Yihe received her Ph.D. degree in Physiology in 2020 from University of Wisconsin-Madison. Her thesis work focused on interrogating hippocampal microcircuits with a hybrid genetically-encoded voltage indicator. In 2021, Yihe joined the Giardino lab as a postdoctoral scholar under the co-mentorship of Dr. William Giardino and Dr. Julie Kauer. At the Giardino lab, Yihe aims to leverage imaging techniques and slice electrophysiology to investigate the underlying mechanism of addiction and sleep disorders in BNST neuropeptide circuits.
Honors & Awards
Biological Sciences Scholar Award, University of Wisconsin-Madison (2012)
Bachelor of Science, Peking University (2012)
Doctor of Philosophy, University of Wisconsin Madison (2020)
B.S., Peking University, Biological Science, Psychology (2012)
Ph.D., University of Wisconsin-Madison, Physiology (2020)
Current Research and Scholarly Interests
Systems & Circuits Neuroscience, Addiction, Stress, Sleep, Plasticity, Imaging
Optical Studies of Action Potential Dynamics with hVOS probes.
Current opinion in biomedical engineering
2019; 12: 51–58
The detection of action potentials and the characterization of their waveform represent basic benchmarks for evaluating optical sensors of voltage. The effectiveness of a voltage sensor in reporting action potentials will determine its usefulness in voltage imaging experiments designed for the study of neural circuitry. The hybrid voltage sensor (hVOS) technique is based on a sensing mechanism with a rapid response to voltage changes. hVOS imaging is thus well suited for optical studies of action potentials. This technique detects action potentials in intact brain slices with an excellent signal-to-noise ratio. These optical action potentials recapitulate voltage recordings with high temporal fidelity. In different genetically-defined types of neurons targeted by cre-lox technology, hVOS recordings of action potentials recapitulate the expected differences in duration. Furthermore, by targeting an hVOS probe to axons, imaging experiments can follow action potential propagation and document dynamic changes in waveform resulting from use-dependent plasticity.
View details for DOI 10.1016/j.cobme.2019.09.007
View details for PubMedID 32864524
View details for PubMedCentralID PMC7449517
Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor
JOURNAL OF NEUROSCIENCE
2017; 37 (38): 9305–19
Genetically encoded voltage indicators create an opportunity to monitor electrical activity in defined sets of neurons as they participate in the complex patterns of coordinated electrical activity that underlie nervous system function. Taking full advantage of genetically encoded voltage indicators requires a generalized strategy for targeting the probe to genetically defined populations of cells. To this end, we have generated a mouse line with an optimized hybrid voltage sensor (hVOS) probe within a locus designed for efficient Cre recombinase-dependent expression. Crossing this mouse with Cre drivers generated double transgenics expressing hVOS probe in GABAergic, parvalbumin, and calretinin interneurons, as well as hilar mossy cells, new adult-born neurons, and recently active neurons. In each case, imaging in brain slices from male or female animals revealed electrically evoked optical signals from multiple individual neurons in single trials. These imaging experiments revealed action potentials, dynamic aspects of dendritic integration, and trial-to-trial fluctuations in response latency. The rapid time response of hVOS imaging revealed action potentials with high temporal fidelity, and enabled accurate measurements of spike half-widths characteristic of each cell type. Simultaneous recording of rapid voltage changes in multiple neurons with a common genetic signature offers a powerful approach to the study of neural circuit function and the investigation of how neural networks encode, process, and store information.SIGNIFICANCE STATEMENT Genetically encoded voltage indicators hold great promise in the study of neural circuitry, but realizing their full potential depends on targeting the sensor to distinct cell types. Here we present a new mouse line that expresses a hybrid optical voltage sensor under the control of Cre recombinase. Crossing this line with Cre drivers generated double-transgenic mice, which express this sensor in targeted cell types. In brain slices from these animals, single-trial hybrid optical voltage sensor recordings revealed voltage changes with submillisecond resolution in multiple neurons simultaneously. This imaging tool will allow for the study of the emergent properties of neural circuits and permit experimental tests of the roles of specific types of neurons in complex circuit activity.
View details for DOI 10.1523/JNEUROSCI.1363-17.2017
View details for Web of Science ID 000411231700016
View details for PubMedID 28842412
View details for PubMedCentralID PMC5607471
Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor
2017; 4 (4)
The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.
View details for DOI 10.1523/ENEURO.0146-17.2017
View details for Web of Science ID 000407416400013
View details for PubMedID 28785728
View details for PubMedCentralID PMC5526655
Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor
JOURNAL OF NEUROPHYSIOLOGY
2015; 113 (4): 1249–59
Genetically encoded voltage sensors expand the optogenetics toolkit into the important realm of electrical recording, enabling researchers to study the dynamic activity of complex neural circuits in real time. However, these probes have thus far performed poorly when tested in intact neural circuits. Hybrid voltage sensors (hVOS) enable the imaging of voltage by harnessing the resonant energy transfer that occurs between a genetically encoded component, a membrane-tethered fluorescent protein that serves as a donor, and a small charged molecule, dipicrylamine, which serves as an acceptor. hVOS generates optical signals as a result of voltage-induced changes in donor-acceptor distance. We expressed the hVOS probe in mouse brain by in utero electroporation and in transgenic mice with a neuronal promoter. Under conditions favoring sparse labeling we could visualize single-labeled neurons. hVOS imaging reported electrically evoked fluorescence changes from individual neurons in slices from entorhinal cortex, somatosensory cortex, and hippocampus. These fluorescence signals tracked action potentials in individual neurons in a single trial with excellent temporal fidelity, producing changes that exceeded background noise by as much as 16-fold. Subthreshold synaptic potentials were detected in single trials in multiple distinct cells simultaneously. We followed signal propagation between different cells within one field of view and between dendrites and somata of the same cell. hVOS imaging thus provides a tool for high-resolution recording of electrical activity from genetically targeted cells in intact neuronal circuits.
View details for DOI 10.1152/jn.00691.2014
View details for Web of Science ID 000349720600019
View details for PubMedID 25411462
View details for PubMedCentralID PMC4329433