Biomedical subjects

B Jill Venton

Publications and source records attributed to B Jill Venton.

11 recordsLinked to original sources

PubMed2007

Subsecond detection of physiological adenosine concentrations using fast-scan cyclic voltammetry.

Adenosine modulates blood flow and neurotransmission and may be protective during pathological conditions such as ischemia and stroke. A real-time sensor of adenosine concentrations is needed to understand its physiological actions and the extent of receptor activation. Microelectrodes are advantageous for in vivo measurements because they are small and can make fast measurements. The goal of this study was to characterize detection of physiological adenosine concentration changes at carbon-fiber microelectrodes with subsecond temporal resolution. The oxidation potential of adenosine is +1.3 V, so fast-scan cyclic voltammetry (FSCV) was performed with an applied potential from -0.4 to 1.5 V and back at 400 V/s every 100 ms. Two oxidation peaks were detected for adenosine with T-650 carbon fibers. The second oxidation peak at 1.0 V occurs after the initial oxidation at 1.5 V and is due to a sequential oxidation step. Adsorption was maximized to obtain detection limits of 15 nM, lower than basal adenosine concentrations in the brain. The electrode was insensitive to the metabolite inosine and seven times more sensitive to adenosine than ATP. The enzymatic degradation of adenosine was monitored with FSCV. This microelectrode sensor will be valuable for biological monitoring of adenosine.

Adenosine↗

PubMed2007

Pharmacologically induced, subsecond dopamine transients in the caudate-putamen of the anesthetized rat.

Subsecond dopamine (DA) concentration transients have previously been observed in behaving rats. Here, we demonstrate for the first time that DA transients can be pharmacologically induced in anesthetized rats. Coadministration of the D2 receptor antagonist, haloperidol, and the DA uptake inhibitor, nomifensine, results in significantly more DA transients than either drug alone. The results show that both D2 autoreceptors and the dopamine transporter regulate subsecond DA neurotransmission.

Anesthesia↗

PubMed2006

Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool.

Cocaine primarily exerts its behavioral effects by enhancing dopaminergic neurotransmission, amplifying dopamine-encoded sensorimotor integration. The presumed mechanism for this effect is inhibition of the dopamine transporter, which blocks dopamine uptake and prolongs the duration of dopamine in the extracellular space. However, there is growing evidence that cocaine can also augment dopamine release. Here, we directly monitored the actions of cocaine on dopamine release by using electrochemical detection to measure extracellular dopamine in the striatum of anesthetized mice. Cocaine enhanced the levels of striatal dopamine produced by electrical stimulation of dopaminergic neurons. Even after pretreatment with alpha-methyl-p-tyrosine, which depletes the readily releasable pool of dopamine, cocaine was still capable of elevating dopamine levels. This suggests that cocaine enhances dopamine release by mobilizing a reserve pool of dopamine-containing synaptic vesicles. To test this hypothesis, we examined electrically evoked dopamine release in synapsin I/II/III triple knock-out mice, which have impaired synaptic vesicle reserve pools. Knock-out of synapsins greatly reduced the ability of cocaine to enhance dopamine release with long stimulus trains or after depletion of the newly synthesized pool. We therefore conclude that cocaine enhances dopamine release and does so by mobilizing a synapsin-dependent reserve pool of dopamine-containing synaptic vesicles. This capacity to enhance exocytotic release of dopamine may be important for the psychostimulant actions of cocaine.

Animals↗

PubMed2006

In vivo measurements of neurotransmitters by microdialysis sampling.

