[ { "id": "authors:q7t8f-g4t66", "collection": "authors", "collection_id": "q7t8f-g4t66", "cite_using_url": "https://authors.library.caltech.edu/records/q7t8f-g4t66", "type": "article", "title": "Recalibrating Olfactory Neuroscience to the Range of Naturally Occurring Odor Concentrations", "author": [ { "family_name": "Wachowiak", "given_name": "Matt", "orcid": "0000-0003-4508-9793" }, { "family_name": "Dewan", "given_name": "Adam", "orcid": "0000-0003-1627-5730" }, { "family_name": "Bozza", "given_name": "Thomas", "orcid": "0000-0002-6574-8154" }, { "family_name": "O'Connell", "given_name": "Tom F.", "orcid": "0000-0001-5107-7479", "clpid": "O'Connell-Tom-F" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "Sensory systems enable organisms to detect and respond to environmental signals relevant for their survival and reproduction. A crucial aspect of any sensory signal is its intensity; understanding how sensory signals guide behavior requires probing sensory system function across the range of stimulus intensities naturally experienced by an organism. In olfaction, defining the range of natural odorant concentrations is difficult. Odors are complex mixtures of airborne chemicals emitting from a source in an irregular pattern that varies across time and space, necessitating specialized methods to obtain an accurate measurement of concentration. Perhaps as a result, experimentalists often choose stimulus concentrations based on empirical considerations rather than with respect to ecological or behavioral context. Here, we attempt to determine naturally relevant concentration ranges for olfactory stimuli by reviewing and integrating data from diverse disciplines. We compare odorant concentrations used in experimental studies in rodents and insects with those reported in different settings including ambient natural environments, the headspace of natural sources, and within the sources themselves. We also compare these values to psychophysical measurements of odorant detection threshold in rodents, where thresholds have been extensively measured. Odorant concentrations in natural regimes rarely exceed a few parts per billion, while most experimental studies investigating olfactory coding and behavior exceed these concentrations by several orders of magnitude. We discuss the implications of this mismatch and the importance of testing odorants in their natural concentration range for understanding neural mechanisms underlying olfactory sensation and odor-guided behaviors.", "doi": "10.1523/jneurosci.1872-24.2024", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "The Journal of Neuroscience", "publication_date": "2025-03-05", "series_number": "10", "volume": "45", "issue": "10", "pages": "e1872242024" }, { "id": "authors:6ygy6-ye120", "collection": "authors", "collection_id": "6ygy6-ye120", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230404-448520900.11", "type": "article", "title": "Lineages to circuits: the developmental and evolutionary architecture of information channels into the central complex", "author": [ { "family_name": "Kandimalla", "given_name": "Pratyush", "orcid": "0000-0003-0426-6095", "clpid": "Kandimalla-Pratyush" }, { "family_name": "Omoto", "given_name": "Jaison Jiro", "orcid": "0000-0003-2032-6350", "clpid": "Omoto-Jaison-Jiro" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Hartenstein", "given_name": "Volker", "orcid": "0000-0001-9676-7393", "clpid": "Hartenstein-Volker" } ], "abstract": "The representation and integration of internal and external cues is crucial for any organism to execute appropriate behaviors. In insects, a highly conserved region of the brain, the central complex (CX), functions in the representation of spatial information and behavioral states, as well as the transformation of this information into desired navigational commands. How does this relatively invariant structure enable the incorporation of information from the diversity of anatomical, behavioral, and ecological niches occupied by insects? Here, we examine the input channels to the CX in the context of their development and evolution. Insect brains develop from\u2009~\u2009100 neuroblasts per hemisphere that divide systematically to form \"lineages\" of sister neurons, that project to their target neuropils along anatomically characteristic tracts. Overlaying this developmental tract information onto the recently generated Drosophila \"hemibrain\" connectome and integrating this information with the anatomical and physiological recording of neurons in other species, we observe neuropil and lineage-specific innervation, connectivity, and activity profiles in CX input channels. We posit that the proliferative potential of neuroblasts and the lineage-based architecture of information channels enable the modification of neural networks across existing, novel, and deprecated modalities in a species-specific manner, thus forming the substrate for the evolution and diversification of insect navigational circuits.", "doi": "10.1007/s00359-023-01616-y", "pmcid": "PMC10354165", "issn": "0340-7594", "publisher": "Springer", "publication": "Journal of Comparative Physiology A", "publication_date": "2023-07", "series_number": "4", "volume": "209", "issue": "4", "pages": "679-720" }, { "id": "authors:xwwfa-b5533", "collection": "authors", "collection_id": "xwwfa-b5533", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182203000.19", "type": "monograph", "title": "Restructuring of olfactory representations in the fly brain around odor relationships in natural sources", "author": [ { "family_name": "Yang", "given_name": "Jie-Yoon", "clpid": "Yang-Jie-Yoon" }, { "family_name": "O'Connell", "given_name": "Thomas