Dr. Daniela Popa
Team Leader École Normale Supérieure de Paris
Postdoctoral Fellow Rutgers University, New Jersey, USA
PhD PhD in Neurosciences, Paris University, France
Growing up in Romania, Dr. Daniela Popa went to medical school without much of an idea from her family or from the media of what working in a hospital would entail. But she had always been puzzled that behavioral differences across people, such as excelling at math versus writing, could arise from the "same" brain structure. So when one of her physiology lecturers, Dr. Leon Zăgrean, who ran one of the only neuroscience labs in Romania at the time, invited her to spend time in his lab, she immediately said yes. Her introduction to the study of neural circuits in the context of neuropathologies in Dr. Zagrean's lab was a formative experience that shaped the trajectory of her own research. Today, Daniela leads the “Neurophysiology of Brain Circuits” team as a co-principal investigator in the Institut de Biologie at École Normale Supérieure, Paris, where her research focuses on multi-region interactions in neural function and dysfunction with the goal of informing better treatments.
Daniela enjoyed research even while in medical school, attending conferences and doing a small independent project on sex differences in sleep patterns. While deliberating over a career in neurology, she came across an opportunity to go to France for a master’s degree. Curious to learn more about academic research, she joined the group of Dr. Michel Hamon, who studied sleep in rodents using tools ranging from molecular pharmacology to behavior. Daniela discovered that she absolutely loved basic research and the ability to delve deeper into mechanistic understanding. Moreover, she found an inspiring role model in her primary mentor, Dr. Joëlle Adrien, who she describes as a strong, independent woman in science. Things seemed to fall into place as the institute had just launched fellowships for international medical doctors interested in pursuing a PhD in psychiatry—it was perfectly tailored for Daniela, and she stayed on after completing her masters to continue her research on sleep.
During her PhD, Daniela focused on the serotonin system and its link not just to sleep but also emotional disorders like depression. Selective serotonin reuptake inhibitors (SSRIs) are in fact among the most commonly prescribed antidepressants. Using mice with serotonin transporters or receptors deleted or ‘knocked out’, she could study serotonergic action with a specificity that earlier pharmacological methods lacked. In one study using knockouts of serotonin transporters, she found that increased serotonergic levels led to sleep impairments as well as depression-like behaviors, which could be reversed by pharmacological interventions during a critical period in early life. Thus, alteration of serotonin reuptake during development, whether by genetic or external factors, could have a lasting impact on serotonin function in adulthood. Moreover, she identified which of the many serotonin receptor types, and thus which neural pathways, were implicated in these effects.
After her PhD, Daniela secured independent funding to do a short stint in another lab to study the mechanisms behind SSRIs using new techniques. Although she had been warned about a toxic lab culture, she was determined to learn what she could and leave the lab within the year. She was appalled by the harassment that several members of the lab experienced and the relative inaction by the department – something Daniela believes would be unacceptable today. Daniela found it hard to work in that environment, especially when the abusive PI did not provide her with the necessary resources and interfered with the publication of her work. Nonetheless, her endurance, financial independence, and supportive collaborators helped bring the project to completion.
For her main postdoc, Daniela wanted to shift to more functional studies to identify what patterns of neural activity ultimately underlie different behaviors. She met Dr. Denis Paré at the annual Society for Neuroscience (SfN) meeting, and after an engaging conversation, asked for a postdoctoral position in his lab at Rutgers University in New Jersey. Even though she had no prior experience with electrophysiology, he was impressed by her enthusiasm for the research questions his lab was pursuing and her motivation to learn the new techniques, and he was happy to have her join the lab. Continuing with her interest in emotional processing and sleep, she focused on limbic circuit function in fear-conditioning behaviors and consolidation of fear memories during sleep. By simultaneously recording activity from many sites such as the hippocampus, prefrontal cortex and amygdala—a more challenging feat in 2008 than nowadays—Daniela could ask how inter-area communication and coordination affects fear learning. She found that animals with more coordinated theta oscillations during REM sleep showed stronger retention of fear memory, and vice versa. Overall, she enjoyed the combination of functional measurements and behavior and decided to carry this approach into her own lab. She also learned from Denis how to structure research programs that set mentees up for success, balancing straightforward “safe” ideas with riskier but potentially high-impact ones.
Towards the end of her postdoc, a previous collaborator Dr. Clément Léna—also a neuroscientist—suggested they team up to start a lab in France. Daniela had worked with Clément since her PhD days and appreciated their complementary strengths. Clément had been trained as a physicist who could apply quantitative methods to study complex patterns of activity while Daniela, trained as a medical doctor, had a holistic approach to biological systems, bridging neuropathologies with neural circuits and plasticity. Together, they decided to focus on long-range interactions between the cerebellum and circuits in the neocortex and basal ganglia. While cerebellar disorders are most visibly associated with motor impairments, Daniela was also interested in the cerebellum’s role in cognitive and emotional behaviors. However, given the challenges of measuring emotional states in animals and convincing funders of “unconventional” ideas, Daniela decided to start with a motor paradigm and establish the tools necessary for studying these distributed circuits. Not long after, she secured funding to start examining the role of cerebellar pathways in emotional processing.
One line of research that particularly captivated Daniela was reports that repetitive cerebellar transcranial magnetic stimulation (rTMS) could reduce dyskinesia (erratic movements) in patients who gradually develop insensitivity to Levodopa (a common drug treatment for Parkinson’s disease). At the time, the mechanism behind this effect was not known. Daniela’s team leveraged a mouse model of Parkinson’s and used cell-type-specific optogenetic stimulation to show that the improvement was mediated by Purkinje cells in the cerebellum. By recording from motor circuits at the same time and immunostaining for transcription factors associated with dyskinesia, they showed that Purkinje cell stimulation led to normalization of aberrant plasticity and downregulation of a factor called fosB in striatum. In another study, the team looked at whether cerebellar stimulation impacted fear-conditioning behaviors. They found that while stimulation had no immediate impact on movement kinematics or freezing, it led to changes in expression of fear memory the following day. In this context, the cerebellum played a role in fear learning, and not motor output.
Daniela and Clément’s joint team continues to investigate the role of cerebellar pathways in motor and emotional learning. They study how the cerebellum controls plasticity in associated areas such as the neocortex, thalamus and striatum, and how this is dysregulated in pathological conditions. Although they are co-PIs, Daniela sometimes senses small differences in how she and Clément are treated, for example, in their interactions in committees. She wishes that senior academics, both men and women, would recognize that women can have both a family and a career, that these responsibilities can be shared equally between partners, and that academia should offer support structures to enable these arrangements. Daniela is grateful for her wonderful mentors and is committed to “not pulling the ladder up after herself” and instead helping to make academia a more equitable and inclusive environment.
Find out more about Daniela and her lab’s research here.
Listen to Margarida’s full interview with Daniela on January 31, 2025 below!
