Browsing by Author "Johnson, Phillip L."

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    Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells
    (Wiley, 2017-05) Salazar, Tatiana E.; Richardson, Matthew R.; Beli, Eleni; Ripsch, Matthew S.; George, John; Kim, Youngsook; Duan, Yaqian; Moldovan, Leni; Yan, Yuanqing; Bhatwadekar, Ashay; Jadhav, Vaishnavi; Smith, Jared A.; McGorray, Susan; Bertone, Alicia L.; Traktuev, Dmitri O.; March, Keith L.; Colon-Perez, Luis M.; Avin, Keith; Sims, Emily; Mund, Julie A.; Case, Jamie; Deng, Shaolin; Kim, Min Su; McDavitt, Bruce; Boulton, Michael E.; Thinschmidt, Jeffrey; Calzi, Sergio Li; Fitz, Stephanie D.; Fuchs, Robyn K.; Warden, Stuart J.; McKinley, Todd; Shekhar, Anantha; Febo, Marcelo; Johnson, Phillip L.; Chang, Lung Ji; Gao, Zhanguo; Kolonin, Mikhail G.; Lai, Song; Ma, Jinfeng; Dong, Xinzhong; White, Fletcher A.; Xie, Huisheng; Yoder, Mervin C.; Grant, Maria B.; Ophthalmology, School of Medicine
    Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief.
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    Identifying the Neural Circuit That Regulates Social Familiarity Induced Anxiolysis (SoFiA)
    (2020-06) Majumdar, Sreeparna; Cummins, Theodore R.; Truitt, William A.; Block, Michelle L.; Johnson, Phillip L.; Engleman, Eric A.
    Mental health is crucially linked to social behavior. A crucial aspect of healthy social behavior involves learning to adapt emotional responses to social cues, for example learning to suppress anxiety through social familiarity, or social familiarity induced anxiolysis (SoFiA). SoFiA is well documented; however, the neural mechanisms of SoFiA are unclear. SoFiA is modeled in rats by employing a social interaction habituation (SI-hab) protocol. Using SI-hab protocol it has been determined that SoFiA represents social safety learning, which requires both anxiogenic stimulus (Anx) and social familiarity (SF) during training sessions (5-6 daily SI sessions), and SoFiA expression is dependent on infralimbic cortex (IL). Based on these findings we hypothesize that Anx and SF are processed by unique neural systems, and repeated convergence of these signals interact within IL to induce plasticity, resulting in social safety learning and anxiolysis. Following SoFiA expression, rats were either sacrificed 30 minutes {for gene expression or Neural Activity Regulated Gene (NARG) analysis} or perfused 90 minutes (for cFos immunoreactivity analysis) after SI session on social training day 5. This led to gaining insights into regions of brain involved in SoFiA response as well as the underlying molecular mechanisms. We identified amygdala, specifically the central amygdala (CeA), basomedial amygdala (BMA) and basolateral amygdala (BLA) as potential candidate regions in SoFiA response. Next, we investigated the role of IL and its efferent pathways in SoFiA expression using inhibitory DREADDs and intersectional chemogenetics to inhibit IL projection neurons and/or axons. We identified that specific projection neurons within the IL are pivotal for SoFiA expression, and that within these projections, the ones that specifically projected to the amygdala are most crucial for expression of SoFiA.
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    Inhibitory and Excitatory Alcohol-Seeking Cues Distinct Roles in Behavior, Neurochemistry, and Mesolimbic Pathway in Alcohol Preferring (P) rats
    (Elsevier, 2023) Hauser, Sheketha R.; Deehan, Gerald A., Jr.; Knight, Christopher P.; Waeiss, R. Aaron; Engleman, Eric A.; Ding, Zheng-Ming; Johnson, Phillip L.; McBride, William J.; Truitt, William A.; Rodd, Zachary A.; Psychiatry, School of Medicine
    Cues associated with alcohol use can readily enhance self-reported cravings for alcohol, which increases the likelihood of reusing alcohol. Understanding the neuronal mechanisms involved in alcohol-seeking behavior is important for developing strategies to treat alcohol use disorder. In all experiments, adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS- associated with the absence of EtOH (extinction training), and a CS0, a neutral stimulus. The data indicated that presentation of an excitatory conditioned cue (CS+) can enhance EtOH- seeking while the CS- can inhibit EtOH-seeking under multiple test conditions. Presentation of the CS+ activates a subpopulation of dopamine neurons within the interfascicular nucleus of the posterior ventral tegmental area (posterior VTA) and basolateral amygdala (BLA). Pharmacological inactivation of the BLA with GABA agonists inhibits the ability of the CS+ to enhance EtOH-seeking but does not alter context-induced EtOH-seeking or the ability of the CS- to inhibit EtOH-seeking. Presentation of the conditioned odor cues in a non-drug-paired environment indicated that presentation of the CS+ increased dopamine levels in the BLA. In contrast, presentation of the CS- decreased both glutamate and dopamine levels in the BLA. Further analysis revealed that presentation of a CS+ EtOH-associated conditioned cue activates GABA interneurons but not glutamate projection neurons. Overall, the data indicate that excitatory and inhibitory conditioned cues can contrarily alter EtOH-seeking behaviors and that different neurocircuitries are mediating these distinct cues in critical brain regions. Pharmacotherapeutics for craving should inhibit the CS+ and enhance the CS- neurocircuits.