Publications

Highlights

(For a full list see below or go to Google Scholar)

A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior.

Wu, Yunming, Limei Ma, Kyle Duyck, Carter C. Long, Andrea Moran, Hayley Scheerer, Jillian Blanck, et al.

Neuron (2018)

Read the article for free at the link above through January 29, 2019

A Developmental Switch of Axon Targeting in the Continuously Regenerating Mouse Olfactory System

The mammalian olfactory system has the natural capacity to regenerate throughout the animal’s life span. Despite constant neurogenesis, olfactory sensory neurons project to precise, stereotypical positions in the brain. Here, we identify a critical period of olfactory sensory axon targeting during postnatal development in mouse. Perturbing axon projection beyond postnatal day 7 permanently disrupts targeting specificity of the sensory neurons. In addition, we find that the establishment of the convergence map requires perinatal sensory neurons. Late-born neurons appear to connect with prospective glomeruli based on homotypic interactions among neurons expressing the same odorant receptor. Our results reveal a developmental switch in axon guidance and a mechanism of circuit integration of adult-born neurons.

Ma, Limei, Yunming Wu, Qiang Qiu, Hayley Scheerer, Andrea Moran, and C. Ron Yu

Science 344, no. 6180 (2014); 194–97

Automated Analyses of Innate Olfactory Behaviors in Rodents

Olfaction based behavioral experiments are important for the investigation of sensory coding, perception, decision making and memory formation. The predominant experimental paradigms employ forced choice operant assays, which require associative learning and reinforced training. Animal performance in these assays not only reflects odor perception but also the confidence in decision making and memory. In this study, we describe a versatile and automated setup, “Poking-Registered Olfactory Behavior Evaluation System” (PROBES), which can be adapted to perform multiple olfactory assays. In addition to forced choice assays, we employ this system to examine animal’s innate ability for odor detection, discrimination and preference without elaborate training procedures. These assays provide quantitative measurements of odor discrimination and robust readouts of odor preference. Using PROBES, we find odor detection thresholds are at lower concentrations in naïve animals than those determined by forced choice assays. PROBES-based automated assays provide an efficient way of analyzing innate odor-triggered behaviors.

Qiu, Qiang, Aaron Scott, Hayley Scheerer, Nirjal Sapkota, Daniel K. Lee, Limei Ma, and C. Ron Yu

PloS One 9, no. 4 (2014); e93468

Integrated action of pheromone signals in promoting courtship behavior in male mice

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior.

Haga-Yamanaka, Sachiko, Limei Ma, Jie He, Qiang Qiu, Luke D. Lavis, Loren L. Looger, and C. Ron Yu

ELife 3 (2014); e03025

Calcium Imaging of Vomeronasal Organ Response Using Slice Preparations from Transgenic Mice Expressing G-CaMP2

The vomeronasal organ (VNO) in vertebrate animals detects pheromones and interspecies chemical signals. We describe in this chapter a Ca(2+) imaging approach using transgenic mice that express the genetically encoded Ca(2+) sensor G-CaMP2 in VNO tissue. This approach allows us to analyze the complex patterns of the vomeronasal neuron response to large number of chemosensory stimuli.

Yu, C. Ron

Methods in Molecular Biology 1068 (2013); 211–20

Distributed Representation of Chemical Features and Tunotopic Organization of Glomeruli in the Mouse Olfactory Bulb

In the mammalian brain, similar features of the sensory stimuli are often represented in proximity in the sensory areas. However, how chemical features are represented in the olfactory bulb has been controversial. Questions have been raised as to whether specific chemical features of the odor molecules are represented by spatially clustered olfactory glomeruli. Using a sensitive probe, we have analyzed the glomerular response to large numbers of odorants at single glomerulus resolution. Contrary to the general view, we find that the representation of chemical features is spatially distributed in the olfactory bulb with no discernible chemotopy. Moreover, odor-evoked pattern of activity does not correlate directly with odor structure in general. Despite the lack of spatial clustering or preference with respect to chemical features, some structurally related odors can be similarly represented by ensembles of spatially distributed glomeruli, providing an explanation of their perceptual similarity. Whereas there is no chemotopic organization, and the glomeruli are tuned to odors from multiple classes, we find that the glomeruli are hierarchically arranged into clusters according to their odor-tuning similarity. This tunotopic arrangement provides a framework to understand the spatial organization of the glomeruli that conforms to the organizational principle found in other sensory systems.

