Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system: Proof of principle: Laboratory investigation

Young M. Shon, Su-Youne Chang, Susannah J Tye, Christopher J. Kimble, Kevin E. Bennet, Charles D. Blaha, Kendall H Lee

Research output: Contribution to journalArticle

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Abstract

Object. The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation-evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). Methods. The WINCS was used for FSCV, which consisted of a triangle wave scanned between -0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ∼ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. Results. The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Conclusions. Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of highfrequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalJournal of Neurosurgery
Volume112
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Adenosine
Neurotransmitter Agents
Dopamine
Deep Brain Stimulation
Microelectrodes
Ventral Tegmental Area
Putamen
Substantia Nigra
Electric Stimulation
Glass
Electrodes
Equipment Safety
Essential Tremor
Neurosurgical Procedures
Urethane
Computer Systems
carbon fiber
Technology
Brain

Keywords

  • Adenosine
  • Deep brain stimulation
  • Neuromodulation
  • Neurotransmitter
  • Voltammetry

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system : Proof of principle: Laboratory investigation. / Shon, Young M.; Chang, Su-Youne; Tye, Susannah J; Kimble, Christopher J.; Bennet, Kevin E.; Blaha, Charles D.; Lee, Kendall H.

In: Journal of Neurosurgery, Vol. 112, No. 3, 03.2010, p. 539-548.

Research output: Contribution to journalArticle

Shon, Young M. ; Chang, Su-Youne ; Tye, Susannah J ; Kimble, Christopher J. ; Bennet, Kevin E. ; Blaha, Charles D. ; Lee, Kendall H. / Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system : Proof of principle: Laboratory investigation. In: Journal of Neurosurgery. 2010 ; Vol. 112, No. 3. pp. 539-548.
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