F.", "clpid": "O'Connell-Thomas-F" }, { "family_name": "Hsu", "given_name": "Wei-Mien M.", "orcid": "0000-0002-4183-1009", "clpid": "Hsu-Wei-Mien-Mendy" }, { "family_name": "Bauer", "given_name": "Matthew S.", "clpid": "Bauer-Matthew-S" }, { "family_name": "Dylla", "given_name": "Kristina V.", "orcid": "0000-0001-7869-9198", "clpid": "Dylla-Kristina-D" }, { "family_name": "Sharpee", "given_name": "Tatyana O.", "orcid": "0000-0002-7483-5081", "clpid": "Sharpee-Tatyana-O" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "A core challenge of olfactory neuroscience is to understand how neural representations of odor are generated and progressively transformed across different layers of the olfactory circuit into formats that support perception and behavior. The encoding of odor by odorant receptors in the input layer of the olfactory system reflects, at least in part, the chemical relationships between odor compounds. Neural representations of odor in higher order associative olfactory areas, generated by random feedforward networks, are expected to largely preserve these input odor relationships. We evaluated these ideas by examining how odors are represented at different stages of processing in the olfactory circuit of the vinegar fly D. melanogaster. We found that representations of odor in the mushroom body (MB), a third-order associative olfactory area in the fly brain, are indeed structured and invariant across flies. However, the structure of MB representational space diverged significantly from what is expected in a randomly connected network. In addition, odor relationships encoded in the MB were better correlated with a metric of the similarity of their distribution across natural sources compared to their similarity with respect to chemical features, and the converse was true for odor relationships encoded in primary olfactory receptor neurons (ORNs). Comparison of odor coding at primary, secondary, and tertiary layers of the circuit revealed that odors were significantly regrouped with respect to their representational similarity across successive stages of olfactory processing, with the largest changes occurring in the MB. The non-linear reorganization of odor relationships in the MB indicates that unappreciated structure exists in the fly olfactory circuit, and this structure may facilitate the generalization of odors with respect to their co-occurence in natural sources.", "doi": "10.1101/2023.02.15.528627", "publication_date": "2023-02-16" }, { "id": "authors:q484n-wh641", "collection": "authors", "collection_id": "q484n-wh641", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182588000.44", "type": "monograph", "title": "Early life experience with natural odors modifies olfactory behavior through an associative process", "author": [ { "family_name": "Dylla", "given_name": "Kristina V.", "orcid": "0000-0001-7869-9198", "clpid": "Dylla-Kristina-V" }, { "family_name": "O'Connell", "given_name": "Thomas F.", "clpid": "O'Connell-Thomas-F" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "Past work has shown that chronic exposure of Drosophila to intense monomolecular odors in early life leads to homeostatic adaptation of olfactory neural responses and behavioral habituation to the familiar odor. Here, we found that, in contrast, persistent exposure to natural odors in early life increases behavioral attraction selectively to familiar odors. Odor experience increases the attractiveness of natural odors that are innately attractive and decreases the aversiveness of natural odors that are innately aversive. These changes in olfactory behavior are unlikely to arise from changes in the sensitivity of olfactory neurons at the first stages of olfactory processing: odor-evoked output from antennal lobe projection neurons was unchanged by chronic exposure to natural odors in terms of olfactory sensitivity, relational distances between odors, or response dynamics. We reveal a requirement for additional features of the environment beyond the odor in establishing odor experience-dependent behavioral plasticity. Passive odor exposure in a featureless environment lacking strong reinforcing cues was insufficient to elicit changes in olfactory preference; however, the same odor exposure resulted in behavioral plasticity when food was present in the environment. Together, these results indicate that behavioral plasticity elicited by persistent exposure to natural odors in early life is mediated by an associative process. In addition, they highlight the importance of using naturalistic odor stimuli for investigating olfactory function.", "doi": "10.1101/2023.01.08.523155", "publication_date": "2023-01-09" }, { "id": "authors:89p7b-z1c58", "collection": "authors", "collection_id": "89p7b-z1c58", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230227-88449200.46", "type": "article", "title": "Olfactory coding", "author": [ { "family_name": "Barnum", "given_name": "George", "orcid": "0000-0002-9669-630X", "clpid": "Barnum-George" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "Modern humans live in real and digital environments dominated by sight and sound, but the vast majority of organisms on the planet rely on information received through air- or water-borne molecules to find food, avoid danger, and reproduce. Olfaction is at once both the primitive sensory modality and one of the hardest to understand, in large part due to the complexity of olfactory stimulus space. Whereas light and sound are easily ordered along natural physical axes that are reflected in their respective sensory codes, the organizational axes of