Manifestaciones atípicas en la siderosis superficial del sistema nervioso central / Atypical manifestations in superficial siderosis of the central nervous system

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The role of spatiotemporal edges in visibility and visual masking.

What parts of a visual stimulus produce the greatest neural signal? Previous studies have explored this question and found that the onset of a stimulus's edge is what excites early visual neurons most strongly. The role of inhibition at the edges of stimuli has remained less clear, however, and the importance of neural responses associated with the termination of stimuli has only recently been examined. Understanding all of these spatiotemporal parameters (the excitation and inhibition evoked by the stimulus's onset and termination, as well as its spatial edges) is crucial if we are to develop a general principle concerning the relationship between neural signals and the parts of the stimulus that generate them. Here, we use visual masking illusions to explore this issue, in combination with human psychophysics, awake behaving primate neurophysiology in the lateral geniculate nucleus of the thalamus, and optical recording in the primary visual cortex of anesthetized monkeys. The edges of the stimulus, rather than its interior, generate the strongest excitatory and inhibitory responses both perceptually and physiologically. These edges can be imaged directly by using optical recording techniques. Excitation and inhibition are moreover most powerful when the stimulus turns both on and off (what might be thought of as the stimulus's temporal edges). We thus conclude that there is a general principle that relates the generation of neural signals (excitatory and inhibitory) to the spatiotemporal edges of stimuli in the early visual system.

Microsaccadic eye movements and firing of single cells in the striate cortex of macaque monkeys.

When viewing a stationary object, we unconsciously make small, involuntary eye movements or 'microsaccades'. If displacements of the retinal image are prevented, the image quickly fades from perception. To understand how microsaccades sustain perception, we studied their relationship to the firing of cells in primary visual cortex (V1). We tracked eye movements and recorded from V1 cells as macaque monkeys fixated. When an optimally oriented line was centered over a cell's receptive field, activity increased after microsaccades. Moreover, microsaccades were better correlated with bursts of spikes than with either single spikes or instantaneous firing rate. These findings may help explain maintenance of perception during normal visual fixation.

Effects of feedback projections from area 18 layers 2/3 to area 17 layers 2/3 in the cat visual cortex.

In the absence of a direct geniculate input, area 17 cells in the cat are nevertheless able to respond to visual stimuli because of feedback connections from area 18. Anatomic studies have shown that, in the cat visual cortex, layer 5 of area 18 projects to layer 5 of area 17, and layers 2/3 of area 18 project to layers 2/3 of area 17. What is the specific role of these connections? Previous studies have examined the effect of area 18 layer 5 blockade on cells in area 17 layer 5. Here we examine whether the feedback connections from layers 2/3 of area 18 influence the orientation tuning and velocity tuning of cells in layers 2/3 of area 17. Experiments were carried out in anesthetized and paralyzed cats. We blocked reversibly a small region (300 microm radius) in layers 2/3 of area 18 by iontophoretic application of GABA and recorded simultaneously from cells in layers 2/3 of area 17 while stimulating with oriented sweeping bars. Area 17 cells showed either enhanced or suppressed visual responses to sweeping bars of various orientations and velocities during area 18 blockade. For most area 17 cells, orientation bandwidths remained unaltered, and we never observed visual responses during blockade that were absent completely in the preblockade condition. This suggests that area 18 layers 2/3 modulate visual responses in area 17 layers 2/3 without fundamentally altering their specificity.

Actions of compounds manipulating the nitric oxide system in the cat primary visual cortex.

1. We iontophoretically applied NG-nitro-L-arginine (L-NOArg), an inhibitor of nitric oxide synthase (NOS), to cells (n = 77) in area 17 of anaesthetized and paralysed cats while recording single-unit activity extracellularly. In twenty-nine out of seventy-seven cells (38%), compounds altering NO levels affected visual responses. 2. In twenty-five out of twenty-nine cells, L-NOArg non-selectively reduced visually elicited responses and spontaneous activity. These effects were reversed by co-application of L-arginine (L-Arg), which was without effect when applied alone. Application of the NO donor diethylamine-nitric oxide (DEA-NO) produced excitation in three out of eleven cells, all three cells showing suppression by L-NOArg. In ten cells the effect of the soluble analogue of cGMP, 8-bromo-cGMP, was tested. In three of those in which L-NOArg application reduced firing, 8-bromo-cGMP had an excitatory effect. In six out of fifteen cells tested, L-NOArg non-selectively reduced responses to NMDA and alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA). Again, co-application of L-Arg reversed this effect, without enhancing activity beyond control values. 3. In a further subpopulation of ten cells, L-NOArg decreased responses to ACh in five. 4. In four out of twenty-nine cells L-NOArg produced the opposite effect and increased visual responses. This was reversed by co-application of L-Arg. Some cells were also affected by 8-bromo-cGMP and DEA-NO in ways opposite to those described above. It is possible that the variety of effects seen here could also reflect trans-synaptic activation, or changes in local circuit activity. However, the most parsimonious explanation for our data is that NO differentially affects the activity of two populations of cortical cells, in the main causing a non-specific excitation.

