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Introduction: Eprosartan is an angiotensin receptor blocker (ARB) used for management of essential hypertension. With unique pharmacological characteristics, dual action mechanism, and clinical effectiveness, eprosartan offers additional advantages over other ARBs in specific patient populations., Areas Covered: A comprehensive review of the literature was performed across publicly available databases, with no time limitations, to ensure the inclusion of all relevant studies. The review focuses on presenting the efficacy and safety profile of eprosartan, alone or in combination with other agents. Additionally, it explores the etiology of hypertension concerning the structure and function of angiotensin II type 1 receptors. Further, the efficacy of eprosartan in special populations and its additional benefits are also discussed., Expert Opinion: Eprosartan effectively reduces blood pressure (BP), with a 24-hour BP-lowering effect at 600 mg/day. Eprosartan demonstrates similar or better efficacy than other ARBs, such as telmisartan and losartan, particularly in managing coagulation-related abnormalities and peripheral resistance. In combination therapy, eprosartan with hydrochlorothiazide significantly enhances BP reduction. Eprosartan is well-tolerated, with a low incidence of adverse events, making it a reliable choice for long-term hypertension management across various patient populations, such as those with comorbid diabetes and renal disease and older adults.

The lithium-pilocarpine rat model is a well-known model of temporal epilepsy. Recently we found that transcranial static magnetic stimulation (tSMS) delay and reduce the signs of EEG in this model. We aim to test the effect of combining the therapeutic action of tSMS and diazepam, a drug used to treat status epilepticus. We induce epilepsy in 12 Sprague-Dawley rats. Animals were classified as "magnet" when a magnetic neodymium cylinder was placed over the skull or "control" when a stainless-steel replica was used. Diazepam was injected 60-min after the second doses of pilocarpine injection. We found a reduction in the number of spikes/minute for magnet condition compared with sham condition, reaching significance at 60 min after diazepam injection. The Root-Mean-Square shown a significant reduction in magnet animals compared with those receiving diazepam (Tukey's-test 30 and 60 min after diazepam injection, p < 0.01; 40 and 50 min after diazepam injection, p < 0.05). Furthermore, the power spectrum analysis shown a reduction in delta, theta, alpha and beta bands, on the diazepam + magnet animals compared to the diazepam + sham group. Analysis of high-frequency oscillations revealed an increased in the ripples due to pilocarpine being reduced by diazepam. Our results demonstrate that application of tSMS previously to diazepam potentiates the effect of the drug by reducing the electroencephalographic pattern associated with epileptiform discharges. We suggest a new synergistic cooperation between pharmacology and neuromodulation as a future treatment for epilepsy., (© 2023. The Author(s).)

Currently, the role of hypothermia in electroencephalography (EEG) is well-established. However, few studies have investigated the effect of hyperthermia on EEG, an important physiological parameter governing brain function. The aim of this work was to determine how neuronal activity in anesthetized mice is affected when the temperature rises above the physiological threshold mandatory to maintain the normal body functions. In this study, a temperature-elevation protocol, from 37 to 42°C, was applied to four female mice of 2-3 months old while EEG was recorded simultaneously. We found that hyperthermia reduces EEG amplitude by 4.36% when rising from 37 to 38 degrees and by 24.33% when it is increased to 42 degrees. Likewise, increasing the body temperature produces a very large impact on the EEG spectral parameters, reducing the frequency power at the delta, theta, alpha, and beta bands. Our results show that hyperthermia has a global effect on the EEG, being able to change the electrical activity of the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Labra, Pardo-Vazquez, Cudeiro and Rivadulla.)

Increasing evidence indicates that static magnetic fields (SMF) reduce cortical activity in both human and animal models. The aim of this work was to investigate the effect of SMF on epileptiform cortical activity, a condition related to an abnormal increase in neuronal excitability. The first experimental block included a Pilocarpine rat model of epilepsy, in which a magnetic neodymium nickel-plated cylinder, a magnetic field of 0.5 T, or "sham" were placed over the skull. In the second experimental block, we recorded epileptic-like activity in the visual cortex of a monkey (Macaca mulatta) under control conditions and in the presence of the magnet. Between 15 and 30 minutes after the second dose of Pilocarpine, EEG changes compatible with seizure like events induced by Pilocarpine were clearly observed in the control animals (sham stimulation). Similar effects were visible in the animals exposed to the real magnet after 1-2 hours. In the monkey, SMF over the cortical focus clearly reduced abnormal activity: the intensity threshold for visual induction increased and the severity and duration decreased. These results reinforce the view that static magnets modulate cortical activity and open the door to the future therapeutic use of SMF in epilepsy as a complement to current pharmacological treatments.