Ma, Limei, Qiang Qiu, Stephen Gradwohl, Aaron Scott, Elden Q. Yu, Richard Alexander, Winfried Wiegraebe, and C. Ron Yu

Proc. Natl. Acad. Sci. U.S.A. no. 109 (2012); 5481-5486

Paradoxical Contribution of SK3 and GIRK Channels to the Activation of Mouse Vomeronasal Organ

The vomeronasal organ (VNO) is essential for intraspecies communication in many terrestrial vertebrates. The ionic mechanisms of VNO activation remain unclear. We found that the calcium-activated potassium channel SK3 and the G protein-activated potassium channel GIRK are part of an independent pathway for VNO activation. In slice preparations, the potassium channels attenuated inward currents carried by TRPC2 and calcium-activated chloride channels (CACCs). In intact tissue preparations, paradoxically, the potassium channels enhanced urine-evoked inward currents. This discrepancy resulted from the loss of a high concentration of lumenal potassium, which enabled the influx of potassium ions to depolarize the VNO neurons in vivo. Both Sk3 (also known as Kcnn3) and Girk1 (also known as Kcnj3) homozygous null mice showed deficits in mating and aggressive behaviors, and the deficiencies in Sk3(-/-) mice were exacerbated by Trpc2 knockout. Our results suggest that VNO activation is mediated by TRPC2, CACCs and two potassium channels, all of which contributed to the in vivo depolarization of VNO neurons.

Kim, SangSeong, Limei Ma, Kristi L. Jensen, Michelle M. Kim, Chris T. Bond, John P. Adelman, and C. Ron Yu

Nature Neuroscience 15, no. 9 (2012); 1236–44

Imaging Neuronal Responses in Slice Preparations of Vomeronasal Organ Expressing a Genetically Encoded Calcium Sensor

The vomeronasal organ (VNO) detects intraspecies chemical signals that convey social and reproductive information. We have performed Ca2+ imaging experiments using transgenic mice expressing G-CaMP2 in VNO tissue. This approach allows us to analyze the complicated response patterns of the vomeronasal neurons to large numbers of pheromone stimuli.

Ma, Limei, Sachiko Haga-Yamanaka, Qingfeng Elden Yu, Qiang Qiu, SangSeong Kim, and C. Ron Yu

JoVE (Journal of Visualized Experiments), no. 58 (2011); e3404

Requirement of Calcium-Activated Chloride Channels in the Activation of Mouse Vomeronasal Neurons

In terrestrial vertebrates, the vomeronasal organ (VNO) detects and transduces pheromone signals. VNO activation is thought to be mediated by the transient receptor potential C2 (TRPC2) channel. The aberrant behavioural phenotypes observed in TRPC2-/- mice are generally attributed to the lost VNO function. Recently, calcium-activated chloride channels have been shown to contribute to VNO activation. Here we show that CACCs can be activated in VNO slice preparations from the TRPC2-/- mice and this activation is blocked by pharmacological agents that inhibit intracellular Ca(2+) release. Urine-evoked Cl(-) current is sufficient to drive spiking changes in VNO neurons from both wild-type (WT) and TRPC2-/- mice. Moreover, blocking Cl(-) conductance essentially abolishes VNO activation in WT neurons. These results suggest a TRPC2-independent signalling pathway in the VNO and the requirement of calcium-activated chloride channels currents to mediate pheromone activation. Our data further suggest that TRPC2-/- mice retain partial VNO function.

Kim, SangSeong, Limei Ma, and C. Ron Yu

Nature Communications 2 (2011); 365

Distinct Signals Conveyed by Pheromone Concentrations to the Mouse Vomeronasal Organ

In mammalian species, detection of pheromone cues by the vomeronasal organ (VNO) at different concentrations can elicit distinct behavioral responses and endocrine changes. It is not well understood how concentration-dependent activation of the VNO impacts innate behaviors. In this study, we find that, when mice investigate the urogenital areas of a conspecific animal, the urinary pheromones can reach the VNO at a concentration of ∼1% of that in urine. At this level, urinary pheromones elicit responses from a subset of cells that are tuned to sex-specific cues and provide unambiguous identification of the sex and strain of animals. In contrast, low concentrations of urine do not activate these cells. Strikingly, we find a population of neurons that is only activated by low concentrations of urine. The properties of these neurons are not found in neurons responding to putative single-compound pheromones. Additional analyses show that these neurons are masked by high-concentration pheromones. Thus, an antagonistic interaction in natural pheromones results in the activation of distinct populations of cells at different concentrations. The differential activation is likely to trigger different downstream circuitry and underlies the concentration-dependent pheromone perception.

