Lighting up Astrocytes: Neuromodulator Activation in the Cerebral Cortex

2016 Seed Grant
Kira E. Poskanzer, Ph.D.
University of California, San Francisco

The monoamine neuromodulators—dopamine, norepinephrine, serotonin—are critical for human behavior and are at the root of many psychiatric and neurological diseases. Most studies that address the function of these neuromodulators in the cerebral cortex, the largest brain region, focus on how neurons respond to these neurotransmitters. However, other cell types are positioned to play key roles in receiving and integrating information encoded by these signals. This project will focus on an abundant cell type in the brain called the astrocyte, each of which can contact more than 100,000 neuronal synapses. Receptors for the monoaminergic neuromodulators are expressed in astrocytes, but the tools to uncover their roles in neural circuit function have not existed until now. In this project, we will use advanced optical techniques to record the activity of astrocytes while precisely activating novel light-activated neuromodulators. Receptors important for neuromodulator signaling in astrocytes will be silenced with cutting-edge genetic techniques while we image the activity of large populations of cells, both astrocytes and neurons, to discover new roles for these neurotransmitters in the neural circuit. In illuminating how a new type of cell responds to these important neuromodulators, the experiments proposed here will open up unexplored targets for the treatment of psychiatric diseases such as depression, schizophrenia, and bipolar disorder.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…