Schizophrenia by Axel Nimmerjahn

The Role of Astrocyte-Neuron Communication in Normal Brain Function and Mental Disorder
2013 Seed Grant

Axel Nimmerjahn, Ph.D.
Department of Biophotonics
The Salk Institute for Biological Studies

Mental disorders represent the single greatest burden of all human diseases, and currently available treatments do not meet the need of most patients. Mental illnesses are associated with changes in the brain’s structure, chemistry and function as revealed by brain imaging techniques such as magnetic resonance imaging (MRI), and positron emission tomography (PET) on the systems-level. However, a complete understanding of what causes mental illness on cellular and molecular levels is still lacking. Anatomical studies have revealed disease-associated changes in both neuronal and glial cell morphology. However, while electrophysiological studies have provided some insight into electrical activity changes in neurons during disease states and drug treatment, very little is known about corresponding changes in glial cells, particularly astrocytes the largest subgroup of glial cells in the brain, which are chemically excitable but electrically largely silent. Astrocytes can communicate chemically with neurons both in vitro and in vivo. However, it is unclear whether astrocyte neuron communication contributes to mental disorders.

Dr. Nimmerjahn’s central hypothesis is that astrocytes significantly contribute to mental illness through aberrant modulation of neural activity thereby presenting a promising new target for future therapeutic interventions. The rationale for his research is that, once the cellular mechanisms by which astrocytes contribute to brain physiology and pathology are known, new and improved treatment strategies can be developed. Focusing on the role of astrocyte-neuron communication in prefrontal cortex, a brain region involved in mental disorders, three specific aims will be pursued: 1) Determine normal forms of astrocyte-neuron communication in the prefrontal cortex of behaving mice; 2) Determine how astrocyte-neuron communication is dysregulated in mouse models of psychosis; and 3) Determine how anti-psychotic drug treatment modulates astrocyte-neuron communication in mentally ill mice. The proposed research will reveal key insights into the cellular mechanisms underlying astrocyte-neuron communication in the normal and diseased mouse brain. This knowledge should pave the way for the development of new and improved drug treatments and their evaluation in preclinical mouse models. If indeed astrocyte-neuron communication contributes to mental illness phenotypes this would profoundly affect our view of the cellular mechanisms underlying brain physiology and pathology.

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