Dopamine evoked by reward cues helps us learn about our world, according to Concordia research
Three students in the Faculty of Arts and Science have completed their undergraduate careers at Concordia with a prestigious feather in their caps: a research article published in the highly respected academic journal Nature Neuroscience.
Working under the supervision of Mihaela Iordanova, Concordia associate professor of psychology, Etienne Maes, Alexandra Usypchuk and Megan Lozzi conducted a series of experiments that clarified the role of the neurotransmitter dopamine in learning.
The researchers used a light-sensitive opsin to hamper the firing of dopamine neurons to reward-predicting cues. They found that cue-evoked dopamine signals function more as errors in predictions than as reward predictions.
Melissa Sharpe of UCLA and Chun Yun Yang, Matthew Gardner and Geoffrey Schoenbaum at the National Institute of Drug Abuse in Baltimore co-authored the paper.
Getting without learning
By attenuating dopamine firing in the brains of rats, the researchers wanted to understand how the neurotransmitter affects learning about upcoming reward.
They used rats that had been genetically modified and expressed a light-sensitive opsin in dopamine neurons. This allowed them to limit the dopamine signal at precise points in time. The rats were placed in an environment where they were trained to expect a reward based on a specific cue, usually a kind of sound or flashing light. A cue that signals upcoming reward normally also evokes spiking in dopamine neurons. So, the researchers disrupted the firing of dopamine neurons by shining a light on them.
“We wanted to see if the rat still expected a reward,” Maes says. “And it did. While we were disrupting the dopamine, we were not disrupting the prediction. However, the disruption did prevent the rat from learning from that cue.”
This, they found, had a profound effect on associative learning: the cue with the attenuated dopamine signal would not reinforce learning to other cues that preceded it. This meant that the dopamine signal evoked by cues that predict reward did not represent a prediction about the upcoming reward but a prediction error based on successive temporal states. This, the researchers say, has implications for the way we learn on a moment-by-moment basis and how we predict our world.
“Our data provides evidence that each bit of time is predicting the next bit of time and this predictability results from the back-propagation of an error signal carried by the phasic firing of dopamine neurons across temporal intervals,” Iordanova explains.
“The extent to which organisms learn about their environment in a moment-to-moment basis naturally results in an ability to predict the next state of the world. This robs one of the excitement of surprise that comes with unpredictability. The extent to which individuals strive to reinstate the joie de vivre and engage in sensation seeking might correlate with this learning and the lack of dopamine response across predictable points in time.”
Maes will be pursuing his studies in the fall at McGill University, where he is enrolled in the MD-PhD program. His Concordia education, and specifically the minor offered by the university’s Science College in multidisciplinary science, provided him with a unique experience cooperating with fellow researchers from across multiple departments. The publication in Nature Neuroscience is a tremendous source of pride.
“To be published at all during undergrad is incredibly exciting and is a testament to the hours of hard work that my colleagues and I have devoted to this project,” Maes notes. “This publication from the Iordanova Lab further exemplifies the cutting-edge research being conducted at Concordia and the community spirit that encourages such collaborative projects.”
The study was supported by the Intramural Research Program at the National Institute on Drug Abuse (NIDA), grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and a Concordia Undergraduate Student Research Award.
Mihaela Iordanova wins the 2020 Canadian Association for Neuroscience Young Investigator Award
On April 17, the Canadian Association for Neuroscience (CAN) announced that Mihaela Iordanova, an associate professor in the department of Psychology, is the winner of the 2020 CAN Young Investigator Award.
“I am utterly elated and incredibly grateful to the committee for winning this award,” says Iordanova.
“To me, this award is essentially a recognition that my approach to neuroscience is yielding important discoveries and that my work is of interest and value beyond my immediate environment. It is an incredible achievement to have people I aspire to tell me, and the world, that I am making an important contribution to neuroscience. It is humbling yet really invigorating.”
“Dr. Iordanova’s research has implications for learning and memory disorders as well as the management of addiction and anxiety, conditions that can be treated clinically by behavior modifying therapies,” notes the CAN in their official announcement.
“Dr. Iordanova has already proven to be an exemplary scientist – we are proud to present her with the CAN 2020 Young Investigator Award.”
Iordanova is a Canada Research Chair (Tier 2) in Behavioural Neuroscience, and a 2016 NARSAD Young Investigator. She was the recipient of a K99/R00 Pathways to Independence award from the National Institute on Drug Abuse in 2012.
Studying how we learn
Iordanova’s research combines sophisticated behavioral models with the latest neuroscience techniques to understand how learning is implemented in the brain. Her work focuses on studying how the brain establishes associative relationships between events in the environment, how it updates prior knowledge with new information, and how it can make novel inferences about the world based on its current knowledge.
Associative learning underscores our ability to make (accurate) predictions about the world, which in turn allows us to behave in a way that is appropriate to a given situation. Iordanova has made key discoveries in the area of associative learning and behavioural neuroscience.
To understand how the brain establishes associative relationships, she has honed in on uncovering the brain mechanism of prediction error, the critical teaching signal that instructs learning. Prediction error occurs when reality fails to match predictions. Iordanova’s research sheds light on how this process occurs in the brain.
