Biomedical subjects

J Cudeiro

Publications and source records attributed to J Cudeiro.

At least 19 recordsLinked to original sources

PubMed2000

A possible role for nitric oxide at the sleep/wake interface.

Cholinergic neurotransmission is known to have important arousal/activating functions. The neurons responsible for those actions also release the atypical neuromodulator nitric oxide (NO), which has been shown in previous studies to be involved in the modulation of sleep/wake states. The present investigation, using an animal model (anesthetized cat) tests the hypothesis that NO cooperates with ACh in controlling rhythmic neuronal activity, which may play a role in sleep/wake transition. We have used extracellular singleunit recording of neurons in the dorsal thalamus and visual cortex with simultaneous iontophoretic application of drugs acting upon the NO system: the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOArg), NO donors, and 8-bromo-cGMP (which mimics the action of NO). Local inhibition of NOS significantly reduced the activity of recorded cells in both thalamus and visual cortex. The opposite effect was achieved with NO donors application. In cortex, ejection of 8-bromo-cGMP or the NO donor diethylamine-nitric oxide (DEA-NO) increased cell firing. Furthermore, the rhythmic firing pattern present in these cortical neurons was disrupted. Taken together, these findings suggest that the NO system collaborates with cholinergic neurotransmission. This collaboration might be involved in the control of different patterns of electrogenic activity during various states of the sleep-wake cycle, via the ability of the NO system to modify rhythmic activity of neurons.

Acetylcholine↗

PubMed2000

The primate pulvinar nuclei: vision and action.

The pulvinar nuclei of the thalamus are proportionately larger in higher mammals, particularly in primates, and account for a quarter of the total mass. Traditionally, these nuclei have been divided into oral (somatosensory), superior and inferior (both visual) and medial (visual, multi-sensory) divisions. With reciprocal connections to vast areas of cerebral cortex, and input from the colliculus and retina, they occupy an analogous position in the extra-striate visual system to the lateral geniculate nucleus in the primary visual pathway, but deal with higher-order visual and visuomotor transduction. With a renewed recent interest in this thalamic nuclear collection, and growth in our knowledge of the cortex with which it communicates, perhaps the time is right to look to new dimensions in the pulvinar code.

Animals↗

PubMed2000

Visual response augmentation in cat (and macaque) LGN: potentiation by corticofugally mediated gain control in the temporal domain.

Visual responses of neurons are dependent on the context of a stimulus, not only in spatial terms but also temporally, although evidence for temporally separate visual influences is meagre, based mainly on studies in the higher cortex. Here we demonstrate temporally induced elevation of visual responsiveness in cells in the lateral geniculate nucleus (LGN) of cat and monkey following a period of high intensity (elevated contrast) stimulation. This augmentation is seen in 40-70% (monkey-cat) of cells tested and of all subtypes. Peaking at approximately 3 min following the period of intense stimulation, it can last for 10-12 min and can be repeated and summed in time. Furthermore, it is dependent on corticofugal input, is seen even when high contrast stimuli of orthogonal orientation are used and therefore results from a/any prior increase in activity in the retino-geniculo-striate pathway. We suggest that this reflects a general mechanism for control of visual responsiveness; both a flexible and dynamic means of changing effectiveness of thalamic activity as visual input changes, but also a mechanism which is an emergent property of the thalamo-cortico-thalamic loop.

Animals↗

PubMed1999

Sight and insight--on the physiological role of nitric oxide in the visual system.

Research in the fields of cellular communication and signal transduction in the brain has moved very rapidly in recent years. Nitric oxide (NO) is one of the latest discoveries in the arena of messenger molecules. Current evidence indicates that, in visual system, NO is produced in both postsynaptic and presynaptic structures and acts as a neurotransmitter, albeit of a rather unorthodox type. Under certain conditions it can switch roles to become either neuronal 'friend' or 'foe'. Nitric oxide is a gas that diffuses through all physiological barriers to act on neighbouring cells across an extensive volume on a specific time scale. It, therefore,has the opportunity to control the processing of vision from the lowest level of retinal transduction to the control of neuronal excitability in the visual cortex.

Animals↗

PubMed1999

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Journal Article↗

PubMed1999

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.

Animals↗

PubMed1998

Enhanced visual responses in cat dLGN--potentiation by priming with excitatory amino acids.

Sustained iontophoresis of NMDA potentiated visual responses for minutes after the application in 16 of 38 cells (42%), peaking 3 min after the end of the application and declining to control levels within 12 min. Potentiation was also seen after application of ACPD (36%, n = 14) and AMPA (29%, n = 14), but not after application of ACh (n = 20). ACh also excites dLGN cells, but does not interact with amino acid receptors, and ACh receptors are not directly involved in the transmission of visual information. We suggest that this modulation is a form of visually induced potentiation which permits dynamic modification of the strength of visual information to be relayed to the cortex depending upon the history of previous activity levels.