odor space are not obvious. The search for systematic relationships between physicochemical characteristics of monomolecular odorants (carbon chain length, bond numbers, functional groups, etc.) and human perception of odorants suggests that olfactory perceptual space is a relatively low-dimensional structure. Odor descriptors provided by human observers are often significantly correlated. For instance, odors perceived as 'woody' are also likely to be described as 'warm', and many studies converge on hedonic valence or 'pleasantness' as being one of the most important dimensions of how people perceive odors. The identification of additional perceptual 'primaries' around which olfaction is organized is an active area of investigation, and a useful account of olfactory coding must explain this transformation of odor stimuli from the high dimensional chemical space to a lower dimensional perceptual space.", "doi": "10.1016/j.cub.2022.10.067", "issn": "0960-9822", "publisher": "Cell Press", "publication": "Current Biology", "publication_date": "2022-12", "series_number": "23", "volume": "32", "issue": "23", "pages": "R1296-R1301" }, { "id": "authors:1385y-ed418", "collection": "authors", "collection_id": "1385y-ed418", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220909-225792000", "type": "article", "title": "Parallel encoding of CO\u2082 in attractive and aversive glomeruli by selective lateral signaling between olfactory afferents", "author": [ { "family_name": "Zocchi", "given_name": "Dhruv", "clpid": "Zocchi-Dhruv" }, { "family_name": "Ye", "given_name": "Emily S.", "clpid": "Ye-Emily-S" }, { "family_name": "Hauser", "given_name": "Virginie", "clpid": "Hauser-Virginie" }, { "family_name": "O'Connell", "given_name": "Thomas F.", "clpid": "O'Connell-Thomas-F" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "We describe a novel form of selective crosstalk between specific classes of primary olfactory receptor neurons (ORNs) in the Drosophila antennal lobe. Neurotransmitter release from ORNs is driven by two distinct sources of excitation: direct activity derived from the odorant receptor and stimulus-selective lateral signals originating from stereotypic subsets of other ORNs. Consequently, the level of presynaptic neurotransmitter release from an ORN can be significantly dissociated from its firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO\u2082\u2014a behaviorally important environmental cue that directly excites a single ORN class\u2014in multiple olfactory glomeruli, each with distinct response dynamics. CO\u2082-sensitive glomeruli coupled to behavioral attraction respond preferentially to fast changes in CO\u2082 concentration, whereas those coupled to behavioral aversion more closely follow absolute levels of CO\u2082. Behavioral responses to CO\u2082 also depend on the temporal structure of the stimulus: flies walk upwind to fluctuating, but not sustained, pulses of CO\u2082. Stimulus-selective lateral signaling generalizes to additional odors and glomeruli, revealing a subnetwork of lateral interactions between ORNs that reshapes the spatial and temporal structure of odor representations in a stimulus-specific manner.", "doi": "10.1016/j.cub.2022.08.025", "pmcid": "PMC9561050", "issn": "0960-9822", "publisher": "Cell Press", "publication": "Current Biology", "publication_date": "2022-10-10", "series_number": "19", "volume": "32", "issue": "19", "pages": "4225-4239.e7" }, { "id": "authors:2z989-pwt85", "collection": "authors", "collection_id": "2z989-pwt85", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210910-223730081", "type": "monograph", "title": "Chronic exposure to odors at naturally occurring concentrations triggers limited plasticity in early stages of Drosophila olfactory processing", "author": [ { "family_name": "Gugel", "given_name": "Zhannetta V.", "clpid": "Gugel-Zhannetta-V" }, { "family_name": "Maurais", "given_name": "Elizabeth", "clpid": "Maurais-Elizabeth" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "In insects and mammals, chronic exposure to odors at high concentrations in early life alters olfactory function, but the role of odor experience-dependent plasticity in more naturalistic contexts is less clear. We investigated olfactory plasticity in the Drosophila antennal lobe by exposing flies to odors at concentrations that are typically encountered in natural odor sources. These stimuli also strongly and selectively activated only a single class of olfactory receptor neuron (ORN) input, facilitating the investigation of input-specific plasticity. Overall, chronic exposure to three such odors elicited limited plasticity in the odor responses of second-order projection neurons (PNs). Exposure to some odors elicited mild increases in PN responses to weak stimuli, extending the lower bound of the dynamic range of PN signaling. When present, plasticity was observed broadly in multiple PN types and thus was not selective for PNs receiving direct input from the chronically active ORNs. Chronic E2-hexenal exposure did not affect PN intrinsic properties, local inhibitory innervation, ORN responses, or ORN-PN synaptic strength, but modestly increased broad lateral excitation evoked by some odors. These results show that PN odor coding is only mildly affected by strong persistent activation of a single olfactory input and highlight the stability of early stages of insect olfactory processing to significant perturbations in the sensory environment.", "doi": "10.1101/2021.09.03.458834", "publication_date": "2021-09-03" }, { "id": "authors:aha8t-83p64", "collection": "authors", "collection_id": "aha8t-83p64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201204-110354387", "type": "monograph", "title": "Stimulus-selective