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Colour and photosensitive epilepsy.

Red-coloured flicker is claimed to be more epileptogenic than white or that of other colours matched for subjective intensity. A feature of the colour opponent system is that the response of luminosity-sensitive cortical units to stimulation of ganglion cells of a particular spectral sensitivity is reduced when cells of other sensitivities are simultaneously stimulated. We hypothesized that the apparent effect of colour on photosensitivity was not a property of red light per se but arose simply from the fact that, with commercially available filters a light can be provided to stimulate only red sensitive cones, but owing to the overlap of the absorption spectra of the visual pigments it is difficult to stimulate only green or blue sensitive cones. Such stimulation of a single cone population can be achieved by the 'silent substitution method' which has been used for evoked response studies. In 12 photosensitive epileptic patients we find that, using stimulus intensities (less than 20 nits) at which white flicker is without effect, stimulation of either red or green cones by the silent substitution method may produce epileptiform discharges, there being a slight (and not significant) excess of patients showing a greater sensitivity for green than for red cone stimulation. The findings are considered to support the hypothesis set out above.

Color Perception↗

Postural interneurons in the abdominal nervous system of lobster. III. Pathways mediating intersegmental spread of excitation.

The multisegmented abdomen of crayfish and lobster assumes a variety of postures as components of different behavioral acts. Experimentally these postures can be maintained by activating any of a number of premotor positioning interneurons. The pathways by which the motor output in two or more segments is coordinated were here investigated for a small group of identified postural interneurons whose somata lie in the 2nd abdominal ganglion (A2). Stimulation of all postural interneurons examined evokes a motor output in other abdominal ganglia through which the axon of the neuron passes as well as in the ganglion of origin (ganglion containing the neuron's cell body). The spread of motor excitation away from the originating ganglion occurs via two general pathways. In the first pathway connections to postural motoneurons are made directly by processes of the postural interneuron which pass into ganglia distal to the originating ganglion. Examples of this are shown for two flexion producing interneurons (FPIs) 201 and 301. Each of these FPIs makes monosynaptic connections with motoneurons in A2 and with a homologous set of motoneurons in A3. All postural interneurons fired a set of corollary discharge interneurons (CDIs) whose activities were recorded from the abdominal connectives. Two FPIs, 202 and 301, and a third interneuron, 503, produced motor outputs in ganglia to which they did not project. The motor specificity established in A2 by stimulation of FPIs 202 and 301 (whose axons pass caudally) was preserved in more rostral ganglia, such as A1. Therefore, different sets of CDIs can be specifically recruited to spread the same motor program that is initiated in the originating ganglion to ganglia that do not receive projections from the stimulated postural interneuron. CDIs, in addition, have the capacity to elicit motor programs in distal ganglia that are markedly different from that expressed in the ganglion of origin. For example, although 503 produced an inhibitory output in the abdominal ganglia that it innervated (A1 and A2), a flexion response was generated by it in more caudal ganglia. The caudal flexion response was mediated in part through a monosynaptic activation of FPI 201 and through other unidentified CDIs. Thus, the interneuronal circuitry for postural control is composed of numerous components, some of which have regional control over different portions of the abdominal nerve cord. Depending upon the required movement, select components are coactivated, either serially or in parallel, to effect a variety of spatially distinct positions.

Abdomen↗

An analysis of action of nicotinic agents on adrenergic nerve terminals in rat isolated vas deferens.

Nicotine and DMPP caused contraction of rat isolated vas deferens. The contractile response was antagonized by hexamethonium, phenoxybenzamine, phentolamine, guanethidine and bretylium, but not by atropine. The response was absent in tissues depleted of their norepinephrine content. Nicotine enhanced the outflow of tritium from tissues preloaded with 3H-norepinephrine. Only 50% of the nicotine-induced tritium outflow was due to unchanged norpinephrine, the rest were due to five metabolites of norepinephrine, chiefly glycol derivatives. As tissues, at the time of exposure to nicotine contained almost all of the tritium in the form of unchanged norepinephrine, it is likely that norepinephrine, only after being released from storage sites by nicotine was acted upon by the catabolizing enzymes to form various metabolites. Desensitization and cross desensitization phenomena were observed to both nicotine and DMPP. The tissues desensitized to nicotine were, however, responsive to norepinephrine, tyramine and transmural stimulation.

Animals↗

Electrical stimulation enhances the survival of axotomized retinal ganglion cells in vivo.

