About

We are interested in tackling basic and translational questions about how the mammalian nervous system encodes thermal sensations

Research topics

• Biology
• Sociology
• Social Science
• Engineering ethics
• Environmental ethics
• Chemistry
• Gender studies
• Neuroscience
• Genetics

Selected publications

• eLife Assessment: Remote automated delivery of mechanical stimuli coupled to brain recordings in behaving mice

  2025-10-17

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

• eLife Assessment: GPR30 in spinal cholecystokinin-positive neurons modulates neuropathic pain

  2025-12-04

  peer-reviewOpen access1st authorCorresponding

  Neuropathic pain, a major health problem affecting 7-10% of the global population, lacks effective treatment due to its elusive mechanisms. Cholecystokinin-positive (CCK+) neurons in the spinal dorsal horn (SDH) are critical for neuropathic pain, yet the underlying molecular mechanisms remain unclear. Here, we show that the membrane estrogen receptor G-protein coupled estrogen receptor (GPER/GPR30) in spinal neurons was significantly upregulated in chronic constriction injury (CCI) mice and that inhibition of GPR30 in CCK+ neurons reversed CCI-induced neuropathic pain. Furthermore, GPR30 in spinal CCK+ neurons was essential for the enhancement of AMPA-mediated excitatory synaptic transmission in CCI mice. Moreover, GPR30 was expressed in spinal CCK+ neurons that received direct projection from the primary sensory cortex (S1-SDH). Chemogenetic inhibition of S1-SDH post-synaptic neurons alleviated CCI-induced neuropathic pain. Conversely, chemogenetic activation of these neurons mimicked neuropathic pain symptoms, which were attenuated by spinal inhibition of GPR30. Finally, we confirmed that GPR30 in S1-SDH post-synaptic neurons was required for CCI-induced neuropathic pain. Taken together, our findings suggest that GPR30 in spinal CCK+ neurons and S1-SDH postsynaptic neurons is pivotal for neuropathic pain, thereby representing a promising therapeutic target for neuropathic pain.

  PublisherDOI

• Activity-driven proprioceptive synaptic refinement in the developing spinal cord by complement signaling mechanisms

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-24

  preprintOpen accessSenior authorCorresponding

  Abstract Proprioceptive group Ia afferents detect muscle stretch to guide effortless and purposeful movement and make monosynaptic connections with spinal α-motor neurons to mediate reflexes, such as the stretch reflex. It is thought that proprioceptive Ia afferents target motor neurons of the same spinal segment; yet, how this specificity, if any, is established during early development is unknown. Using ex vivo spinal cord electrophysiology preparations from neonatal mice of both sexes, we identified a developmental period during which proprioceptive la afferents evoke both segmental and intersegmental responses at monosynaptic latencies. We provide anatomical evidence that motor neurons in the lumbar segment 4 (L4) receive direct input from proprioceptive Ia afferents in L5 during early postnatal development. Intersegmental responses (L4/L5) were prominent at postnatal days (P) 4–7 but were virtually absent by P11–13. To test the role of proprioceptor activity on segmental specification, we analyzed Na V 1.6 conditional knockout mice (Na V 1.6 cKO ), in which proprioceptor signaling is impaired, and found that intersegmental responses persist up to P11–13 but were absent in age-matched floxed controls. We predict this is due to impaired activation of complement signaling pathways, as Na V 1.6 cKO mice showed reduced C1qA expression in the ventral spinal cord at P9. Consistent with this, C1qA knockout mice also retain intersegmental responses at P11–13. Collectively, these findings identify an important postnatal window during which segmental specificity of proprioceptive circuits emerges and suggest that proprioceptor activity induces C1qA-mediated elimination of excessive intersegmental connectivity.

  PublisherOA PDFDOI

• eLife Assessment: Precision cutaneous stimulation in freely moving mice

  2025-04-14

  peer-reviewOpen access1st authorCorresponding

  Somatosensation connects animals to their immediate environment, shaping critical behaviors essential for adaptation, learning, and survival. Probing the relationships between somatosensory inputs and behavior in mice presents substantial challenges, primarily due to the practical difficulties of delivering stimuli to the skin in moving mice. To address this problem, we have developed a system for precise cutaneous stimulation of mice as they walk and run through environments. The system employs real-time body part tracking and targeted optical stimuli, offering precision while preserving the naturalistic context of the behaviors studied to overcome the traditional trade-offs between precision and animal behavior. We demonstrate the system across nociceptive testing conducted in standard small chambers to behavior in large complex environments, such as mazes. We observed that cutaneous inputs evoke rapid responses, which modify behavior when stimuli are applied during motion. This system provides a means to explore the diverse and integrative nature of somatosensation, from reflexes to decision-making, in naturalistic settings.