lateral signaling between olfactory afferents enables parallel encoding of distinct CO\u2082 dynamics", "author": [ { "family_name": "Zocchi", "given_name": "Dhruv", "clpid": "Zocchi-Dhruv" }, { "family_name": "Ye", "given_name": "Emily S.", "clpid": "Ye-Emily-S" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "An important problem in sensory processing is how lateral interactions that mediate the integration of information across sensory channels function with respect to stimulus tuning. We demonstrate a novel form of selective crosstalk between specific olfactory channels that occurs between primary olfactory receptor neurons (ORNs). Neurotransmitter release from ORNs can be driven by two distinct sources of excitation, feedforward activity derived from the odorant receptor and lateral input originating from specific subsets of other ORNs. Consequently, levels of presynaptic release can become dissociated from firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO\u2082, a behaviorally important environmental cue that elicits spiking in only a single ORN class, in multiple olfactory channels. Different CO\u2082-responsive channels preferentially transmit distinct stimulus dynamics, thereby expanding the coding bandwidth for CO\u2082. These results generalize to additional odors and olfactory channels, revealing a subnetwork of lateral interactions between ORNs that reshape the spatial and temporal structure of odor representations in a stimulus-specific manner.", "doi": "10.1101/2020.12.03.410571", "publication_date": "2020-12-04" }, { "id": "authors:yg0p3-km189", "collection": "authors", "collection_id": "yg0p3-km189", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191204-154512546", "type": "article", "title": "A structured representation of odors in the fly mushroom body", "author": [ { "family_name": "Hong", "given_name": "Elizabeth", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "[no abstract]", "doi": "10.1093/chemse/bjz035", "issn": "0379-864X", "publisher": "Oxford University Press", "publication": "Chemical Senses", "publication_date": "2019-09", "series_number": "7", "volume": "44", "issue": "7", "pages": "E27-E28" }, { "id": "authors:4a70h-p6y44", "collection": "authors", "collection_id": "4a70h-p6y44", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190627-094320796", "type": "article", "title": "Mapping Odor to Action: (Dopaminergic) Timing Is Everything", "author": [ { "family_name": "Dylla", "given_name": "Kristina V.", "clpid": "Dylla-K-V" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" } ], "abstract": "Animal brains use the relative timing between sensory cues and behaviorally salient events to form predictive associations about their environment. Handler and colleagues provide new mechanistic insights into how differential signaling downstream of dopamine receptors couples this timing to the dynamic reweighting of synapses that link sensation to action.", "doi": "10.1016/j.cell.2019.06.010", "issn": "0092-8674", "publisher": "Elsevier", "publication": "Cell", "publication_date": "2019-06-27", "series_number": "1", "volume": "178", "issue": "1", "pages": "5-7" }, { "id": "authors:c0ex1-vb791", "collection": "authors", "collection_id": "c0ex1-vb791", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171219-101419416", "type": "article", "title": "Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT)", "author": [ { "family_name": "Huang", "given_name": "Ting-hao", "orcid": "0000-0002-2546-3525", "clpid": "Huang-Ting-Hao" }, { "family_name": "Niesman", "given_name": "Peter", "clpid": "Niesman-P" }, { "family_name": "Arasu", "given_name": "Deepshika", "clpid": "Arasu-D" }, { "family_name": "Lee", "given_name": "Donghyung", "clpid": "Lee-Donghyung" }, { "family_name": "De La Cruz", "given_name": "Aubrie", "orcid": "0000-0002-7351-0285", "clpid": "De-La-Cruz-A" }, { "family_name": "Callejas", "given_name": "Antuca", "orcid": "0000-0002-2236-9197", "clpid": "Callejas-A" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Lois", "given_name": "Carlos", "orcid": "0000-0002-7305-2317", "clpid": "Lois-C" } ], "abstract": "Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (TRAnsneuronal Control of Transcription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand ('donor' neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners ('receiver' neurons). Upon ligand-receptor binding at synapses the receptor is cleaved in its transmembrane domain and releases a protein fragment that activates transcription in the synaptic partners. Using TRACT in Drosophila we have confirmed the connectivity between olfactory receptor neurons and their postsynaptic targets, and have discovered potential new connections between neurons in the circadian circuit. Our results demonstrate that the TRACT method can be used to investigate the connectivity of neuronal circuits in the brain.", "doi": "10.7554/eLife.32027", "pmcid": "PMC5777821", "issn": "2050-084X", "publisher": "eLife Sciences Publications", "publication": "eLife", "publication_date": "2017-12-12", "volume": "6", "pages": "Art. No. e32027" }, { "id": "authors:v0ymm-fpm03", "collection": "authors", "collection_id": "v0ymm-fpm03", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-145751125", "type": "article", "title": "Simultaneous Encoding of Odors by Channels with Diverse Sensitivity to Inhibition", "author": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Wilson", "given_name": "Rachel I.", "clpid": "Wilson-R-I" } ], "abstract": "Odorant receptors in the periphery map precisely