Browsing by Author "Yin, Henry"
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Item Open Access A craniofacial-specific monosynaptic circuit enables heightened affective pain.(Nature neuroscience, 2017-12) Rodriguez, Erica; Sakurai, Katsuyasu; Xu, Jennie; Chen, Yong; Toda, Koji; Zhao, Shengli; Han, Bao-Xia; Ryu, David; Yin, Henry; Liedtke, Wolfgang; Wang, FanHumans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PBL), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than of the hindpaw. Using a novel activity-dependent technology called CANE developed in our laboratory, we identified and selectively labeled noxious-stimulus-activated PBL neurons and performed comprehensive anatomical input-output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PBL-nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PBL projection induced robust escape and avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.Item Open Access Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.(Nat Commun, 2016-05-10) Wang, Xiaoming; Bey, Alexandra L; Katz, Brittany M; Badea, Alexandra; Kim, Namsoo; David, Lisa K; Duffney, Lara J; Kumar, Sunil; Mague, Stephen D; Hulbert, Samuel W; Dutta, Nisha; Hayrapetyan, Volodya; Yu, Chunxiu; Gaidis, Erin; Zhao, Shengli; Ding, Jin-Dong; Xu, Qiong; Chung, Leeyup; Rodriguiz, Ramona M; Wang, Fan; Weinberg, Richard J; Wetsel, William C; Dzirasa, Kafui; Yin, Henry; Jiang, Yong-HuiHuman neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4-22 (Δe4-22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4-22(-/-) mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs.Item Open Access Striatal Pathways for Action Counting and Steering(2024) Fallon, IsabellaThe mechanisms by which the nervous system generates action are subjects of ongoing debate. A large body of research supports a role for the striatal direct and indirect pathways in regulating actions. On the one hand, these pathways are critical for discrete decision-making, action initiation, and coordinating sequences of actions. These findings have led to the development of action selection models of striatal circuits. On the other hand, they also play a role in steering motion direction, are related to the kinematics of individual body parts, and coordinated movements. These insights have led to competing hypotheses about their control over bodily kinematics. These divergent hypotheses may have arisen from the functional diversity of subpopulations within striatal neurons. However, prior work supporting these hypotheses of striatal function has not measured both the discrete and continuous features of actions while recording and manipulating striatal pathways. To address this limitation, we designed a novel lever press count task that allows for this combined measurement. Our results show that mice accurately estimate press count and use it to decide when to approach a food port. Optogenetic manipulations reveal that the direct and indirect pathways oppositely control mice’s proximity to task-relevant landmarks and to the press count goal. In-vivo calcium imaging reveals distinct population activities that are correlated with mice’s displacement from task-relevant landmarks and completion of the press count. A striatal push-pull circuit is described that computes the mouse’s proximity to task-relevant landmarks and the press count through subtraction of population activity over time. This work sheds light on a potentially general function of striatal neurons in regulating action during goal pursuit, with implications for understanding action dysregulation in many conditions.