Struggling to forget: Memory researcher studies PTSD causes and cure

Why is it that after a shocking or terrifying experience, some people can move on with life while others — unable to control or contain fear memories — suffer with the stultifying effects associated with post-traumatic stress disorder (PTSD)?

It’s a question that compels memory expert Maria Morena, a postdoctoral scholar in the Hotchkiss Brain Institute, at the Cumming School of Medicine, who is looking to the brain’s circuitry and chemistry for answers. She studies how memories are created, how those memories are tagged with significance like "danger" or "fear," and how the brain works to dim or detag those associations over time.

A key player in that memory mechanism appears to be the endocannabinoid system, a part of the brain that reacts to cannabinoids like marijuana, and also creates its own cannabis-like chemicals. Morena’s hope is that a pharmacological fix can be found that enhances that system when the brain’s detagging or fear extinction process goes awry, as it does in memory disorders like PTSD.

Morena is one of 24 University of Calgary postdoctoral scholars to earn an Alberta Innovates - Health Solutions (AIHS) postgraduate fellowship this year.

University scholars earned 24 of the 34 awards from AIHS, which supports highly competitive and internationally recognized training awards in the area of health and translational research. The university’s recipients (full list below) work in the Cumming School of Medicine, the Faculty of Veterinary Medicine, the Faculty of Kinesiology, the Faculty of Science and the Schulich School of Engineering.

“With the support of AIHS, the University of Calgary is progressively building our understanding of important mental health challenges like post-traumatic stress disorder,” says Ed McCauley, vice-president (research). “These exceptional early career researchers, like Maria, are making invaluable contributions to our leading research teams.”

A highly complementary collaboration

Morena’s fear memory research focuses on the chemical pathways and brain regions associated with their creation and extinction.

“That process is a little bit complicated,” says an understated Morena, who in addition to an AIHS fellowship has earned Eyes High, Cumming School, and The Mathison Centre for Mental Health Research & Education postdoctoral scholarships, and is the winner of the 2015 HBI Postdoctoral Researcher of the Year award. “Fear extinction is not the erasure of memory. It’s not forgetting; it’s the untangling of fear from an associated memory.”

A native of Italy, Morena completed her PhD at Sapienza University of Rome. She was drawn to the University of Calgary to work with her supervisor, Matthew Hill, PhD, a Cumming School of Medicine researcher and professor, member of the HBI, and Tier II Canada Research Chair in Neurobiology.

“It’s a highly complementary fit; Maria brings a lot of knowledge and expertise to the lab,” Hill says. This research combines Hill’s expertise on stress and its impact on neural functioning and behaviour with Morena’s knowledge about in memory systems, consolidation and extinction.

“This is an excellent training environment,” Morena says. “There is a rich collaboration between labs, I have access to the equipment, the techniques, the tools to do my work, and feel very supported.”

“Mental health research is a priority for Alberta,” says Dr. Pam Valentine, CEO Interim of Alberta Innovates – Health Solutions.  “AIHS is committed to supporting advancements in our fundamental understanding of brain mechanisms underlying mental health issues that will ease the burden on Albertans and people throughout the world.  AIHS is also proud to play a role in supporting the next generation of researchers, like Dr. Morena, who will ultimately contribute to highly skilled workforce within the Province.”

Unchecked fear and anxiety likened to a runaway, reinless horse carriage

Morena is searching for clues about fear memory extinction in two parts of the brain — the amygdala and the prefrontal cortex — and in the communication between the two. The amygdala is the part of the brain that assigns environmental and experiential cues what neuroscientists call valence, or emotional significance. The prefrontal cortex regulates thoughts and governs social control.

“Think of the amygdala as the horses on a carriage, and the prefrontal cortex as the reins,” Hill says. What brain imaging demonstrates is that when the amygdala is running unchecked, there is more fear, more omnipresence of a memory, more anxiety. By contrast people who have a more active prefrontal cortex (i.e.  a lot of control over the reins) are really good at extinguishing bad memories.

The buffer between those two regions could be the endocannabinoid system, which responds to the brain’s own version of cannabis in much the same way as the brain produces and responds to endorphins, its own version of morphine.

Okay, so what about cannabis?

It is widely documented that some people with PTSD self medicate with cannabis, but what isn’t yet understood, Morena and Hill say, is whether there is any scientific basis to support the claims that marijuana can help.

Morena’s AIHS-funded research, which examines the involvement of the endocannabinoid system in fear memory extinction in animal models, will bring more sound data to that scientific discussion.

Could the introduction of a cannabinoid from outside the brain boost the endocannabinoid system, and get fear memory extinction back on track? That’s what Morena is trying to find out with research that is paving the way, perhaps, for a new potential therapeutic intervention: a drug that could at once calm the horses and strengthen the reins as it were, alleviating the anxiety and stress associated with memory disorders like PTSD.