onto olfactory glomeruli (\"coding channels\") in the brain. However, the odor tuning of a glomerulus is not strongly correlated with its spatial position. This raises the question of whether lateral inhibition between glomeruli is specific or nonspecific. Here we show that, in the Drosophila brain, focal activation of even a single glomerulus recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of interneuron activity in different glomeruli is largely odor invariant. Although interneurons are recruited nonspecifically, glomeruli differ dramatically in their sensitivity to interneuron activity, and this is explained by their varying sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel by channels having high and low sensitivity to inhibition. Because lateral inhibition confers both costs and benefits, the brain might rely preferentially on \"high\" and \"low\" channels in different behavioral contexts.", "doi": "10.1016/j.neuron.2014.12.040", "pmcid": "PMC5495107", "issn": "0896-6273", "publisher": "Elsevier", "publication": "Neuron", "publication_date": "2015-02-04", "series_number": "3", "volume": "85", "issue": "3", "pages": "573-589" }, { "id": "authors:wnpx1-kdy11", "collection": "authors", "collection_id": "wnpx1-kdy11", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-150600571", "type": "article", "title": "Synaptic and circuit mechanisms promoting broadband transmission of olfactory stimulus dynamics", "author": [ { "family_name": "Nagel", "given_name": "Katherine I.", "orcid": "0000-0002-6701-3901", "clpid": "Nagel-K-I" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Wilson", "given_name": "Rachel I.", "clpid": "Wilson-R-I" } ], "abstract": "Sensory stimuli fluctuate on many timescales. However, short-term plasticity causes synapses to act as temporal filters, limiting the range of frequencies that they can transmit. How synapses in vivo might transmit a range of frequencies in spite of short-term plasticity is poorly understood. The first synapse in the Drosophila olfactory system exhibits short-term depression, but can transmit broadband signals. Here we describe two mechanisms that broaden the frequency characteristics of this synapse. First, two distinct excitatory postsynaptic currents transmit signals on different timescales. Second, presynaptic inhibition dynamically updates synaptic properties to promote accurate transmission of signals across a wide range of frequencies. Inhibition is transient, but grows slowly, and simulations reveal that these two features of inhibition promote broadband synaptic transmission. Dynamic inhibition is often thought to restrict the temporal patterns that a neuron responds to, but our results illustrate a different idea: inhibition can expand the bandwidth of neural coding.", "doi": "10.1038/nn.3895", "pmcid": "PMC4289142", "issn": "1097-6256", "publisher": "Nature Publishing Group", "publication": "Nature Neuroscience", "publication_date": "2015-01", "series_number": "1", "volume": "18", "issue": "1", "pages": "56-65" }, { "id": "authors:jk8bm-t5r21", "collection": "authors", "collection_id": "jk8bm-t5r21", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-153440112", "type": "article", "title": "Quantitative profiling of peptides from RNAs classified as noncoding", "author": [ { "family_name": "Prabakaran", "given_name": "Sudhakaran", "clpid": "Prabakaran-S" }, { "family_name": "Hemberg", "given_name": "Martin", "clpid": "Hemberg-M" }, { "family_name": "Chauhan", "given_name": "Ruchi", "clpid": "Chauhan-R" }, { "family_name": "Winter", "given_name": "Dominic", "clpid": "Winter-D" }, { "family_name": "Tweedie-Cullen", "given_name": "Ry Y.", "clpid": "Tweedie-Cullen-R-Y" }, { "family_name": "Dittrich", "given_name": "Christian", "clpid": "Dittrich-C" }, { "family_name": "Hong", "given_name": "Elizabeth", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Gunawardena", "given_name": "Jeremy", "clpid": "Gunawardena-J" }, { "family_name": "Steen", "given_name": "Hanno", "clpid": "Steen-H" }, { "family_name": "Kreiman", "given_name": "Gabriel", "clpid": "Kreiman-G" }, { "family_name": "Steen", "given_name": "Judith A.", "clpid": "Steen-J-A" } ], "abstract": "Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences\u2014including introns and several classes of noncoding RNAs (ncRNAs)\u2014do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here we use computational methods to identify the products of non-canonical translation in mouse neurons by analysing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from antisense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential.", "doi": "10.1038/ncomms6429", "pmcid": "PMC4416701", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2014-11", "series_number": "11", "volume": "5", "issue": "11", "pages": "Art. No. 5429" }, { "id": "authors:hxkey-c0m79", "collection": "authors", "collection_id": "hxkey-c0m79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-151634768", "type": "article", "title": "Olfactory Neuroscience: Normalization Is the Norm", "author": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Wilson", "given_name": "Rachel I.", "clpid": "Wilson-R-I" } ], "abstract": "A recent study shows that neural circuits from vertebrates and invertebrates use common strategies to stabilize odor representations across a wide range of concentrations.", "doi": "10.1016/j.cub.2013.10.056", "issn": "0960-9822", "publisher": "Cell Press", "publication": "Current Biology", "publication_date": "2013-12-16", "series_number": "24", "volume": "23", "issue": "24", "pages": "R1091-R1093" }, { "id": "authors:gftq0-61v62", "collection": "authors", "collection_id": "gftq0-61v62", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-152052536", "type": "article", "title": "Asymmetric