Bernhard Lüscher awarded Faculty Scholar Medal for Outstanding Achievement

Bernhard Lüscher, professor of biology and of biochemistry and molecular biology, has received a 2018 Faculty Scholar Medal for Outstanding Achievement. Established in 1980, the award recognizes scholarly or creative excellence represented by a single contribution or a series of contributions around a coherent theme. A committee of peers reviews nominations and selects candidates.

Lüscher, who was awarded the Faculty Scholar Medal in Life Sciences, was Penn State’s first neurobiologist to be promoted to professor and has been instrumental in building a sizeable and internationally recognized group of neurobiology faculty members.

He has served as co-director of the neuroscience graduation program, as interim co-director of the Penn State Neuroscience Institute and as director of the Center for Molecular Investigation of Neurological Disorder.

Lüscher researches the role of the principal inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and its major receptors in brain function. These receptors serve as the principal mediators of neural inhibition in the brain and also as targets for some of the most frequently prescribed psychoactive drugs such as those used to treat anxiety.

Lüscher’s research also provides insights into the role these receptors play in emotion-related behavior. Based on initial findings by his laboratory, he proposed that comparatively small defects in the function of GABA receptors could serve as culprits of Major Depressive Disorder (MDD). Lüscher found that antidepressant drug therapies were reversing the consequences of GABA receptor defects, despite being designed to increase the function of two other neurotransmitters (serotonin or norepinephrine).

“MDD is the leading cause of total disability and, through suicide, a primary cause of death among young people,” a nominator said. “Currently available therapies for MDD are ineffective in almost half of patients, indicating that Lüscher’s studies address one of the foremost health concerns of modern society.”

Lüscher’s two key findings bettered our understanding of MDD and ways to treat it.

First, Luscher demonstrated that GABA receptor mutant mice, which exhibit signs of depression, suffer from a compensating downregulation of the function of the second major neurotransmitter in the brain, glutamate.

“Most remarkably, treatment of these mice with an experimental antidepressant drug (ketamine) reversed both the glutamate and GABA defects of the mutant mice and also normalized their behavior,” a nominator said.

Second, Lüscher’s group asked whether enhancing the function of GABA can end depression. This treatment is currently used, although ineffectively, at treating depression. Lüscher explained one reason these drugs might be ineffective is that they enhance GABA function indiscriminately and independent of the level of brain activity. To enhance the function of GABA in a brain-activity-dependent manner, Lüscher designed an innovative strategy to genetically increase the activity of GABA-producing cells in mice and then showed that these animals behaved as if they had been treated with antidepressant drugs.

“Lüscher’s work represents a seminal contribution to the detailed understanding of MDD and antidepressant drug action,” a nominator said. “He has provided a rigorous intellectual framework for his work and gone on to experimentally prove that his predictions were correct.”