An unusual effect of application of the amino acid L-arginine on cat visual cortical cells.

Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17 of the anaesthetized/paralysed cat. Duration was long, and cells did not recover pre-application activity levels, indicating permanent decline. This effect was obtained without change in the extracellularly recorded wave-form, demonstrating that this did not result from depolarization block. In the remaining 55 cells, application of L-Arg alone, at levels capable of eliciting inhibition as described above, was without effect. In 29 cells, L-Arg application was able to reverse the effect of inhibition of nitric oxide (NO) production. Populations of cells showing the depressive effect described above and those affected by NO modulation levels were mutually exclusive.

The influence of nitric oxide on perigeniculate GABAergic cell activity in the anaesthetized cat.

We have tested the effect of iontophoretic application of the nitric oxide synthase inhibitor L-nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during L-nitroarginine application (n = 15), the visually elicited responses were markedly reduced, on average by 63 +/- 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co-application of the substrate for nitric oxide synthase, L-arginine, but not by the inactive D-isoform, although application of L-arginine alone was without effect. Pressure application of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n = 12). The nitric oxide synthase inhibitor L-nitroarginine was applied to a sub-population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 +/- 14%) with little or no effect on the excitation mediated by alpha-amino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) or quisqualate (effects not statistically significant), and it had no effect (n = 7) on excitation mediated by the metabotropic agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the actions of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and Y type cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co-localized with nitric oxide synthase at both sites). We propose that within the PGN nitric oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non-specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex.

Further observations on the role of nitric oxide in the feline lateral geniculate nucleus.

We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L-arginine, but not the biologically inactive isomer, D-arginine. Nitroprusside and S-nitroso-N-acetylpenicillamine (SNAP), nitric oxide donors, but not L-arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.

[Thyrotoxic periodic paralysis: an exceptional case report in Spanish population]. / Parálisis periódica tirotóxica: una observación excepcional en nuestro medio.

Thyrotoxic periodic paralysis is a rare clinical manifestation of thyrotoxicosis in spanish population. Patients show weakness and frecuently, paralysis and low levels of potassium in serum. The episode can be triggered by eating high carbohydrate diet, exercise, stress and some drugs. We present a new case of thyrotoxic periodic paralysis in a Grave's disease patient. Only four cases have been reported in the spanish literature. We conclude that a functional evaluation of thyroid gland is necessary in thyrotoxic periodic paralysis patients.

The role of nitric oxide in the transformation of visual information within the dorsal lateral geniculate nucleus of the cat.

We have shown that application of an inhibitor of the enzyme nitric oxide synthase (NOS) effectively suppresses the visual responses of relay cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized paralysed cat. Such suppression seems to result from a specific reduction in transmission via N-methyl-D-aspartic acid (NMDA) receptors, since iontophoretic application of the inhibitor of NOS selectively and in a dose-dependent manner decreased the responses to exogenously applied NMDA. Responses to other exogenously applied amino acid agonists, such as quisqualate (Quis), kainate (Kain) and alpha-amino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) were largely unaffected. Furthermore, the excitatory action of acetylcholine (ACh), normally co-localized with NOS in axonal terminals within the dLGN arising from the brainstem, was also unaffected. Unlike some other actions of nitric oxide (NO), this role seems not to involve an increase in production of cyclic guanosine-3',5'-mono-phosphate (cGMP), since application of the membrane permeable cGMP analogue 8-bromo-cGMP did not alter the suppressive effect of NOS inhibitors on either visual or NMDA evoked responses. We conclude that the normal function of NO at this level of the visual system is permissive, allowing full expression of NMDA mediated visually elicited information.

Modulatory influence of putative inhibitors of nitric oxide synthesis on visual processing in the cat lateral geniculate nucleus.

1. Using an in vivo preparation we have examined the actions of two inhibitors of nitric oxide synthase (NOS), NG-nitro-L-arginine (L-NOArg) and NG-methyl-L-arginine (L-MeArg), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances during visual stimulation with those elicited by visual stimulation alone. The effects of concurrent ejection of L-arginine (L-Arg), the normal physiological substrate of NOS, and D-arginine, the inactive isomer, were tested on these responses. 2. Extracellular application of L-NOArg and L-MeArg produced clear and repeatable effects, consisting of substantial reduction in discharge rate without affecting response selectivity, on 94% of tested cells. These effects were prevented by simultaneous application of L-Arg, which when ejected alone produced no change on visual evoked responses. 3. The data suggest that nitric oxide (NO) is necessary for the transmission of the visual input under normal visual stimulation and show a direct involvement of NO in visual information processing at the level of dLGN, suggesting that its contribution to brain mechanisms is more profound than previously thought.