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Audrey Brumback, MD, PhD, Assistant Professor of Neurology at Dell Medical School at The University of Texas at Austin, has been awarded a three-year, $1,500,000 grant from the National Institute of Mental Health entitled “Functional Architecture of the Mediodorsal Thalamus.” Brumback’s team will use mice to map the structure and function of a part of the thalamus that is thought to affect conditions such as autism, attention-deficit/hyperactivity disorder, and schizophrenia.

The thalamus is typically considered a relay center that facilitates the transfer of incoming sensory messages to the brain cortex. But the thalamus is likely a more sophisticated structure that uses the incoming sensory information to orchestrate the activity of higher cortical brain areas. As one of the largest thalamic nuclei, the mediodorsal thalamus reciprocally connects with multiple cortical and subcortical brain regions, provides a strong projection to the medial prefrontal cortex, and coordinates the activity of cortical microcircuits there during prefrontal-dependent behaviors. But despite the importance of the mediodorsal thalamus in a range of behaviors and human disease, little is known about the physiology of the neurons in this region or how they influence behavior.

In preliminary work, Brumback discovered that two populations of neurons in the mediodorsal thalamus have distinct structural and functional profiles. She hypothesizes that each thalamic circuit is responsible for a different aspect of behavior: one circuit is responsible for social or emotional behaviors, while the other circuit modulates cognitive functions like attention and working memory.

In the funded work, Brumback’s team will directly test this model using a neuromodulation approach called optogenetics. Using flashes of light delivered directly into the brain via a fiber optic probe, she will activate or inactivate specific populations of neurons with millisecond precision while mice perform a battery of behavioral tasks. By turning each of the proposed circuits on or off during different types of behavior, she can test which circuit is important for each type of behavior. The team will also determine how individual neurons in these two thalamic circuits integrate synaptic inputs from different brain regions.

“The ability to noninvasively alter the activity of specific populations of neurons has enormous implications. The more specific we can be when targeting neurons, the greater the likelihood of finding an effective treatment with few side effects.”

E. Steve Roach, MD

The team’s future work will decipher how these and other thalamic circuits are altered in autism and whether they can be modified to treat cognitive or social-emotional symptoms. “The ability to noninvasively alter the activity of specific populations of neurons has enormous implications,” said E. Steve Roach, MD, Brumback’s Austin colleague. “The more specific we can be when targeting neurons, the greater the likelihood of finding an effective treatment with few side effects.”