Psychiatry: Faculty and Staff
Uniformed Services University of the Health Sciences
Department of Psychiatry
4301 Jones Bridge Road
Bethesda, Maryland 20814-4799
Phone: (301) 295-3294
Fax: (301) 295-1536
He Li, M.D., Ph.D.
Associate Professor, Dept. of Psychiatry and Neuroscience Program
The ultimate goal of my research is to acquire and provide the knowledge that is necessary for the development of novel and effective molecular and pharmacological means that will prevent or treat stress-related affective disorders, such as post-traumatic stress disorder (PTSD). Many lines of evidence have suggested a central role of the amygdala in stress-related emotional illnesses and PTSD. In fear conditioning (an experimental paradigm that is similar to PTSD and other anxiety disorders), the amygdala appears to be the site of emotional memory storage. The amygdala also plays a
very important role in modulating the consolidation on emotional memory. In PTSD patients, the amygdala displays hypertrophy and hyperexcitability. For these reasons, my research program has been centered in the amygdala cellular neurobiology. My objectives are as follows:
- To understand the neuronal physiology and mechanisms of synaptic plasticity in the amygdala. Included in this objective is the identification of the role of neuromodulators that are known to affect emotional behavior and affective disorders.
- To determine how amygdala physiology and plasticity are altered following exposure to a stressor that mimics traumatic stressors that result in PTSD. The accomplishment of this objective requires the use of an appropriate animal model. The inescapable tail-shock paradigm in rats that I have developed in my laboratory has been shown to induce elevated basal corticosterone levels, weight loss, deficits in escape/avoidance learning and an exaggerated startle response, all of which have been observed in PTSD patients.
- To develop pharmacological interventions that will prevent or treat stress-induced pathophysiological alterations of the amygdala. To date, my research group has made significant strides in the accomplishment of these objectives. There is significant potential
for the development of improved strategies for the prevention and/or treatment of PTSD based on the research carried out in my laboratory.
1. Post, R.M., Weiss, S.R., Smith, M., Li, H. & McCann, U.: Kindling versus quenching: Implications for the evolution and treatment of posttraumatic stress disorder. Ann. N.Y. Acad. Sci. 821:285-295, 1997.
2. Post, R.M., Weiss, S.R.B., Li, H., Smith, M.A., Zhang, L.X., Xing, G., Osuch, E.A. & McCann, U.D.: Neural plasticity and emotional memory. Development and Psychopathology, 10: 829-855, 1998.
3. Li, H. & Henry, J.L.: Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of adenosine in hippocampus in vitro. European Journal of Pharmacology, 347(2-3): 173-182, 1998.
4. Li, H. & Rogawski, M.A.: GluR5 mediated synaptic transmission in basolateral amygdala in vitro. Neuropharmacology, 37: 1279-1286, 1998.
5. Li, H., Weiss, S.R.B., Chuang, D-M., Post, R.M. & Rogawski, M.A.: Bidirectional synaptic plasticity in the rat basolateral amygdala: characterization of an activity-dependent switch sensitive to the presynaptic metabotropic glutamate receptor antagonist 2S-α-Ethylglutamic acid. The Journal of Neuroscience, 18(5): 1662-1670, 1998.
6. Post, R.M., Weiss, S.R.B., Li, H., Leverich, G.S. and Pert, A.: Sensitization components of post-traumatic stress disorder: implications for therapeutics. Seminars in clinical neuropsychiatry, 1999 Oct;4(4):282-94. Review.
7. Post, R.M., Speer, A., Weiss, S. and Li, H.: Seizure Models: Anticonvulsant effects of ECT and rTMS. Progress in Neuropsychopharmacology and Biological Psychiatry, 2000 Nov;24(8):1251-73. Review.
8. Post, R.M., Weiss, R.B., Clark,M., Chuang, De-maw, Hough, Christopher and
Li, H.: Lithium, Carbamazepine, and Valproate in Affective Illness: Biochemical and Neurobiological Mechanisms. Biopolar Medications, Mechanisms of Action. Chapter 10, 219-248, 1999.
