Construction of Training Sets for Valid Calibration of in Vivo Cyclic Voltammetric Data by Principal Component Analysis

Rodeberg, Nathan T.; Johnson, Justin A.; Cameron, Courtney M.; Saddoris, Michael P.; Carelli, Regina M.; Wightman, R. Mark

doi:10.1021/acs.analchem.5b03222

Cited by 53 publications

(99 citation statements)

References 46 publications

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“…; Sigma-Aldrich). Animals were then anesthetized (urethane, 1.5 g/kg), after which VTA stimulation was delivered to construct voltammograms for principal component analysis using an in vitro calibration factor (10 nA/μM) (56). Only transients exceeding three times the SD of the noise in dopamine traces obtained by principal component regression were considered spontaneous dopamine.…”

Section: Methodsmentioning

confidence: 99%

Cross-hemispheric dopamine projections have functional significance

Fox

Mikhailova

Bass

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine-lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.dopamine | voltammetry | synchrony | nucleus accumbens | dorsal striatum D opamine neurotransmission modulates arousal and motivation, and is important to the expression of reward-seeking behavior. Dopamine is released on a subsecond timescale during unexpected reward (1, 2), and becomes time-locked to cues that predict reward (3-7). 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. 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). Although numerous studies have summarized the function of dopamine circuits in reward-based behaviors (15, 16) and motor control (17-19), anatomic descriptions of dopamine projections are conflicting (20-23). Recent evidence suggests that some dopamine neurons project contralateral to their origin (22, 23), contradictory to the uncrossed dopamine system described previously (20, 21). To date, the significance of contralaterally projecting dopamine neurons, and how they may contribute to cross-hemispheric signaling, have not been established.A potential role for contralateral dopamine projections emerged in a recent study on brain stimulation reward (24). When rats were trained to self-stimulate the VTA, infusion of dopamine receptor antagonists in the NAc suppressed stimulation. This effect was seen whether the infusion was contralateral or ipsilateral to the stimulation site, reflecting cross-hemispheric modulation of the behavior. Furthe...

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Section: Methodsmentioning

confidence: 99%

Cross-hemispheric dopamine projections have functional significance

Fox

Mikhailova

Bass

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…In a subset of animals, 5 mg/kg idazoxan was given with naloxone to elicit norepinephrine overflow. One hour after naloxone administration, animals were anesthetized with urethane (1.5 g/kg), and the VTA/VNB was electrically stimulated using constant current isolators (Neurologs, model NL800) to obtain voltammograms for principal component analysis (PCA) (Rodeberg et al, 2015). We extracted dopamine currents using PCA and converted current to concentration using an averaged in vitro calibration factor (10 nA/μM).…”

Section: Voltammetric Catecholamine Measurementsmentioning

confidence: 99%

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal

Fox

Rodeberg

Wightman

2016

Neuropsychopharmacol

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Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST). We compared dopamine transients in the NAc with norepinephrine concentration changes in the vBNST, and correlated release with specific withdrawal-related behaviors. Morphine increased dopamine transients in the NAc, but did not elicit norepinephrine responses in the vBNST. Conversely, dopamine output was decreased during withdrawal, while norepinephrine was released in the vBNST during specific withdrawal symptoms. Both norepinephrine and withdrawal symptoms could be elicited in the absence of morphine by administering naloxone with an α 2 antagonist. The data support reciprocal roles for dopamine and norepinephrine signaling during drug exposure and withdrawal. The data also support the allostasis model and show that negative-reinforcement may begin working after a single exposure/withdrawal episode.

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“…These were generated for each subject in the course of developing a training set specific for each electrode and at each recording location (Rodeberg et al, 2015). These electrically generated stimulations allowed for comparison of reward-evoked DA events to the typical clearance rate owing to transporter-based kinetics in the recorded region (see Supplementary Methods for more detail).…”

Section: Behaviormentioning

confidence: 99%

Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell

Saddoris

Sugam

Carelli

2016

Neuropsychopharmacol

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Dopamine signals have repeatedly been linked to associative learning and motivational processes. However, there is considerably less agreement on a role for dopamine in reward processing, and therefore whether neuroplastic changes in dopamine function following chronic exposure to drugs of abuse such as cocaine may impair appropriate valuation of rewarding stimuli. To quantify this, we voltammetrically measured real-time dopamine release in the nucleus accumbens (NAc) core or shell while rats received unsignaled deliveries of either a small (1 pellet) or large (2 pellets) reward. In drug-naive controls, core dopamine signals did not discriminate between reward size at any point, while in the shell dopamine encoded magnitude differences only in a slower postpeak period. Despite this lack of discrimination between rewards by the peak DA response, controls easily discriminated between reward options in a subsequent choice task. In contrast, phasic dopamine reward signals were strongly altered by cocaine experience; core dopamine decreased peak response but increased discrimination between reward magnitudes while shell lost phasic responses to reward receipt altogether. Notably, animals with cocaine-associated alterations in dopamine signals for reward magnitude failed to subsequently discriminate between reward options. These findings suggest that cocaine self-administration alters the ability for dopamine signals to appropriately assign value to rewards and thus may in part contribute to later deficits in behaviors that depend on appropriate outcome valuation.

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Construction of Training Sets for Valid Calibration of in Vivo Cyclic Voltammetric Data by Principal Component Analysis

Cited by 53 publications

References 46 publications

Cross-hemispheric dopamine projections have functional significance

Cross-hemispheric dopamine projections have functional significance

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal

Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell

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