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Getting the neurons firing

The networks inside our minds
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It’s almost like a spark. As I put fingers to keys to write this article, and as you read and understand it, tiny electrical signals pass between synapses within our brains. Although estimates vary, some say there are around one billion neurons in the brain and up to one hundred trillion synapses between these neurons. What makes this number so staggeringly large is the fact that synapses and neurons connect with each other in many different and constantly changing ways, multiplying the total number of patterns. In an interview with The Varsity, Dr. Sheena Josselyn, a neuroscientist at U of T, quotes Richard Morris and colleagues in the Annual Review of Neuroscience: “It is a big leap from the synapse to the behaving animal — and the chasm in between is the neural network.”

These neural networks may be one of the most complex systems we know of, but recent technological advances have lead to significant advances in our understanding of the brain and how it works. Research into neural networks at U of T is helping us to understand how we learn, why we feel stress, and how to treat the causes of mental illness.

Learning and Memory


Amidst the loud music, stale beer, late-night pizza, movie marathons, and time-consuming extra-curriculars of undergrad, it’s often hard to remember that we’re actually here to learn. But as exams loom on the horizon, many of us will need a little insight into how to learn effectively — or maybe just quickly.

In the brain, learning begins as physical changes to the connectivity of individual neurons and overall neural patterns, known as synaptic memory consolidation.  This important process occurs in a structure near the centre of the brain known as the hippocampus, and involves changes in the expression of proteins in the neurons within minutes of a learning episode. Over longer periods of time, memories that were first encoded in the hippocampus move into more stable, long-term storage in the pre-frontal cortex. This process is called systems consolidation. Some hypothesize that systems consolidation occurs only while we’re asleep. So pulling an all-nighter may not be the best way to cram all of European history into your head. However, getting a decent night of sleep after a long day’s studying may, in fact, help to lock that information into your neural networks.

Josselyn, a senior scientist in neurosciences and mental health at SickKids research institute and a U of T associate professor of physiology, studies learning and memory, with a focus on fear memory.

“Using a variety of different methods we have been able to identify the precise brain cells within the amygdala that store key components of a fear memory.  When we selectively ablate these neurons, it is as if the fear memory is erased!  We are very excited about this work and are now examining whether this general principle applies to other types of biologically important memories (such as memory of a food location, etc),” she writes.

Being able to selectively erase certain memories is amazing enough by itself, but Josselyn anticipates practical applications as well. “By being able to identify and then manipulate the small number of brain cells involved in a given memory, we hope to one day help people that either remember too much (or too vividly), such as those suffering from post-traumatic stress disorder (ptsd).  If we can identify the precise brain cells that make up this intrusive and unwanted memory, perhaps we can decrease just this memory (leaving all other memories intact).”

As for learning, Josselyn has some clear, practical advice for students, which stems from her neural expertise and experience as a professor.

“Don’t cram for an exam, study a little bit over a longer period of time.  In flies, slugs, and mice, it has been clearly shown that memory is better when learning bouts are spaced apart. Ebbinghaus, one of the forefathers of psychology, noted this trial spacing effect in his own memory. Studying a little bit every day is one good piece of advice that translates from the lab to the classroom!

A second principle is attending to what is being learned. If you want to learn and remember something, don’t multi-task. Divided attention is bad for memory.  We see this in the lab (and I see it when I teach in the classroom). Bottom line: in class or when studying, turn off your phone, shut down your Facebook page, and refrain from following what Lindsay Lohan is tweeting about.  You will learn and remember much better.”


For students, stress and learning seem unavoidably linked. From a neurophysiological point of view, however, a stressful exam season may be affecting more than your emotional state and caffeine intake. When you’re stressed, certain hormones are released into your brain and these can negatively affect your ability to form new memories
and retrieve existing ones.

One stress-related hormone, cortisol, is known to impair memory formation and retrieval, especially if there are high levels of it for long periods of time. Cortisol is known to negatively affect the functions of the pre-fontal cortex. This area of the brain is where long-term memory storage occurs, and it is also responsible for executive functions such as decision-making and working memory. Working memory, somewhat like ram on a computer, is the information that you are actively using or holding in mind at a given time. Especially when combined with decision-making, working memory is important for handling tasks such as, for example, writing three essays about Shakespeare in three hours. Cortisol in the pre-frontal cortex can also lessen your mental flexibility and reduce your ability to focus.

When you add up the effects of stress on learning and recalling knowledge, it may be more valuable to relax before your exams and between study sessions, rather than using those extra minutes to cram.

Mental Illness 

For many students, stress doesn’t end after the last exam. Beyond the normal demands of school, work, family, and social life, many of us must also cope with mental health issues. An estimated 3.2 million young people in Canada are at risk of mental illnesses and students are among the demographics most at risk.

Mental illness is widely studied but not well understood. Researchers can detect structural and neuronal changes in the brain that characterize different disorders, but have little insight into causes and remedies. At present, most mental health treatments focus on mitigating symptoms, and are only effective in a portion of cases. For example, only about 50 per cent of patients with major depressive disorder find treatment helpful.

Dr. Roger McIntyre, a professor of Psychiatry and Pharmacology at U of T, studies persistent mood disorders. In an email interview with The Varsity, he explained some of the flaws in current mental health treatment, and how his work is offering new alternatives.

“Available treatments for depression and dementia are not ‘disease modifying,’ because they do not target the pathology but suppress the symptoms. We hope our work provides a disease modifying treatment and possible prevention for mood and degenerative disorders and possibly a cure.”

McIntyre is currently studying the role of insulin in the brain. Insulin is usually associated with diabetes, but it is also active in the brain — affecting learning, memory, cell survival, and cell death. McIntyre emphasizes the link between insulin’s role in diabetes and the brain.

“It is better to prevent problems from the beginning rather than treating them after they have started, and we also believe that younger people, by living healthier lifestyles and avoiding diabetes and insulin resistance, would be at lower risk of developing depression and dementing disorders, since we know that metabolic problems [such as diabetes] cause [them].”

McIntyre’s work has also shown that administering insulin in the brain via nasal inhalation could be an effective treatment for the cause of these disorders, going beyond merely mitigating symptoms.

Overall, the field of neuroscience is only beginning to explore the endless possibilities of the brain and to what magnitude it affects one’s wellbeing. “Technological advances have allowed us for the first time to answer some very fundamental questions about how the brain works,” writes Josselyn.

When asked what he saw as frontiers for neuroscience in the near future, McIntyre had a lot to say about the dizzying potential of this field: “Major advances will be elucidating intracellular mechanism, mediating brain disease, characterizing brain circuits, and understanding more fully the interrelationship of how physical health affects the brain.” Josselyn concluded more simply, “It’s an exciting time to be a neuroscientist!”