He, Jie, Limei Ma, Sangseong Kim, Joel Schwartz, Michael Santilli, Christopher Wood, Michael H. Durnin, and C. Ron Yu

Journal of Neuroscience 30, no. 22 (2010); 7473–83

Encoding Gender and Individual Information in the Mouse Vomeronasal Organ

The mammalian vomeronasal organ detects complex chemical signals that convey information about gender, strain, and the social and reproductive status of an individual. How these signals are encoded is poorly understood. We developed transgenic mice expressing the calcium indicator G-CaMP2 and analyzed population responses of vomeronasal neurons to urine from individual animals. A substantial portion of cells was activated by either male or female urine, but only a small population of cells responded exclusively to gender-specific cues shared across strains and individuals. Female cues activated more cells and were subject to more complex hormonal regulations than male cues. In contrast to gender, strain and individual information was encoded by the combinatorial activation of neurons such that urine from different individuals activated distinctive cell populations. Mice can recognize the pheromones from individual mice through unique patterns of receptor activation in the vomeronasal organ. Mice can recognize the pheromones from individual mice through unique patterns of receptor activation in the vomeronasal organ.

He, Jie, Limei Ma, SangSeong Kim, Junichi Nakai, and C. Ron Yu

Science 320, no. 5875 (2008); 535–38

 

Full List

A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period
Wu, Yunming, Limei Ma, Kyle Duyck, Carter C. Long, Andrea Moran, Hayley Scheerer, Jillian Blanck, et al.
Neuron (2018)

A Developmental Switch of Axon Targeting in the Continuously Regenerating Mouse Olfactory System
Ma, Limei, Yunming Wu, Qiang Qiu, Hayley Scheerer, Andrea Moran, and C. Ron Yu
Science 344, no. 6180 (2014); 194–97

Automated Analyses of Innate Olfactory Behaviors in Rodents
Qiu, Qiang, Aaron Scott, Hayley Scheerer, Nirjal Sapkota, Daniel K. Lee, Limei Ma, and C. Ron Yu
PloS One 9, no. 4 (2014); e93468

Integrated action of pheromone signals in promoting courtship behavior in male mice
Haga-Yamanaka, Sachiko, Limei Ma, Jie He, Qiang Qiu, Luke D. Lavis, Loren L. Looger, and C. Ron Yu
ELife 3 (2014); e03025

Calcium Imaging of Vomeronasal Organ Response Using Slice Preparations from Transgenic Mice Expressing G-CaMP2
Yu, C. Ron
Methods in Molecular Biology 1068 (2013); 211–20

Distributed Representation of Chemical Features and Tunotopic Organization of Glomeruli in the Mouse Olfactory Bulb
Ma, Limei, Qiang Qiu, Stephen Gradwohl, Aaron Scott, Elden Q. Yu, Richard Alexander, Winfried Wiegraebe, and C. Ron Yu
Proc. Natl. Acad. Sci. U.S.A. no. 109 (2012); 5481-5486

Paradoxical Contribution of SK3 and GIRK Channels to the Activation of Mouse Vomeronasal Organ
Kim, SangSeong, Limei Ma, Kristi L. Jensen, Michelle M. Kim, Chris T. Bond, John P. Adelman, and C. Ron Yu
Nature Neuroscience 15, no. 9 (2012); 1236–44

Imaging Neuronal Responses in Slice Preparations of Vomeronasal Organ Expressing a Genetically Encoded Calcium Sensor
Ma, Limei, Sachiko Haga-Yamanaka, Qingfeng Elden Yu, Qiang Qiu, SangSeong Kim, and C. Ron Yu
JoVE (Journal of Visualized Experiments), no. 58 (2011); e3404

Requirement of Calcium-Activated Chloride Channels in the Activation of Mouse Vomeronasal Neurons
Kim, SangSeong, Limei Ma, and C. Ron Yu
Nature Communications 2 (2011); 365

Distinct Signals Conveyed by Pheromone Concentrations to the Mouse Vomeronasal Organ
He, Jie, Limei Ma, Sangseong Kim, Joel Schwartz, Michael Santilli, Christopher Wood, Michael H. Durnin, and C. Ron Yu
Journal of Neuroscience 30, no. 22 (2010); 7473–83

Encoding Gender and Individual Information in the Mouse Vomeronasal Organ
He, Jie, Limei Ma, SangSeong Kim, Junichi Nakai, and C. Ron Yu
Science 320, no. 5875 (2008); 535–38