The ability to update previously established predictions and in turn modify behaviour allows us to reduce or even eliminate inefficient actions.
A second important concept Iordanova is studying focuses on this process of updating specifically when our predictions about upcoming events surpass reality.
This form of learning leads to a downward adjustment of our predictions and an inhibition of established behaviour. Work done in the Iordanova laboratory studies this learning across a variety of conditions and has led to important insight into cortical and subcortical brain regions in this learning.
Finally, the Iordanova laboratory also investigates how emotional memories can become linked to memories from the past or generalized to newly acquired memories, thus adding an emotional component to normally neutral memories. For example, a specific cue can be associated with a fear inducing outcome, and a second, initially neutral cue, once associated with the first cue, may become emotionally charged (fear producing). Iordanova has been studying the neurobiology of how emotional memories propagate across the memory network.
By bringing together many different aspect of learning, from initial learning to updating, across different emotional states, from appetitive (reward) to aversive (fear), Iordanova’s research has led to a better understanding of the complex interaction of brain regions, and signals that promote learning and memory.
Praise from her colleagues
The importance of Iordanova’s work goes beyond the basic science of understanding how the brain responds to reward and fear – it is relevant to clinical settings as behavioural and pharmacological approaches used to reduce unwanted behaviour are the backbone to clinical treatments for anxiety and addiction, such as cue exposure therapy.
“Mihaela’s focus is to bridge the gap between the appetitive and aversive fields and understand how these events interact behaviorally and in the brain,” says Geoffrey Schoenbaum, branch chief and distinguished investigator at the National Institute on Drug Abuse.
“This line of research is completely novel and will sure make an important impact on the field. Thus she has continued to make fundamental discoveries with regard to behavioral neuroscience and has become a strong leader in the field.”
“Dr. Mihaela Iordanova has proven to be a deep-thinker who has made unique and very important contributions to the field of neuroscience,” says Cecilia Flores, a professor McGill University’s department of Psychiatry.
‘This award has given me the green light’
“I have had some ideas float around in my head about what new things we could do,” says Iordanova about her future plans.
“I have wanted to expand the team and get into some questions on categorization. We are constantly putting information into categories. Right now, during the COVID 19 crisis, we are probably all preoccupied with classifying places and objects that may increase our likelihood of encountering the contagion. It’s an adaptive and efficient way of processing information. I want to start looking into how the brain classifies information from the environment on the basis of predictive history.”
“The award has given me the green light to bring those ideas forward and explore their potential realization.”
Iordanova’s research is supported by federal and provincial funding agencies including the Canadian Institutes of Health Research, the National Sciences and Engineering Research Council, and Fonds de Recherche du Quebec – Nature et Technologies. She is a member of the College of reviewers and serves on the editorial boards of eLife, The Journal of Neuroscience, Scientific Reports, Behavioural Neuroscience, Learning & Behaviour, and The Journal of Experimental Psychology: Animal Learning and Cognition.
Curb the habit — permanently
Iordanova, an assistant professor in the Department of Psychology and Canada Research Chair in Behavioural Neuroscience, will receive $677,025 over five years.
Her research project will look at the neural circuity involved in the modification of unwanted behaviour, specifically behaviour related to sugary treats. Her goal is to uncover ways that will reduce such habits permanently. A member of the Center for Studies in Behavioral Neurobiology, Iordanova will work with her team to apply a combination of two behaviour modification protocols — overexpectation and extinction.
Overexpectation and extinction are essentially two sides of the same coin. In overexpectation, behaviour is modified by manipulating one’s expectations, whereas in extinction this is done by manipulating – or omitting – the delivery of the outcome that serves to reinforce the unwanted behaviour. Iordanova will use both paradigms to understand how the brain can alter behavioural patterns in a wholistic task-independent manner.
Once armed with how behaviour can be altered using these paradigms, Iordanova and her team will share new ways to mitigate potentially bad behaviours.
‘Our lab will push the boundaries’
Mihaela Iordanova, one of four new Canada Research Chairs, tackles the neurobiology of fear
Mihaela Iordanova, an assistant professor in Concordia’s Department of Psychology, is the new Canada Research Chair in Behavioural Neuroscience. Her lab — which studies fear, reward and memory — is a Canada Foundation for Innovation (CFI)project with a total value of approximately $375,000 (including cash contributions from Québec’s Ministère de l’Éducation et de l’Enseignement supérieur and from Concordia, and in-kind contributions from equipment suppliers).
What is the goal of your research?
Mihaela Iordanova: The research in my lab focuses on understanding the behavioural and neural mechanisms that guide learning about the world around us. We seek to understand what neural circuits are involved in how we come to expect rewarding or fearful events, as well as how we update these expectations in our dynamic environments.
Updated memories can be fickle and subject to disruption, so we aim to develop ways to strengthen such recent memories. Sometimes, the stimuli that we base our expectations on are complex mnemonic events, which combine cues from diverse modalities such as a particular place or time. Our work also seeks to understand the nature of such complex memories.
