Dr Luke Johnson

PhD

Group Leader

Projects

Microantomy of memory and stress

MEMORY

Understanding the physical encoding of a memory by networks of neurons, known as the engram, is a fundamental question in neuroscience. Work in my lab seeks to decode aspects of the engram of an individual fear memory in the amygdala by identifying the intrinsic pattern of amygdala neurons which are systematically activated during the acquisition of a memory, using statistical methods. Identifying this intrinsic pattern is a key step in the quest to ultimately decoding memory storage. Our data from ongoing work suggest the first evidence for a unique neural topography associated with formation of a fear memory.  The consistency of the spatial pattern across animals that encoded the same associative memory demonstrates that the pattern of neurons (pMAPK activity) observed in the present data-set was reliable and non-random.   Evidence for a stable topography of neurons that participate in fear memory formation may be a fundamental feature by which fear memory is represented in the amygdala. In addition we recently identified that this pattern of neurons is updated during memory reconsolidation. This work is ongoing and will incorporate reconsolidation; auditory and visual conditioned stimuli and second order conditioning. This work was recently summarized by MBF Bioscience http://www.mbfbioscience.com/blog/2011/03/bethesda-scientists-use-neurolucida-to-map-memories-in-the-brain/

 MICROANATOMY OF HIGH AND LOW FEAR MEMORY PHENOTYPES

A current ongoing project in Johnson lab involves a colony of backcrossed F8 generation C57BL/6J and DBA/2J (B6D2F1) mice which are being phenotyped for high and low Pavlovian fear conditioning. These mice are being studied for cellular mechanisms of plasticity underlying the differences in their behavior. This work was recently reported on as a Nature News Feature. The mice fear phenotype project is collaboration with Dr Abraham Palmer of the Dept of Human Genetics at the University of Chicago. Data to date has identified increased at rest neural activity in High Fear compared to Low Fear mice using manganese-enhanced magnetic resonance imaging (MEMRI).  These differences included a strong contribution from hippocampus, amygdala, and cortex, indicating that the limbic circuit is more active in High Fear mice.  Basal corticosterone levels were greater in High Fear animals. Hypothalamic CRH mRNA levels were increased and MR and CRHR1 mRNA levels were decreased in High Fear compared to Low Fear animals, indicating an altered HPA-axis. In parallel cohorts fear memory strength and fear generalization were greater in the High Fear line. These data provide the first at-rest physiological profile of fear resilient and susceptible individuals. Future experiments will investigate the behavioral and physiological responses on the High and Low fear lines to aspects of fear learning and memory and to stress.   This work was recently summarized in Nature News http://www.nature.com/news/stress-the-roots-of-resilience-1.11570

 MICROANTOMY OF STRESS EFFECTS ON  MEMORY

How stress mediates its lasting effects on the brain and on memory itself is not fully understood, yet it is an essential puzzle to be solved if the etiology of stress-related disorders is to be identified and successfully treated. As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress interacts with synaptic transmission and memory are only beginning to be identified.  My work was the first to provide anatomical evidence for localization of MR and GR directly at the mammalian synapse. A body of functional data complements our anatomical evidence localizing MR and GR to the postsynaptic membrane. Finally, accumulating data also suggest the possibility that mMRs and mGRs may show an inverted U–shaped dose response, whereby glutamatergic synaptic transmission is increased by low doses of corticosterone acting at MRs and decreased by higher doses acting at mGRs. Future work in my lab will investigate behavioral aspects of these proposed stress mechanisms. This work was recently summarized in our paper in Science Signaling http://stke.sciencemag.org/cgi/content/gloss/sigtrans;2/86/re5

Microanatomy of memory and stress

About me

 

Luke Johnson obtained his PhD from the University of Oxford. He has held postdoctoral and academic postions at Yale University, New York University and Uniformed Services University School of Medicine, Bethesda, Maryland, USA. 

Research in my lab seeks to address fundamental questions in the neurobiology of fear and stress with the aim of providing vital basic knowledge into the way the brain encodes normal and pathological fear memories. Normal fear memory and fear responses are an essential part of any person’s or animal’s survival mechanism. Using fear memory an organism can learn to associate and remember new threats with physical danger. Fear pathology includes the anxiety disorders and post-traumatic stress disorder (PTSD). Anxiety and PTSD can be characterized by pathology in fear memory where responses are amplified and become debilitating. These disorders can thus be thought of as either pathology of the acquisition of fear memory or as pathology in the expression of an otherwise normal fear memory. Knowledge of where and how the brain processes fear and fear learning has greatly increased in the last few decades. This research has identified neural circuits that mediate synaptic plasticity at input synapses to the lateral amygdala (LA). However, knowledge of the cellular encoding of fear memory within the LA network is crucially lacking. My lab seeks to quantify the neural circuits of the LA and also the organization of fear memories encoded by groups of LA neurons. In addition the Lab also seeks to directly understand the microanatomy of how stress interacts with the fear system. One of the key mechanisms of the stress response is regulation of the HPA axis including modulation of adrenal steroids. The Johnson lab also investigates the microanatomy of glucorticoid receptors and their regulation of LA network behavior. We study fear and stress using Pavlovian fear conditioning in rats and mice including phenotype models of mice selected for High and Low fear behavior. I have coined this approach the study of the Microanatomy of Fear and Stress.