9. Weiss, S.R.B., Li, H., Sitcoske-OShea, M. and Post, R.M.: Amygdala plasticity: the neurobiological implications of kindling. The Amygdala, second edition, Oxford University, chapter 4, 155- 194, 2000.
10. Li, H. and Henry, J.L.: Inhibitory effects of adenosine on interneuron and interneuronal synaptic transmission in rat hippocampus in vitro. European Journal of Pharmacology, 407(3): 237-44. 2000.
11. Li, H. and Henry, J.L.: Adenosine receptor blockade reveals NMDA receptor- and voltage-sensitive dendritic spikes in rat hippocampal CA1 pyramidal cells in vitro. Neuroscience, 100(1): 21-31, 2000.
12. Rogawski, M., Hurzman, P., Yamaguchi, S. and Li, H.: Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology, 40(1): 28 35, 2001.
13. Aroniadou-Anderjaska, V., Post, R. M., Rogawski, M. A. and Li, H.: Input-specific LTP and depotentiation in basolateral amygdala. NeuroReport 12: 635-640, 2001.
14. Li, H., Chen, A., Xing, G., Wei, M. and Rogawski, M.A.: Kainate Receptor Mediated Heterosynaptic Facilitation in the Amygdala. Nature Neuroscience, 4(6): 612-620, 2001.
15. Braga, M.F.M., Aroniadou-Anderjaska, V., Post, R.M. and Li, H.: Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: Implications for its effects in seizure- and affective disorders. Neuropharmacology, 42:522-529, 2002.
16. Rogawski, M.A., Gryder, D., Castanada, D. Yonekawa, W. and Li, H.: Kainate receptor mediated long- term plasticity, seizures and epileptogenesis in the amygdala. New York Academy of Sciences, 985, 150-162, 2003.
17. Braga, M. F., Aroniadou-Anderjaska, V., Xie, J, and Li, H. Bidirectional modulation of GABA release by presynaptic glutamate 5 kaiante receptors in the basolateral amygdala. Journal of Neuroscience. 23(1), 442-452. 2003.
18. Chen, A., Hough, C.J. and Li, H. 5-HT2 Receptor activation facilitates synaptic plasticity via NMDA-Mediated mechanism in the basolateral amygdala. Neuroscience, 119, 53-63, 2003.
19. Braga, M. F., Aroniadou-Anderjaska, V., Manion, S.T., Hough, C.J., and Li, H. Stress impairs 1Adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala. Neuropsychopharmacology. 29,45- 58, 2004
20. Braga, M., Aroniadou-Anderjaska, V. and Li, H. : The physiological role of GluR5 kainate receptors in neuronal excitability and neuroplasticity in the rat amygdala. An invited review paper for Molecular Neurobiology 30(2):127-141, 2004
21. Osuch E, Ursano R, Li H, Webster M, Hough C, Fullerton C, Leskin G. Brain environment interactions: stress, posttraumatic stress disorder, and the need for a postmortem brain collection. Psychiatry. 2004 Winter;67(4):353-83.
22. Zhang, ZJ, Jiang XL, Zhang SE, Hough, CJ, Li, H., Chen, JG, Zhen, XCh: The paradoxical effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic reflex paradigm. Neuroscience Letters (382:134-138. 2005)
23. Jiang, X.L., Chen A.Q. and Li, H.: Histaminergic Modulation of Excitatory Synaptic Transmission in the Rat Basolateral Amygdala. Neuroscience (131(3), 609: 2005)
24. Zhang, L., Zhou, R., Xing, G., Hough, C.J. Li, H.: Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical applications in PTSD. Medical Hypotheses. In press, 2006
25. Zhang, L., Zhou, R., Li, X.X., Li, H.: Stress-induced change of mitochondria membrane potential regulated by genomic and nongenomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD Medical Hypotheses, In press, 2006