neurotransmitter release enables rapid odour lateralization in Drosophila", "author": [ { "family_name": "Gaudry", "given_name": "Quentin", "clpid": "Gaudry-Q" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Kain", "given_name": "Jamey", "clpid": "Kain-J" }, { "family_name": "de Bivort", "given_name": "Benjamin L.", "clpid": "de-Biivort-B-L" }, { "family_name": "Wilson", "given_name": "Rachel I.", "clpid": "Wilson-R-I" } ], "abstract": "In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odours. Nevertheless, walking or flying Drosophila reportedly turn towards the antenna that is more strongly stimulated by odour. Here we show that each ORN spike releases approximately 40% more neurotransmitter from the axon branch ipsilateral to the soma than from the contralateral branch. As a result, when an odour activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and at a 30\u2009to\u200950% higher rate than contralateral neurons. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn towards the odour in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behaviour.", "doi": "10.1038/nature11747", "pmcid": "PMC3590906", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2013-01-17", "series_number": "7432", "volume": "493", "issue": "7432", "pages": "424-428" }, { "id": "authors:zhka2-38r94", "collection": "authors", "collection_id": "zhka2-38r94", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-154745989", "type": "article", "title": "Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection", "author": [ { "family_name": "Flavell", "given_name": "Steven W.", "clpid": "Flavell-S-J" }, { "family_name": "Kim", "given_name": "Tae-Kyung", "clpid": "Kim-Tae-Kyung" }, { "family_name": "Gray", "given_name": "Jesse M.", "clpid": "Gray-J-M" }, { "family_name": "Harmin", "given_name": "David A.", "clpid": "Harmin-D-A" }, { "family_name": "Hemberg", "given_name": "Martin", "clpid": "Hemberg-M" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Markenscoff-Papadimitriou", "given_name": "Eirene", "clpid": "Markenscoff-Papadimitriou-E" }, { "family_name": "Bear", "given_name": "Daniel M.", "clpid": "Bear-D-M" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" } ], "abstract": "Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development.", "doi": "10.1016/j.neuron.2008.11.029", "pmcid": "PMC2630178", "issn": "0896-6273", "publisher": "Elsevier", "publication": "Neuron", "publication_date": "2008-12-26", "series_number": "6", "volume": "60", "issue": "6", "pages": "1022-1038" }, { "id": "authors:96hn2-zq551", "collection": "authors", "collection_id": "96hn2-zq551", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-161441116", "type": "article", "title": "A Biological Function for the Neuronal Activity-Dependent Component of Bdnf Transcription in the Development of Cortical Inhibition", "author": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "McCord", "given_name": "Alejandra E.", "clpid": "McCord-A-E" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" } ], "abstract": "Neuronal activity-regulated gene expression has been suggested to be an important mediator of long-lasting, experience-dependent changes in the nervous system, but the activity-dependent component of gene transcription has never been selectively isolated and tested for its functional significance. Here, we demonstrate that introduction of a subtle knockin mutation into the mouse Bdnf gene that blocks the ability of the activity-regulated factor CREB to bind Bdnf promoter IV results in an animal in which the sensory experience-dependent induction of Bdnf expression is disrupted in the cortex. Neurons from these animals form fewer inhibitory synapses, have fewer spontaneous inhibitory quantal events, and exhibit reduced expression of inhibitory presynaptic markers in the cortex. These results indicate a specific requirement for activity-dependent Bdnf expression in the development of inhibition in the cortex and demonstrate that the activation of gene expression in response to experience-driven neuronal activity has important biological consequences in the nervous system.", "doi": "10.1016/j.neuron.2008.09.024", "pmcid": "PMC2873221", "issn": "0896-6273", "publisher": "Elsevier", "publication": "Neuron", "publication_date": "2008-11-26", "series_number": "4", "volume": "60", "issue": "4", "pages": "610-624" }, { "id": "authors:9cj5m-39y29", "collection": "authors", "collection_id": "9cj5m-39y29", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-162305172", "type": "article", "title": "Developmental axon pruning mediated by BDNF-p75NTR\u2013dependent axon degeneration", "author": [ { "family_name": "Singh", "given_name": "Karun K.", "clpid": "Singh-K-K" }, { "family_name": "Park", "given_name": "Katya J.", "clpid": "Park-K-J" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Kramer", "given_name": "Bianca M.", "clpid": "Kramer-B-M" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" }, { "family_name": "Kaplan", "given_name": "David R.", "clpid": "Kaplan-D-R" }, { "family_name": "Miller", "given_name": "Freda D.", "clpid": "Miller-F-D" } ], "abstract": "The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration.", "doi": "10.1038/nn.2114", "issn": "1097-6256", "publisher": "Nature Publishing Group", "publication": "Nature Neuroscience", "publication_date": "2008-06", "series_number": "6", "volume": "11", "issue": "6", "pages": "649-658" }, { "id": "authors:a1bes-1pg44", "collection": "authors", "collection_id": "a1bes-1pg44", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-163319702", "type": "article", "title": "Brain-Derived