In awake monkeys, we used repetitive transcranial magnetic stimulation (rTMS) to focally inactivate visual cortex while measuring the responsiveness of parvocellular lateral geniculate nucleus (LGN) neurons. Effects were noted in 64/75 neurons, and could be divided into 2 main groups: (1) for 39 neurons, visual responsiveness decreased and visual latency increased without apparent shift in receptive field (RF) position and (2) a second group (n = 25, 33% of the recorded cells) whose excitability was not compromised, but whose RF position shifted an average of 4.5°. This change is related to the retinotopic correspondence observed between the recorded thalamic area and the affected cortical zone. The effect of inactivation for this group of neurons was compatible with silencing the original retinal drive and unmasking a second latent retinal drive onto the studied neuron. These results indicate novel and remarkable dynamics in thalamocortical circuitry that force us to reassess constraints on retinogeniculate transmission., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Noninvasive brain stimulation techniques have been successfully used to modulate brain activity, have become a highly useful tool in basic and clinical research and, recently, have attracted increased attention due to their putative use as a method for neuro-enhancement. In this scenario, transcranial static magnetic stimulation (SMS) of moderate strength might represent an affordable, simple, and complementary method to other procedures, such as Transcranial Magnetic Stimulation or direct current stimulation, but its mechanisms and effects are not thoroughly understood. In this study, we show that static magnetic fields applied to visual cortex of awake primates cause reversible deficits in a visual detection task. Complementary experiments in anesthetized cats show that the visual deficits are a consequence of a strong reduction in neural activity. These results demonstrate that SMS is able to effectively modulate neuronal activity and could be considered to be a tool to be used for different purposes ranging from experimental studies to clinical applications., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: The application of transcranial static magnetic field stimulation (tSMS) in humans reduces the excitability of the motor cortex for a few minutes after the end of stimulation. However, when tSMS is applied in humans, the cortex is at least 2 cm away, so most of the strength of the magnetic field will not reach the target. The main objective of the study was to measure the strength and reproducibility of static magnetic fields produced by commercial neodymium magnets., Methods: We measured the strength and reproducibility of static magnetic fields produced by four different types of neodymium cylindrical magnets using a magnetic field-to-voltage transducer., Results: Magnetic field strength depended on magnet size. At distances <1.5 cm, the magnetic field strength was affected by the presence of central holes (potentially useful for recording electroencephalograms). At distances >1.5 cm, the measurements made on the cylinder axis and 1.5 cm off the axis were comparable. The reproducibility of the results (i.e., the consistency of the field strength across magnets of the same size) was very high., Conclusions: These measurements offer a quantitative empirical reference for developing devices useful for tSMS protocols in both humans and animals., (© 2013 International Neuromodulation Society.)

The lateral geniculate nucleus is the gateway for visual information en route to the visual cortex. Neural activity is characterized by the existence of two firing modes: burst and tonic. Originally associated with sleep, bursts have now been postulated to be a part of the normal visual response, structured to increase the probability of cortical activation, able to act as a "wake-up" call to the cortex. We investigated a potential role for burst in the detection of novel stimuli by recording neuronal activity in the lateral geniculate nucleus (LGN) of behaving monkeys during a visual detection task. Our results show that bursts are often the neuron's first response, and are more numerous in the response to attended target stimuli than to unattended distractor stimuli. Bursts are indicators of the task novelty, as repetition decreased bursting. Because the primary visual cortex is the major modulatory input to the LGN, we compared the results obtained in control conditions with those observed when cortical activity was reduced by TMS. This cortical deactivation reduced visual response related bursting by 90%. These results highlight a novel role for the thalamus, able to code higher order image attributes as important as novelty early in the thalamo-cortical conversation.