The brain contains a vast network of neurons that connect with each other at specialized junctions called synapses.A synapse consists of a presynaptic terminal (the "sending"neuron) and a postsynaptic bouton (the "receiving" neuron)that are separated by a gap of 5-50 nm (Figure 1). Chemicals released into this synaptic gap interact with receptors on the postsynaptic neuron. This leads to intracellular changes in the postsynaptic neuron-for example, an altered membrane potential or gene expression. The chemical signal is terminated by transporter proteins that transfer transmitter molecules across the membrane to the intracellular space (a process known as "reuptake")or enzymes that degrade the transmitter in the vicinity of the synapse (Figure 1). This classical view of neurotransmission might be considered point-to-point or"wired" communication because neurons communicate only with neurons to which they are specifically connected. In addition,neurotransmitters can activate receptors at more distant sites either by escaping the synapse or by being directly released into extrasynaptic space. This longer-range communication has been called "volume" transmission (1, S1; S references can be found in Supporting Information). All brain functions, from controlling movement to emotions, involve these two forms of chemical communication. Analytical chemistry has an important role to play in developing our understanding of the brain by providing tools for identification and measurement of the many chemicals involved in neurotransmission.

Brain Chemistry↗

PubMed2006

Dynamic amino acid increases in the basolateral amygdala during acquisition and expression of conditioned fear.

Glutamate and gamma-aminobutyric acid (GABA) release in the amygdala are thought to be crucial for the acquisition and expression of fear memories, but the time course of amino acid changes during conditioning is unknown. We used rapid-sampling microdialysis with 14 s temporal resolution to address this issue. During auditory fear conditioning, large, rapid and transient increases in glutamate and GABA were detected, but only during the first noise-shock pairing. In contrast, rats receiving unsignaled shocks during contextual fear conditioning showed no changes in GABA and less glutamate release for the initial shock, but increased glutamate release during later shocks. Expression of conditioned fear to either a white noise or the context previously paired with shock produced similar rapid and transient increases in many amino acids in the amygdala. These experiments demonstrate glutamate and GABA levels in the amygdala are differentially modulated during auditory and contextual fear learning, and are transiently increased during the expression of fear memories.

Amino Acids↗

PubMed2005

Transient changes in nucleus accumbens amino acid concentrations correlate with individual responsivity to the predator fox odor 2,5-dihydro-2,4,5-trimethylthiazoline.

Predator odors elicit fear and defensive behavioral responses in rats, but a wide range of individual responsivity exists. The aim of this study was to examine whether individual differences in behavioral responsivity correlate with differences in amino acid neurotransmission to a predator fox odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). We investigated the time course of behaviorally evoked amino acid neurotransmitter changes in the nucleus accumbens using on-line microdialysis coupled to capillary electrophoresis with 14-s temporal resolution. One subset of animals (high responders) showed a large, biphasic increase in amino acids, such as glutamate and GABA, which lasted about 3 min. These neurochemical changes were highly correlated with increases in locomotion and burrowing, but lagged behind the behavioral changes by 2 min. A second subset of rats (low responders) showed neither behavioral activation nor changes in amino acid neurotransmission. As a positive control, rats were subjected to tail pinch, which evoked transient changes in amino acids in all animals. Cocaine (2 mg/kg, i.v.) increased locomotion but not amino acid levels. This work demonstrates that rapid and transient increases in amino acid neurotransmitters correlate with behavioral reactivity to salient stimuli.

Amino Acids↗

PubMed2003

Correlation of local changes in extracellular oxygen and pH that accompany dopaminergic terminal activity in the rat caudate-putamen.

Terminal activity causes an increase in local cerebral blood flow that can be quantified by measuring the accompanying increase in tissue oxygen. Alkaline pH changes can also follow neuronal activation. The purpose of these studies was to determine whether these changes in extracellular oxygen and pH correlate. Fast-scan cyclic voltammetry was used to detect changes in dopamine, pH and oxygen levels simultaneously in the caudate-putamen after electrical stimulation of the substantia nigra in anesthetized rats. The biphasic increases in oxygen and pH followed similar time courses, and were delayed a few seconds from the immediate release and uptake of dopamine. The changes following administration of neurotransmitter receptor antagonists as well as agents that modulate blood flow were identical for oxygen and pH. Two distinct mechanisms were identified that give rise to the oxygen and pH changes: blood vessel dilatation caused by nitric oxide synthesis after muscarinic receptor activation and adenosine receptor activation. We conclude that changes in blood flow accompanying terminal activity cause alkaline pH shifts by the rapid removal of carbon dioxide, a component of the extracellular brain buffering system.

