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LAB FOCUS
The Ressler lab at Yerkes National Primate Research Center is focused on the molecular and cellular mechanisms of fear learning and the process of extinction of fear in mouse models. The primary objective of the work in the Ressler lab is to utilize the power of molecular genetics to understand the molecular biology, the neural circuitry, and the behavioral biology of fear and extinction of fear in mouse models.
Dr. Ressler is also a practicing psychiatrist with an interest in translational and clinical research on fear-based psychiatric disorders. During his clinical time, Dr. Ressler is co-director of a newly created Post-traumatic Stress Disorders Clinic at the Adult Outpatient Psychiatry Clinic at Grady Memorial Hospital. We hope that by understanding how fear works in the mammalian brain in the laboratory, it will improve our understanding of and provide translational treatments and possibly prevention for fear-based disorders, such as Post-traumatic Stress Disorder, Phobic Disorders, and Panic Disorder.
PTSD: Grady Trauma Project
Selected References (see PAPERS for more complete references):
Behavioral / Basic Neuroscience:
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V. (2011) Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011 Feb 24;470(7335):492-7.
Choi DC, Maguschak KA, Ye K, Jang SW, Myers KM, Ressler KJ. (2010) Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2675-80.
Andero R, Heldt SA, Ye K, Liu X, Armario A, Ressler KJ. (2010) Effect of
7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning. Am J
Psychiatry. 2011 Feb;168(2):163-72.
Mou L, Heldt SA, Ressler KJ. (2010) Rapid brain-derived neurotrophic factor-dependent
sequestration of amygdala and hippocampal GABA(A) receptors via different
tyrosine receptor kinase B-mediated phosphorylation pathways. Neuroscience. 2011
Mar 10;176:72-85.
Ressler KJ. (2010) Amygdala activity, fear, and anxiety: modulation by stress. Biol Psychiatry. 2010 Jun 15;67(12):1117-9. Biol Psychiatry 67(12):1117-9.
Heldt SA, Ressler KJ. (2010) Amygdala-specific reduction of alpha1-GABAA receptors disrupts the anticonvulsant, locomotor, and sedative, but not anxiolytic, effects of benzodiazepines in mice. J Neurosci. 2010 May 26;30(21):7139-51. J Neurosci 30(21):7139-51.
Jang SW, Liu X, Chan CB, France SA, Sayeed I, Tang W, Lin X, Xiao G, Andero R, Chang Q, Ressler KJ, Ye K. (2010) Deoxygedunin, a natural product with potent neurotrophic activity in mice. PLoS One. 2010 Jul 13;5(7):e11528. PloS One 5(7): e11528.
Martin EI*, Ressler KJ*, Jasnow AM, Dabrowska J, Hazra R, Rainnie DG, Nemeroff CB, Owens MJ. (2010) A Novel Transgenic Mouse for Gene-Targeting Within Cells That Express Corticotropin-Releasing Factor. Biol Psychy. 67(12):1212-6. Biol Psychiatry 67(12): 1212-6.
Lee SE, Simons SB, Heldt SA, Zhao M, Schroeder JP, Vellano CP, Cowan DP, Ramineni S, Yates CK, Feng Y, Smith Y, Sweatt JD, Weinshenker D, Ressler KJ, Dudek SM, Hepler JR. (2010) RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci U S A. 2010;107(39):16994-8. Proc Natl Acad Sci 107(39): 16994-8.
Xu X, Yang H, Lin YF, Li X, Cape A, Ressler KJ, Li S, Li XJ (2010) Neuronal Abelson helper integration site-1 (Ahi1)
deficiency in mice alters TrkB signaling with a
depressive phenotype Proc Natl Acad Sci U S A. early edition Proc Natl Acad Sci online before print.
Heldt SA, Ressler KJ. The Use of Lentiviral Vectors and Cre/loxP to Investigate the Function of Genes in Complex Behaviors. (2010) Front Mol Neurosci. 2009;2:22.
Heldt SA, Davis M, Ratti E, Corsi M, Trist D, Ressler KJ. (2009) Anxiolytic-like effects of the neurokinin 1 receptor antagonist GR-205171 in the elevated plus maze and contextual fear-potentiated startle model of anxiety in gerbils. Behav Pharmacol. Aug 11. [Epub ahead of print] PubMed PMID: 19675456.
Jasnow AM, Ressler KJ, Hammack SE, Chhatwal JP, Rainnie DG. (2009) Distinct subtypes of cholecystokinin (CCK)-containing interneurons of the basolateral amygdala identified using a CCK promoter-specific lentivirus. J Neurophysiol. 2009 Mar;101(3):1494-506.
