Method Article

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0

DOI:

10.3791/55595

June 5th, 2017

In This Article

Summary

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Fast-scan cyclic voltammetry can monitor in vivo dopamine neurotransmission in the context of drugs, disease, and other experimental manipulations. This work describes the implementation of QNsim1.0, a software to model electrically stimulated dopamine responses according to the quantitative neurobiological model to quantify estimates of dopamine release and reuptake dynamics.

Abstract

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Introduction

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Dopamine (DA) neurotransmission plays an essential role in various cognitive and behavioral functions, and its dysfunction is implicated in several common diseases and disorders. As such, it is critical to develop accurate methods of quantitatively studying DA neurotransmission in vivo to evaluate how DA neurotransmission is altered in the contexts of disease models and drug pharmacology. Fast-scan cyclic voltammetry (FSCV) allows for monitoring in vivo DA neurotransmission with fine spatial and temporal resolution. While it is possible to monitor physiological DA neurotransmission in awake, freely behaving animals, the electrical stimulation of asce....

Access restricted. Please log in or start a trial to view this content.

Protocol

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

1. Installation, Data Preparation, and Launching QNsim1.0

  1. Download "QNsim1.0.zip" (provided as a supplement) and extract it to a desired directory.
  2. Prepare stimulated DA response data for modeling with the software program by organizing a spreadsheet in which each column contains a temporal DA response converted to µM DA concentrations. Save this (.xlsx) file to the same directory as the program files.
    Note: The spreadsheet can contain multiple responses in an individual experiment or multiple studies containing a fixed number of responses (see "Sample.xlsx" for an example).
  3. Open the programming environment software, navig....

Access restricted. Please log in or start a trial to view this content.

Results

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Included with the software program are sample DA neurotransmission data obtained from the rat dorsal striatum (Study 1) and the nucleus accumbens (Study 2) that are compiled into "Sample.xlsx." The spreadsheet contains the DA concentration data of the baseline responses to 60 Hz, 10 s and 5 s stimulations and a response to a 60 Hz, 5 s stimulation 35 min after the administration of the DA transport inhibitor methylphenidate (MPH) (10 mg/kg, i.p.). The stimulated DA response data is organized into columns, as demonstrated.......

Access restricted. Please log in or start a trial to view this content.

Discussion

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

The use of FSCV to study in vivo stimulated DA neurotransmission originated in the 1980s30 and still continues to be a rich source of in vivo neurotransmission data with unparalleled spatial and temporal resolution. Stimulated DA responses reflect a complex balance of DA release and reuptake that are modulated by the electrical stimulations themselves. The QN model incorporates principles from contemporary neurotransmission research to model in vivo stimulated DA neurotr.......

Access restricted. Please log in or start a trial to view this content.

Disclosures

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

The authors have nothing to disclose.

Acknowledgements

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

We acknowledge the UPMC Rehabilitation Institute for supporting this work.

....

Access restricted. Please log in or start a trial to view this content.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
MATLAB R2016a for Mac Mathworks
QNsim1.0In house software packageSoftware to model FSCV data using the QN framework

References

Loading...
$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,
  1. Taylor, I. M., et al. Kinetic diversity of dopamine transmission in the dorsal striatum. J Neurochem. 133 (4), 522-531 (2015).
  2. Harun, R., Grassi, C. M., Munoz, M. J., Torres, G. E., Wagner, A. K. Neurobiological model of stimulated dopami....

Access restricted. Please log in or start a trial to view this content.

Reprints and Permissions

Request permission to reuse the text or figures of this JoVE article

Request Permission

Tags

Fast scan Cyclic VoltammetryDopamine NeurotransmissionQNsim1 0 SoftwareElectrical StimulationDopamine ReleaseDopamine ReuptakeStriatal DopamineNucleus AccumbensDorsal StriatumParameter Modeling

Related Articles