Acetylcholine↗

PubMed1997

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.

Acetylcholine↗

PubMed1996

Spatial frequency tuning of orientation-discontinuity-sensitive corticofugal feedback to the cat lateral geniculate nucleus.

1. The influence of spatial frequency on the inhibitory component of the effects mediated by feedback from the visual cortex has been examined in X and Y cells in the A laminae of the feline dorsal lateral geniculate nucleus (dLGN). Experiments utilized a concentric, bipartite visual stimulus centered over the receptive fields of the cells studied. The responses of dLGN cells to selective stimulation of receptive field centre (with the inner window) were compared with those to stimulation of centre and surround mechanisms (both inner and outer window), with the stimuli either in or out of orientation alignment. 2. With these same stimuli, layer VI cells in the visual cortex showed a marked increase in response magnitude when the inner and outer components of the stimulus were in orientation alignment, and presented at the preferred orientation. In the case of dLGN X and Y cells we observed an enhancement of the surround antagonism of the centre response when the inner and outer sections of the stimulus were in orientation alignment. 3. The effects of varying spatial frequency on these responses were examined in dLGN cells in the presence of corticofugal feedback. With the stimulus sections in orientation alignment, surround stimulation produced a powerful and significant reduction in the response to stimulation of centre mechanism alone with the most marked effects for stimuli in the range 0.1-0.85 cycles per degree (c.p.d.). The reduction produced by surround stimulation in the range 0.1-0.5 c.p.d. was notably more potent in X cells than in Y cells. 4. The responses to the same stimuli were examined in dLGN cells with the corticofugal feedback inactivated. Comparison of data from cells studied with and without feedback revealed a significant decrease in surround-mediated attenuation of the centre response in Y cells for spatial frequencies in the range 0.1-0.85 c.p.d. For X cells the decrease in strength of the surround antagonism was also clear and significant but only seen in the range 0.1-0.5 c.p.d. 5. The influence of the orientation alignment of inner and outer stimulus sections revealed a marked difference between cells studied with and without feedback. In the presence of feedback fully aligned stimuli enhanced surround antagonism of centre responses for spatial frequencies in the range 0.1-0.5 c.p.d., in X and Y cells. In the absence of corticofugal feedback this alignment effect was essentially eliminated. 6. These data show that surround antagonism of the centre response is influenced by orientation alignment of the stimulus sections at low spatial frequencies and in the presence of corticofugal feedback. They support a cortically driven enhancement of the inhibitory mechanisms reinforcing surround mechanisms in the dLGN. We propose that feedback enhances a low spatial frequency cut-off in the dLGN, that this effect is maximal for a continuous iso-orientated contour, but diminished whenever there is an orientation discontinuity. The hyperpolarizing influence underlying this effect may contribute to the recently described synchronizing influence of the direct corticofugal contacts onto relay cells. We suggest feedback of the cortical level of analysis refines the transfer of the visual input at geniculate level in a stimulus-context-dependent fashion.

Animals↗

PubMed1996

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.

Afferent Pathways↗

PubMed1996

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.

Animals↗

PubMed1995

Visual cortical mechanisms detecting focal orientation discontinuities.

Neurons in the primary visual cortex (V1) respond in well defined ways to stimuli within their classical receptive field, but these responses can be modified by stimuli overlying the surrounding area. For example patch-suppressed cells respond to gratings of a specific orientation within their classical receptive field, but the response diminishes if the grating is expanded to cover the surrounding area. We report here more complex effects in many such cells. When stimulated at their optimal orientation, introducing a surrounding field at a significantly different (for example, orthogonal) orientation enhanced their output by both a disinhibitory mechanism and an active facilitatory mechanism producing 'supra-optimal' responses. Importantly, some cells responded well if the orientations of centre and surround stimuli were swapped. The output reflected the discontinuity because neither stimulus component alone was effective. Under these stimulus conditions simultaneously recorded cells with orthogonally oriented receptive fields showed correlated firing consistent with neuronal binding to the configuration. We propose a mechanism integrating orientation-dependent information over adjacent areas of visual space to represent focal orientation discontinuities such as junctions or corners.

Animals↗

PubMed1994

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.

Amino Acid Oxidoreductases↗

PubMed1994

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.

Amino Acid Oxidoreductases↗

PubMed1993

Orientational influences of layer V of visual area 18 upon cells in layer V of area 17 in the cat cortex.

