What causes fear to spiral out of control in the brain, fueling mental health conditions like panic disorder and posttraumatic stress? After three years of research, a Fordham biology professor and her students have shed new light on how this happens, potentially paving the way for new treatments.
Their focus is memories that evoke fear, said the professor, Kaoutsar Nasrallah, PhD. In research to be submitted for publication this fall, she and her students showed how fears can run amok if not for a critical “braking” mechanism in the brain. It’s a finding with bearing on mental illness but also other things like epilepsy and the anxiety that can spike during the reproductive cycle, she said.
“If fear memory is not regulated properly, this can lead to pathological conditions … where the fear is generalized or where the fear is present when we don’t need to have it,” she said. “But at the same time, it’s important to form fear memories, because that helps us to survive.”
Moderating the Spread of Fearful Memories
Nasrallah’s lab studies a brain chemical called GABA that calms the nervous system by preventing neurons from overfiring. When a fearful memory is being formed, it keeps the memory from spreading to too many neurons in the hippocampus, the brain’s seat of memory and learning, Nasrallah said.
This process is important so that, for instance, someone who survived a house fire as a child doesn’t overreact years later to the tiny flames involved in cooking a meal or boiling an egg, she said.
Sometimes this inhibition happens through a brief interaction between GABA and the target neuron. But this process has another variety, dubbed “tonic,” or prolonged: sometimes GABA interacts with different receptors on a neuron and exerts a more subtle, sustained inhibition—like gently riding the brake “with a continuous pressing,” rather than pumping it hard just once, Nasrallah said.
This tonic process is underexplored, she said, so she and her students put it to the test: by studying it in the brains of laboratory mice, they found that it prevents runaway, overgeneralized fear, helping to limit it to the precise memory that originally sparked it.
Treating Anxiety and Epilepsy
By providing new insight into how the brain usually regulates fearful memories, the finding advances the search for treatments that could be used in concert with psychiatric therapy. The tonic process also generated interest in her lab because it’s sensitive to hormone fluctuations. Nasrallah’s students are studying how this process might play a role in the estrous cycle in mice, hoping for insight into its possible role in easing women’s anxiety disorders that can be magnified during the menstrual cycle, she said.
Her lab is also exploring how the tonic calming of neurons relates to epilepsy, in which seizures are triggered by electrical storms in the brain.
Research that Empowers
One junior in Nasrallah’s lab, biological sciences major Zariyat Ahmed, has spent the summer studying a particular aspect of fear regulation. Working with mice, she’s examining the role of tonic inhibition in fear extinction—a process used in exposure therapy, in which fear is addressed through controlled exposure to the activity or situation that originally caused it.
She joined Nasrallah’s lab out of interest in psychology and neuroscience—“finding out exactly why this therapy works, exactly what gene is maybe causing these strong reactions with trauma and fear and anxiety,” said Ahmed, a Clare Boothe Luce scholar taking part in the summer research program at Fordham College at Rose Hill.
Another fun aspect? Learning to explain the biology of things like anxiety to her fellow students, which can make it seem more manageable.
“It’s always interesting if you understand the biological pathways of it,” she said.
