As the bright white rat looked up at the camera and froze, I started my stopwatch. His body halted all movement, frozen in time for 1, 2, 3,…9 seconds before wandering to the other end of the chamber. I pause the stopwatch as soon as his body lurches forward to end his trance. This ordinary Tuesday for me makes my parents scratch their heads. How could any of this work help us better understand post-traumatic stress disorder (PTSD)?
All humans, at some point, experience moments that really unsettle them. Something that leaves them feeling cautious, more vigilant. Some humans go on to avoid certain places constantly, feel high levels of stress or guilt, or feel intrusive fearful memories entering their minds by surprise. I research how the brain stores memories of traumatic events, and why only some people experience a fear response in places unrelated to the trauma. By creating fearful memories in the domesticated Sprague Dawley rat, I can study this variation in humans to better understand PTSD.
Because our goal is to understand the biology of human fear, rat fear must be artificially created in my experiments. Animals enter a behavioral chamber, where a 2-second footshock is delivered to create a fearful memory of that location. My animal research is tightly regulated by the American Association for Accreditation of Laboratory Animal Care, my university’s Unit for Laboratory Animal Medicine, and the Institutional Animal Care and Use Committee. These three groups must approve any and all experimental treatments using live animals, for the simple fact that rats are living creatures who feel and think. Any groups working with animals for research are constantly monitored, guided, and counseled to ensure excess stress does not occur.
My fear experiments have three key days: 1) Receive Shock, 2) “Relaxing” Day, and 3) Return to Shock Location. The electric shock on the first day teaches the rats this box is an unsafe location. The next day, animals are placed in a chamber they have never seen before, with new smells and visuals. The last day sees animals return to the same boxes where they formed the fear memory. For reasons I am still researching, a select group of rats freeze all body movement in the “Relaxing” Day’s chamber, but not when returning to the actual box they learned to be afraid of. This generalization of the original fearful memory to a place that they should not be afraid of is a behavior humans do as well. I can then look at their brains to identify the biological reasons the fear memory was generalized.
I am well aware of the fact I am making another living creature experience distress so I can help my own species. No computer model exists that perfectly replicates how the brain stores memories, so animal research provides a way to understand this important topic. All researchers are trained to openly discuss ethical responsibility as experiments are designed. I altered my strategy to ensure every step of the experiment includes respect for the animals’ lives. I tickle and gently groom every animal before my experiments begin. My heart smiles when I see them run to the edge of the cage to play with me. I minimize how much time the animals actually spend in my hands, so the majority of their lives can be spent in their home-cage with unlimited food and water. I train - and often scold - my students on proper handling techniques to prevent pain when animals are moved. I shower with the same soaps and shampoo before entering the behavioral room to eliminate the smell of my cat at home. Laboratory veterinarians come check on all animals daily, and provide care the moment something seems off. Suffering is an unpleasant feature of living. It will always exist, though we always have the power to mitigate it.
To create memory, a collection of neurons in your brain link themselves together in a large circuit. You can think of it like a series of train tracks, connecting numerous hubs to one another. One of those hubs, the hippocampus, has a subregion scientists call CA1. This part of the hippocampus sends tracks to the amygdala, the brain’s fear center. Current research suggests this CA1 path to the amygdala is essential for storing memories of fearful locations. The actual process of storing memories here seems to vary from human to human and in rat to rat. This research will help us better understand what specific biological process is happening in CA1 neurons, improving our ability to detect, treat, and prevent the development of PTSD in humans.
The differences in how my rats behave after fear learning reveals a human truth: individual variation exists in our responses to stress.
As a neuroscientist, it would be deeply foolish of me not to apply this lesson to the wonderful students I interact with in the laboratory. One of my undergraduate mentees wanted to apply to graduate school and had some difficulty writing application essays. I noticed every time I would ask for a draft, her movements would shift; brows flattened, shoulders shrunk inward, and a trampoline magically appeared under their leg.
I asked her, “How does it feel when you sit down to write a draft?”. I listened to the earnest outpour of stressors overwhelming my student’s mind, and the gradual introduction of widened eyes, relaxed shoulders, and deepened breaths. I understood that shift in behavior as her realization that I only sought to help her. Together we created a writing-wellness plan: 1) must be seated in the sunlight by water, 2) have a separate document to write frustrations and ideas, and 3) NO ONE CAN CHEW FOOD NEARBY! She was extremely adamant about that last one. She certainly loved to write, but felt that she froze up when writing about personal experiences. Our plan acknowledged and anticipated this freeze response; the next week she had gone from a rough paragraph and a few bullets to a fully completed draft.
The nervous system that exists throughout our bodies serves to protect and guide us. Even now as you read this, millions of tiny cells are calculating inputs from other cells, allowing your eyes to move across the sentence, and for you to understand their words, and for you to feel the sense of being you! When traumatic experiences occur, each individual nervous system responds within a measurable spectrum. My ongoing research seeks to understand why some of those responses lead to PTSD. As I strive to understand these fear responses in my animal model, my work has taught me how to add kindness to interactions with other humans. All of us can generate fear responses, even when we are in a safe place. Accepting that reality gives me the skill to anticipate freezing from those around me, time it, and offer kindness to address whatever part of the brain was crying out for help.
