Dr Luke Johnson

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