Deciphering how the brain encodes the continuous flow of information contained in natural stimuli requires understanding the spontaneous activity of functional assemblies in multiple neuronal populations. A promising integrative approach that combines multisite recordings of local field potentials (LFP) with an independent component analysis (ICA) enables continuous readouts of population specific activities of functionally different neuron groups to be obtained. We previously used this technique successfully in the hippocampus, a single-layer neuronal structure. Here we provide numerical evidence that the cytoarchitectonic complexity of other brain structures does not compromise the value of the ICA-separated LFP components, given that spatial sampling of LFP is representative. The spatial distribution of an LFP component may be quite complex due to folded and multilayered structure of the neuronal aggregate. Nevertheless, the time course of each LFP component is still a reliable postsynaptic convolution of spikes fired by a homogeneous afferent population. This claim is supported by preliminary experimental data obtained in the lateral geniculate nucleus of the awake monkey.

Rationale: Endocannabinoids have emerged as a modulatory brain system affecting different types of synapses, broadly distributed throughout the CNS, which explain the diverse psychophysical effects observed following activation of the endocannabinoid system., Objectives and Methods: The present study aimed to characterize the effect of CB1-mediated activity in the visual thalamus. In vivo single-unit extracellular recordings were performed in anaesthetized adult pigmented rats, measuring visual and spontaneous activity, combined with application of CB1 receptor agonists (anandamide, 2-AG, and O2545) and one antagonist, AM251., Results: CB1 receptors activation revealed two cellular populations, with excitatory effects on ∼28% of cells and inhibitory in ∼72%, actions which were blocked by the antagonist AM251. The agonist action significantly altered both spontaneous and visual activity, shifting the signal-to-noise ratio (S/N), with accompanying changes in the variability within the visual response. Increased responses by agonist application were accompanied by a decrease in S/N and an increase in variability, while those cells inhibited by the agonist showed an increase in S/N and a decrease in variability. There was no obvious correlation between the two effects and any other response property suggesting a more general role in modulating all information passing from LGN to cortex., Conclusions: Our data support a role for CB1 at the level of the thalamus acting as a dynamic modulator of visual information being sent to the cortex, apparently maintaining the salience of the signal within upper and lower boundaries. This may account for some of the behavioral effects of cannabis.

Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14 hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ~30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging.

Understanding the link between neuronal responses (NRs) and metabolic signals is fundamental to our knowledge of brain function and it is a milestone in our efforts to interpret data from modern non invasive optical techniques such as fMRI, which are based on the close coupling between metabolic demand of active neurons and local changes in blood flow. The challenge is to unravel the link. Here we show, using spectrophotometry to record oxyhaemoglobin and methemoglobin (surrogate markers of cerebral flow and nitric oxide levels respectively) together with extracellular neuronal recordings in vivo and applying a multiple polynomial regression model, that the markers are able to predict up about 80% of variability in NR. Furthermore, we show that the coupling between blood flow and neuronal activity is heavily influenced by nitric oxide (NO). While NRs show the typical saturating response, blood flow shows a linear behaviour during contrast-response curves, with nitric oxide from different sources acting differently for low and high intensity.

Compounds known to inhibit or disfacilitate cells in cat dorsal lateral geniculate nucleus (dLGN) were applied iontophoretically in vivo. Application of GABA, or agonists of GABA(A) and GABA(B) receptors, markedly decreased responses to low frequency periodic visual stimulation, but, while causing some increases in burst firing, cells continued to produce tonic spikes even when firing was reduced to near zero. Similar actions were seen with compounds manipulating the cholinergic system. Inhibition of local Nitric Oxide production reduced firing rates but did not affect burst firing. Significant levels of tonic firing were found mixed with burst firing throughout the recordings even under conditions most favourable for bursting. We suggest that the local synaptic input to an individual dLGN cell is sufficiently dynamic to prevent the prolonged periods of burst firing which can be evoked in brain slice preparations.

Transcranial magnetic stimulation (TMS) of the cortex can modify activity noninvasively and produce either excitatory or inhibitory effects, depending on stimulus parameters. Here we demonstrate controlled inhibitory effects on the large corticogeniculate feedback pathway from primary visual cortex to cells of the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible-induced by either single pulses or trains of pulses of TMS. These effects selectively suppress the sustained component of responses to flashed spots or moving grating stimuli and are the result of loss of spikes fired in tonic mode, whereas the number of spikes fired in bursts remain the same. We conclude that acute inactivation of the corticogeniculate downflow selectively affects the tonic mode. We found no evidence to suggest that cortical inactivation increased burst frequency.

