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Ulf T Eysel

Publications and source records attributed to Ulf T Eysel.

At least 19 recordsLinked to original sources
PubMed2006

Model-based analysis of excitatory lateral connections in the visual cortex.

Excitatory lateral connections within the primary visual cortex are thought to link neurons with similar receptive field properties. Here we studied whether this rule can predict the distribution of excitatory connections in relation to cortical location and orientation preference in the cat visual cortex. To this end, we obtained orientation maps of areas 17 or 18 using optical imaging and injected anatomical tracers into these regions. The distribution of labeled axonal boutons originating from large populations of excitatory neurons was then analyzed and compared with that of individual pyramidal or spiny stellate cells. We demonstrate that the connection patterns of populations of nearby neurons can be reasonably predicted by Gaussian and von Mises distributions as a function of cortical location and orientation, respectively. The connections were best described by superposition of two components: a spatially extended, orientation-specific and a local, orientation-invariant component. We then fitted the same model to the connections of single cells. The composite pattern of nine excitatory neurons (obtained from seven different animals) was consistent with the assumptions of the model. However, model fits to single cell axonal connections were often poorer and their estimated spatial and orientation tuning functions were highly variable. We conclude that the intrinsic excitatory network is biased to similar cortical locations and orientations but it is composed of neurons showing significant deviations from the population connectivity rule.

Animals↗
PubMed2006

Dynamics and specificity of cortical map reorganization after retinal lesions.

Neurons in the mature visual cortex deprived of their normal retinotopic inputs by matched binocular retinal lesions are initially silenced but become reactivated with time when the "blind" cortical lesion projection zone (LPZ) is filled in by new suprathreshold visual responses. In an attempt to gain further insight into the dynamics of this process, we investigated in detail the spatiotemporal pattern of single-cell properties and recording probability during cortical reorganization up to 12 months after retinal lesions. In the early phases of filling in, a transient peak of hyperactivity moves from the border of the normal cortex into the LPZ and forms the leading edge of a functional reconnection process. In the course of this process hyperactive cells inside the LPZ develop ectopic receptive fields that are initially enlarged and regain orientation specificity. During the proceeding recovery, hyperactivity and receptive field size normalize, while the quality of orientation tuning remains reduced at longer distances inside the LPZ at all stages of recovery up to 1 year. Within the adult anatomical framework of cortical connectivity, the maximal lateral distance of reconnection is limited, and the probability to encounter spiking cells decreases with increasing distance inside the LPZ. However, this recording probability was significantly increased after 1 year.

Animals↗
PubMed2006

Effects of repetitive TMS on visually evoked potentials and EEG in the anaesthetized cat: dependence on stimulus frequency and train duration.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High-frequency rTMS leads primarily to facilitation, whereas low-frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high-frequency trains seem to be more effective than longer trains, and low-frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size.

Animals↗
PubMed2006

Visual resolution with retinal implants estimated from recordings in cat visual cortex.

We investigated cortical responses to electrical stimulation of the retina using epi- and sub-retinal electrodes of 20-100 microm diameter. Temporal and spatial resolutions were assessed by recordings from the visual cortex with arrays of microelectrodes and optical imaging. The estimated resolutions were approximately 40 ms and approximately 1 degrees of visual angle. This temporal resolution of 25 frames per second and spatial resolution of about 0.8 cm at about 1m and correspondingly 8 cm at 10 m distance seems sufficient for useful object recognition and visuo-motor behavior in many in- and out-door situations of daily life.

Action Potentials↗
PubMed2006

Strabismic suppression is mediated by inhibitory interactions in the primary visual cortex.

Most strabismic observers do not suffer from double vision because of suppression from conscious perception of 1 of the 2 eyes' conflicting views. Direct evidence for the site and neural substrate of strabismic suppression has not been available so far, although psychophysical data suggest a cortical origin. On the other hand, cross-orientation suppression among conflicting stimuli presented monocularly has recently been shown to have a strong thalamic component. Here we present evidence, using both visual stimulation and pharmacological techniques, that strabismic suppression occurs in the primary visual cortex and involves gamma-amino butyric acid (GABA)-mediated inhibition. We show that its dependency on the drift rate of the suppressing stimulus is consistent with a cortical origin; unlike monocular cross-orientation suppression, it cannot be evoked by very fast-moving stimuli. Furthermore, strabismic suppression is greatly reduced when GABAergic inhibition is locally blocked by the GABA(A) antagonist bicuculline.

Animals↗
PubMed2006

Reduced presynaptic efficiency of excitatory synaptic transmission impairs LTP in the visual cortex of BDNF-heterozygous mice.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, axonal and dendritic growth and synapse formation. BDNF has also been reported to mediate visual cortex plasticity. Here we studied the cellular mechanisms of BDNF-mediated changes in synaptic plasticity, excitatory synaptic transmission and long-term potentiation (LTP) in the visual cortex of heterozygous BDNF-knockout mice (BDNF(+/-)). Patch-clamp recordings in slices showed an approximately 50% reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) compared to wild-type animals, in the absence of changes in mEPSC amplitudes. A presynaptic impairment of excitatory synapses from BDNF(+/-) mice was further indicated by decreased paired-pulse ratio and faster synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. In accordance, presynaptic theta-burst stimulation (TBS) failed to induce LTP at layer IV to layers II-III synapses during extracellular field-potential recordings in BDNF(+/-) animals. Changes in postsynaptic function could not be detected, as no changes were observed in either the amplitudes of evoked EPSCs, the ratios of AMPA : NMDA currents or the kinetics of evoked AMPA and NMDA EPSCs. In line with this observation, an LTP pairing paradigm that relies on direct postsynaptic depolarization under patch-clamp conditions could be induced successfully in BDNF(+/-) animals. These data suggest that a chronic reduction in the expression of BDNF to nearly 50% attenuates the efficiency of presynaptic glutamate release in response to repetitive stimulation, thereby impairing presynaptically evoked LTP in the visual cortex.