Neurotrophic Factor Expression and Respiratory Function Improve after Ampakine Treatment in a Mouse Model of Rett Syndrome", "author": [ { "family_name": "Ogier", "given_name": "Michael", "clpid": "Ogier-M" }, { "family_name": "Wang", "given_name": "Hong", "clpid": "Wang-Hong" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Wang", "given_name": "Qifang", "clpid": "Wang-Qifang" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" }, { "family_name": "Katz", "given_name": "David M.", "clpid": "Katz-D-M" } ], "abstract": "Rett syndrome (RTT) is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Although MeCP2 is thought to act as a transcriptional repressor of brain-derived neurotrophic factor (BDNF), Mecp2 null mice, which develop an RTT-like phenotype, exhibit progressive deficits in BDNF expression. These deficits are particularly significant in the brainstem and nodose cranial sensory ganglia (NGs), structures critical for cardiorespiratory homeostasis, and may be linked to the severe respiratory abnormalities characteristic of RTT. Therefore, the present study used Mecp2 null mice to further define the role of MeCP2 in regulation of BDNF expression and neural function, focusing on NG neurons and respiratory control. We find that mutant neurons express significantly lower levels of BDNF than wild-type cells in vitro, as in vivo, under both depolarizing and nondepolarizing conditions. However, BDNF levels in mutant NG cells can be increased by chronic depolarization in vitro or by treatment of Mecp2 null mice with CX546, an ampakine drug that facilitates activation of glutamatergic AMPA receptors. Ampakine-treated Mecp2 null mice also exhibit marked functional improvement, characterized by restoration of normal breathing frequency and minute volume. These data demonstrate that BDNF expression remains plastic in Mecp2 null mice and raise the possibility that ampakine compounds could be of therapeutic value in the treatment of RTT.", "doi": "10.1523/JNEUROSCI.1869-07.2007", "pmcid": "PMC6672830", "issn": "0270-6474", "publisher": "Society for Neuroscience", "publication": "Journal of Neuroscience", "publication_date": "2007-10-03", "series_number": "40", "volume": "27", "issue": "40", "pages": "10912-10917" }, { "id": "authors:62jar-fme34", "collection": "authors", "collection_id": "62jar-fme34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-164205825", "type": "article", "title": "Polarized Signaling Endosomes Coordinate BDNF-Induced Chemotaxis of Cerebellar Precursors", "author": [ { "family_name": "Zhou", "given_name": "Pengcheng", "clpid": "Zhou-Pengcheng" }, { "family_name": "Porcionatto", "given_name": "Marimelia", "clpid": "Porcionatto-M" }, { "family_name": "Pilapil", "given_name": "Mariecel", "clpid": "Pilapil-M" }, { "family_name": "Chen", "given_name": "Yicheng", "clpid": "Chen-Yicheng" }, { "family_name": "Choi", "given_name": "Yoojin", "clpid": "Choi-Yoojin" }, { "family_name": "Tolias", "given_name": "Kimberley F.", "clpid": "Tolias-K-F" }, { "family_name": "Bikoff", "given_name": "Jay B.", "clpid": "Bokoff-J-B" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" }, { "family_name": "Segal", "given_name": "Rosalind A.", "clpid": "Segal-R-A" } ], "abstract": "During development, neural precursors migrate in response to positional cues such as growth factor gradients. However, the mechanisms that enable precursors to sense and respond to such gradients are poorly understood. Here we show that cerebellar granule cell precursors (GCPs) migrate along a gradient of brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle trafficking is critical for this chemotactic process. Activation of TrkB, the BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient gradient. The BDNF gradient stimulates endocytosis of TrkB and associated signaling molecules, causing asymmetric accumulation of signaling endosomes at the subcellular location where BDNF concentration is maximal. Thus, regulated BDNF exocytosis and TrkB endocytosis enable precursors to polarize and migrate in a directed fashion along a shallow BDNF gradient.", "doi": "10.1016/j.neuron.2007.05.030", "pmcid": "PMC2661852", "issn": "0896-6273", "publisher": "Elsevier", "publication": "Neuron", "publication_date": "2007-07-05", "series_number": "1", "volume": "55", "issue": "1", "pages": "53-68" }, { "id": "authors:hw77m-h7e71", "collection": "authors", "collection_id": "hw77m-h7e71", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-165128774", "type": "article", "title": "Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation", "author": [ { "family_name": "Zhou", "given_name": "Zhaolan", "clpid": "Zhou-Zhaolan" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Cohen", "given_name": "Sonia", "clpid": "Cohen-S" }, { "family_name": "Zhao", "given_name": "Wen-ning", "clpid": "Zhao-Wen-ning" }, { "family_name": "Ho", "given_name": "Hsin-yi Henry", "clpid": "Ho-Hsin-yi-Henry" }, { "family_name": "Schmidt", "given_name": "Lauren", "clpid": "Schmidt-L" }, { "family_name": "Chen", "given_name": "Wen G.", "clpid": "Chen-Wen-G" }, { "family_name": "Lin", "given_name": "Yingxi", "clpid": "Lin-Yingxi" }, { "family_name": "Savner", "given_name": "Erin", "clpid": "Savner-E" }, { "family_name": "Griffith", "given_name": "Eric C.", "clpid": "Griffith-E-C" }, { "family_name": "Hu", "given_name": "Linda", "clpid": "Hu-Linda" }, { "family_name": "Steen", "given_name": "Judith A. J.", "clpid": "Steen-J-A-J" }, { "family_name": "Weitz", "given_name": "Charles