Glutamate is thought to be the excitatory neurotransmitter in the lateral geniculate nucleus (LGN) of the cat, mediating visual transmission from the retina via ionotropic receptors of both D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate and N-methyl-D-aspartate subtypes. Moreover, glutamate also exerts an important modulatory influence on LGN cells, where metabotropic glutamate receptors (mGluRs) seem to play a crucial role. Here we show in anesthetized adult cats that iontophoretic application of the specific mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) produced two, distinctly different, effects on LGN neurons. Visual responses to flashing spots and drifting gratings were attenuated (decreased by an average of 59%) in 13 of 23 of the cells but augmented (increased by an average of 60%) in 10 of 23 of the cells. Further, in each case when the specific mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine was applied, the effects obtained were the opposite to those of MPEP. Data obtained in a second group of experiments to determine a possible interaction between mGluR5 blockade by MPEP and glutamate ionotropic receptors show that, in the majority of neurons (11 of 15, 73%), the MPEP-mediated effects seem to be independent of N-methyl-D-aspartate and D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate receptor activity. Our results demonstrate a physiological role for mGluR5 in controlling retinal input and show, in vivo, a more intricate scenario than previously suggested, highlighting the complexity of metabotropic receptor interactions with excitatory and inhibitory elements in the thalamus.

The cutaneous primary afferents from the upper trunk and forelimbs reach the medial cuneate nucleus in their way towards the cerebral cortex. The aim of this work was twofold: (i) to study the mechanisms used by the primary afferents to relay cutaneous information to cuneate cuneolemniscal (CL) and noncuneolemniscal (nCL) cells, and (ii) to determine the intracuneate mechanisms leading to the elaboration of the output signal by CL cells. Extracellular recordings combined with microiontophoresis demonstrated that the primary afferent cutaneous information is communicated to CL and nCL cells through AMPA, NMDA and kainate receptors. These receptors were sequentially activated: AMPA receptors participated mainly during the initial phase of the response, whereas kainate- and NMDA-mediated activity predominated during a later phase. The involvement of NMDA receptors was confirmed by in vivo intracellular recordings. The cutaneous-evoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine-sensitive site, indicating that glycine indirectly affects CL cells. Two subgroups of nCL cells were distinguished based on their sensitivity to iontophoretic ejection of glycine and strychnine. Overall, the results support a model whereby the primary afferent cutaneous input induces a centre-surround antagonism in the cuneate nucleus by activating (via AMPA, NMDA and kainate receptors) and disinhibiting (via serial glycinergic-GABAergic interactions) a population of CL cells with overlapped receptive fields that at the same time inhibit (via GABAergic cells) other neighbouring CL cells with different receptive fields.

There are two recognised modes of firing activity in thalamic cells, burst and tonic. A low-threshold (LT) burst (referred to from now on as 'burst') comprises a small number of high-frequency action potentials riding the peak of a LT Ca(2+) spike which is preceded by a silent hyperpolarised state > 50 ms. This is traditionally viewed as a sleep-like phenomenon, with a shift to tonic mode at wake-up. However, bursts have also been seen in the wake state and may be a significant feature for full activation of recipient cortical cells. Here we show that for visual stimulation of anaesthetised cats, burst firing is restricted to a reduced area within the receptive field centre of lateral geniculate nucleus cells. Consistently, the receptive field size of all the recorded neurons decreased in size proportionally to the percentage of spikes in bursts versus tonic spikes, an effect that is further demonstrated with pharmacological manipulation. The role of this shrinkage may be distinct from that also seen in sleep-like states and we suggest that this is a mechanism that trades spatial resolution for security of information transfer.

The ascending cutaneous transmission through the middle cuneate nucleus is subject to cortico-feedback modulation. This work studied the intracuneate cellular mechanisms underlying the corticocuneate influence. Single unit extracellular records combined with iontophoresis showed that the corticocuneate input activates cuneo-lemniscal (CL) and noncuneo-lemniscal (nCL) cells via N-methyl-D-aspartate (NMDA) and non-NMDA receptors as shown by the decrease of the cortical-induced activation on ejection of CNQX and APV, either alone or in combination. These results were confirmed by in vivo intracellular recordings. Two subgroups of nCL cells were distinguished according to their sensitivity to iontophoretic ejection of glycine and its antagonist, strychnine. Finally, the corticalevoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine-sensitive site, indicating that glycine indirectly affects the cuneo-lemniscal transmission. A model is proposed whereby the cortex influences CL cells through three different mechanisms, producing 1) activation via non-NMDA and NMDA receptors, 2) inhibition through GABAergic nCLs, and 3) disinhibition via serial glycinergic-GABAergic nCL cells. These corticocuneate feedback effects serve to potentiate the activity of CL cells topographically aligned through direct activation and disinhibition, while inhibiting, via GABAergic cells, other CL neurons not topographically aligned.

