Perspectives on Behavioural Function of Dopamine in the Nucleus Accumbens

Re: poster 516

John Salamone

On Sun Dec 6, grover wrote
>Dr. Salamone: Hope you are enjoying the meeting.  Great poster.  What physiological or biochemical factors enter into the mechanism of nuclear accumbens DA release?
>Thanks for the comment. In general I think it is useful to consider at least three categories of factors that affect neurotransmitter release.  One category would be actions upon the DA neuron cell body, which would affect the resting membrane potential, and ultimately the frequency and pattern of action potentials. For understanding the factors that affect this process, one needs to look at the sytems that project to SNc/VTA and form synapses with DA neurons. We need to examine these transmitter systems, and understand what activates or inhibits these input neurons.  Also, one area that needs to be examined in greater detail is the local circuitry of the area surrounding the DA neurons. Another category involves the fact that the DA neurons are highly branched, with many varicose terminals along each branch. The estimates are that there are several tens of thousands of varicosities per DA cell body. Thus, there are many questions about the biophysics of action potential propagation in such a highly branched system, and questions about potential neurochemial modulation of action potential propagation in some branches, as opposed to others, due to modulation of potassium and sodium channels. Another factor in operation here is the precise nature of the excitation-secretion coupling in DA neurons. A person who as offered a very elegant look at release processes from individual varicosities is David Sulzer. Finally, people also need to think in terms of presynaptic modulation of DA from terminals, due to the actions of other transmitters on heteroreceptors located directly on the terminals. The independent regulation of the terminal release processes and axonal/somatic action potential generating processes means it is difficult to make interences about release from a terminal based solely upon recording of the action potential. For example, it is possible to have a situation in which a neuron shows an increase in firing rate, yet release processes at the site of the terminal are muted due to presynaptic regulatory effects.

Very complex, but loads of fun, isn't it?????

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