Beyond Neurotransmission: Exploring Roles for Synaptic Dopaminylation in Drug-induced Plasticity

2017 Seed Grant
Ian Maze, Ph.D.
Icahn School of Medicine at Mount Sinai

Substance use disorder is a chronic, relapsing illness that affects millions of individuals worldwide; however, few effective treatment options for substance abuse and addiction exist. Here, employing a unique combination of biochemical, molecular and behavioral approaches, we examine a highly novel role for the neurotransmitter dopamine in the direct regulation of protein function at reward circuitry synapses, processes that likely contribute to addictive behaviors. This pilot proposal therefore aims to transformatively integrate expertise from multiple disciplines (e.g., chromatin biochemistry, neuroepigenetics and behavioral neuroscience) to begin characterizing so-called protein “dopaminylation” in the central nervous system, as well as to elucidate its potential role in compulsive cocaine seeking. The overarching goal of this work is thus to identify novel molecular underpinnings of life-long addiction that will allow for the development of more effective therapeutic interventions.

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…