Casto Rivadulla

Foci of orientation plasticity in visual cortex

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.

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.

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 α‐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.

Receptive field structure of burst and tonic firing in feline lateral geniculate nucleus

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 Ca2+ 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 lemniscal–cuneate recurrent excitation is suppressed by strychnine and enhanced by GABAA antagonists in the anaesthetized cat

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.

Endocannabinoid CB1 receptors modulate visual output from the thalamus

RationaleEndocannabinoids 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 methodsThe 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.ResultsCB1 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.ConclusionsOur 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.

Magnetic Field Strength and Reproducibility of Neodymium Magnets Useful for Transcranial Static Magnetic Field Stimulation of the Human Cortex

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.

Vasomotion and Neurovascular Coupling in the Visual Thalamus "In Vivo"

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 (0.14hz) 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.

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 ∼ 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.

Different sources of nitric oxide mediate neurovascular coupling in the lateral geniculate nucleus of the cat

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.