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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.
European Journal of Neuroscience 11/2007; 26(7):2046-54. · 3.63 Impact Factor
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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 ∼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.
European Journal of Neuroscience 09/2007; 26(7):2046 - 2054. · 3.63 Impact Factor
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ABSTRACT: Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI. Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7 mm and 2.9 mm; 4 m/sec) over the right parietal cortex or sham surgery. For days 1-6 post-surgery, the beam balance and beam walking tasks were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7-14 post-surgery. Injured rats displayed a significant, but transient, deficit on each motor task (p < 0.0001). Open Field results showed that injured rats had lower activity levels than shams (p < 0.0001), displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (p < 0.0001). Y-maze results suggest that injured rats spent less time in the novel arm versus the familiar arms when compared to shams (p < 0.0001). For FCN, injured rats were less active (p < 0.05) and spent less time and had fewer interactions with objects in the novel environment compared to shams (p < 0.05). These results suggest that several ethological factors contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described. Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.
Journal of Neurotrauma 09/2007; 24(8):1308-20. · 3.65 Impact Factor
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ABSTRACT: Dopamine neurotransmission has been implicated in the modulation of many cognitive processes. Both rapid (phasic) and slower (tonic) changes in its extracellular concentration contribute to its complex actions. Fast in vivo electrochemical techniques can measure extracellular dopamine on a rapid time scale but without the selectivity afforded with slower techniques that use chemical separations. Cyclic voltammetry improves chemical resolution over other electrochemical methods, and it can resolve dopamine changes in the brains of behaving rodents over short epochs (<10 s). With this method, however, selective detection of slower dopamine changes is still elusive. Here we demonstrate that principal component regression of cyclic voltammetry data enables quantification of changes in dopamine and extracellular pH. Using this method, we show that cocaine modifies dopamine release in two ways: dopamine concentration transients increase in frequency and magnitude, whereas a gradual increase in steady-state dopamine concentration occurs over 90 s.
Proceedings of the National Academy of Sciences 08/2005; 102(29):10023-8. · 9.68 Impact Factor
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ABSTRACT: The ability to monitor the concentration of neurotransmitters in the extracellular space of living brain is crucial to improving our understanding of the neurochemical aspects of brain function and the dysfunction associated with numerous neurological disorders. Microdialysis probes and electrochemical microsensors are often used for in-vivo neurotransmitter monitoring, but these are invasive devices that are implanted directly into brain tissue. Although the selectivity, sensitivity, and temporal resolution of these devices have been characterized in detail, less attention has been paid to the impact of the trauma that they inflict on the tissue or the effect of any such trauma on the outcome of the measurements that they are used to perform. In this paper, we describe emerging evidence that suggests trauma effects deserve closer consideration than they have received to date.
TrAC Trends in Analytical Chemistry 22(8):503-508. · 6.27 Impact Factor
