Researchers identify potential cause of schizophrenic symptoms

Imagine a waking nightmare.

That’s how Elyn Saks, law professor and mental health advocate, describes the delusions, hallucinations, memory loss and mental fragmentation that schizophrenia causes.

The mental disorder affects millions of people worldwide but the cause of its wide-ranging symptoms remains largely unknown.

At Brandeis University, researchers believe they have discovered an abnormality in the schizophrenic brain that could be responsible for many of the disease’s symptoms and could provide a drug target for therapeutic treatments.

John Lisman photo/Mike Lovett
John Lisman photo/Mike Lovett

Led by John Lisman, the Zalman Abraham Kekst Chair in Neuroscience and professor of biology, and Matthew Wilson of MIT, the research team published their findings in a recent issue of the Journal of Biological Psychiatry. The paper was co-authored by Aranda Duan, Carmen Varela, Yuchun Zhang, Yinghua Shen, Lealia Xiong, and Matthew Wilson.

Unusual neural oscillations — brain waves — have long been associated with schizophrenia. The oscillations, called delta waves, are similar to slow oscillations seen in normal brains during sleep, but in schizophrenic brains, they occur during wakefulness. The connection between these oscillations and schizophrenic symptoms, particularly cognitive deficits such as memory impairment, has long been unclear.

Lisman and his team set out to understand that connection by artificially producing delta waves in mammalian brains using a new technique called optogenetics, which activates brain signals using light.

When the delta frequency light was turned on, Lisman observed disruption in the working memory of rats. When it was turned off, the rodents were once again able to perform working memory tasks. More important, Lisman and his team were able activate the abnormal oscillations only in a tiny subpart of the thalamus, a region of the brain that has long been a focus of schizophrenia research.

An information hub and relay center, the thalamus is central to working memory, sleep, consciousness and sensory-information processing.

“The oscillations produce an artificial signal that jams normal communication,” Lisman says. “The part of the thalamus that is supposed to carry information about working memory couldn’t do the task at all with these sleep-like delta waves. We suspect the abnormal delta oscillations seen in patients with schizophrenia are producing a similar jamming of normal signals.”

The green axons of thalamic neurons can be seen as they innervate the hippocampus. It is these axons, when stimulated by light, that jam communication. Courtesy/Lisman Lab
The green axons of thalamic neurons can be seen as they innervate the hippocampus. It is these axons, when stimulated by light, that jam communication. Courtesy/Lisman Lab

Delta waves require a specific type of ion channel called a T-type Ca channel. These channels are of particular interest because they are one of the few types of ion channel implicated in schizophrenia by genetic studies. The next step, Lisman says, is to figure out what kind of agents could be used to block these channels.

“If you could block these channels, you could block these bad oscillations,” he says. “That may have therapeutic value in patients.”

We are Brandeis Science: Jenny Klein

There is no rule that says scientists have to look or act a certain way. Scientists can be funny and outgoing, athletic and artistic. They come from all different backgrounds and have all different interests. At Brandeis, our scientists are as diverse as the groundbreaking research they engage in. This on-going series is inspired by This is What a Scientist Looks Like

This post was written by Jenny Klein, a research technician in professor Nelson Lau’s biology lab.

 The thrill of discovery

Jenny Klein and her sister after skydiving
Jenny Klein and her sister after skydiving

As a kid, what did you want to be when you grew up?

As a really little kid I wanted to be an artist, and then I wanted to be a vet because I love animals. But I actually knew partway through high school that I wanted to be involved in research science.

What do you research?

I study the CRISPR/Cas9 genome editing system. It is the latest generation of genome editing technology that allows the researcher to create specific mutations in the genomes of their model systems. This allows you to understand what a specific gene does and why it is important. I’m working to improve the efficiency of the system to add in specific mutations.

How do you define discovery and how does it make you feel?

Discovery means being the first person ever to see a result or data trend — and recognizing that it means something. I get an absolute thrill from making a discovery — it’s better than any other adrenaline jolt out there (and I’ve gone skydiving a couple times). The quest keeps me motivated, especially during the stretches when nothing seems to be working with my project.

Besides science, what do you nerd out about?

Outside of the lab, I love science fiction/fantasy books, movies and TV shows. I even took a class in college called “Tolkien’s Middle Earth” — it was pretty awesome, especially since our homework most of the semester consisted of reading “The Lord of the Rings.”

What’s one, non-career goal?

I’d love to become totally fluent in Spanish. I’ve studied it for years and have spent time in Spain, so I would still describe myself as proficient. I’m planning a trip to South America soon and hope I can get over the hump there.