In view of recent reports on the survival promotion of damaged spiral ganglion cells and motoneurons by electrical stimulation, we hypothesized that an electrical stimulation of the cut optic nerve (ON) may promote the survival of axotomized retinal ganglion cells (RGCs) in vivo. To test this hypothesis, we examined 1 week after ON transection the RGC densities in the retinas with or without electrical stimulation. The densities of surviving RGCs in the retinas with the electrical stimulation increased as compared with those without the electrical stimulation. We concluded that electrical stimulation of the ON enhances the survival of axotomized RGCs in vivo, probably due to electrical activation of their soma.

Animals↗

Both synaptic and antidromic stimulation of neurons in the rat superior cervical ganglion acutely increase tyrosine hydroxylase activity.

Electrical stimulation of the preganglionic cervical sympathetic trunk produces an acute increase in the rate of DOPA synthesis in the rat superior cervical ganglion. The present study was designed to test the possibility that this acute transsynaptic stimulation of catechol biosynthesis could be, at least in part, a consequence of an increase in the firing rate of the postganglionic sympathetic neurons. For this purpose, the effect of stimulation in vitro of the preganglionic cervical sympathetic trunk was compared to that of stimulation of the predominantly postganglionic internal and external carotid nerves. Stimulation of the cervical sympathetic trunk at 10 Hz for 30 min produced a 4.6-fold increase in DOPA synthesis, while simultaneous stimulation of the two postganglionic trunks produced a 3.1-fold increase. The internal carotid nerve is known to contain a small population of preganglionic fibers that synapse on principal neurons in the ganglion before entering this nerve trunk. To eliminate the possibility that the effect of stimulation of the internal carotid nerve is mediated by synaptic stimulation via these preganglionic "through fibers", the effect of stimulation of previously decentralized ganglia was examined. While decentralization reduced the magnitude of the effect of stimulation of the internal and external carotid nerves, a 2.0-fold increase in DOPA synthesis was still seen. In addition, when these nerve trunks were stimulated in control ganglia that had been maintained in organ culture for 48 h to allow time for the degeneration of afferent nerve terminals, DOPA synthesis increased 4.1-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of nicotine on dopamine and DOPAC output from rat striatal tissue.

The effects of varying doses of nicotine infusion upon spontaneous (basal) and subsequent potassium chloride-stimulated dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) output from superfused corpus striatal tissue fragments of male rats were tested. Spontaneous dopamine and DOPAC outputs were increased in response to 1, 5 and 10, but not to 0.1 and 0 (control) microM concentrations of nicotine. Interestingly, the subsequent K+-stimulated (30 mM) dopamine output was completely abolished in preparations infused with the 5 and 10 microM nicotine, but not with the 1 or 0.1 microM nicotine. No overall significant differences in K+-stimulated DOPAC were obtained among the five doses. In experiment 2, the effects of an initial infusion of amphetamine (10 microM), potassium chloride (30 mM), nicotine (10 microM) or normal superfusion medium (control) were compared upon subsequent K+-evoked dopamine release. The amount of dopamine released in response to the second (subsequent) infusion of K+ was significantly greater in the potassium chloride and control conditions versus the nicotine and amphetamine stimulated groups. No overall differences in DOPAC output were observed among the four conditions of experiment 2. These results demonstrate that nicotine can exert differential modulatory effects upon striatal dopaminergic activity as a function of the dose. The augmented levels of DOPAC output along with the abolition of the K+-stimulated dopamine release in response to the 5 and 10 microM nicotine doses suggest that these doses may simultaneously produce an activation of intraneuronal metabolism of dopamine to DOPAC along with an activation of release and inhibition of uptake to diminish stores available for subsequent responses to K+ stimulation.

3,4-Dihydroxyphenylacetic Acid↗

Herpes simplex virus latency in human cornea.

The authors attempted to demonstrate the latency of herpes simplex virus type 1 (HSV-1) in corneas obtained during penetrating keratoplasty from patients with herpetic stromal keratitis in the nonactive (subsided) stage. The subjects comprised 20 patients (9 men, 11 women; average age 43.5 years). Infectious virus was not detected in the supernatants following corneal homogenization and centrifugation. Latent virus was detected in the cultured supernatants of the corneal sections from 8 patients. Although the ganglion trigger theory by Hill et al is conventionally supported as the mechanism of recurrence of herpetic keratitis, the present results suggest a ganglion and skin trigger theory, in which proliferation from latent HSV-1 in the cornea (peripheral tissue) might stimulate the ganglion.

