Contribution of L-type Ca2+ channel subtypes to burst firing of dopaminergic cells in the mouse ventral tegmental area

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Increased dopamine in the brain is believed to contribute to addiction and psychosis, it is therefore important to understand how dopamine output is regulated. Cells that make and release dopamine fire in different temporal patterns, clustered firing in short bursts has been found to be more effective in raising dopamine levels. We have previously reported that the L-type calcium channel is involved in generating this particular firing pattern, now we propose to examine this in more detail using mice that do not have one subtype of the ion channel. The ion channel in question is important for many functions, it is expected that a given subtype may be more implicated in a particular functions involving a specific group of cells in the brain. We will first examine which subtype is important for encoding burst firing to release more dopamine. We further reason that different dopamine cells may have different subtypes of the L-type ion channel that are connected to different parts of the brain. These subtypes will then be involved in regulating dopamine output to different parts of the brain depending on their connectivity. The proposed experiments in this program of research will provide necessary details for us to understand the workings of the brain dopamine system and will also provide clues as to how to target the system in the management of addiction and psychosis.