Animals↗

PubMed2003

Real-time decoding of dopamine concentration changes in the caudate-putamen during tonic and phasic firing.

The fundamental process that underlies volume transmission in the brain is the extracellular diffusion of neurotransmitters from release sites to distal target cells. Dopaminergic neurons display a range of activity states, from low-frequency tonic firing to bursts of high-frequency action potentials (phasic firing). However, it is not clear how this activity affects volume transmission on a subsecond time scale. To evaluate this, we developed a finite-difference model that predicts the lifetime and diffusion of dopamine in brain tissue. We first used this model to decode in vivo amperometric measurements of electrically evoked dopamine, and obtained rate constants for release and uptake as well as the extent of diffusion. Accurate predictions were made under a variety of conditions including different regions, different stimulation parameters and with uptake inhibited. Second, we used the decoded rate constants to predict how heterogeneity of dopamine release and uptake sites would affect dopamine concentration fluctuations during different activity states in the absence of an electrode. These simulations show that synchronous phasic firing can produce spatially and temporally heterogeneous concentration profiles whereas asynchronous tonic firing elicits uniform, steady-state dopamine concentrations.

Action Potentials↗

PubMed2003

Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo.

BACKGROUND: Dopamine is a potent neuromodulator in the brain, influencing a variety of motivated behaviors and involved in several neurologic diseases. Measurements of extracellular dopamine in the brains of experimental animals have traditionally focused on a tonic timescale (minutes to hours). However, dopamine concentrations are now known to fluctuate on a phasic timescale (subseconds to seconds). APPROACH: Fast-scan cyclic voltammetry provides analytical chemical measurements of phasic dopamine signals in the rat brain. CONTENT: Procedural aspects of the technique are discussed, with regard to appropriate use and in comparison with other methods. Finally, examples of data collected using fast-scan cyclic voltammetry are summarized, including naturally occurring dopamine transients and signals arising from electrical stimulation of dopamine neurons. SUMMARY: Fast-scan cyclic voltammetry offers real-time measurements of changes in extracellular dopamine concentrations in vivo. With its subsecond time resolution, micrometer-dimension spatial resolution, and chemical selectivity, it is the most suitable technique currently available to measure transient concentration changes of dopamine.

Animals↗

PubMed2002

Response times of carbon fiber microelectrodes to dynamic changes in catecholamine concentration.

The electrode response time and the measured concentrations during dynamic catecholamine changes were compared using constant potential amperometry and fast-scan cyclic voltammetry. The amperometric response to a rectangular pulse of catecholamine is more rectangular than the cyclic voltammetric response; however, the response times are very similar when, during cyclic voltammetry, the temporal lag due to adsorption and desorption of catecholamine to the electrode is removed by deconvolution. Deconvolution of cyclic voltammetry data was applied to stimulated dopamine release in vivo, allowing for modeling of release and uptake kinetics and to measure catecholamine release from single cells, resulting in better resolution of peaks from single vesicles. In vitro postcalibrations were performed to calculate concentrations of catecholamine measured with cyclic voltammetry and amperometry. The addition of 600 microM ascorbic acid to the postcalibration buffer, allowing a catalytic reaction to regenerate dopamine, resulted in similar calculated concentrations for stimulated release of dopamine using amperometry and cyclic voltammetry. Using deconvoluted cyclic voltammetry to remove the response time lag and adding ascorbic acid to the calibration buffer, the shape and concentration of dynamic catecholamine changes are very similar when measured with constant potential amperometry and cyclic voltammetry.

Animals↗

PubMed2002

Neurochemistry and electroanalytical probes.

Electroanalytical techniques have been applied to monitoring chemical events including neurotransmitter release during rodent behaviour and the release of zeptomoles of molecules from single cells. Transgenic mice models have been developed and studied to identify specific cell types in vitro. Characterization and surface modification of electroanalytical probes has enhanced the selectivity and sensitivity of measurements.

Animals↗