UofL News: What are you researching this summer?聽

Ava Peruski: This summer I am researching autobiographical memory in the NeuroImaging Laboratory of Cognitive, Affective and Motoric Processes with cognitive neuroscientist Brendan Depue and a few other undergraduate students.

UofL News: Describe some of your experiences.

Peruski: Since we are working with neuroimaging data, I have been learning how neuroimaging works, along with how to perform preprocessing tasks and different analyses on raw data. I also will help run analyses on our project鈥檚 data.

UofL News: What are you learning about research as part of this program?聽

Peruski: So far, I have learned that research involves a lot of trial and error, and collaboration. Every meeting, we work through data and studies together, hypothesizing about different outcomes and sharing our thoughts. Collaboration allows everyone to learn from each other and formulate creative ideas.

UofL News: What are some of the key takeaways from your mentor (Dr. Brendan Depue)?

Peruski: Dr. Depue is a fantastic mentor! One of the main lessons that I have learned from studying with him is that it鈥檚 okay to be unsure and to make mistakes. He often has the other undergraduates and me try things for the purpose of getting hands-on experience and ‘learning by doing.’

This has included writing up my project proposal for SROP, as well as presenting a neuroimaging study to our lab group. Obviously, I have not had much experience with either of these, so I made a lot of mistakes. But, Dr. Depue was always completely encouraging and made sure I learned from my mistakes, and in the future, I鈥檒l be better equipped. As someone who is a bit of a perfectionist, having a mentor show me it鈥檚 okay to make mistakes has been such a beneficial lesson.聽

UofL News: What are your future career goals and how is this experience shaping your aspirations?聽

Peruski: My main future career goal is to go to graduate school and then have a career in research, likely as a college professor. This experience has shown me a lot about the ‘behind the scenes’ of a college professor and a career in research. I鈥檝e also been able to talk to Dr. Depue and other graduate students in the lab about applying to and being in graduate school, and they have given me some incredibly helpful and insightful advice.

UofL News: Do you feel this summer experience is a unique opportunity that UofL offers undergraduates?聽

Peruski: I know many colleges offer summer research programs for their students, however, I think that UofL鈥檚 SROP program stands out in that it allows undergraduates a lot of freedom to really make this experience their own. We also have professional development seminars we attend weekly, which I think is unique and very helpful.

UofL News: Anything else you鈥檇 like to share?

Peruski: If you are an undergraduate looking to get involved in research, I would highly recommend applying to SROP. I had no prior research experience before SROP, and this summer has been invaluable to my academic and career development.

Typically, adult neurons cannot make new synaptic connections as easily as developing neurons. That limits the potential for recovery from injury to the brain and spinal cord. One type of neurons in the retinas of mice, OFF-type retinal bipolar cells, has the unusual ability to make new connections into adulthood. Under normal conditions however, these cells only develop new connections with a few cells and within a limited area known as a tile. The function of these cells is to receive information from photoreceptor cells and send it along the optic nerve to the brain.

鈥淭hese neurons continue to develop and elaborate their connections within their established group of cone cells in the retina,鈥� Borghuis said. 鈥淭his suggests synaptic plasticity, or the ability for the neurons to create new connections with other neurons. This is significant because in brain disease, you want to transplant and regenerate neurons and integrate them through the formation of new synapses with other neurons.鈥�

In the first stage of the work, a team of researchers at the University of Idaho led by Peter Fuerst, PhD, determined that removing the gene encoding a protein known as Down syndrome cell-adhesion molecule (DSCAM) allows these cells to extend neuronal connections beyond their normal tile barriers. They genetically modified the mice to omit DSCAM from those cells, after which the cells were seen to form apparent contacts with neurons outside their tiles.

However, the researchers were unable to determine whether those apparent neural connections were, in fact, functional and capable of transmitting visual information.

That鈥檚 where Borghuis comes in. Using a unique imaging and recording technique pioneered in his laboratory at UofL, two-photon fluorescence-guided electrophysiology in deep layers of the neural retina, Borghuis recorded the bipolar cells鈥� responses to visual stimulation. His measurements showed enlarged visual receptive fields in the genetically manipulated retinal neurons, demonstrating that the extended cells made new, functional synapses onto cones.

鈥淩ight off the bat we could see that the receptive fields were larger, so we could tell that their visual responses were consistent with neural outgrowth and new synapse formation,鈥� Borghuis said.

These tests proved the neural outgrowth seen by the Idaho team led to stable, functional connections with new cells.

A new joint research grant from the National Institutes of Health, awarded equally to Borghuis and Fuerst, will fund the collaborative research for another two years. During that time, they will induce the DSCAM knockout later in the lifespan to determine the identity and strength of the new synapses. In addition, they also will perform studies of neurons at later synaptic stages within the retina to determine other potential consequences of increased neuron growth at the level of the visual input.

鈥淲e have known about the tiling or mosaic structure of these cells for decades, and there are models and ideas for why neurons should tile. Now that we have a genetic tool that allows us to disrupt tiling within a neuron population experimentally, we can finally test these models,鈥� Borghuis said.

The ability to stimulate neural outgrowth with new synaptic connections may ultimately improve humans鈥� ability to recover from brain and spinal cord injury or disease by supplying new neural connections. Even more promising, it could lead to neural regeneration and transplantation-based therapies for restoring visual function in retinal diseases such as diabetic retinopathy and macular degeneration.