Adult↗

Converging and diverging cholinergic inputs from submucosal neurons amplify activity of secretomotor neurons in guinea-pig ileal submucosa.

The organization of synaptic connections between guinea-pig ileal submucosal neurons was examined using intracellular recordings from single or pairs of submucosal neurons. Synaptic inputs were elicited by stimulating cholinergic neurons using pressure-pulse application of 5-hydroxytryptamine (5-HT) in ganglia adjacent to those where intracellular recordings were obtained. In addition, when pairs of intracellular recordings were obtained, one neuron was activated by intracellular stimulation and synaptic responses were recorded in the other neuron. Neurobiotin-filled microelectrodes were employed to characterize cells electrophysiologically and immunohistochemically. Recordings were obtained from 176 (173 S-type and three AH-type) neurons; 81% of cells were classified as vasoactive intestinal peptide (VIP) neurons. No fast excitatory postsynaptic potentials and only rare slow excitatory postsynaptic potentials were recorded following intracellular stimulation of paired S-type neurons. However, when paired intracellular recordings were obtained from neurons within the same ganglion and 5-HT was applied to an adjacent ganglion, this stimulation evoked synchronized fast excitatory postsynaptic potentials in 94% of pairs. In contrast, when cell bodies of VIP-VIP pairs were located in different ganglia, fast synaptic activation evoked by 5-HT stimulation was not synchronized in 87% of pairs. When intracellular recordings were obtained from a single neuron and two separate ganglia were stimulated by 5-HT pressure-pulse activation, fast excitatory postsynaptic potentials originating from both sources were recorded in the same VIP neuron. Morphological study of 34 S-type and three AH-type horseradish peroxidase-labeled neurons was conducted. AH-type neurons had multiple axonal branches with dense arborization of collaterals containing numerous varicosities in three to nine ganglia, whereas axons of S-type neurons exhibited relatively rare collaterals and varicosities within adjacent ganglia. These results demonstrate that cholinergic neurons provide both diverging and converging inputs to VIP neurons, providing a mechanism to enhance activation of VIP secretomotor neurons. The axonal projections of AH-type neurons suggest they are likely candidates to provide diverging inputs to multiple VIP neurons.

Animals↗

Trophic support of mouse inner ear by neural stem cell transplantation.

In the auditory system, efforts to reduce degeneration of spiral ganglion neurons have the immediate objective of improving clinical benefits of cochlear implants, which are small devices designed to stimulate spiral ganglion neurons electronically. Recent studies have indicated several neurotrophins can enhance survival of spiral ganglion neurons. However, the strategy for application of neurotrophins in inner ear is still a matter of debate. In this study, we examined the potential of cell therapy as a strategy for application of neurotrophins in the inner ear. Neural stem cells obtained from green fluorescent protein-transgenic mice were used as donor cells. Medium containing neural stem cells was injected into mouse inner ear. Histological analysis 4 weeks later revealed that transplant-derived cells survived in inner ear and that most transplant-derived cells in the cochlea had differentiated into glial cells. Moreover, expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor was observed in transplant-derived cells. These findings indicate that transplantation of neural stem cells can be a useful strategy for application of neurotrophins in inner ear.

Animals↗

Depressor responses to spinal stimulation in the pithed rat.

1. Electrical stimulation of the spinal nerves in the pithed rat preparation produces a pressor response due to sympathetic vasoconstriction.2. When the vasoconstrictor effect of sympathetic stimulation is abolished by guanethidine or hexamethonium and the blood pressure is raised by noradrenaline infusion, spinal stimulation produces depressor responses or complex responses containing depressor components.3. Contractions of skeletal muscle caused by stimulation of motor nerves result in complex changes in blood pressure consisting of a pressor component due to clamping of muscle blood vessels and a secondary depressor phase due to functional hyperaemia.4. The depressor response is partly due to stimulation of cholinergic postganglionic fibres. The acetylcholine released, which causes vasodilatation, may be the overflow from neuromuscular junctions or ganglionic synapses.5. Stimulation of the nerves to the adrenal medulla causes release of adrenaline which has a vasodilator effect during noradrenaline infusion.

Adrenalectomy↗

Functional neuroanatomy of the rhinophore of Aplysia punctata.