We examined the orientation tuning curves of 86 cells located in layer V of area 17, before, during, and after focal blockade of a small (300-microns diameter) region of near-retinotopic register in layer V of area 18 of quantitatively established orientation preference. Such focal blockade revealed three distinct populations of area 17 layer V cells-cells with decreased responses to stimuli of some orientations (21%), cells with increased responses to stimuli of some orientations (43%), and cells unaffected by the focal blockade (36%). These effects were clearcut, reproducible, and generally directly related to the known receptive field properties of the cell recorded in area 18 at the center of the zone of blockade. These effects were also analyzed in terms of alterations in orientation bandwidth in the cells in area 17 as a result of the blockade-bandwidth increases (22%) and decreases (24%) were found; however, these changes were essentially unrelated to the measured receptive field properties. Inhibitory and excitatory effects were most pronounced when the regions in areas 17 and 18 were of like ocular dominance and were of similar orientation preference. Inhibitory effects (suggesting a normally excitatory input) were most dependent upon the similarity of receptive fields; excitatory effects (suggesting a normally inhibitory input) were less heavily dependent.

Animals↗

PubMed1993

Orientation sensitive elements in the corticofugal influence on centre-surround interactions in the dorsal lateral geniculate nucleus.

In a previous study, we have shown that the corticofugal projection to the dLGN enhances inhibitory mechanisms underlying length tuning. This suggests that the inhibitory influences deriving from the corticofugal feedback should exhibit characteristics that reflect the response properties of orientation-tuned layer VI cells. Here we report data obtained from experiments using a bipartite visual stimulus, with an inner section over the dLGN cell receptive field centre and an outer section extending beyond it. For both X and Y cells there was a modulation of the strength of the surround antagonism of centre responses that was dependent on the orientation alignment of contours in the two components of the stimulus. Layer VI cells showed maximal responses when the two components were aligned to the same orientation; dLGN cells showed a minimal response. Varying the orientation alignment of the inner and outer components of the stimulus in a randomised, interleaved fashion showed that bringing the stimulus into alignment resulted in a 24.28% increase in the surround antagonism of the centre response. Blocking cortical activity showed this effect of alignment to be strongly dependent on corticofugal feedback. This effect of orientation alignment appears to apply for any absolute orientation of the alignment condition and supports the view that an entire subset of cortical orientation columns generate the feedback influencing any given dLGN cell. This mechanism makes dLGN cells sensitive to the orientation domain discontinuities in elongated contours moving across their receptive field.

Animals↗

PubMed1993

Influence of layer V of area 18 of the cat visual cortex on responses of cells in layer V of area 17 to stimuli of high velocity.

Focal blockade of restricted regions in layer V of area 18 was used to assess the contribution of this region to the responses to high-velocity stimuli of cells in retinotopically matched, layer V in area 17. In 40% of cases, blockade within area 18 revealed responses of area 17 cells to high-velocity stimuli to which they previously showed only poor responses. Stimulus specificity of the cells in area 17 was otherwise unaltered. All effects were reversible and repeatable. We suggest that a component of the output of layer V from area 18 normally suppresses the responses of retinotopically matched cells within area 17 to stimuli of high velocity, thereby enhancing the specificity of those cells to stimuli of low velocity.

Animals↗

PubMed1990

Lateral-posterior and pulvinar reaching cells--comparison with parietal area 5a: a study in behaving Macaca nemestrina monkeys.

In a previous study we have demonstrated the existence of pulvinar (puv) cells which were optimally activated when a monkey executed reaching movements with his limbs (Acuña et al 1983). We now describe further observations in four Macaca nemestrina monkeys trained to perform goal directed reaching movements aimed at four different positions in space. Extracellular unit activity in the lateralis posterior (lp) and puv nuclei, together with electrooculograms were recorded during the execution of the task. Seven hundred and sixty neurons were studied in the lp-puv complex. One hundred and twenty three cells (16%) showed changes in activity related to the reaching movements. Reaching related cells fell into two categories: goal direction sensitive (28/123 = 23%) and pandirectional (95/123 = 77%). Goal direction sensitive cells showed different responses depending on the direction of the goal relative to the starting point of the movement. The responses of the pandirectional cells were independent of goal direction. The activity of the remaining cells (637/760) could not be correlated with reaching movements. In a smaller number of area 5a (PE) cells (n = 109) studied in one monkey, 82 (75%) were classified as reaching related cells. Of these, 76% (62/82) were goal direction sensitive and 24% (20/82) pandirectional. The lp-puv cells were more dependent on the intentionality of movement than area 5a cells, and not reliably activated by passive manipulation of the limb. After injection of HRP-WGA in area 5a, where the reaching cells were recorded, labeled cells and terminals were located in the lp-puv zones where reaching cells were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