  PublisherDOI

• Juneteenth in STEMM and the barriers to equitable science

  UNC Libraries · 2025-03-19

  articleOpen access
  PublisherDOI

• Differential encoding of mammalian proprioception by voltage-gated sodium channels

  Science Advances · 2025-01-08 · 6 citations

  articleOpen accessSenior authorCorresponding

  Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the essential nature of proprioceptive signaling in daily life, the mechanisms governing proprioceptor activity are poorly understood. Here, we identified nonredundant roles for two voltage-gated sodium channels (Na V s), Na V 1.1 and Na V 1.6, in mammalian proprioception. Deletion of Na V 1.6 in somatosensory neurons (Na V 1.6 cKO mice) causes severe motor deficits accompanied by loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target Na V 1.1 (Na V 1.1 cKO ). In Na V 1.6 cKO animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in Na V 1.1 cKO mice. We attribute the differential contributions of Na V 1.1 and Na V 1.6 to distinct cellular localization patterns. Collectively, we provide evidence that Na V s uniquely shape neural signaling within a somatosensory modality.

  PublisherDOI

• eLife Assessment: Remote automated delivery of mechanical stimuli coupled to brain recordings in behaving mice

  2025-09-08

  peer-reviewOpen access1st authorCorresponding

  The canonical framework for testing pain and mechanical sensitivity in rodents is manual delivery of stimuli to the paw. However, this approach is time consuming, produces variability in results, requires significant training, and is ergonomically unfavorable to the experimenter. To circumvent limitations in manual delivery of stimuli, we have created a device called the ARM (Automated Reproducible Mechano-stimulator). Built using a series of linear stages, cameras, and stimulus holders, the ARM is more accurate at hitting the desired target, delivers stimuli faster, and decreases variability in delivery of von Frey hair filaments. We demonstrate that the ARM can be combined with traditional measurements of pain behavior and automated machine-learning based pipelines. Importantly, the ARM enables remote testing of mice with experimenters outside the testing room. Using remote testing, we found that mice habituated more quickly when an experimenter was not present and experimenter presence leads to significant sex-dependent differences in paw withdrawal and pain associated behaviors. Lastly, to demonstrate the utility of the ARM for neural circuit dissection of pain mechanisms, we combined the ARM with cellular-resolved microendoscopy in the amygdala, linking stimulus, behavior, and brain activity of amygdala neurons that encode negative pain states. Taken together, the ARM improves speed, accuracy, and robustness of mechanical pain assays and can be combined with automated pain detection systems and brain recordings to map central control of pain.

  PublisherDOI

• eLife Assessment: GPR30 in spinal cholecystokinin-positive neurons modulates neuropathic pain

  2025-10-03

  peer-reviewOpen access1st authorCorresponding

  Neuropathic pain, a major health problem affecting 7-10% of the global population, lacks effective treatment due to its elusive mechanisms. Cholecystokinin-positive (CCK+) neurons in the spinal dorsal horn (SDH) are critical for neuropathic pain, yet the underlying molecular mechanisms remain unclear. Here, we show that the membrane estrogen receptor G-protein coupled estrogen receptor (GPER/GPR30) in spinal neurons was significantly upregulated in chronic constriction injury (CCI) mice and that inhibition of GPR30 in CCK+ neurons reversed CCI-induced neuropathic pain. Furthermore, GPR30 in spinal CCK+ neurons was essential for the enhancement of AMPA-mediated excitatory synaptic transmission in CCI mice. Moreover, GPR30 was expressed in spinal CCK+ neurons that received direct projection from the primary sensory cortex (S1-SDH). Chemogenetic inhibition of S1-SDH post-synaptic neurons alleviated CCI-induced neuropathic pain. Conversely, chemogenetic activation of these neurons mimicked neuropathic pain symptoms, which were attenuated by spinal inhibition of GPR30. Finally, we confirmed that GPR30 in S1-SDH post-synaptic neurons was required for CCI-induced neuropathic pain. Taken together, our findings suggest that GPR30 in spinal CCK+ neurons is pivotal for neuropathic pain and GPR30 mediates descending facilitation by corticospinal direct projections, thereby representing a promising therapeutic target for neuropathic pain.

