PittsburghV1, Main, Exploration, bibRecord, 000413

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

Identifieur interne : 000413 ( Main/Exploration ); précédent : 000412; suivant : 000414

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

Auteurs : Rashed Harun [États-Unis] ; Christine M. Grassi [États-Unis] ; Miranda J. Munoz [États-Unis] ; Gonzalo E. Torres [États-Unis] ; Amy K. Wagner [États-Unis]

Source :

Brain research [ 1872-6240 ] ; 2015.

RBID : pubmed:25527399

Descripteurs français

English descriptors

KwdEn :
- Animals, Carbon, Corpus Striatum (drug effects), Corpus Striatum (physiology), Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (metabolism), Dopamine Uptake Inhibitors (pharmacology), Electric Stimulation (methods), Electrodes, Implanted, Medial Forebrain Bundle (drug effects), Medial Forebrain Bundle (physiology), Methylphenidate (pharmacology), Models, Neurological, Rats, Sprague-Dawley, Signal Processing, Computer-Assisted, Synaptic Transmission (drug effects), Synaptic Transmission (physiology), Thermodynamics.
MESH :
- chemical , metabolism : Dopamine, Dopamine Plasma Membrane Transport Proteins.
- chemical , pharmacology : Dopamine Uptake Inhibitors, Methylphenidate.
- chemical : Carbon.
- drug effects : Corpus Striatum, Medial Forebrain Bundle, Synaptic Transmission.
- methods : Electric Stimulation.
- physiology : Corpus Striatum, Medial Forebrain Bundle, Synaptic Transmission.
- Animals, Electrodes, Implanted, Models, Neurological, Rats, Sprague-Dawley, Signal Processing, Computer-Assisted, Thermodynamics.

Abstract

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology.

DOI: 10.1016/j.brainres.2014.12.020
PubMed: 25527399

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology.</div>
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Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

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Descripteurs français

English descriptors

Abstract

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Le document en format XML

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