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Article ; Online: Monitoring molecules: insights and progress.

Wightman, R Mark

ACS chemical neuroscience

2015 Volume 6, Issue 1, Page(s) 5–7

Abstract: In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the ... ...

Abstract	In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the 1970s. Here, the advances in this field are documented, including its advance into understanding the actions that specific neurotransmitters mediate during behavior.
MeSH term(s)	Biosensing Techniques/history ; Biosensing Techniques/methods ; Biosensing Techniques/trends ; Brain Chemistry ; History, 20th Century ; History, 21st Century ; Humans ; Neurosciences/history ; Neurosciences/methods ; Neurosciences/trends
Language	English
Publishing date	2015-01-21
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/cn500324m
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Article ; Online: How cancer cells make and respond to interferon-I.

Cheon, HyeonJoo / Wang, Yuxin / Wightman, Samantha M / Jackson, Mark W / Stark, George R

Trends in cancer

2022 Volume 9, Issue 1, Page(s) 83–92

Abstract: Acute exposure of cancer cells to high concentrations of type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic exposure to low concentrations provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene ( ... ...

Abstract	Acute exposure of cancer cells to high concentrations of type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic exposure to low concentrations provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene (ISG) factor 3 (ISGF3) drives acute deleterious responses to IFN-I, whereas unphosphorylated (U-)ISGF3, lacking tyrosine phosphorylation, drives essential constitutive prosurvival mechanisms. Surprisingly, programmed cell death-ligand 1 (PD-L1), often expressed on the surfaces of tumor cells and well recognized for its importance in inactivating cytotoxic T cells, also has important cell-intrinsic protumor activities, including dampening acute responses to cytotoxic high levels of IFN-I and sustaining the expression of the low levels that benefit tumors. More thorough understanding of the newly recognized complex roles of IFN-I in cancer may lead to the identification of novel therapeutic strategies.
MeSH term(s)	Humans ; Interferons/metabolism ; Interferon-Stimulated Gene Factor 3/genetics ; Interferon-Stimulated Gene Factor 3/metabolism ; Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics ; Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism ; Signal Transduction ; Tyrosine ; Neoplasms/drug therapy ; Neoplasms/genetics
Chemical Substances	Interferons (9008-11-1) ; Interferon-Stimulated Gene Factor 3 ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; Tyrosine (42HK56048U)
Language	English
Publishing date	2022-10-08
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2022.09.003
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Article ; Online: How intravesicular composition affects exocytosis.

Mark Wightman, R / Domínguez, Natalia / Borges, Ricardo

Pflugers Archiv : European journal of physiology

2018 Volume 470, Issue 1, Page(s) 135–141

Abstract: Large dense core vesicles and chromaffin granules accumulate solutes at large concentrations (for instance, catecholamines, 0.5-1 M; ATP, 120-300 mM; or ... ...

Abstract	Large dense core vesicles and chromaffin granules accumulate solutes at large concentrations (for instance, catecholamines, 0.5-1 M; ATP, 120-300 mM; or Ca
MeSH term(s)	Animals ; Catecholamines/metabolism ; Chromaffin Granules/metabolism ; Chromaffin Granules/physiology ; Chromogranins/metabolism ; Electrochemical Techniques/methods ; Exocytosis ; Humans ; Synaptic Transmission
Chemical Substances	Catecholamines ; Chromogranins
Language	English
Publishing date	2018
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-017-2035-6
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Article ; Online: Contrasting Regulation of Catecholamine Neurotransmission in the Behaving Brain: Pharmacological Insights from an Electrochemical Perspective.

Fox, Megan E / Wightman, R Mark

Pharmacological reviews

2017 Volume 69, Issue 1, Page(s) 12–32

Abstract: Catecholamine neurotransmission plays a key role in regulating a variety of behavioral and physiologic processes, and its dysregulation is implicated in both neurodegenerative and neuropsychiatric disorders. Over the last four decades, in vivo ... ...