BACKGROUND: For marine snails, olfaction represents a crucial sensory modality for long-distance reception, as auditory and visual information is limited. The posterior tentacle of Aplysia, the rhinophore, is a chemosensory organ and several behavioural studies showed that the rhinophores can detect pheromones, initiate orientation and locomotion toward food. However the functional neuroanatomy of the rhinophore is not yet clear. Here we apply serotonin-immunohistochemistry and fluorescent markers in combination with confocal microscopy as well as optical recording techniques to elucidate the structure and function of the rhinophore of the sea slug Aplysia punctata. RESULTS: With anatomical techniques an overview of the neuroanatomical organization of the rhinophore is presented. Labelling with propidium iodide revealed one layer of cell nuclei in the sensory epithelium and densely packed cell nuclei beneath the groove of the rhinophore, which extends to about two third of the total length of the rhinophore. Serotonin immunoreactivity was found within the olfactory glomeruli underneath the epithelium as well as in the rhinophore ganglion. Retrograde tracing from the rhinophore ganglion with 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide (DiA) demonstrated the connection of glomeruli with the ganglion. Around 36 glomeruli (mean diameter 49 microm) were counted in a single rhinophore. Fluorimetric measurements of intracellular Ca2+ levels using Fura-2 AM loading revealed Ca2+-responses within the rhinophore ganglion to stimulation with amino acids. Bath application of different amino acids revealed differential responses at different positions within the rhinophore ganglion. CONCLUSION: Our neuroanatomical study revealed the number and position of glomeruli in the rhinophore and the rhinophore ganglion as processing stage of sensory information. Serotonin-immunoreactive processes were found extensively within the rhinophore, but was not detected within any peripheral cell body. Amino acids were used as olfactory stimuli in optical recordings and induced sensory responses in the rhinophore ganglion. The complexity of changes in intracellular Ca2+-levels indicates, that processing of odour information takes place within the rhinophore ganglion. Our neuroanatomical and functional studies of the rhinophore open up a new avenue to analyze the olfactory system in Aplysia.

Journal Article↗

Blood-brain barrier opened by stimulation of the parasympathetic sphenopalatine ganglion: a new method for macromolecule delivery to the brain.

OBJECT: Drug delivery across the blood-brain barrier remains a significant challenge. Based on earlier findings, the authors hypothesized that parasympathetic innervation of the brain vasculature could be used to augment drug delivery to the brain. METHODS: Using a craniotomy-cerebrospinal fluid superfusate paradigm in rats with an intravenous injection of tracer the authors demonstrated that stimulation of the postganglionic parasympathetic fibers of the sphenopalatine ganglion (SPG) increased the concentration of fluorescein isothiocyanate-dextran (4-250 kD) in the superfusate by two- to sixfold. A histological examination indicated the presence of dextran in the parenchyma. In another experiment the amount of Evans blue dye in the brain following SPG activation was similarly significantly elevated. The chemotherapeutic agents anti-HER2 monoclonal antibody and etoposide were also delivered to the brain and reached therapeutic concentrations. Brain homeostasis was not disturbed by this procedure; a measurement of nicotinamide adenine dinucleotide reduction did not show a decrease in the tissue metabolic state and brain water content did not increase significantly. CONCLUSIONS: Sphenopalatine ganglion activation demonstrates a promising potential for clinical use in the delivery of small and large molecules to the brain.

Animals↗

Antro-pancreatic reflexes: long- and short-route reflexes in exocrine and endocrine pancreatic secretion in dogs.

Pancreatic exocrine secretion is known to be facilitated by gastric antral distension via long- and short-route reflexes. In this study, we studied the effects of gastric distension on intra-pancreatic nerve discharges and blood insulin level as well as pancreatic exocrine secretion. Mongrel dogs were anesthetized with ketamine and thiopental, and immediately decerebrated. This study consisted of two series of experiments. In the first series, efferent discharges in an intra-pancreatic nerve branch were recorded, and its responses to antral distension were analyzed. In the second series, effects of antral distension on pancreatic exocrine secretion and blood insulin level were observed before and after vagotomy in splanchnicectomized dogs. Efferent discharges in a pancreatic nerve branch were increased by antral distension. Neither vagotomy nor splanchnicectomy produced obvious changes in the neural response. In splanchnicectomized dogs, antral distension elevated blood insulin level and increased pancreatic exocrine secretion. After subsequent vagotomy, these effects were reduced, but the increases were still greater than 50%. These results indicate that the antro-pancreatic short-route reflex plays a significant role in exocrine secretion, and also suggest that insulin release is increased by antral distension independent of blood glucose level.

Action Potentials↗