Problems with Attention Traced to Specific Brain Circuit

Bo Li, Ph.D. - Brain and behavior research expert on schizophrenia
Bo Li, Ph.D.

People with schizophrenia, for example, often find it difficult to focus their attention on a task or conversation. But now scientists can use new technologies to try to isolate the specific brain areas and circuits that help enable concentration.

In a paper published online December 15th in Nature Neuroscience, a team that included three NARSAD grant recipients described a specific circuit that filters out “irrelevant” information from “relevant” information entering the brain at the same time. The ability to do so lies at the heart of the attention problem in schizophrenia and other psychiatric disorders.

The research was led by 2010 NARSAD Young Investigator grantee Bo Li, Ph.D. His team included 2011 Distinguished Investigator grantee Z. Josh Huang, Ph.D., and 2013 NARSAD Young Investigator grantee Sarah Ahrens, Ph.D., all of Cold Spring Harbor Laboratory in New York.

The team confirmed a long-held theory that a part of the brain called the TRN (thalamic reticular nucleus) serves as a kind of filter. The TRN receives information coming from the senses, and filters out what is non-essential, passing on what is relevant to a structure called the thalamus. The thalamus is considered a “gateway” to higher processing areas in the brain’s cortex. Previously, no one had been able to isolate the specific types of nerve cells in the TRN from others nearby, thus making it impossible to accurately tease out its role.

The team’s most important discovery sheds light on what causes the TRN-thalamus-cortex circuit to perform abnormally. Dr. Li and colleagues observed the behavior of mice when a cellular receptor called ErbB4 was experimentally repressed in certain neurons of the TRN. They learned that the ability of the mice to switch attention between conflicting sensory cues was impaired.

This inability of the mice to properly focus––much like attention deficit in people with schizophrenia––was intriguing for several reasons. First, the ErBb4 receptor and the molecule known as neuregulin-1 that normally connects, or “docks” with it, have repeatedly been observed to be irregular in genetic studies of people with schizophrenia. The team’s results are additional evidence that these proteins are abnormally regulated in schizophrenia.

The experiments also explain what appears to go wrong when ErbB4 is not expressed properly in the TRN. “When it is absent, we saw that the connections between the TRN and the cortex become much stronger,” Dr. Li explains. Loss of ErbB4, then, unbalances the circuit that normally filters out the irrelevant from the relevant. Dr. Li and colleagues hope that it may be possible to track down how that imbalance is created when ErbB4 is missing or deficient, and to discover medications that can restore balance to this part of the circuit.

Read the abstract.