In the somatosensory system, cuneolemniscal (CL) cells fire high frequency doublets of spikes facilitating the transmission of sensory information to diencephalic target cells. We studied how lemniscal feedback affects ascending transmission of cutaneous neurons of the middle cuneate nucleus. Electrical stimulation of the contralateral medial lemniscus and of the skin at sites evoking responses with minimal threshold induced recurrent activation of CL cells at a latency of 1-3.5 ms. The lemniscal feedback activation was suppressed by increasing the stimulating intensity at the same sites, suggesting recurrent-mediated lateral inhibition. The glycine antagonist strychnine blocked the recurrent excitatory responses while GABAA antagonists uncovered those obscured by stronger stimulation. CL cells sharing a common receptive field (RF) potentiate one another by recurrent activation and disinhibition, the disinhibition being produced by serial interactions between glycinergic and GABAergic interneurons. Conversely, CL cells with different RFs inhibit each other through recurrent GABA-mediated inhibition. The lemniscal feedback would thus enhance the surround antagonism of a centre response by increasing the spatial resolution and the transmission of weak signals.

The way in which the brain deals with sensory information relies not only on feedforward processing of signals from the periphery but also on feedback inputs. This is the case of the massive projection back from layer 6 in the visual cortex to the thalamus, for which, despite being the greatest single source of synaptic contacts, the functional role still remains unclear. In the cat lateral geniculate nucleus, part of this cortical feedback is mediated by type 1 metabotropic glutamate receptors (mGluR1s), which are exclusively located on distal segments of the relay-cell dendrites. Here we show that in adult cats the cortex uses a synaptic drive mediated by these receptors (mGluR1) specifically to enhance the excitatory center of the thalamic receptive field. Moreover the effect is maximum in response to those stimuli that effectively drive cortical cells, and importantly, it does not affect the spatiotemporal structure of the thalamic receptive field. Therefore, cortex, by closing this corticofugal "loop," is able to increase the gain of its thalamic input within a focal spatial window, selecting key features of the incoming signal.

Cortical areas are generally assumed to be uniform in their capacity for adaptive changes or plasticity. Here we demonstrate, however, that neurons in the cat striate cortex (V1) show pronounced adaptation-induced short-term plasticity of orientation tuning primarily at specific foci. V1 neurons are clustered according to their orientation preference in iso-orientation domains that converge at singularities or pinwheel centres. Although neurons in pinwheel centres have similar orientation tuning and responses to those in iso-orientation domains, we find that they differ markedly in their capacity for adaptive changes. Adaptation with an oriented drifting grating stimulus alters responses of neurons located at and near pinwheel centres to a broad range of orientations, causing repulsive shifts in orientation preference and changes in response magnitude. In contrast, neurons located in iso-orientation domains show minimal changes in their tuning properties after adaptation. The anisotropy of adaptation-induced orientation plasticity is probably mediated by inhomogeneities in local intracortical interactions that are overlaid on the map of orientation preference in V1.

Cells in the superficial layers of primary visual cortex (area 17) are distinguished by feedforward input from thalamic-recipient layers and by massive recurrent excitatory connections between neighboring cells. The connections use glutamate as transmitter, and the postsynaptic cells contain both NMDA and AMPA receptors. The possible role of these receptor types in generating emergent responses of neurons in the superficial cortical layers is unknown. Here, we show that NMDA and AMPA receptors are both involved in the generation of direction-selective responses in layer 2/3 cells of area 17 in cats. NMDA receptors contribute prominently to responses in the preferred direction, and their contribution to responses in the nonpreferred direction is reduced significantly by GABAergic inhibition. AMPA receptors decrease spatial phase-selective simple cell responses and generate phase-invariant complex cell responses.

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.

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.

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.

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.

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.