J.", "clpid": "Weitz-C-J" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" } ], "abstract": "Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT.", "doi": "10.1016/j.neuron.2006.09.037", "pmcid": "PMC3962021", "issn": "0896-6273", "publisher": "Elsevier", "publication": "Neuron", "publication_date": "2006-10-19", "series_number": "2", "volume": "52", "issue": "2", "pages": "255-269" }, { "id": "authors:cdper-7pw60", "collection": "authors", "collection_id": "cdper-7pw60", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151005-170024822", "type": "article", "title": "Transcriptional control of cognitive development", "author": [ { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "West", "given_name": "Anne E.", "clpid": "West-A-E" }, { "family_name": "Greenberg", "given_name": "Michael E.", "clpid": "Greenberg-M-E" } ], "abstract": "Cognitive development is determined by both genetics and environment. One point of convergence of these two influences is the neural activity-dependent regulation of programs of gene expression that specify neuronal fate and function. Human genetic studies have linked several transcriptional regulators to neurodevelopmental disorders including mental retardation and autism spectrum disorders. Recent reports on two such factors, CREB-binding protein and methyl-CpG-binding protein 2, have begun to reveal how epigenetics and neuronal activity act to modulate the program of gene expression required for synaptic development and function.", "doi": "10.1016/j.conb.2005.01.002", "issn": "0959-4388", "publisher": "Elsevier", "publication": "Current Opinion in Neurobiology", "publication_date": "2005-02", "series_number": "1", "volume": "15", "issue": "1", "pages": "21-28" }, { "id": "authors:4adq6-hhc44", "collection": "authors", "collection_id": "4adq6-hhc44", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111017-105733837", "type": "article", "title": "A reporter for amyloid precursor protein \u03b3-secretase activity in Drosophila", "author": [ { "family_name": "Guo", "given_name": "Ming", "clpid": "Guo-Ming" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Fernandes", "given_name": "Jolene", "clpid": "Fernandes-J" }, { "family_name": "Zipursky", "given_name": "S. Larry", "clpid": "Zipursky-S-L" }, { "family_name": "Hay", "given_name": "Bruce A.", "clpid": "Hay-B-A" } ], "abstract": "A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as \u03b2-amyloid (A\u03b2) that is derived from the amyloid precursor protein (APP). A proteolytic activity called \u03b3-secretase cleaves APP in the transmembrane domain and is required for A\u03b2 generation. Aberrant \u03b3-secretase cleavage of APP underlies the majority of early onset, familial AD. \u03b3-Secretase resides in a large multi-protein complex, of which Presenilin, Nicastrin, APH-1 and PEN-2 are four essential components. Thus, identifying components and pathways by which the \u03b3-secretase activity is regulated is crucial to understanding the mechanisms underlying AD pathogenesis, and may provide new diagnostic tools and therapeutic targets. Here we describe the generation of Drosophila that act as living reporters of \u03b3-secretase activity in the fly eye. In these reporter flies the size of the eye correlates with the level of endogenous \u03b3-secretase activity, and is very sensitive to the levels of three genes required for APP \u03b3-secretase activity, presenilin, nicastrin and aph-1. Thus, these flies provide a sensitized system with which to identify other components of the \u03b3-secretase complex and regulators of its activity. We have used these flies to carry out a screen for mutations that suppress \u03b3-secretase activity and have identified a small chromosomal region that contains a gene or genes whose products may promote \u03b3-secretase activity.", "doi": "10.1093/hmg/ddg292", "issn": "0964-6906", "publisher": "Oxford University Press", "publication": "Human Molecular Genetics", "publication_date": "2003-10-15", "series_number": "20", "volume": "12", "issue": "20", "pages": "2669-2678" }, { "id": "authors:0rxsn-gex86", "collection": "authors", "collection_id": "0rxsn-gex86", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141117-132359069", "type": "article", "title": "Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors", "author": [ { "family_name": "Lois", "given_name": "Carlos", "orcid": "0000-0002-7305-2317", "clpid": "Lois-C" }, { "family_name": "Hong", "given_name": "Elizabeth J.", "orcid": "0000-0003-3866-418X", "clpid": "Hong-Elizabeth-J" }, { "family_name": "Pease", "given_name": "Shirley", "clpid": "Pease-Shirley-S" }, { "family_name": "Brown", "given_name": "Eric J.", "clpid": "Brown-Eric-J" }, { "family_name": "Baltimore", "given_name": "David", "orcid": "0000-0001-8723-8190", "clpid": "Baltimore-D" } ], "abstract": "Single-cell mouse embryos were infected in vitro with recombinant lentiviral vectors to generate transgenic mice carrying the green fluorescent protein (GFP) gene driven by a ubiquitously expressing promoter. Eighty percent of founder mice carried at least one copy of the transgene, and 90% of these expressed GFP at high levels. Progeny inherited the transgene(s) and displayed green fluorescence. Mice generated using lentiviral vectors with muscle-specific and T lymphocyte\u2013specific promoters expressed high levels of GFP only in the appropriate cell types. We have also generated transgenic rats that express GFP at high levels, suggesting that this technique can be used to produce other transgenic animal species.", "doi": "10.1126/science.1067081", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2002-02-01", "series_number": "5556", "volume": "295", "issue": "5556", "pages": "868-872" } ]