photon miniature microscope (2P-FCM) to the laboratories of five users studying neural activity to understand vocal learning and communication, decision making, the role of the cerebellum in cognition and locomotion, social interactions and oligodendrogenesis in various species. During my sabbatical in 2018 we deployed the 2P-FCM to the laboratories of Drs. Isabel Llano and Michael Graupner in the University of Paris to study cerebellar function. We are incorporating holographic optogenetic stimulation in the 2P-FCM. Deployment of the device is implemented in partnership with Intelligent Imaging Innovations, Inc. Funded by the NINDS BRAIN Initiative U01NS099577, Restrepo (Corresponding PI) and Gibson (PI). |
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Olfactory receptors for semiochemical detection in the main olfactory system
(collaboration with Drs. Vijay Ramakrishnan, CU Anschutz Otolaryngology and Joel Mainland, Monell Chemical Senses Center). We examine olfactory sensory neurons (OSNs) from the main olfactory epithelium of mice and humans to identify olfactory receptors that respond to semiochemicals including putative pheromones, major histocompatibility complex peptides and body fluids. RNAseq after flow cytometry of OSNs expressing nuclear mCherry under the OMP promoter and GFP under the TRPM5 promoter have identified a subset of olfactory receptors differentially expressed in this population of cells. Responsiveness of these olfactory receptors is being characterized with a high throughput assay testing thousands of stimuli by our collaborator Dr. Joel Mainland at Monell. Funded by NIDCD R01DC014253, Restrepo (PI), Ramakrishnan (Co-PI) and Mainland (Co-PI). |
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Cortical circuit dysfunction in fragile x syndrome
(collaboration with Dr. Molly Huntsman). The experiments define in an animal model system for Fragile X Syndrome mechanisms resulting in faulty activation of a small yet powerful population of inhibitory interneurons, and identify modes of corrective restoration through pharmacologic and genetic approaches. Funded by NINDS R01NS095311, Huntsman (PI), Restrepo (Co-PI) |
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Proof-of-concept fiber-based miniature multiphoton microscope using adaptable optics
(collaboration with Drs. Emily Gibson, CU Anschutz Bioengineering, Juliet Gopinath, CU Boulder, and Victor Bright). We present an affordable solution for a portable, versatile, fiber-coupled optical imaging/optogenetic photoactivation system that can be used for studies on awake, behaving animals. Studies under this grant will provide us with proof-of-concept data that will position us to successfully translate the device into the market place. Funded by NSF PFI:AIR-TT 1602128 Gibson (PI), Restrepo (PI), Gopinath (PI) and Bright (PI) |
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NCS-FO: Collaborative Research: Rebuilding neural pathway function using miniature integrated optics for neuron-level readout and feedback
(collaboration with Drs. Emily Gibson, CU Anschutz Bioengineering, Juliet Gopinath, CU Boulder, and Victor Bright). This proposal would demonstrate for the first time the actual recovery of function in an awake-behaving animal using an engineered optical feedback system. The project is being performed by a highly interdisciplinary team with extensive expertise in neuroscience, optogenetics, and cognitive research in awake behaving animals along with experts in optical and mechanical engineering. Funded by NSF CBET-1631912 Gibson (PI), Restrepo (PI), Gopinath (PI) and Bright (PI). |
3D-Fast optical interface for rapid volumetric neural sensing and modulation
(collaboration with Drs. Cristin Welle, CU Anschutz Neurosurgery, Emily Gibson, CU Anschutz Bioengineering, Doug Shepherd, CU Anschutz Pharmacology and Ioannis Kymissis, Columbia University). We are developing an optical device (‘3D-FAST’) that allows for rapid, real-time volumetric neural recording and precise optical stimulation. By pairing miniature arrays of micropatterned LED emitters with the axial focusing capabilities of electrowetting lens technologies, we will achieve duplex recording and stimulation of many thousands of neurons. Welle (PI) and Gibson (PI). Funded by NIH BRAIN Initiative R21EY029458 Welle (PI) and Gibson (PI). |
