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Charles Benson Olson Lab Group Meeting July 14th, 2017
Olson Research Group University of California, Davis
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Why do we care? Post-traumatic stress disorder (PTSD):
Chronic and debilitating 7.8% life-time prevalence More likely in trauma-exposed patients Symptoms: Persistent re-experiencing of memories Avoidance of cues/situations Emotional numbing Hyperarousal Olson Research Group University of California, Davis
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Pavlovian Fear Conditioning and Extinction
Thorpe, L. (2014). Reconciling the past with pills. Knowing neurons. Retrieved from Olson Research Group University of California, Davis
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Pavlovian Fear Conditioning and Extinction
Flores, Á., Saravia, R., Maldonado, R., & Berrendero, F. (2015). Orexins and fear: Implications for the treatment of anxiety disorders. Trends in Neurosciences, 38(9), 550–559. Olson Research Group University of California, Davis
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Clearing the Air: mTOR mTOR – mammalian/mechanistic Target of Rapamycin mTOR kinase structure Rapamycin mTOR downstream signaling pathway Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013). mTOR is a key modulator of ageing and age-related disease. Nature, 493(7432), 338–45. Olson Research Group University of California, Davis
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Clearing the Air: Intracellular Signaling Cascades
PIP3/Akt/mTOR Pathway Serine/threonine kinase mechanism Duran, A., Amanchy, R., Linares, J. F., Joshi, J., Abu-Baker, S., Porollo, A., … Diaz-Meco, M. T. (2011). P62 Is a Key Regulator of Nutrient Sensing in the mTORC1 Pathway. Molecular Cell, 44(1), 134–146. Olson Research Group University of California, Davis
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mTOR’s Role in Plasticity
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016). Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine, 22(3), 238–249. Olson Research Group University of California, Davis
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Ketamine Facilitates Cued Fear Extinction Learning
Olson Research Group University of California, Davis
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Ketamine Reduces Fear Recovery
Olson Research Group University of California, Davis
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Ketamine Increases mTOR Signaling
Olson Research Group University of California, Davis
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Ketamine-facilitated Fear Extinction is mTOR-dependent
Olson Research Group University of California, Davis
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Ketamine-facilitated Fear Extinction is mTOR-dependent
Olson Research Group University of California, Davis
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Influence of Ketamine on cFos Expression
Olson Research Group University of California, Davis
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Ketamine-facilitated Fear Extinction is AMPAR-dependent
Olson Research Group University of California, Davis
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Thanks for listening! Any questions? Olson Research Group
University of California, Davis
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