Abstract	Catecholamine neurotransmission plays a key role in regulating a variety of behavioral and physiologic processes, and its dysregulation is implicated in both neurodegenerative and neuropsychiatric disorders. Over the last four decades, in vivo electrochemistry has enabled the discovery of contrasting catecholamine regulation in the brain. These rapid and spatially resolved measurements have been conducted in brain slices, and in anesthetized and freely behaving animals. In this review, we describe the methods enabling in vivo measurements of dopamine and norepinephrine, and subsequent findings regarding their release and regulation in intact animals. We thereafter discuss key studies in awake animals, demonstrating that these catecholamines are not only differentially regulated, but are released in opposition of each other during appetitive and aversive stimuli.
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; Brain/cytology ; Brain/drug effects ; Brain/metabolism ; Catecholamines/metabolism ; Dopamine/metabolism ; Humans ; Membrane Potentials ; Models, Animal ; Neuronal Plasticity ; Neurons/drug effects ; Neurons/metabolism ; Neurotransmitter Agents/pharmacology ; Substance-Related Disorders/metabolism ; Substance-Related Disorders/physiopathology
Chemical Substances	Catecholamines ; Neurotransmitter Agents ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2017-02-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	209898-2
ISSN	1521-0081 ; 0031-6997
ISSN (online)	1521-0081
ISSN	0031-6997
DOI	10.1124/pr.116.012948
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Article ; Online: Evaluation of Drug Concentrations Delivered by Microiontophoresis.

Kirkpatrick, Douglas C / Wightman, R Mark

Analytical chemistry

2016 Volume 88, Issue 12, Page(s) 6492–6499

Abstract: Microiontophoresis uses an electric current to eject a drug solution from a glass capillary and is often utilized for targeted delivery in neurochemical investigations. The amount of drug ejected, and its effective concentration at the tip, has ... ...

Abstract	Microiontophoresis uses an electric current to eject a drug solution from a glass capillary and is often utilized for targeted delivery in neurochemical investigations. The amount of drug ejected, and its effective concentration at the tip, has historically been difficult to determine, which has precluded its use in quantitative studies. To address this, a method called controlled iontophoresis was developed which employs a carbon-fiber microelectrode incorporated into a multibarreled iontophoretic probe to detect the ejection of electroactive species. Here, we evaluate the accuracy of this method. To do this, we eject different concentrations of quinpirole, a D2 receptor agonist, into a brain slice containing the dorsal striatum, a brain region with a high density of dopamine terminals. Local electrical stimulation was used to evoke dopamine release, and inhibitory actions of quinpirole on this release were examined. The amount of drug ejected was estimated by detection of a coejected electrochemical marker. Dose response curves generated in this manner were compared to curves generated by conventional perfusion of quinpirole through the slice. We find several experimental conditions must be optimized for accurate results. First, selection of a marker with an identical charge was necessary to mimic the ejection of the cationic agonist. Next, evoked responses were more precise following longer periods between the end of the ejection and stimulation. Lastly, the accuracy of concentration evaluations was improved by longer ejections. Incorporation of these factors into existing protocols allows for greater certainty of concentrations delivered by controlled iontophoresis.
MeSH term(s)	Animals ; Brain/metabolism ; Corpus Striatum/metabolism ; Dopamine Agonists/administration & dosage ; Dopamine Agonists/analysis ; Dopamine Agonists/pharmacokinetics ; Drug Delivery Systems/methods ; Iontophoresis/methods ; Male ; Quinpirole/administration & dosage ; Quinpirole/analysis ; Quinpirole/pharmacokinetics ; Rats, Sprague-Dawley ; Receptors, Dopamine D2/agonists
Chemical Substances	Dopamine Agonists ; Receptors, Dopamine D2 ; Quinpirole (20OP60125T)
Language	English
Publishing date	2016-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.6b01211
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Article ; Online: Dopamine's Effects on Corticostriatal Synapses during Reward-Based Behaviors.