What do you hope will be the impact on society and your field of study?
MI: Our work examines both fear and reward, and we hope to integrate and better understand the interaction between these opposing motivational states.
We seek to uncover which circuits, as opposed to individual brain areas, process reward and fear, as well as provide a novel understanding of their interaction behaviourally and neutrally, something that has remained largely elusive but has attracted much interest in recent times.
Indeed, exaggeration in the processing of rewarding events translates to similar exaggerated processing of aversive events, and this has been linked to addiction.
The paradigms we use in our work represent animal models of psychopathologies such as addiction, obesity and anxiety. Examining the integration of fear and reward will provide a novel take on the psychological and neural mechanisms of these conditions. Ultimately, we hope to establish behavioural paradigms, which can inform and lead to the development of novel treatments for addiction, obesity and anxiety.
Now that you’ve won a Canada Research Chair (CRC), what next steps do you hope to take?
MI: The CRC will allow the lab to continue our research on fear and reward, but will also provide us with a way to delve into these questions using advanced optogenetic, pharamacogenetic and real-time neural recording techniques.
This provides a means to elucidate the neural mechanisms of reward and fear from the cell to the circuit level. Our lab will push the boundaries of the neurobiology of fear and reward expectation, as well as memory formation by integrating theoretical stipulations of learning with neural techniques that prod brain function in real time and examine how alterations in brain function influence information processing.
Meet Concordia’s new Canada Research Chairs
From poetics to behavioural neuroscience, these professors advance ‘several areas of strategic importance’
This week, the Honourable Kirsty Duncan, Minister of Science, announced a $260-million investment in the Canada Research Chairs (CRC) program. The funding will support a total of 305 new and renewed chairs, appointed at 53 post-secondary institutions across the country.
Mihaela Iordanova, an assistant professor in the Department of Psychology, is the new Canada Research Chair in Behavioural Neuroscience.
Quick facts on the Canada Research Chair Program
- Created in 2000, the Canada Research Chairs Program has helped attract and retain some of the world’s most accomplished and promising minds. Canada Research Chairs deepen our knowledge, enhance our quality of life and grow our economy.
- Nearly 1,700 Canada Research Chair holders are working at over 70 post-secondary institutions across the country in a wide range of fields.
- The Research Support Fund covers a portion of the costs associated with managing research at Canadian institutions such as administrative support, training costs for workplace health and safety, maintenance costs for libraries and laboratories, and administrative costs.
- The Canada Foundation for Innovation gives researchers the tools they need to innovate by investing in state-of-the-art facilities and equipment in Canada’s universities, colleges, research hospitals and not-for-profit research institutions.
Pavlovian Society featured faculty
Dr. Mihaela Iordanova is an Assistant Professor in the Department of Psychology at Concordia University. Dr. Iordanova earned her doctorate in the laboratory of Dr. Fred Westbrook at the University of New South Wales, and conducted her postdoctoral training at both Cardiff University and the National Institute of Drug Abuse. Currently, the Iordanova Lab employs cutting-edge techniques with meticulously-designed, theoretically-based behavior to study how the brain changes in response to prediction error and fine tune our understanding of this type of learning.
What project are you currently most excited about in your lab?
We are currently looking at how fear memories are inferred across time. Whether rats do this retrospectively or prospectively makes such memories differentially dependent on the original emotional event and are thus underscored by different associative architecture. We are using the Fos-lacZ transgenic rat to determine whether deletion of neuronal ensembles activated by the original emotional memory affects the integrity of inferred memories. This allows us to look at the interdependence of memories and explore how different brain areas and circuits support this learning. I am very excited about this, because it exemplifies the complexity of normal memory but also bears relevance to the difficulty of treating trauma-based psychopathologies in humans.
Are there any benefits to being a woman in learning?
It is a great time to be a woman in the field of learning and neuroscience. Awareness of the hardship faced by women is growing fast and I feel lucky that this is happening in my lifetime. It also gives us an opportunity to make a difference that will benefit the next generation of female researchers. I also feel really blessed to be part of a network comprised of strong like-minded junior and established female scientists.
What advice would you give yourself 10 years ago?
Travel more. You don’t have to spend every weekend in the lab to be productive.
What is a fun fact about you that people might be surprised to know?
I love jumping, so I recently bought a fitness trampoline. Now, I mostly spend my time negotiating with my kids when my turn to jump is.
What has been your favorite place you’ve traveled to so far?
A little village in the northeastern part of Bulgaria right by the Romanian border on the Black Sea. I went there with a close friend many years ago and we spent the time philosophizing about life, while listening to music, smoking cigarettes, and drinking wine.
Who is your favorite band or artist?
This changes all the time for me. Right now, it’s Parov Stelar. He combines some of my favourite music genres – jazz, house, electro.
Finally, what do you love about the Pavlovian Society?
The great thing about the Pavlovian Society is that it has really deep behavioral roots, yet this does not come at the expense of cutting-edge neuroscience. Without understanding behavior, there is no hope of understanding brain function. The Pavlovian Society does not compromise and really has this right. I am really proud to be a part of it.