  PublisherDOI

• Thermal escape box: A cost-benefit evaluation paradigm for investigating thermosensation and thermal pain

  Neurobiology of Pain · 2024-01-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  Thermosensation, the ability to detect and estimate temperature, is an evolutionarily conserved process that is essential for survival. Thermosensing is impaired in various pain syndromes, resulting in thermal allodynia, the perception of an innocuous temperature as painful, or thermal hyperalgesia, an exacerbated perception of a painful thermal stimulus. Several behavioral assays exist to study thermosensation and thermal pain in rodents, however, most rely on reflexive withdrawal responses or the subjective quantification of spontaneous nocifensive behaviors. Here, we created a new apparatus, the thermal escape box, which can be attached to temperature-controlled plates and used to assess temperature-dependent effort-based decision-making. The apparatus consists of a light chamber with an opening that fits around temperature-controlled plates, and a small entryway into a dark chamber. A mouse must choose to stay in a brightly lit aversive area or traverse the plates to escape to the enclosed dark chamber. We quantified escape latencies of adult C57Bl/6 mice at different plate temperatures from video recordings and found they were significantly longer at 5 °C, 18 °C, and 52 °C, compared to 30 °C, a mouse’s preferred ambient temperature. Differences in escape latencies were abolished in male Trpm8−/− mice and in male Trpv1−/− animals. Finally, we show that chronic constriction injury procedures or oxaliplatin treatement significantly increased escape latencies at cold temperatures compared to controls, the later of which was prevented by the analgesic meloxicam. This demonstrates the utility of this assay in detecting cold pain. Collectively, our study has identified a new and effective tool that uses cost-benefit valuations to study thermosensation and thermal pain.

  PublisherDOI

• SanPy: Software for the analysis and visualization of whole-cell current-clamp recordings

  Biophysical Journal · 2024-02-27 · 2 citations

  articleOpen access

  The analysis of action potentials and other membrane voltage fluctuations provides a powerful approach for interrogating the function of excitable cells. However, a major bottleneck in the interpretation of this critical data is the lack of intuitive, agreed-upon software tools for its analysis. Here, we present SanPy, an open-source and freely available software package for the analysis and exploration of whole-cell current-clamp recordings written in Python. SanPy provides a robust computational engine with an application programming interface. Using this, we have developed a cross-platform desktop application with a graphical user interface that does not require programming. SanPy is designed to extract common parameters from action potentials, including threshold time and voltage, peak, half-width, and interval statistics. In addition, several cardiac parameters are measured, including the early diastolic duration and rate. SanPy is built to be fully extensible by providing a plugin architecture for the addition of new file loaders, analysis, and visualizations. A key feature of SanPy is its focus on quality control and data exploration. In the desktop interface, all plots of the data and analysis are linked, allowing simultaneous data visualization from different dimensions with the goal of obtaining ground-truth analysis. We provide documentation for all aspects of SanPy, including several use cases and examples. To test SanPy, we performed analysis on current-clamp recordings from heart and brain cells. Taken together, SanPy is a powerful tool for whole-cell current-clamp analysis and lays the foundation for future extension by the scientific community.

  PublisherOA PDFDOI

Frequent coauthors

• Ellen A. Lumpkin

  University of California, Berkeley

  11 shared

• Cheyanne M. Lewis

  University of California, Davis

  10 shared

• Cyrrus M. Espino

  University of California, Davis

  7 shared

• Darik A. O’Neil

  Columbia University Irving Medical Center

  6 shared

• Kaylee M Wells

  Marine Biological Laboratory

  6 shared

• Katherine Wilkinson

  San Jose State University

  5 shared

• Phuong T. Nguyen

  University of California, Davis

  5 shared

• Serena Ortiz

  San Jose State University

  5 shared

Labs

• Griffith LabPI