Cellular and circuitry mechanisms underlying pathological neural plasticity
Emotion and motivation are two basic, interlinked concepts in neuroscience, with ramifying connotations across psychology and philosophy. Thus far, neuroscience cannot yet provide coherent explanations for why some stimuli cheer us up whereas others make us sad, why my fishing trip to a picturesque river is given up in favor of typing this paragraph, and why reading and memorizing knowledge that used to be so boring for me as a kid become so rewarding after a 20-year of “habituation”.
Our long-term research goal is to understand the neural mechanisms underlying emotional and motivational responses. We focus on animal models related to drug addiction. Addictive drugs are among the most effective and efficient external stimuli that evoke the strongest emotional and motivational states. Once “hijacked” into the addictive state, an individual will be primarily motivated by an exceedingly strong emotional state, the drug-seeking/craving state.
We hypothesize that strong incentive stimuli, such as experience of drugs of abuse, shift the emotional and motivational states by rewiring the neural circuits in the brain reward pathway. To test this hypothesis, we have been examining several novel forms of neural plasticity upon exposure to cocaine.
Two related research areas are depression, which is characterized in part as a lack of motivation, and sleep, which modulates the emotional and motivational state across most species.
These lines of research in the laboratory are currently carried out by several highly motivated young souls, who are equipped with a combination of molecular, cellular, electrophysiological, and behavioral expertise.
Ishikawa, M., Otaka, M., Huang, Y.H., Neumann, P.A., Winters, B.D., Grace, A.A., Schlüter, O.M., Dong, Y. Dopamine triggers Heterosynaptic Plasticity. Journal of Neuroscience. 33(16):6759-6765, 2013.
Otaka, M., Ishikawa, M., Lee, B.R., Liu, L., Neumann, P.A., Cui, R., Huang, Y.H., Schlüter, O.M., Dong, Y. Exposure to Cocaine Regulates Inhibitory Synaptic Transmission in the Nucleus Accumbens. Journal of Neuroscience. Featured Article. 33(16): 6753-6758, 2013.
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Huang, Y.H., Ishilawa, M., Lee, B.R., Schlüter, O.M., Dong, Y. Searching for Presynaptic NMDA receptors in the Nucleus Accumbens. Journal of Neuroscience. 31(50): 18453-18463, 2011.
Brown, T.E., Lee, B.R., Mu, P., Huang, Y.H,, Sorg, B.A., Zukin ,R.S., Nestler,, E.J., Dong, Y., Schlüter, O.M. A Silent Synapse-based Mechanism for Cocaine-induced Locomotor Sensitization. Journal of Neuroscience. 31(22): 8163-8174, 2011.
Ferguson, S.M., Eskenazi, D., Ishikawa, M., Wanat ,M.J., Phillips, P.E.M., Dong, Y., Roth, B.L., Neumaier, J.F. Transient Neuronal Silencing Reveals Opposing Actions of Indirect and Direct Pathway Neurons on Amphetamine Sensitization. Nature Neuroscience. 14(1):22-4, 2011.
Mu, P., Neumann, P,, Panksepp, J., Schlüter, O.M., Dong, Y. Exposure to Cocaine alters Dynorphin-mediated Regulation of Excitatory Synaptic Transmission in Nucleus Accumbens Neurons. Biological Psychiatry. 69(3):228-35, 2011.
Mu, P., Moyer, J.T., Panksepp, J., Sorg, B.A., Schlüter, O.M., Dong, Y. Exposure to Cocaine Dynamically Regulates the Membrane Excitability of Nucleus Accumbens Neurons. Journal of Neuroscience. 30(10): 3689-3699, 2010.
Huang, Y.H., Lin, Y., Mu, P., Lee, B.R., Brown, T.E., Wayman, G.A., Marie, H., Liu, W,, Yan, Z., Sorg, B.A., Schlüter, O.M., Zukin, R.S., Dong, Y. In vivo Cocaine Experience Generates Silent Synapses. Neuron. 63:40-47. PMID: 19607791; PMCID: PMC2721479, 2009.
Ishikawa, M., Moyer, J., Wolf, J.A., Quock, R.M., Davis, N.M., Schlüter, O.M., Dong, Y. Homeostatic Synapse-driven Membrane Plasticity in Nucleus Accumbens Neurons. Journal of Neuroscience. 29(18): 5820-31, 2009.
Huang, Y.H., Lin, Y., Brown, T., Han, M.H., Saal, D., Neve, R.L., Zukin, R.S., Sorg, B.A., Nestler, E.J., Malenka, R.C., Dong, Y. CREB modulates the upstate of nucleus accumbens neurons: A critical role of synaptic NMDA receptors. Journal of Biological Chemistry, 283(5): 2751-60, 2008.