Browsing by Author "Lu, Jinghao"
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Item Metadata only Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit(Neuron, 2016-11-23) Sakurai, Katsuyasu; Zhao, Shengli; Takatoh, Jun; Rodriguez, Erica; Lu, Jinghao; Leavitt, Andrew D; Fu, Min; Han, Bao-Xia; Wang, Fan© 2016 Elsevier Inc.We developed a technology (capturing activated neuronal ensembles [CANE]) to label, manipulate, and transsynaptically trace neural circuits that are transiently activated in behavioral contexts with high efficiency and temporal precision. CANE consists of a knockin mouse and engineered viruses designed to specifically infect activated neurons. Using CANE, we selectively labeled neurons that were activated by either fearful or aggressive social encounters in a hypothalamic subnucleus previously known as a locus for aggression, and discovered that social-fear and aggression neurons are intermixed but largely distinct. Optogenetic stimulation of CANE-captured social-fear neurons (SFNs) is sufficient to evoke fear-like behaviors in normal social contexts, whereas silencing SFNs resulted in reduced social avoidance. CANE-based mapping of axonal projections and presynaptic inputs to SFNs further revealed a highly distributed and recurrent neural network. CANE is a broadly applicable technology for dissecting causality and connectivity of spatially intermingled but functionally distinct ensembles.Item Open Access General anesthetics activate a potent central pain-suppression circuit in the amygdala.(Nature neuroscience, 2020-05-18) Hua, Thuy; Chen, Bin; Lu, Dongye; Sakurai, Katsuyasu; Zhao, Shengli; Han, Bao-Xia; Kim, Jiwoo; Yin, Luping; Chen, Yong; Lu, Jinghao; Wang, FanGeneral anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeAGA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeAGA neurons. CeAGA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeAGA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeAGA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeAGA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeAGA as a potential powerful therapeutic target for alleviating chronic pain.Item Open Access Somatosensory Cortical Representation of Facial Nociception and Vibrotactile Touch Induced Analgesia(2021) Lu, JinghaoPain relief by vibrotactile touch is a common human experience. Previous neurophysiological investigations focused on spinal mechanisms in anesthetized animals. However, whether and how cortex, especially the primary somatosensory cortex (S1), is involved in this process in behaving animals remains unknown. Here I used awake behaving mice to study this touch induced pain relief. First, I discovered that vibrotactile reafferent signals from self-generated whisking significantly reduce facial nociception. Second, I showed that specific blocking of touch transmission from thalamus to barrel cortex (S1B) abolished whisking induced analgesia. Third, I developed a neuron extraction pipeline for 1-photon based calcium imaging and used in vivo imaging to show that tactile and noxious stimuli differentially activate S1B neurons. Lastly, I applied the intrinsic manifold analysis of S1B population activity to reveal that whisking pushes the transition of neural state induced by noxious stimuli towards the state encoding non-nocifensive actions. I concluded with an awake behaving mouse model for studying S1B touch induced pain relief, and that S1B contains nociceptive representations and integrates tactile and painful signals to enable touch mediated pain relief.