Autism and Neuroscience Innovators: Awardees Share Their Research at the Annual Retreat

How do we track development in a minuscule, embryonic mouse brain? Are seizures linked to how neurons fire in — or out — of sync with brain waves? And what goes on in the brain and body to give you information about internal states like hunger? These are just a few of the questions at the heart of research projects being carried out by members of the Simons Foundation’s Fellows-to-Faculty program. This program supports talented early-career scientists and their research vision as they transition into tenure-track or equivalent faculty positions.

The fellows met last spring for the program’s 2025 meeting to share their latest findings and make scientific connections. Read on for highlights of exciting work from some of the fellows.

A Specialized Microscope to Study Mouse Embryos

To best study neurodevelopmental disorders, scientists need better ways to examine what happens in the brain during very early development, as this is when many critical changes that could contribute to conditions like autism are thought to occur. Fellows-to-Faculty awardee Martin Munz, an assistant professor at the University of Alberta, shared his technique called ‘para-uterine imaging’ which allows scientists to study the embryotic developmental period by stabilizing an embryo within the mother mouse’s abdomen and placing it under a microscope.

“All of this lays the foundation so that we can look at different genes associated with autism and examine how that impacts development,” Munz says.

Embryonic development is a particularly sensitive period that is hard to study because there cannot be any interruption of blood flow to the embryo and the embryo must also be stabilized so that scientists can perform microscopy.

Para-uterine imaging has enabled researchers to better examine the neocortex, even allowing deep penetrance into the cortex’s fifth layer, where many autism-related genes are thought to be expressed. By analyzing this fifth layer, they discovered heightened activity in these neurons already before birth, likely due to changes in expression among these autism-related genes.

Brain Waves Provide Clues to Seizure Vulnerability

Across the brain, neurons tend to fire in synchrony with theta waves, which form the organizational structure of learning and memory in the brain. This phenomenon, called theta phase locking, is the focus of Fellows-to-Faculty Fellow Zoé Christenson Wick’s research at the Icahn School of Medicine at Mount Sinai in the lab of Tristan Shuman.

Why are so many disorders with heightened risk of seizures (e.g., epilepsy, autism, Alzheimer’s, substance use or traumatic brain injury) all associated with changes in theta phase locking? To study this, Christenson Wick models temporal lobe epilepsy in mice and identifies changes in the rodents’ neurophysiology that might contribute to seizure disorders in humans. She discovered that in healthy, non-seizure-prone mice, neurons tend to fire together at the troughs of theta oscillations. However, for mice prone to seizures, their neurons fire in rhythms that are out of sync with these points. She believes that this loss of synchronicity, especially among inhibitory neurons, underlies seizure vulnerability in both rodents and humans.

For her current research, Christenson Wick wonders if she can eliminate this seizure vulnerability by restoring that inhibitory synchronicity. She developed and released a tool called PhaSER (which performs theta phase-locked manipulations) in which she can introduce wavelengths of light to excite or inhibit neurons at specific points in the theta oscillation, including at the peak or trough. PhaSER is freely available, and other labs already have been able to adopt it smoothly for their own research. This tool allows neuroscientists to manipulate and simultaneously monitor theta phase locking patterns at will, allowing deeper research into how this phenomenon impacts brain function at large.

Using this tool, Christenson Wick has shown that this inhibitory synchronicity is indeed a driver of seizure vulnerability.

Mapping the Senses of Internal Organs

Fellows-to-Faculty member Chen Ran, an assistant professor of neuroscience at the Scripps Institute, points out that while we have senses like touch and smell, the brain also generates signals related to its internal system. This “sixth sense” is called interoception, which is first processed in a brainstem structure called the nucleus tractus solitarus (NTS), which acts as the organs’ gateway to the brain. Understanding interoception is critical for understanding the brain’s internal state, a central tenet of the Simons Foundation Collaboration on the Global Brain.

Ran became curious about the NTS after he noticed that identical signals could be shared by organs but convey different meanings toward behavior. For instance, distension in the stomach conveys that you should stop eating, but distension in the bladder means you need to urinate. So Ran investigated how the brain generates the diversity of purpose in the same sensation from different organs.

Ran’s team precisely stimulated mice’s organs while using two-photon microscopy to image their NTS to understand the logic by which brain represents visceral organ signals: Does stomach stretch and intestinal stretch activate the same group of neurons? How about intestinal stretch versus intestinal nutrients? From this work, Ran created a topographical map of internal organs in the brain, finding that most neurons in the NTS are dedicated to sensing a particular organ.

He notes that the Fellows-to-Faculty Award has been crucial in enabling this work and expanding his network. “I feel very lucky to have the support of the Simons Foundation and to have access to this outstanding community.”