Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens.
Many individual neurons within the intact brain fire in stochastic patterns that arise from interactions with the neuronal circuits that they comprise. However, the chemical communication that is evoked by these firing patterns has not been characterized because sensors suitable to monitor subsecond chemical events in micron dimensions have only recently become available. Here we employ a voltammetric sensor technology coupled with principal component regression to examine the dynamics of dopamine concentrations in the nucleus accumbens (NAc) of awake and unrestrained rats. The sensor has submillimeter dimensions and provides high temporal (0.1 s) resolution. At select locations spontaneous dopamine transient concentration changes were detected, achieving instantaneous concentrations of approximately 50 nm. At other locations, transients were absent even though dopamine was available for release as shown by extracellular dopamine increases following electrical activation of dopaminergic neurons. At sites where dopamine concentration transients occur, uptake inhibition by cocaine enhances the frequency and magnitude of the rapid transients while also causing a more gradual increase in extracellular dopamine. These effects were largely absent from sites that did not support ongoing transient activity. These findings reveal an unanticipated spatial and temporal heterogeneity of dopamine transmission within the NAc that may depend upon the firing of specific subpopulations of dopamine neurons.
Wightman
R Mark
RM
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA. rmw@unc.edu
Heien
Michael L A V
ML
Wassum
Kate M
KM
Sombers
Leslie A
LA
Aragona
Brandon J
BJ
Khan
Amina S
AS
Ariansen
Jennifer L
JL
Cheer
Joseph F
JF
Phillips
Paul E M
PE
Carelli
Regina M
RM
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000295:instrumentation / Q000379:methods; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D003042:Cocaine; D004298:Dopamine