Journal
JOURNAL OF NEUROCHEMISTRY
Volume 87, Issue 5, Pages 1284-1295Publisher
WILEY
DOI: 10.1046/j.1471-4159.2003.02109.x
Keywords
amperometry; caudate-putamen; cocaine; diffusion; steady state; volume transmission
Categories
Funding
- NIDA NIH HHS [DA 07418] Funding Source: Medline
- NINDS NIH HHS [NS 15841, NS 35298] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS015841, R15NS035298] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R29DA007418, R01DA007418, R55DA007418] Funding Source: NIH RePORTER
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The fundamental process that underlies volume transmission in the brain is the extracellular diffusion of neurotransmitters from release sites to distal target cells. Dopaminergic neurons display a range of activity states, from low-frequency tonic firing to bursts of high-frequency action potentials (phasic firing). However, it is not clear how this activity affects volume transmission on a subsecond time scale. To evaluate this, we developed a finite-difference model that predicts the lifetime and diffusion of dopamine in brain tissue. We first used this model to decode in vivo amperometric measurements of electrically evoked dopamine, and obtained rate constants for release and uptake as well as the extent of diffusion. Accurate predictions were made under a variety of conditions including different regions, different stimulation parameters and with uptake inhibited. Second, we used the decoded rate constants to predict how heterogeneity of dopamine release and uptake sites would affect dopamine concentration fluctuations during different activity states in the absence of an electrode. These simulations show that synchronous phasic firing can produce spatially and temporally heterogeneous concentration profiles whereas asynchronous tonic firing elicits uniform, steady-state dopamine concentrations.
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