Novel molecular genetic tool for large-scale labeling and modulating activity of neurons associated with particular physiological processes and behaviors

Harvard Medical School, Boston MA

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Abstract

We propose to develop a novel technology for large-scale labeling and modulating activity of neurons associated with particular physiological processes and behaviors. This technology will be different from all other technologies that are currently used in biological research because it is based on the novel idea that particular neuronal assembles can be targeted by driving the expression of a reporter protein specifically in the neurons that are both active and exposed to the near-infrared light. We will produce vectors in which expression of a reporter protein (such as fluorescent protein mCherry) is controlled by both an activity-sensitive promoter and bacterial phytochrome-1 (BphP1) photoreceptor. Therefore, this protein will not be expressed in neurons that are either active but not exposed to the near-infrared light or exposed to the near-infrared light but not active. Expression of the protein will occur only if the neuron is both active and exposed to the near- infrared light. Because the light can be turned on and off, our proposed tool will allow precise temporal correspondence between the light exposure and the behavior. Such correspondence is critical for labeling neurons during the behaviors that are not sustained in time. By visualizing the pattern of the mCherry expression, we will be able to identify the neurons that are active during specific behaviors (e.g., exploring new object, grooming) or physiological states (e.g., rapid eye movement sleep). We plan to apply this technology in sleep research studies, but it can be also applied in a wide range of neurobiology studies.