The hybrid voltage sensor (hVOS) technique enables researchers to use green fluorescent protein and other fluorescent proteins to image membrane potential. Because hVOS probes are encoded by DNA, genetic techniques can be used to target them to specific types of cells. This project will develop mice with hVOS probes targeted to specific types of neurons in the mouse brain. Animals will be developed with hVOS probes expressed in a wide variety of brain regions and cell types. Animals will also be developed that can be used to target very specific populations of cells. Slices of brain prepared from these animals will be very useful in imaging experiments. Essentially any brain region and any nerve cell type will be accessible to studies using the strategy advanced in this work. With these animals researchers will be able to study the electrical activity of large numbers of cells simultaneously. A hVOS probe developed in this laboratory was found to preferentially target axons. Animals expressing this hVOS probe will be useful in general studies of axonal excitability.

Public Health Relevance

The general approach advanced by this project will provide researchers with a power tool for the general study of neural circuitry. This will make it possible to study the neural networks responsible for movement, perception, learning, and memory. This method will thus help us understand these brain functions better and also help us understand neurological and psychiatric conditions involving dysfunction of these circuits.

National Institute of Health (NIH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Stewart, Randall R
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University of Wisconsin Madison
Schools of Medicine
United States
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Ghitani, Nima; Bayguinov, Peter O; Ma, Yihe et al. (2015) Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor. J Neurophysiol 113:1249-59
Ghitani, Nima; Bayguinov, Peter O; Vokoun, Corinne R et al. (2014) Excitatory synaptic feedback from the motor layer to the sensory layers of the superior colliculus. J Neurosci 34:6822-33
Wright, Brandon J; Jackson, Meyer B (2014) Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus. J Neurosci 34:9743-53
Jackson, Meyer B (2013) Recall of spatial patterns stored in a hippocampal slice by long-term potentiation. J Neurophysiol 110:2511-9