Piecing Together Autism Spectrum Disorder: Fordham Student’s Research on Inhibitory Neurons in Mouse Brains

Autism Spectrum Disorder is a complicated neurodevelopmental disorder that is slowly being pieced apart by the research of those in the neuroscience field. Taking on a piece of the puzzle is Fordham University student Celia Hans, with the help of Dr. Batista-Brito and her research lab at Albert Einstein College of Medicine. Hans is a senior Cellular-Molecular Neuroscience major, who has worked in the lab at Einstein for almost two years.

Hans embarked on an independent research project that studies the effects of the removal of Mef2c in mice. Mef2c is an important genomic transcription factor for brain development and function. Deletion of this gene has been previously implicated in Autism Spectrum Disorder research, as well as schizophrenia. Hans uses the haploinsufficiency model in her research, which removes Mef2c from all of the cells in the bodies of the mice, and results in a phenotype very similar to humans with Autism Spectrum Disorder. In both mice and humans, this phenotype involves increased risk of seizure activity, intellectual development disorders, decreased neurogenesis, and increased ratio of excitatory to inhibitory neuron transmission, among other things.

The role of inhibitory neurons in the brain mainly regulates the rate that excitatory neurons send signals. This system of balance is essential for correct brain development. In previous research, removal of Mef2c in excitatory neurons did not produce all of the signs of Autism Spectrum Disorder in mice, that are seen in humans. Hans thinks this is because a lack of Mef2c in inhibitory neurons is critical to the development of these symptoms.

In order to test this theory, Hans studies inhibitory neurons in the brain that normally have Mef2c. These neurons are called parvalbumin-expressing GABA-ergic inhibitory interneurons (for simplicity, PV-INs). These inhibitory neurons, when mature, are wrapped in a protecting layer of extracellular matrix called perineuronal nets, or PNNs. PNNs support the functioning of PV-IN inhibition, essential for the critical balance of excitatory and inhibitory neuron fire, and thus necessary for correct brain development. PNNs also promote PV-IN development, maturation, and stability. The key fact behind Hans’ research is that PNNs need Mef2c to develop correctly.

Therefore, using the haplo-insufficiency model, in which all cells lack a copy of Mef2c, Hans hypothesizes that she will observe fewer, less intense, and less integrated PNNs surrounding the inhibitory neurons in the brain, compared to normal mouse brains. If she is correct, this will mean that incorrect development of inhibitory neurons plays an integral role in creating the symptoms of Autism Spectrum Disorder that we recognize in humans, and that lack of Mef2c in these neurons causes this incorrect development. This knowledge would add to our overall understanding of Autism Spectrum Disorder and allow researchers to move on to the next question. If incomplete development of PNNs does cause many of the disorder’s phenotypes, it begs the question if there is anything we can do to prevent the PNNs from not functioning properly, which could greatly help those who suffer from Autism. Hans’ preliminary results are looking promising.

Hans says that she has learned a lot from working in Dr. Batista-Brito’s lab at Albert Einstein, and loves “being in an environment where [she] can ask anybody anything.” Surrounded by PhD students, PIs, and postdocs, Hans works with experts in the field. This has been a humbling and invaluable experience for her. She is grateful for the opportunities the lab has given her to do her own research, which has helped her discover her strengths in brain data analysis and other aspects of research.

As she prepares for graduation, Hans wants to remain in the neuroscience field, but is unsure what career she wants to pursue; her passion for neuroscience is extensive. In addition to neurodevelopmental research, Hans is interested in data mining and the science of meditation and mindfulness. She also works for a non-Profit called Love Your Brain, teaching yoga classes to those who suffer from traumatic brain injury, which she loves as well. “Neuroscience is a great major because it is so interdisciplinary… there are so many things that can be done with it,” Hans says. Continuing her work in research is just one of many possibilities she envisions for her future.

By Emily Huegler, FCRH ‘22


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