Faculty of Health,
School of Biomedical Sciences
BiographyLuke Johnson PhD
MICRO ANTATOMY OF FEAR AND STRESS
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.
MICROANATOMY OF PAVLOVIAN FEAR
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
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
- Visiting Fellow
Faculty of Health,
School of Biomedical Sciences
- Kelvin Grove Q Block Membership
Institute of Health Biomedical Innovation (IHBI),
IHBI Health Projects
- Kelvin Grove Q Block Membership
Translational Research Institute (TRI)
Institute of Health and Biomedical Innovation (IHBI)
Department of Psychology and Counselling
My research program investigates fundamental questions in the neurobiology of fear memory and stress with the aim of providing vital basic knowledge into the way the brain encodes normal and pathological fear memories. Experimental models used include: Pavlovian fear conditioning, quantitative microanatomy of phosophorylated proteins and adrenal steroid receptors in amygdala networks, and the effect of brain injury on fear memories. My Lab seeks to measure and understand the organization of fear memories encoded by amygdala neurons and their interaction with regulators of stress. We have also established a colony of fear resilient and fear susceptible mice - we are currently identifying the physiological traits associated with these fear behavior phenotypes. I have coined my research program the study of the Microanatomy of Fear and Stress.
- McGuire J, Bergstrom H, Parker C, Le T, Morgan M, Tang H, Selwyn R, Silva A, Choi K, Ursano R, Palmer A, Johnson L, (2013) Traits of fear resistance and susceptibility in an advanced intercross line, European Journal of Neuroscience, 38 (9), pp. 3314-3324.
- Coyner J, McGuire J, Parker C, Ursano R, Palmer A, Johnson L, (2014) Mice selectively bred for High and Low fear behavior show differences in the number of pMAPK (p44/42 ERK) expressing neurons in lateral amygdala following Pavlovian fear conditioning, Neurobiology of Learning and Memory, 112, pp. 195-203.
- Bergstrom H, McDonald C, Dey S, Fernandez G, Johnson L, (2013) Neurons activated during fear memory consolidation and reconsolidation are mapped to a common and new topography in the lateral amygdala, Brain Topography, 26 (3), pp. 468-478.
- Bergstrom H, McDonald C, Dey S, Tang H, Selwyn R, Johnson L, (2013) The structure of Pavlovian fear conditioning in the amygdala, Zeitschrift fur Anatomie und Entwicklungsgeschichte, 218 (6), pp. 1569-1589.
- Johnson L, McGuire J, Lazarus R, Palmer A, (2012) Pavlovian fear memory circuits and phenotype models of PTSD, Neuropharmacology, 62 (2), pp. 638-646.
- Prager E, Bergstrom H, Grunberg N, Johnson L, (2011) The importance of reporting housing and husbandry in rat research, Frontiers in Behavioral Neuroscience, 5, pp. 1-4.
- Choi K, Le T, Xing G, Johnson L, Ursano R, (2011) Analysis of kinase gene expression in the frontal cortex of suicide victims: implications of fear and stress, Frontiers in Behavioral Neuroscience, 5, pp. 1-9.
- Bergstrom H, McDonald C, Johnson L, (2011) Pavlovian fear conditioning activates a common pattern of neurons in the lateral amygdala of individual brains, PLoS One, 6 (1), pp. 1-8.
- Johnson L, Hou M, Prager E, LeDoux J, (2011) Regulation of the fear network by mediators of stress: norepinephrine alters the balance between cortical and subcortical afferent excitation of the lateral amygdala, Frontiers in Behavioral Neuroscience, 5, pp. 1-7.
- Prager E, Brielmaier J, Bergstrom H, McGuire J, Johnson L, (2010) Localization of mineralocorticoid receptors at mammalian synapses, PLoS One, 5 (12), pp. 1-10.