 

Publications

Recent publications

Jennifer L McGuire, Hadley C Bergstrom, Clarissa C Parker, Thien Le, Maria Morgan, Haying Tang, Reed Selwyn, Afonso C Silva, Kwang Choi, Robert J Ursano, Abraham A Palmer, Luke R Johnson (2013). Traits of Fear Resilience and Susceptibility in a Selected Mouse Line. European Journal of Neuroscience, Aug 22. PMID: 23968228

http://www.ncbi.nlm.nih.gov/pubmed/23968228

Jennifer Coyner, Jennifer L McGuire, Clarissa C Parker, Robert J Ursano, Abraham A Palmer, Luke R Johnson (2013).  High and Low fear phenotype mice from an advanced intercross line show differences in pMAPK (p44/42 ERK) expressing neuron number in lateral amygdala following Pavlovian fear conditioning. Neurobiology of Learning and Memory, Jun 28. PMID: 23811025

http://www.ncbi.nlm.nih.gov/pubmed/23811025

Bergstrom HC, McDonald CG, Dey S, Fernandez GM, Johnson LR. (2013) Neurons activated during fear memory consolidation and reconsolidation share a common topography in the lateral amygdala. Brain Topogr. 2013 Jan 16 PMID: 23322210

http://www.ncbi.nlm.nih.gov/pubmed/23322210

Bergstrom HC, McDonald CG, Dey , Tang H, Selwyn RG, Johnson LR. (2012) The structure of Pavlovian fear conditioning in the amygdala. Brain Struct Funct. 2012 Nov 20. PMID: 23179863

http://www.ncbi.nlm.nih.gov/pubmed/23179863

Johnson LR, McGuire J, Lazarus R, Palmer AA. (2012) Pavlovian fear memory circuits and phenotype models of PTSD. Neuropharmacology. 2011 Jul 20.  PMID:  21782833

http://www.ncbi.nlm.nih.gov/pubmed/21782833

Choi KH, Le T, McGuire J, Coyner J, Higgs BW, Diglisic S, Johnson LR, Benedek DM, Ursano RJ. (2012) Expression profiles of mitochondrial genes in the frontal cortex and the caudate nucleus of developing humans and mice selectively bred for high and low fear. PLoS One. 2012;7(11):e49183. doi: 10.1371/journal.pone.0049183. Epub 2012 Nov 13. PMID: 23152871

http://www.ncbi.nlm.nih.gov/pubmed/23152871

Choi K, Le T, McGuire J, Xing G, Zhang L, Li H, Parker CC, Johnson LR, Ursano RJ (2012). Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear.

J Psychiatr Res. 2012 Apr 23 PMID: 22534181

http://www.ncbi.nlm.nih.gov/pubmed/22534181

Choi K, Le T, McGuire J, Xing G, Zhang L, Li H, Parker CC, Johnson LR, Ursano RJ. (2012). Analysis of kinase gene expression in the frontal cortex of suicide victims: implications of fear and stress. Front Behav Neurosci. 2011;5:46. Epub 2011 Jul 28.

http://www.ncbi.nlm.nih.gov/pubmed/21847376

Johnson, L.R., Hou, M., Prager, E.M., LeDoux, J.E. (2011) Regulation of the fear network by mediators of stress: norepinephrine alters the balance between cortical and subcortical afferent excitation of the lateral amygdala. Front Behav Neurosci, 5:23. PMCID: PMC3102213.

http://www.ncbi.nlm.nih.gov/pubmed/21647395

Bergstrom HC, McDonald CG, Johnson LR. (2011) Pavlovian fear conditioning activates a common pattern of neurons in the lateral amygdala of individual brains. PLoS One.Jan 12, 6(1). e15698. PMID: PMC3020219.

http://www.ncbi.nlm.nih.gov/pubmed/21264324

Prager EM, Bergstrom HC, Grunberg NE, Johnson LR. (2011) The importance of reporting housing and husbandry in rat research.  Front Behav Neurosci. 2011;5:38. Epub 2011 Jul 27. PMID:  21847375 

http://www.ncbi.nlm.nih.gov/pubmed/21847375

Ursano RJ, Goldenberg M, Zhang L, Carlton J, Fullerton CS, Li H, Johnson L, Benedek D. (2010) Posttraumatic stress disorder and traumatic stress: from bench to bedside, from war to disaster. Ann N Y Acad Sci. 2010 Oct;1208:72-81.PMID: 20955328

http://www.ncbi.nlm.nih.gov/pubmed/20955328

Prager EM, Brielmaier J, Bergstrom HC, McGuire J, Johnson LR. (2010) Localization of mineralocorticoid receptors at mammalian synapses. PLoS One. 5 (12). e14344. PMID: PMC3002274.

http://www.ncbi.nlm.nih.gov/pubmed/21179518

Prager EM, Johnson LR. (2009) Stress at the synapse: signal transduction mechanisms of adrenal steroids at neuronal membranes. Science Signaling, Sep 1;2(86):re5.

http://www.ncbi.nlm.nih.gov/pubmed/19724063