This week (March 14 – 20) marks Brain Awareness Week, a global campaign to increase public awareness of the progress and benefits of brain research.

Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six strategic research themes guiding the University of Calgary toward its ‘Eyes High’ goals.

2015 AIHS Postgraduate Fellows

Following are the recipients of the 2015 competition, together with their sponsoring supervisors (in brackets) and project title:

Elliot Brown, (Zelma Kiss), Clinical Neurosciences 
"Integrating Electrophysiology and Neuroimaging Markers for Treatment Prediction in Deep Brain Stimulation for Depression"

Lisa Buchy (Jean Addington), Psychiatry 
"Brain Effects of Prospective Memory Training in First-episode Schizophrenia"

Burkinshaw, Brianne ( Tao Dong), Ecosystem and Public Health 
"Structural and Functional Characterization of a Vibrio Cholerae Type VI Secreted Effector Protein in Complex with T6SS Chaperone, Tip and Immunity Protein"

Maria Gandini (Gerald Zamponi), Physiology & Pharmacology 
"Regulation of Voltage-gated Calcium Channels by Rabconnectin-3B: Insights into 18q-syndrome"

Deepak Kaushik (Voon Wee Yong), Clinical Neurosciences 
"EMMPRIN and Monocarboxylate Transporters on Astrocytes: Relevance to Multiple Sclerosis"

Pierre-Yves Lagace, Pierre-Yves (Steven Boyd), Radiology 
"Monitoring Early Changes in the Human Knee following ACL Reconstruction"

Arthur Lau (Daniel Muruve), Medicine 
"Intravital Multiphoton Microscopy to Characterize Inflammation and Tubular Epithelial Cell Biology in the Pathogenesis of Kidney Disease"

Benamin Lau (Stephanie Borgland), Physiology & Pharmacology 
"Cellular Mechanisms Underlying Compulsive Behaviour in the Orbitofrontal Cortex"

Fernando Lopes (Derek McKay), Physiology & Pharmacology 
"Mitochondria, Endoplasmic Reticulum (ER Stress) and Autophagy Regulate Gut Permeability"

Jessica McNeil (Chistine Friedenreich), Oncology 
"Standing Up to Prevent Breast Cancer: Energy Compensation and a Non-exercise/Light-intensity Physical Activity Intervention to Prevent Breast Cancer"

Said M'Dahoma (Gerald Zamponi), Physiology & Pharmacology 
"Optogenetic Approaches towards Dissecting Chronic Pain"

Christine Michaels-Igbokwe (Gillian Currie), Pediatrics 
"Incorporating Individual Preferences into Economic Evaluations: An Assessment of the Impact of Preference Heterogeneity on Estimates of Cost Effectiveness"

Eng Kuan Moo (Walter Herzog) 
"Understanding the Mechanism of Load Bearing in Articular Cartilage on the Molecular Scale"

Maria Morena (Matthew Hill) Cell Biology & Anatomy 
"Examination of the Role of Endocannabinoids in the Amygdala-prefrontal Cortex Circuit during the Extinction of Aversive Memories: Implications for the Treatment of Post-traumatic Stress Disorder"

Ciaran Murphy-Royal (Jaideep Bains) Physiology & Pharmacology 
"Stress-induced Functional Plasticity in Neuron-glia Interactions"

Kewir Nyuyki (Quentin Pittman), Physiology & Pharmacology 
"Dissecting the Role of Neuropeptides in Behavioral Comorbidities Associated with Inflammatory Bowel Diseases"

Christopher Percival (Benedikt Hallgrimsson), Cell Biology & Anatomy 
"The Contribution of Angiogenesis Dysregulation to Midfacial Hypoplasia"

Priyatha Premnath (Roman Krawetz), Surgery 
"Will Enhanced Repair Capacity in Subchondral Bone Delay Onset of OA?"

Cailin Rothwell (Kenneth Lukowiak), Physiology & Pharmacology 
"The Influence of Environmental Stressors on Memory Forming Ability across the Lifespan of Lymnaea"

Giriraj Sahu (Raymond Turner), Cell Biology & Anatomy 
"Molecular Activation of IsAHP Channel, IKCa, in Hippocampal Pyramidal Neurons"

Hongfu Sun (Bruce Pike)Radiology 
"Assessment of White Matter Pathology in Multiple Sclerosis using Quantitative Susceptibility Mapping"

Le Tang (Tao Dong) Ecosystem and Public Health 
"Characterization of Type VI Secretion Systems in the Emerging Human Pathogen Photorhabdus Asymbiotica"

Sophia van Hees, Sophia (Penny Pexman) Psychology 
"Learning-Related Change in the Neural Dynamics of Language Processing"

Beibei Wang (Peter Tieleman), Biological Sciences 
"The Architecture of the Mycobacterium Tuberculosis Cell Envelope"