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PubMed1983

The section-Golgi impregnation procedure. 1. Description of the method and its combination with histochemistry after intracellular iontophoresis or retrograde transport of horseradish peroxidase.

A method is described for impregnating neurons by the Golgi procedure in sections of brain tissue that are of a thickness 80-100 microns, so allowing a variety of histochemical procedures to be carried out prior to Golgi-impregnation. The method has been applied to the retina of the adult primate and to brain sections incubated to reveal horseradish peroxidase activity with substrates that give electron-dense reaction products. Sections containing neurons that have been filled with horseradish peroxidase by intracellular iontophoresis following electrophysiological characterization, or containing neurons retrogradely labelled by horseradish peroxidase, can be impregnated by this Golgi procedure. Subsequent gold-toning of the Golgi-impregnated neurons makes it possible to study, in the electron-microscope, both Golgi-impregnated and peroxidase-containing neurons and their afferent and efferent synaptic contacts within the same section. The procedure also makes it possible to repeat Golgi impregnation on sections already Golgi-impregnated and gold-toned, or to repeat the Golgi impregnation if the first impregnation is not satisfactory. The procedure is illustrated by examples from the monkey retina, cat visual cortex and rat neostriatum.

Animals↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2004

Iontophoresis for palmoplantar hyperhidrosis.

The pathogenesis of palmoplantar hyperhidrosis (HH) remains unknown. A causative therapy is therefore not possible yet. Step by step treatment for palmoplantar HH is advised. This includes: topical aluminium salts, tap water iontophoresis (TWI), botulinum toxin (BTX) injections and endoscopic thoracoscopic sympathectomy (ETS). The mechanism of action of TWI has been previously studied but is still not completely understood. A widely accepted hypothesis is that the anodal current causes accumulation of H(+) within the sweat duct. It is presumed that this causes an unknown lesion in the acrosyringium that inhibits sweating. TWI is non-invasive, safe, well tolerated, efficient and cheap. The patient can perform the therapy at home without medical assistance. TWI remains the best treatment for palmoplantar HH that has defied aluminium salts. This article provides a review of the literature concerning TWI, including its historical development, its mechanism of action and its indication and also describes the method of administration of this helpful treatment.

Journal Article↗

PubMed1998

Real-time assessments of dopamine function during behavior: single-unit recording, iontophoresis, and fast-scan cyclic voltammetry in awake, unrestrained rats.

Although ample evidence implicates the dopamine (DA) projection to the neostriatum and nucleus accumbens in motor and motivational processes, relatively little information is available on how DA alters neostriatal or accumbal functions under naturally occurring behavioral conditions. Further insight into neuron-behavior relationships can be achieved with the application of single-unit recording techniques, including iontophoresis and fast-scan cyclic voltammetry (FSCV), to awake, unrestrained animals. Single-unit recording has revealed that amphetamine, a widely abused psychomotor stimulant, activates motor-, but inhibits nonmotor-related neurons in neostriatum and nucleus accumbens. Although either response can be blocked by DA receptor antagonists, the amphetamine-induced activation also depends on an intact corticostriatal system, suggesting a role for glutamate (GLU). Both neostriatal and accumbal neurons are sensitive to iontophoretic application of either DA or GLU, but when applied during low-dose application of DA, the GLU signal is enhanced relative to background activity. In effect, DA appears to modulate GLU by strengthening the GLU signal-to-noise ratio. To assess DA release under behaviorally relevant conditions, FSCV has been used to obtain real-time measurements of DA efflux in a free-choice novelty test. DA efflux increased only during the brief period of entry into novelty, and the increase was confined to accumbal shell and the shell-core transition zone, the so-called shore. Neither accumbal core nor the overlying neostriatum showed a novelty-related DA change. Thus, DA release during behavior is not uniform and in the case of novelty appears targeted to the limbic-related area of accumbal shell. Further application of these and other in vivo technologies to ambulant animals is required to identify the complex mechanisms underlying both the release of DA and its effect on neostriatal and accumbal neurons during behavior.

Alcoholism↗

PubMed2003

Iontophoresis: fundamentals, developments and application.

The skin is an excellent barrier to the transport of charged compounds and large molecules. Many substances of present and potential therapeutic utility carry charge at physiological pH, have high molecular weights and/or are hydrophilic and, consequently, do not transport well across the skin. Pathways for the transport of small ions do appear to exist through the skin and flow along these pathways can be substantially enhanced by iontophoresis.

Journal Article↗

PubMed1988

Responses of neurons in somatosensory cortical area II of cats to high-frequency vibratory stimuli during iontophoresis of a GABA antagonist and glutamate.

