Summary of Current Research
My research is focused on understanding how new memories form and how, once formed, these memories can be modulated or weakened through environmental and pharmacological interventions. Research in my lab investigates memory at three different levels of analysis. At the behavioral level, we are interested in how different environmental experiences can cause memories to be formed or suppressed. At the neurobiological systems level, we focus on how brain circuits that mediate memory are altered by behavioral experience. At the molecular level, we investigate whether manipulating epigenetic processes can modulate long-term memories. Recent work has focused on the control of gene expression by pharmacological modulation of chromatin, the protein complex that packages genomic DNA. Relaxing chromatin structure by administering a histone deacetylase (HDAC) inhibitor can promote gene expression by facilitating interactions between transcription factors and DNA. We have found that HDAC inhibitors promote the development and persistence of different kinds of memories. At a molecular level, these findings reinforce the idea that regulation of gene expression via chromatin modification is critical for memory. At a clinical level, these findings suggest that modulating chromatin modification during an episode of learning may lead to a persistent form of memory.
2010-2016 Associate Professor, Department of Behavioral Neuroscience, OHSU
2005-2010 Assistant Professor, Department of Behavioral Neuroscience, OHSU
1998-2004 Post-Doctoral Fellow, Department of Biology, University of Pennsylvania (Advisor: Ted Abel)
Areas of interest
- Neurobiology of learning and memory
- Models of substance abuse and post-traumatic stress disorder
- Learning theory
- Pharmacological approaches to enhancing memory
- Epigenetic mechanisms of memory
- B.A., University of California San Diego 1993
- Ph.D., University of Pennsylvania 1998
Abraham, A.D., Neve, K.A., & Lattal, K.M. (2016). Effects of D1 receptor knockout on fear and reward learning. Neurobiology of Learning & Memory, 133, 265-273.
Abraham, A.D., Neve, K.A., & Lattal, K.M. (2016). Activation of D1/5 dopamine receptors: A common mechanism for enhancing extinction of fear and reward-seeking behaviors. Neuropsychopharmacology, 41, 2072–2081.
Crabbe, J.C., Schlumbohm, J. P., Hack, W., Barkley-Levenson, A. M., Metten, P., & Lattal, K.M. (2016). Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking. Alcohol, 52, 25-32.
Tipps, M.E., Raybuck, J.D., Buck, K.J., & Lattal, K.M. (2014). Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: Issues of measurement and performance. Learning & Memory, 21, 380-393.
Hitchcock, L.N., Cunningham, C.L., & Lattal, K.M. (2014). Cue configuration effects in acquisition and extinction of a cocaine-induced place preference. Behavioral Neuroscience, 128, 217-227.
Stafford, J.M., Maughan, D.K., Ilioi, E.C., & Lattal, K.M. (2013). Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits. Learning & Memory, 20, 156-163.
Lattal, K.M. & Wood, M.A. (2013). Epigenetics and persistent memory: Implications for reconsolidation and silent extinction beyond the zero. Nature Neuroscience, 16, 124-129.
Stafford, J.M., Raybuck, J.D., Ryabinin, A., & Lattal, K.M. (2012). Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biological Psychiatry, 72, 25-33.
- "Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference" NeuroReport December 19 2012
- "Delay and trace fear conditioning in C57BL/6 and DBA/2 mice" Learning and Memory 2014
- "Cellular Learning Theory" Behavioral Neuroscience October 2007
- "Epigenetics and persistent memory" Nature Neuroscience February 2013
- "The histone deacetylase inhibitor sodium butyrate modulates acquisition and extinction of cocaine-induced conditioned place preference" Pharmacology Biochemistry and Behavior May 2013
- "Epigenetics and memory" Genes, Brain and Behavior January 1 2015
- "Facets of Pavlovian and operant extinction" Behavioural Processes May 2012
- "Context effects on choice" Journal of the Experimental Analysis of Behavior 1998
- "Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos" NeuroToxicology August 2012
- "Dopamine and extinction" Neurobiology of Learning and Memory February 2014
- "Post-conditioning propranolol disrupts cocaine sensitization" Pharmacology Biochemistry and Behavior October 2012
- "Anisomycin disrupts a contextual memory following reactivation in a cocaine-induced locomotor activity paradigm" Behavioral Neuroscience February 2007
- "Postretrieval propranolol disrupts a cocaine conditioned place preference" NeuroReport September 2006
- "Behavioral impairments caused by injections of the protein synthesis inhibitor anisomycin after contextual retrieval reverse with time" Proceedings of the National Academy of Sciences of the United States of America March 30 2004
- "Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival" Journal of Cerebral Blood Flow and Metabolism October 2013
- "Substance abuse, memory, and post-traumatic stress disorder" Neurobiology of Learning and Memory 2014
- "Modulation of Chromatin Modification Facilitates Extinction of Cocaine-Induced Conditioned Place Preference" Biological Psychiatry January 1 2010
- "Effects of post-session injections of anisomycin on the extinction of a spatial preference and on the acquisition of a spatial reversal preference" Behavioural Brain Research August 31 2004
- "Estimation of animal intelligence by university students in Japan and the United States" Anthrozoos 2002
- "Direct comparisons of the size and persistence of anisomycin-induced consolidation and reconsolidation deficits" Learning and Memory August 2009
- "Overexpectation in appetitive pavlovian and instrumental conditioning" Animal Learning and Behavior 1998
- "Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice" Current Aging Science 2009
- "Extinction, renewal, and spontaneous recovery of a spatial preference in the water maze" Behavioral Neuroscience October 2003
- "Histone-mediated epigenetics in addiction" Progress in Molecular Biology and Translational Science 2014
- "Large-scale topology and the default mode network in the mouse connectome" Proceedings of the National Academy of Sciences of the United States of America December 30 2014
- "Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB" Journal of Neuroscience June 6 2007
- "Modafinil reinstates a cocaine conditioned place preference following extinction in rats" Behavioural Brain Research December 1 2009
- "Double dissociation of amygdala and hippocampal contributions to trace and delay fear conditioning" PLoS One 2011
- "An immediate-shock freezing deficit with discrete cues" Journal of Experimental Psychology: Animal Behavior Processes October 2001
- "Systemic or Intrahippocampal Delivery of Histone Deacetylase Inhibitors Facilitates Fear Extinction" Behavioral Neuroscience October 2007