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Bernhard Luscher

Bernhard Luscher

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Professor of Biology, Biochemistry and Molecular Biology, and Psychiatry

209 Life Sciences
University Park, PA 16802
Phone: (814)865-5549
Lab Address: 203/208 Life Sciences
Lab Phone: (814) 865-5563


  1. Diploma in Natural Sciences/Biochemistry, Swiss Federal Institute of Technology (ETH) Zurich, 1983
  2. Ph.D. in Molecular Biology, University of Zurich, 1987
  3. Postdoc, Department of Biochemistry, HHMI, UC Berkeley, 1987-90

Research Interests

We are working to improve our understanding of the role and function of GABAergic transmission in health and disease. GABA (gamma-aminobutyric acid) is the principal inhibitory neurotransmitter in the brain and known to exert most of its function by activation of so-called GABA(A) receptors. These receptors are GABA-gated chloride channels and they serve as the targets of several classes of clinically and therapeutically important psychoactive drugs, most notably the benzodiazepines (Valium, Xanax, Versed, etc). Based on knowledge derived from these drugs, GABA(A) receptors are known to modulate virtually every higher-order brain function (learning, memory, cognition, emotion, pain, motivation, muscle tension, etc).

A first line of research uses mouse genetics to model and investigate the molecular mechanisms underlying neuropsychiatric disorders. In particular, we are interested in the etiology of Major Depressive Disorder (MDD), a leading cause of total disability affecting about 17 percent of the human population at least once in their lives. Recent clinical evidence points to functional impairment of certain GABA-releasing interneurons and reduced brain concentrations of GABA as a likely cause of MDD. Using targeted mutagenesis in mice, we have shown that modest deficits in GABAergic transmission are sufficient to reproduce behavioral, cognitive, cellular, endocrine, and pharmacological alterations expected of a mouse model of depression. These mice, therefore, provide strong evidence that GABA deficits are not just an epiphenomenon of MDD, but that they can, in fact, be causal for MDD (reviewed in Luscher et al 2011, Mol. Psychiatry). Using these mice we have shown that defects in GABergic transmission can be causal for defects in the function of glutamate, the primary excitatory neurotransmitter in the brain, and that the defects in both GABA and glutamate can be reversed with the rapid-acting antidepressant, ketamine (Ren et al 2016)  

In a second line of research, we are elucidating the mechanisms of antidepressant drug action. It is becoming increasingly clear that antidepressants act to ultimately increase and normalize GABAergic synaptic transmission even if they are designed to enhance the function of other neurotransmitters (serotonin, norepinephrine, glutamate, and their receptors. Therefore, we asked whether genetically enhancing the function of certain GABA-releasing interneurons would be sufficient to mimic the effects of above antidepressant drug treatments. We succeeded in showing that genetically increasing the excitability of GABA-producing interneurons known as somatostatin cells reproduced both biochemical and behavioral consequences of antidepressant drug treatment (Fuchs et al 2017). 

Ongoing research seeks to better understand the molecular and cellular changes underlying MDD and antidepressant drug action, with the aim to design novel antidepressant drug treatments.        

Selected Publications

Link to complete list of publications on Research Gate

Luscher B, and Mohler H. (2019) Brexanolone, a neurosteroid antidepressant, vindicates the GABAergic deficit hypothesis of depression and may foster resilience. F1000Research. 8, 751.

Feng M, Crowley NA, Patel A, Guo Y, Bugni SE, Luscher B (2019)Reversal of a treatment-resistant, depression-related brain state with the Kv7 channel opener retigabine.  Neuroscience 406:109-25.  

Fuchs T,  Jefferson SJ, Hooper H, Yee P-HP, Maguire J, and Luscher B. (2017). Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state. Molecular Psychiatry 22, 920-930.  Commentary by Zhang et al.

Ren Z, Pribiag H, Jefferson SJ, Shorey M, Fuchs T, Stellwagen D, and Luscher B (2016): Bidirectional homeostatic regulation of a depression-related brain state by GABAergic deficits and ketamine treatment. Biol Psychiatry, 80, 457–468.  Commentary by JW Murrough.

Luscher B, Fuchs T (2015). GABAergic control of depression-related brain states. Advances in Pharmacology 73, 97-144.

Luscher B., Fuchs T and Kilpatrick C. 2011. GABA-A receptor trafficking-mediated plasticity of inhibitory synapses. Neuron 12, 385-409.

Shen Q., R. Lal, B. A. Luellen, J. C. Earnheart, A. M. Andrews,  and B. Luscher. 2010. GABA-A receptor deficits cause hypothalamic-pituitary-adrenal axis hyperactivity and antidepressant drug sensitivity characteristic of melancholic depression. Biol. Psychiatry 68: 512-520.

Crestani F, M. Lorez, K. Baer, C. Essrich, D. Benke, JP Lauren, C. Belzung, JM Fritschy, B. Luscher and H. Mohler. 1999. Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat. Neurosci. 2, 833-839.

Essrich C, Lorez M, Benson JA, Fritschy JM, B. Luscher. 1998. Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci. 1:563-71.