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Miniature fiber coupled microscope for neuronavigation
(collaboration with Drs. Aviva Abosch, CU Anschutz Neurosurgery and Emily Gibson, CU Anschutz Bioengineering). We are developing a fiber-coupled imaging device to improve greatly upon existing surgical techniques in order (a) to improve targeting during deep brain stimulation placement, (b) to minimize or eliminate the need for microelectrode recording which requires extensive training and expertise and (c) to reduce patient discomfort and risk. Funded by a State of Colorado Advanced Industries Acceleration Grant. Abosch (PI), Gibson (Co-PI), Restrepo (Co-PI). |
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Optical, behavioral and electrical probing of the inhibitory cerebellar circuit during a reward-oriented task
(collaboration with Drs. Isabell Llano, University of Paris, Laure Rondi-Reig, University of Paris and Emily Gibson, CU Anschutz Bioengineering). This project aims to decipher how information processing by the interneurons of the cerebellar cortex depends on the reward context of a motor task. The will focus on examining and manipulating the activity of GABA-releasing neurons of the cerebellar cortex in mice performing behaviors with different reward contents. The work will involve 2 photon calcium imaging and optogenetic manipulations in behaving mice. Funded by the French national Agency of Research (ANR) and the NINDS Brain Initiative project (Llano, PI, Rondi-Reig, Co-PI, Restrepo, Co-PI). |
1. Gire DH, Whitesell JD, Doucette W, Restrepo D. Information for decision-making and stimulus identification is multiplexed in sensory cortex. Nat Neurosci. 2013;16(8):991-3. Epub 2013/06/25. doi: 10.1038/nn.3432. PubMed PMID: 23792942; PMCID: PMC3725200.
2. Guthman EM, Ma M, Chu P, Baca SM, Restrepo D, Huntsman MM. Cell type specific control of basolateral amygdala plasticity via feedforward inhibition. bioRxiv. 2018. doi: https://doi.org/10.1101/348524.
3. Gould EA, Busquet N, Shepherd D, Dietz RM, Herson PS, Simoes de Souza FM, Li A, George NM, Restrepo D, Macklin WB. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone. Elife. 2018;7. Epub 2018/02/14. doi: 10.7554/eLife.34783. PubMed PMID: 29436368; PMCID: PMC5828668.
4. Ozbay BN, Futia GL, Ma M, Bright VM, Gopinath JT, Hughes EG, Restrepo D, Gibson EA. Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning. Sci Rep. 2018;8(1):8108. Epub 2018/05/29. doi: 10.1038/s41598-018-26326-3. PubMed PMID: 29802371; PMCID: PMC5970169.
5. Ryan DP, Gould EA, Seedorf GJ, Masihzadeh O, Abman SH, Vijayaraghavan S, Macklin WB, Restrepo D, Shepherd DP. Automatic and adaptive heterogeneous refractive index compensation for light-sheet microscopy. Nat Commun. 2017;8(1):612. doi: 10.1038/s41467-017-00514-7. PubMed PMID: 28931809.
2. Guthman EM, Ma M, Chu P, Baca SM, Restrepo D, Huntsman MM. Cell type specific control of basolateral amygdala plasticity via feedforward inhibition. bioRxiv. 2018. doi: https://doi.org/10.1101/348524.
3. Gould EA, Busquet N, Shepherd D, Dietz RM, Herson PS, Simoes de Souza FM, Li A, George NM, Restrepo D, Macklin WB. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone. Elife. 2018;7. Epub 2018/02/14. doi: 10.7554/eLife.34783. PubMed PMID: 29436368; PMCID: PMC5828668.
4. Ozbay BN, Futia GL, Ma M, Bright VM, Gopinath JT, Hughes EG, Restrepo D, Gibson EA. Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning. Sci Rep. 2018;8(1):8108. Epub 2018/05/29. doi: 10.1038/s41598-018-26326-3. PubMed PMID: 29802371; PMCID: PMC5970169.
5. Ryan DP, Gould EA, Seedorf GJ, Masihzadeh O, Abman SH, Vijayaraghavan S, Macklin WB, Restrepo D, Shepherd DP. Automatic and adaptive heterogeneous refractive index compensation for light-sheet microscopy. Nat Commun. 2017;8(1):612. doi: 10.1038/s41467-017-00514-7. PubMed PMID: 28931809.
