N-Methyl-D-Aspartate Receptor Activation Interacts with Electrical High Frequency Stimulation in the Rat Caudate Nucleus in vitro and in vivo

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 high-frequency 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.

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GABA outflow is modulated by electrical high frequency pulses during N-methyl-D-aspartate receptor activation in the rat caudate nucleus

Aktuelle Neurologie ◽

10.1055/s-2007-987678 ◽

2007 ◽

Vol 34 (S 2) ◽

Author(s):

H Füllgraf ◽

S Kretschmer ◽

A Moser

Keyword(s):

Caudate Nucleus ◽

High Frequency ◽

Receptor Activation ◽

Aspartate Receptor

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Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00209.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. H565-H573 ◽

Cited By ~ 20

Author(s):

Masahide Harada ◽

Yukiomi Tsuji ◽

Yuko S. Ishiguro ◽

Hiroki Takanari ◽

Yusuke Okuno ◽

...

Keyword(s):

Action Potential ◽

High Frequency ◽

Rabbit Heart ◽

Left Ventricular ◽

High Frequency Stimulation ◽

Electrophysiological Properties ◽

Rate Dependent ◽

Frequency Stimulation ◽

And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

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Orbitofrontal-striatal potentiation underlies stimulant induced hyperactivity

10.1101/802900 ◽

2019 ◽

Author(s):

Sebastiano Bariselli ◽

Nanami Miyazaki ◽

Alexxai Kravitz

Keyword(s):

Real Time ◽

High Frequency ◽

High Frequency Stimulation ◽

Locomotor Sensitization ◽

Real Time Monitoring ◽

Frequency Stimulation ◽

Brain Pathways ◽

Dorsomedial Striatum ◽

Stimulation Of

AbstractStimulants are one of the most widely prescribed classes of pharmaceuticals, but it is unclear which brain pathways underlie their therapeutic and adverse actions. Here, with real-time monitoring of circuit plasticity, we demonstrate that psychostimulants strengthen orbitofrontal (OFC) to dorsomedial striatum (DMS) pathway synapses, and increase striatal output in awake mice. In vivo high-frequency stimulation of OFC-DMS pathway blocked stimulant-induced potentiation and the expression of locomotor sensitization, thereby directly linking OFC-DMS plasticity to hyperactivity.

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