A Family of GFP-like Proteins with Different Spectral Properties in Lancelet Branchiostoma Floridae
Baumann, Diana, Malcolm Cook, Limei Ma, Arcady Mushegian, Erik Sanders, Joel Schwartz, and C. Ron Yu
Biology Direct 3 (2008); 28

Encoding Gender and Individual Information in the Mouse Vomeronasal Organ
He, Jie, Limei Ma, Sangseong Kim, Junichi Nakai, and C. Ron Yu
Science 320, no. 5875 (2008); 535–38

Distinct Signals Conveyed by Pheromone Concentrations to the Mouse Vomeronasal Organ
He, Jie, Limei Ma, Sangseong Kim, Joel Schwartz, Michael Santilli, Christopher Wood, Michael H. Durnin, and C. Ron Yu
Journal of Neuroscience 30, no. 22 (2010); 7473–83.

Requirement of Calcium-Activated Chloride Channels in the Activation of Mouse Vomeronasal Neurons
Kim, SangSeong, Limei Ma, and C. Ron Yu
Nature Communications 2 (2011); 365

Imaging Neuronal Responses in Slice Preparations of Vomeronasal Organ Expressing a Genetically Encoded Calcium Sensor
Ma, Limei, Sachiko Haga-Yamanaka, Qingfeng Elden Yu, Qiang Qiu, Sangseong Kim, and C. Ron Yu
https://doi.org/10.3791/3404

Distributed Representation of Chemical Features and Tunotopic Organization of Glomeruli in the Mouse Olfactory Bulb
Ma, Limei, Qiang Qiu, Stephen Gradwohl, Aaron Scott, Elden Q. Yu, Richard Alexander, Winfried Wiegraebe, and C. Ron Yu
Proc. Natl. Acad. Sci. U.S.A. no. 109 (2012); 5481-5486

Paradoxical Contribution of SK3 and GIRK Channels to the Activation of Mouse Vomeronasal Organ
Kim, SangSeong, Limei Ma, Kristi L. Jensen, Michelle M. Kim, Chris T. Bond, John P. Adelman, and C. Ron Yu
Nature Neuroscience 15, no. 9 (2012); 1236–44

Calcium Imaging of Vomeronasal Organ Response Using Slice Preparations from Transgenic Mice Expressing G-CaMP2
Yu, C. Ron
Methods in Molecular Biology 1068 (2013); 211–20

A Developmental Switch of Axon Targeting in the Continuously Regenerating Mouse Olfactory System
Ma, Limei, Yunming Wu, Qiang Qiu, Hayley Scheerer, Andrea Moran, and C. Ron Yu
Science 344, no. 6180 (2014); 194–97

Automated Analyses of Innate Olfactory Behaviors in Rodents
Qiu, Qiang, Aaron Scott, Hayley Scheerer, Nirjal Sapkota, Daniel K. Lee, Limei Ma, and C. Ron Yu
PloS One 9, no. 4 (2014); e93468

Integrated Action of Pheromone Signals in Promoting Courtship Behavior in Male Mice
Haga-Yamanaka, Sachiko, Limei Ma, Jie He, Qiang Qiu, Luke D. Lavis, Loren L. Looger, and C. Ron Yu
ELife 3 (2014); e03025

Intracellular Chloride Concentration of the Mouse Vomeronasal Neuron
Kim, SangSeong, Limei Ma, Jay Unruh, Sean McKinney, and C. Ron Yu
MC Neuroscience 16 (2015); 90

Tuning Properties and Dynamic Range of Type 1 Vomeronasal Receptors
Haga-Yamanaka, Sachiko, Limei Ma, and C. Ron Yu
Frontiers in Neuroscience 9 (2015); 244

TRICK or TRP? What Trpc2(-/-) Mice Tell Us about Vomeronasal Organ Mediated Innate Behaviors
Yu, C. Ron
Frontiers in Neuroscience 9 (2015); 221

Pronounced Strain-Specific Chemosensory Receptor Gene Expression in the Mouse Vomeronasal Organ
Duyck, Kyle, Vasha DuTell, Limei Ma, Ariel Paulson, and C. Ron Yu
BMC Genomics 18, no. 1 (2017); 965

A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period
Wu, Yunming, Limei Ma, Kyle Duyck, Carter C. Long, Andrea Moran, Hayley Scheerer, Jillian Blanck, et al.
Neuron (2018)