Bamford, Nigel S / Wightman, R Mark / Sulzer, David

Neuron

2018 Volume 97, Issue 3, Page(s) 494–510

Abstract: Many learned responses depend on the coordinated activation and inhibition of synaptic pathways in the striatum. Local dopamine neurotransmission acts in concert with a variety of neurotransmitters to regulate cortical, thalamic, and limbic excitatory ... ...

Abstract	Many learned responses depend on the coordinated activation and inhibition of synaptic pathways in the striatum. Local dopamine neurotransmission acts in concert with a variety of neurotransmitters to regulate cortical, thalamic, and limbic excitatory inputs to drive the direct and indirect striatal spiny projection neuron outputs that determine the activity, sequence, and timing of learned behaviors. We review recent advances in the characterization of stereotyped neuronal and operant responses that predict and then obtain rewards. These depend on the local release of dopamine at discrete times during behavioral sequences, which, acting with glutamate, provides a presynaptic filter to select which excitatory synapses are inhibited and which signals pass to indirect pathway circuits. This is followed by dopamine-dependent activation of specific direct pathway circuits to procure a reward. These steps may provide a means by which higher organisms learn behaviors in response to feedback from the environment.
MeSH term(s)	Animals ; Behavior, Animal ; Cerebral Cortex/physiology ; Conditioning, Operant ; Corpus Striatum/physiology ; Dopamine/physiology ; Neural Pathways/physiology ; Neurons/physiology ; Receptors, Dopamine D1/physiology ; Receptors, Dopamine D2/physiology ; Reward ; Synapses/physiology
Chemical Substances	Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2018-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.01.006
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Measurement of Basal Neurotransmitter Levels Using Convolution-Based Nonfaradaic Current Removal.

Johnson, Justin A / Rodeberg, Nathan T / Wightman, R Mark

Analytical chemistry

2018 Volume 90, Issue 12, Page(s) 7181–7189

Abstract: Fast-scan cyclic voltammetry permits robust subsecond measurements of in vivo neurotransmitter dynamics, resulting in its established use in elucidating these species' roles in the actions of behaving animals. However, the technique's limitations, namely ...

Abstract	Fast-scan cyclic voltammetry permits robust subsecond measurements of in vivo neurotransmitter dynamics, resulting in its established use in elucidating these species' roles in the actions of behaving animals. However, the technique's limitations, namely the need for digital background subtraction for analytical signal resolution, have restricted the information obtainable largely to that about phasic neurotransmitter release on the second-to-minute time scale. The study of basal levels of neurotransmitters and their dynamics requires a means of isolating the portion of the background current arising from neurotransmitter redox reactions. Previously, we reported on the use of a convolution-based method for prediction of the resistive-capacitive portion of the carbon-fiber microelectrode background signal, to improve the information content of background-subtracted data. Here we evaluated this approach for direct analytical signal isolation. First, protocol modifications (i.e., applied waveform and carbon-fiber type) were optimized to permit simplification of the interfering background current to components that are convolution-predictable. It was found that the use of holding potentials of at least 0.0 V, as well as the use of pitch-based carbon fibers, improved the agreement between convolution predictions and the observed background. Subsequently, it was shown that measurements of basal dopamine concentrations are possible with careful control of the electrode state. Successful use of this approach for measurement of in vivo basal dopamine levels is demonstrated, suggesting the approach may serve as a useful tool in expanding the capabilities of fast-scan cyclic voltammetry.
MeSH term(s)	Animals ; Dopamine/analysis ; Electrochemical Techniques ; Electrodes ; Male ; Neurotransmitter Agents/analysis ; Rats ; Rats, Sprague-Dawley ; Software ; Surface Properties
Chemical Substances	Neurotransmitter Agents ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2018-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.7b04682
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Article ; Online: Electrochemical Analysis of Neurotransmitters.

Bucher, Elizabeth S / Wightman, R Mark

Annual review of analytical chemistry (Palo Alto, Calif.)

2015 Volume 8, Page(s) 239–261

Abstract: Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for ...

