2019 — 2021 |
He, Zhigang Wang, Fan [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cortical Signature and Modulation of Pain
Cortical Signature and Modulation of Pain Abstract/Project Summary Pain perception contains two main dimensions: the sensory-discriminative and the affective-cognitive aspects. In this proposal, we will focus on the cortical signature and modulations of the sensory aspects of pain using mouse models. Pain can be largely divided into inflammatory or neuropathic pain. A common condition in both types of pain is mechanical allodynia: externally applied innocuous gentle touch becomes painful. Paradoxically, pain elicits self-initiated recuperative behaviors such as rubbing and massaging of the painful regions; and the mechanical stimuli from such self-generated behaviors generally relieve pain. The neural circuit mechanisms underlying the opposite effects of external versus self-applied mechanical stimuli in pain conditions remain poorly understood. Based on previous research as well as our preliminary studies, we hypothesize that corticospinal projecting neurons from primary somatosensory (S1) cortex facilitate mechanical hypersensitivity in pain models, whereas specific motor cortex projection neurons play key roles in suppressing tactile allodynia in self-initiated recuperative behaviors (such as licking and wiping in mice). We further hypothesize that the cortical pain signature can be read out from activity patterns of large populations of individual S1 neurons by comparing their activities in the painful versus non-painful or pain- relieved conditions. We will use a combination of viral-genetic labeling of specific cortical neurons, in vivo calcium imaging and in vivo multi-electrode extracellular recording in freely behaving mice, optogenetics- assisted slice physiology, opto/chemicogenetic manipulations, and computational analyses to test our hypotheses.
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0.97 |
2019 — 2021 |
He, Zhigang |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Viral Module
Project Summary Virus-based technology has emerged as a powerful tool in neuroscience and vision research, enabling optogenetic and chemogenetic manipulation of brain activity, circuit tracing, and gain- and loss-of-function genetic modifications in the retina and brain. Electrophysiology- and imaging-focused laboratories, however, often lack the expertise and resources needed to effectively employ these molecular biology approaches, and standardized methods can enhance the productivity of even experienced molecular neuroscience groups. The Viral Module was created to fill this need by generating, maintaining, and designing high-quality viruses for vision applications. Led by Dr. Zhigang He, and a staff of experienced molecular biologists, the Viral module will serve as a repository for the proper storage, maintenance, handling, and distribution of pre-made viral vectors and also assist in the design, optimization, and generation of custom viral constructs. Despite its recent addition to the Vision Core, the Viral Module has already been utilized by a significant number of investigators working in both rodents and primates and constitutes an essential resource for the wider Harvard vision research community.
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0.934 |