Maguschak K and Ressler KJ (2008) b -catenin is required for the consolidation of fear memories in adult mice. Nature Neuroscience 2008 Nov;11(11):1319-26.
Jones SV, Choi DC, Davis M, Ressler KJ. (2008) Learning-dependent structural plasticity in the adult olfactory pathway. J Neurosci. 2008 Dec 3;28(49):13106-11.
Chattwal, J., Gutman, A.R., Maguschak, K.M., Yang, Y., Bowser, M.,Davis, M., and Ressler, K.J. (2009) Functional Interactions Between Endocannabinoid and CCK Neurotransmitter Systems May Be Critical for Extinction Learning. Neuropsychopharmacology. 2009 Jan;34(2):509-21.
Keen-Rhinehart E, Michopoulos V, Toufexis DJ, Martin EI, Nair H, Ressler KJ, Davis M, Owens MJ, Nemeroff CB, Wilson ME. (2009)Continuous expression of corticotropin-releasing factor in the central nucleus of the amygdala emulates the dysregulation of the stress and reproductive axes. Molecular Psychiatry. 2009 Jan;14(1):37-50.
Ressler KJ and Mayberg HS (2007) Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nature Neuroscience 2007 10(9): 1116-1124.
Heldt SA, Stanek L, Chhatwal JP, and Ressler KJ (2007) Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Molecular Psychiatry; 12 (7): 656-70.
Chhatwal JP, Stanek-Rattiner L, Davis M, Ressler KJ. (2006) Amygdala BDNF signaling is required for consolidation but not encoding of extinction. Nature Neuroscience 2006 9(7): 870-872.
Chhattwal, J., Myers, K., Ressler, K.J., and Davis, M. (2005) Differential Modulation of Gephyrin and GABAA Receptors during Fear Conditioning and Extinction. J Neuroscience , 25(2):502-506.
Chhatwal, J.P., Davis, M., Maguschak, K.A. and Ressler, K.J. (2005) Enhancing Cannabinoid Neurotransmission Augments the Extinction of Conditioned Fear. Neuropsychopharmacology, 30(3):516-524.
Rattiner, L., Davis, M., French, C.T. and Ressler, K.J. (2004) Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in amygdala-dependent fear conditioning. J. Neuroscience, 24(20):4796-4806.
Ressler, K.J., Paschall, G., Zhou, X.L., and Davis, M. (2002) Regulation of Synaptic Plasticity Genes During Consolidation of Fear Conditioning. J. Neuroscience 22(18): 7892-7902.
Walker, D., Ressler, K.J., Lu, K-T., and Davis, M. (2002) Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. J. Neuroscience, 22(6), 2343-2351.
Clinical / Translational Neuroscience:
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V. (2011) Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011 Feb 24;470(7335):492-7.
Norrholm SD, Jovanovic T, Olin IW, Sands LA, Karapanou I, Bradley B, Ressler
KJ. (2011) Fear extinction in traumatized civilians with posttraumatic stress disorder:
relation to symptom severity. (2011) Biol Psychiatry. 2011 Mar 15;69(6):556-63.
Tang YL, Khoury L, Bradley B, Gillespie CF, Ressler KJ, Cubells JF. Substance
Use Disorders Assessed Using the Kreek-McHugh-Schluger-Kellogg (KMSK) Scale in an
Urban Low-Income and Predominantly African American Sample of Primary Care
Patients. (2011) Am J Addict. 2011 May;20(3):292-9.
Skelton K, Ressler KJ, Norrholm SD, Jovanovic T, Bradley-Davino B. (2011) PTSD and
gene variants: New pathways and new thinking. (2011) Neuropharmacology. 2011 Feb 26.
Khoury L, Tang YL, Bradley B, Cubells JF, Ressler KJ. Substance use, childhood
traumatic experience, and Posttraumatic Stress Disorder in an urban civilian
population. (2010) Depress Anxiety. 2010 Dec;27(12):1077-86.
Jovanovic T, Ressler KJ. (2010) How the Neurocircuitry and Genetics of Fear Inhibition May Inform Our Understanding of PTSD. Am J Psychiatry. [Epub ahead of print] PubMed PMID: 20231322
Ressler KJ, Bradley B, Mercer KB, Deveau TC, Smith AK, Gillespie CF, Nemeroff
CB, Cubells JF, Binder EB. (2010) Polymorphisms in CRHR1 and the serotonin transporter
loci: gene x gene x environment interactions on depressive symptoms. Am J Med
Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):812-24. Am J Med Genet B 153B (3): 812-
Jovanovic T, Norrholm SD, Blanding NQ, Davis M, Duncan E, Bradley B, Ressler
KJ. (2010) Impaired fear inhibition is a biomarker of PTSD but not depression. Depress
Anxiety. Mar;27(3):244-51. Depression Anxiety 27(3):244-
Binder EB, Owens MJ, Liu W, Deveau TC, Rush AJ, Trivedi MH, Fava M, Bradley B,
Ressler KJ, Nemeroff CB. (2010) Association of polymorphisms in genes regulating the
corticotropin-releasing factor system with antidepressant treatment response.