Abstract	Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.
MeSH term(s)	Animals ; Biosensing Techniques/methods ; Electrochemical Techniques/methods ; Humans ; Neurotransmitter Agents/analysis
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2398707-8
ISSN	1936-1335 ; 1936-1327
ISSN (online)	1936-1335
ISSN	1936-1327
DOI	10.1146/annurev-anchem-071114-040426
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Article ; Online: Removal of Differential Capacitive Interferences in Fast-Scan Cyclic Voltammetry.

Johnson, Justin A / Hobbs, Caddy N / Wightman, R Mark

Analytical chemistry

2017 Volume 89, Issue 11, Page(s) 6166–6174

Abstract: Due to its high spatiotemporal resolution, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes enables the localized in vivo monitoring of subsecond fluctuations in electroactive neurotransmitter concentrations. In practice, resolution of ...

Abstract	Due to its high spatiotemporal resolution, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes enables the localized in vivo monitoring of subsecond fluctuations in electroactive neurotransmitter concentrations. In practice, resolution of the analytical signal relies on digital background subtraction for removal of the large current due to charging of the electrical double layer as well as surface faradaic reactions. However, fluctuations in this background current often occur with changes in the electrode state or ionic environment, leading to nonspecific contributions to the FSCV data that confound data analysis. Here, we both explore the origin of such shifts seen with local changes in cations and develop a model to account for their shape. Further, we describe a convolution-based method for removal of the differential capacitive contributions to the FSCV current. The method relies on the use of a small-amplitude pulse made prior to the FSCV sweep that probes the impedance of the system. To predict the nonfaradaic current response to the voltammetric sweep, the step current response is differentiated to provide an estimate of the system's impulse response function and is used to convolute the applied waveform. The generated prediction is then subtracted from the observed current to the voltammetric sweep, removing artifacts associated with electrode impedance changes. The technique is demonstrated to remove select contributions from capacitive characteristics changes of the electrode both in vitro (i.e., in flow-injection analysis) and in vivo (i.e., during a spreading depression event in an anesthetized rat).
MeSH term(s)	Animals ; Carbon Fiber/chemistry ; Electrochemical Techniques ; Male ; Microelectrodes ; Neurotransmitter Agents/analysis ; Rats ; Rats, Sprague-Dawley ; Software
Chemical Substances	Carbon Fiber ; Neurotransmitter Agents
Language	English
Publishing date	2017-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.7b01005
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Article ; Online: Simultaneous fMRI and fast-scan cyclic voltammetry bridges evoked oxygen and neurotransmitter dynamics across spatiotemporal scales.

Walton, Lindsay R / Verber, Matthew / Lee, Sung-Ho / Chao, Tzu-Hao Harry / Wightman, R Mark / Shih, Yen-Yu Ian

NeuroImage

2021 Volume 244, Page(s) 118634

Abstract: The vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect ... ...

Abstract	The vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect neurotransmission in high magnetic field environments are limited. Here, we propose an experimental setting enabling simultaneous fast-scan cyclic voltammetry (FSCV) and blood oxygenation level-dependent functional magnetic imaging (BOLD fMRI) to measure both local tissue oxygen and dopamine responses, and global BOLD changes, respectively. By using MR-compatible materials and the proposed data acquisition schemes, FSCV detected physiological analyte concentrations with high temporal resolution and spatial specificity inside of a 9.4 T MRI bore. We found that tissue oxygen and BOLD correlate strongly, and brain regions that encode dopamine amplitude differences can be identified via modeling simultaneously acquired dopamine FSCV and BOLD fMRI time-courses. This technique provides complementary neurochemical and hemodynamic information and expands the scope of studying the influence of local neurotransmitter release over the entire brain.
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Electrochemical Techniques/methods ; Magnetic Resonance Imaging/methods ; Male ; Neuroimaging ; Neurotransmitter Agents/physiology ; Oxygen ; Rats ; Synaptic Transmission
Chemical Substances	Neurotransmitter Agents ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2021.118634
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