Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens

Abstract

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.

Cross-hemispheric dopamine projections have functional significance

“…FSCV has been used to measure dopamine fluctuations in a number of studies; however, to date, all awake-animal measurements have been restricted to a single hemisphere (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(31)(32)(33)(34)(35). To investigate connectivity between hemispheres, we measured dopamine transients bilaterally in the NAc of freely moving rats.…”

“…Dopamine transients in the nucleus accumbens (NAc) occur as a result of cell firing in the ventral tegmental area (VTA) (8,9), and in rats reach concentrations of 50-200 nM before returning to baseline (10,11). Striatal dopamine transients also occur spontaneously during periods of rest (10,11), reflecting endogenous dopamine modulation. The magnitude and frequency of dopamine transients increase in response to drugs of abuse (12,13), which is thought to contribute to their reinforcing properties (14).…”

“…Dopamine is released on a subsecond timescale during unexpected reward (1,2), and becomes time-locked to cues that predict reward (3)(4)(5)(6)(7). Dopamine transients in the nucleus accumbens (NAc) occur as a result of cell firing in the ventral tegmental area (VTA) (8,9), and in rats reach concentrations of 50-200 nM before returning to baseline (10,11). Striatal dopamine transients also occur spontaneously during periods of rest (10,11), reflecting endogenous dopamine modulation.…”

Dynamic changes in accumbens dopamine correlate with learning during intracranial self-stimulation

“…Instead, the data reveal the complexity of chemical signaling during behavior. Unlike conventional chemical probes that provide an average concentration over a relatively large region, the carbon-fiber electrode reports temporal fluctuations from a microscopic local environment immediately adjacent to the electrode (36). Although the NAc shell functions as a unit that may influence behavior, the fluctuations in amplitude of dopamine release appear to indicate that the behavior is not specific to a single set of terminals.…”

Affective neuroscience of pleasure: reward in humans and animals

“…Each hotspot may be merely a cubic millimeter or so in volume in the rodent brain (and should be a cubic centimeter or so in humans, if proportional to whole brain volume) and is capable of generating enhancements of 'liking' reactions to a sensory pleasure such as sweetness, when opioid, endocannabinoid, or other neurochemical receptors within it are stimulated (Mahler et al 2007;Peciña and Berridge 2005;Peciña et al 2006;Smith and Berridge 2005;Smith et al 2008). Anatomical hotspot coding indicates a surprisingly high degree of localization of function for sufficient-cause pleasure mechanisms in the brain, and hotspot segregation within a limbic structure might provide a way for opioid or related brain signals to disambiguate pleasure versus pain via localization of function if the same neurochemical signal mediates both types of valence (Petrovic 2008;Reynolds and Berridge 2002;Scott et al 2007;Smith et al 2008;Wager et al 2004;Wightman et al 2007).…”