Areas in the second somatic sensory cortex (SII) of cats that responded vigorously to low-amplitude, high-frequency vibratory stimulation were mapped with respect to the surrounding somatotopic organization. Neurons with these properties were found in the posterior and medial parts of the distal forelimb zone and were judged as receiving input from Pacinian mechanoreceptors. The responses of these neurons to sinusoidal vibrotactile stimulation were studied during iontophoretic administration of glutamate or bicuculline methiodide (BMI) to determine if the temporal fidelity of these cortical neurons was controlled by inhibitory circuits that used gamma-aminobutyric acid (GABA) as a neurotransmitter. The data from 19 Pacinian-sensitive neurons were analyzed for changes in the mean firing rate, the percentage of entrainment, and the pattern of periodicity as revealed by autocorrelograms and interval histograms. Iontophoresis of BMI or glutamate caused significant increases in mean firing rates during low- and high-frequency vibratory stimulation. The pattern of increased activity produced by BMI was characterized by a small, yet significant, reduction in the percentage of entrainment, whereas glutamate caused smaller and fewer significant changes in this measure. Analysis of autocorrelation and interval histograms suggested that BMI increased the probability of firing on consecutive stimulus cycles in small segments of the stimulus duration.

Afferent Pathways↗

PubMed1991

Evidence for GABA-mediated control of putative nociceptive modulating neurons in the rostral ventromedial medulla: iontophoresis of bicuculline eliminates the off-cell pause.

This study was undertaken to test the hypothesis that gamma-aminobutyric acid (GABA) is an endogeneous neurotransmitter regulating the activity of a class of putative nociceptive modulatory neurons (termed "off-cells") in the rostral ventromedial medulla (RVM) of the barbiturate-anesthetized rat. Off-cells, which are believed to correspond to the RVM output neuron that inhibits nociceptive processing at the level of the spinal cord, exhibit an abrupt pause in firing that begins immediately prior to the occurrence of the tail flick response (TF), a nocifensive reflex evoked by application of noxious heat to the tail. Single-unit recording and iontophoretic techniques were used to examine the ability of the GABAA receptor antagonist bicuculline methiodide (BIC) to antagonize selectively the characteristic off-cell pause. Iontophoretic application of BIC (5-30 nA) blocked the TF-related pause in each of the off-cells tested. This effect of BIC was generally slow in onset, and outlasted the period of application by several minutes. BIC iontophoresis also eliminated the cyclic alternation between active and silent periods that is often displayed by off-cells in lightly anesthetized rats. BIC application did not have a consistent effect on the firing of two other classes of RVM neurons ("on-cells" and "neutral cells"). Iontophoretically applied BIC antagonized the inhibitory effect of iontophoretically applied GABA, but not that produced by glycine. The glycine receptor antagonist strychnine did not mimic the action of BIC on off-cell activity. These data demonstrate antagonism of a synaptically evoked response using iontophoretic application of BIC, and provide strong evidence that the inhibitory neurotransmitter GABA mediates the TF-related off-cell pause. Taken together with behavioral experiments demonstrating that a GABA-mediated inhibitory process within RVM is crucial in permitting execution of the TF response, the present observations point to the significant functional relevance of GABA transmission within RVM in modulation of nociception.

Afferent Pathways↗

PubMed1989

Modulation of single cell responses and neuronal interactions produced by iontophoresis of glutamate in adult cat visual cortex.

Single neuron responses and interneuronal coordinations after microiontophoretic injections of L-glutamic acid (glutamate) were examined in cats striate cortex with an aid of multielectrode extracellular recording and crosscorrelation analysis. The effects of 15 min long stimulation with glutamate were compared with spontaneous mutability observed within at least 1.5 h. A mutability coefficient was suggested for quantitative data analysis. Spontaneous changes were analyzed in 144 neuronal pairs in two anesthetized and seven pretrigeminal cats. Differences in spontaneous mutability between these groups were not significant. Fluctuations of crosscorrelograms were smaller than fluctuations of poststimulus time histograms (PST). The type of correlogram and receptive field preferred orientation and direction never changed. The effect of glutamate injection was studied in 157 neuronal pairs in four anesthetized and eight pretrigeminal cats. Excitatory responses were observed in 69% of neurons, inhibitory in 18%. The excitatory response to glutamate was accompanied with enhanced visual response in 47% of cases and with reduced visual response in 18%. Crosscorrelogram strength was reduced in 43% of pairs with excitatory response to glutamate and increased only in 23%. After the termination of iontophoresis a persistent increase of the shared input coordination was observed in two pairs in anesthetized animals and in three pairs in pretrigeminal cats. The appearance of direct excitatory coordination was found in one case in pretrigeminal cats. Alterations of PST histograms did not exceed the range of spontaneous mutability. We infer that in a small percent of neuronal pairs the short glutamate stimulation can affect interneuronal links even in adult cat.

Animals↗

PubMed1978

Iontophoresis of enkephalins potentiates evoked field potentials in the in vitro rat hippocampus.

Effects of iontophoresis of an active opioid peptide, D-Ala2-Met-enkephalinamide (2dA), on evoked field potentials were studied in the hippocampus in vitro preparation. Population spike responses which correspond to the summatory firing of the pyramidal neurons were recorded with glass microelectrodes from the CA1 cell layer. It is found that 2dA greatly enhanced the amplitude of population spike. The excitatory effect was opiate-specific, because it was antagonized by iontophoretically applied naloxone, a potent narcotic antagonist. On the contrary, an inactive enkephalin analog, N-acetyl-(D-Ala2, Lys3)-Met-enkephalinamide, was without effect. It is concluded that opioid peptides exert a specific excitatory action on the pyramidal neurons in the in vitro hippocampus.

Action Potentials↗

PubMed1949