Arch Gen Psychiatry. 2010 Apr;67(4):369-79. AGP 67(4):369-79.
Jovanovic T, Norrholm SD, Blanding NQ, Phifer JE, Weiss T, Davis M, Duncan E,
Bradley B, Ressler K. Fear potentiation is associated with
hypothalamic-pituitary-adrenal axis function in PTSD. Psychoneuroendocrinology.
2010 Jul;35(6):846-57.PNEC 35(6): 846-57.
Wingo AP, Wrenn G, Pelletier T, Gutman AR, Bradley B, Ressler KJ. Moderating
effects of resilience on depression in individuals with a history of childhood
abuse or trauma exposure. J Affect Disord. 2010 Nov;126(3):411-4. JAD 126(3); 126(3): 411-4.
Wingo AP, Fani N, Bradley B, Ressler KJ. Psychological resilience and
neurocognitive performance in a traumatized community sample. Depress Anxiety.
2010 Aug;27(8):768-74. Depression Anxiety 27(8): 768-774.
Heim C, Bradley B, Mletzko TC, Deveau TC, Musselman DL, Nemeroff CB, Ressler
KJ, Binder EB. Effect of Childhood Trauma on Adult Depression and Neuroendocrine
Function: Sex-Specific Moderation by CRH Receptor 1 Gene. Front Behav Neurosci.
2009 Nov 6;3:41.Front Behav Neurosci 3:41.
Kohli MA, Salyakina D, Pfennig A, Lucae S, Horstmann S, Menke A, Kloiber S,
Hennings J, Bradley BB, Ressler KJ, Uhr M, Müller-Myhsok B, Holsboer F, Binder
EB. Association of genetic variants in the neurotrophic receptor-encoding gene
NTRK2 and a lifetime history of suicide attempts in depressed patients. Arch Gen
Psychiatry. 2010 Apr;67(4):348-59. AGP 67(4):348-359.
Binder EB, Bradley RG, Epstein M, ...Cubells JF, and Ressler KJ. (2008) FKBP5 Polymorphisms Moderate Effects of Child Abuse on Risk for PTSD in Adults. Archives of General Psychiatry Journal of the American Medical Association, Mar 19; 299(11): 1291-1305.
Bradley RG, Binder EB, Epstein MP, Tang Y, Nair HP, Liu W, Gillespie CF, Berg T, Evces M, Newport DJ, Stowe ZN, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, and Ressler KJ (2008) Influence of Child Abuse on Adult Depression is Moderated by the Corticotropin Releasing Hormone Receptor Gene. Archives of General Psychiatry Archives of General Psychiatry 2008 65(2): 190-200.
Powers A, Ressler KJ, Bradley RG. The protective role of friendship on the effects of childhood abuse and depression. (2008) Depression and Anxiety; October; 2008 Epub before Print.
Davis RG, Ressler KJ, Schwartz AC, Stephens KJ, Bradley RG. Treatment barriers for low-income, urban African Americans with undiagnosed posttraumatic stress disorder. (2008) J Trauma Stress. 2008 Apr;21(2):218-22.
Gerardi, M., Rothbaum, B.O., Ressler, K., Heekin, M., and Rizzo, A. (2008) Virtual Reality Exposure Therapy Using a Virtual Iraq: Case Report. Journal of Traumatic Stress, 21(2): 209-213.
Schwartz, A., Penza, K., Bradley, R., Jay, D., Haggard, P., Sexton, M., Garlow, S. and Ressler, K.J (2006) Increased use of Opiate and Non-Opiate Pain Medication Use in Patients with PTSD. Psychosomatics, Mar-Apr;47(2):136-42 .
Schwartz, A., Sexton, M., Sherry, A., Bradley, R., and Ressler, K.J. (2005) Trauma in the Inner City: Prevalence and Comorbidity of PTSD in an Urban African American Population. Psychiatric Services, 56(2): 212-5.Psychiatric Services, 56(2): 212-215.
Ressler, K.J. , Rothbaum, B.O., Anderson, P., Zimand, E., Tannenbaum, L., Hodges, L., and Davis, M. (2004) D-Cycloserine, a Putative Cognitive Enhancer, Accelerates Extinction of Fear in Humans. Archives of General Psychiatry, 61:1136-44.
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