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Micro RNA and dopamine-induced dentritic protein synthesis

Institution: California Institute of Technology
Investigator(s): Hwan-Ching Tai, B.S.
Award Cycle: 2005 (Cycle 14) Grant #: 14DT-0040 Award: $59,000
Subject Area: Nicotine Dependence
Award Type: Dissertation Awards

Initial Award Abstract
Nicotine, the major addictive component of cigarette smoke, strongly affects the reward circuitry of the brain. Nicotine leads to enhanced secretion of dopamine, a molecule secreted by the brain to transmit signals related to rewards. Dopamine has important effects on the connection of nerve cells in the reward circuitry. The points of contact between nerve cells, called synapses, can undergo long term changes in response to transient dopamine signals.

Our laboratory recently discovered that dopamine promotes the synthesis of new proteins in dendrites. Dendrites are extensions of nerve cells which receive input signals from other nerve cells via synapses. Proteins make up the majority of molecular machinery in cells, and the synthesis of new proteins in dendrites can provide the molecular components required for changes occurring in synapses. Hence, dopamine-induced protein synthesis in dendrites can have far-reaching consequences in terms of regulating how nerve cells are connected. This may be one of the fundamental reasons that nicotine can cause long-lasting changes in our reward circuitry.

We would like to further study the function of proteins synthesized in response to dopamine stimulation. We are trying to develop a new genetic tool that would allow us to inhibit the synthesis of specific proteins in dendrites. Our genetic approach utilizes a new class of small RNAs called microRNAs, which were recently discovered for their inhibitory effects on protein synthesis. This microRNA tool will help us understand the functions of proteins that are synthesized in dendrites due to dopamine signaling. In turn, this will further our understanding of the specific changes occurring in synapses when the brain is exposed to addictive substances.