Q&A with Alex Major, PhD Candidate

Alex Major, PhD Candidate, is studying specialized neurons that play a role in working memory. With a curiosity for the pharmacology of the brain, he hopes his research will help establish a better understanding of the frontal cortex, as well as effective treatments for diseases like Alzheimer’s. A trainee with the Graduate Program in Neuroscience, Major is supervised by Robarts scientist Stefan Everling, PhD.
In this Q&A, Major discusses his current research projects and the valued support he receives from the Alzheimer Society of London and Middlesex.

What current research projects are you working on?

Along with other members of the Everling lab, I explore the function of the neurotransmitter acetylcholine in the frontal cortex. This neurotransmitter activates cholinergic receptors to modulate neuronal activity throughout the brain. I investigate how specialized neurons in frontal cortex, thought to be involved in working memory and representation of abstract rules, change their activity profile after targeting these cholinergic receptors.
For example, we have found that blocking these receptors reduces neurons' ability to maintain rule information over short-term working memory intervals. We are currently investigating whether stimulation of specific subtypes of cholinergic receptors can lead to more robust representation of rules in working memory.
What is the potential impact of this research?

Common problems in Alzheimer’s disease include a lack of acetylcholine, an important chemical for attention and memory, and the accumulation of toxic proteins such as amyloid beta and hyperphosphorylated tau. This is thought to lead to cognitive deficits such as loss of short-term memory. It is because of this deficit of acetylcholine that one of the principal treatments for Alzheimer’s disease is acetylcholinesterase inhibitors, which slow the breakdown of any remaining acetylcholine.
My projects look at the frontal cortex, a brain region important for complex cognitive functions, and explore the role of these cholinergic receptors at the level of individual neurons.

Recently-developed drugs targeting a specific subtype of cholinergic receptors, M1 muscarinic receptors, can imitate the action of acetylcholine and may also counteract toxic protein accumulation. Currently in clinical trials, we hope these drugs will improve cognition and possibly even slow the progression of neurodegeneration.

What type of support and recognition have you received for your research?

I am extremely grateful to receive scholarships from the Natural Science and Engineering Research Council of Canada (NSERC) and the Alzheimer Society of London and Middlesex.

This local branch of the Alzheimer Society was generous to invite me for a tour of their offices and explain the support system they provide for families affected by Alzheimer's disease and other dementias. From educational resources and counselling to in-home memory screening and social events, I'm grateful for the services they provide to our community. This experience was important for me to appreciate the weight of dementias outside of my typical lab setting.

What motivates you in pursuing this type research?

The brain has been a curiosity of mine since high school. How can this single organ perceive the world around us, control our bodies, think, and remember? What causes the brain to degenerate or produce erratic behaviour? The pharmacology of the brain is especially interesting to me. Our neurons are constantly exposed to varying levels of neuromodulators that adjust the activity of our brain circuitry, but we are far from comprehensively understanding how this occurs and why our current pharmacological treatments are effective.

What is your education background?

After completing my BMSc with Honours Specialization in Physiology and Pharmacology at Schulich Medicine & Dentistry, I finished my MSc in Neuroscience in the Everling lab. I'm currently in the second year of my PhD in Neuroscience with the Everling lab.

What's next for your research?

My future PhD work will explore the effects of stimulating specific cholinergic receptors subtypes in frontal cortex and how they may be involved in cognitive behaviour.