Animals↗
PubMed2005

Neuroscience: rewiring the adult brain.

Any analysis of plastic reorganization at a neuronal locus needs a veridical measure of changes in the functional output--that is, spiking responses of the neurons in question. In a study of the effect of retinal lesions on adult primary visual cortex (V1), Smirnakis et al. propose that there is no cortical reorganization. Their results are based, however, on BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging), which provides an unreliable gauge of spiking activity. We therefore question their criterion for lack of plasticity, particularly in the light of the large body of earlier work that demonstrates cortical plasticity.

Action Potentials↗
PubMed2005

Paired-pulse transcranial magnetic stimulation protocol applied to visual cortex of anaesthetized cat: effects on visually evoked single-unit activity.

In this study, we tested the paired-pulse transcranial magnetic stimulation (ppTMS) protocol - a conditioning stimulus (CS) given at variable intervals prior to a test stimulus (TS) - for visually evoked single-unit activity in cat primary visual cortex. We defined the TS as being supra-threshold when it caused a significant increase or decrease in the visually evoked activity. By systematically varying the interstimulus interval (ISI) between 2 and 30 ms and the strength of CS within the range 15-130% of TS, we found a clear dependence of the ppTMS effect on CS strength but little relation to ISI. The CS effect was strongest with an ISI of 3 ms and steadily declined for longer ISIs. A switch from enhancement of intracortical inhibition at short ISIs (2-5 ms, SICI) to intracortical facilitation (ICF) at longer ISIs (7-30 ms), as demonstrated for human motor cortex, was not evident. Whether the CS caused facilitation or suppression of the TS effect mainly depended on the strength of CS and the polarity of the TS effect: within a range of 60-130% a positive correlation between ppTMS and TS effect was evident, resulting in a stronger facilitation if the TS caused facilitation of visual activity, and more suppression if the TS was suppressive by itself. The correlation inverted when CS was reduced to 15-30%. The ppTMS effect was not simply the sum of the CS and TS effect, it was much smaller at weak CS strength (15-50%) but stronger than the sum of CS and TS effects at CS strength 60-100%. Differences in the physiological state between sensory and motor cortices and the interactions of paired synaptic inputs are discussed as possible reasons for the partly different effects of ppTMS in cat visual cortex and human motor cortex.

Action Potentials↗
PubMed2005

Loss of connexin36 increases retinal cell vulnerability to secondary cell loss.

Accruing evidence indicates that gap junctions are involved in neuronal survival after brain injury. The present study was aimed at clarifying the contribution of the neuronal gap-junction protein connexin36 (Cx36) to secondary cell loss after injury in the mouse retina. A focal retinal lesion was induced by infrared laser photocoagulation. Remarkably, this model allowed spatial and temporal definition of the lesion with high reproducibility. Moreover, Cx36 is abundantly expressed in the retina and plays an essential role in the visual transmission process. Taking advantage of these features, cell death was assessed using TUNEL assay and light and electron microscopy, and the extent of Cx36 expression was studied by immunohistochemistry, Western blot, in situ hybridization and real-time RT-PCR. Secondary cell loss was most prominent between 24 and 48 h after lesioning. This peak was accompanied by an increase in Cx36 expression. When cultured explanted retinas were subjected to gap-junction blockers a significant increase in the extent of secondary cell loss after laser photocoagulation became evident. Using the same experimental paradigm we compared the incidence of cell death in wild-type and Cx36(-/-) mice. A significant increase in total number of TUNEL-positive cells occurred in the Cx36(-/-) mice compared to controls. From these data we conclude that Cx36 contributes to the survival and resistance against damage of retinal cells and thus constitutes a protective factor after traumatic injury of the retina.

Analgesics, Non-Narcotic↗
PubMed2005

Cortical activation via an implanted wireless retinal prosthesis.

PURPOSE: To demonstrate local cortical activations in the primary visual cortex of the cat as a result of retinal electrical stimulation by means of a completely wireless-controlled, implantable retinal prosthesis in a series of acute experiments. METHODS: The transfer of energy to drive the device and signals to activate any combination of 25 retinal electrodes was achieved completely wirelessly by an external transmitter positioned in front of the eye. Individually configured electrical stimuli were applied via any combination of 25 electrodes, on sending the necessary pulse parameters to the implant. Placement of the implant onto the retinal surface was achieved after lensectomy and vitrectomy in the cat. Fixation was performed with a retinal tack. Cortical activation patterns were recorded by means of optical imaging of intrinsic signals. RESULTS: Implantation and fixation were successfully performed in three cats. Wireless activation of the implant by radiofrequency was demonstrated by recording of stimulus artifacts from the sclera. Local activation of the visual cortex measured by optical imaging of intrinsic signals revealed a shift of cortical response that was well correlated with a change in the position of the activated retinal electrodes. CONCLUSIONS: The results demonstrate the retinotopic activation of the visual cortex using a completely wireless, remote-controlled retinal implant.

Animals↗
PubMed2004

Lesion-induced enhancement of LTP in rat visual cortex is mediated by NMDA receptors containing the NR2B subunit.

There is emerging evidence that injury of the cerebral cortex is followed by processes of enhanced neuroplasticity. In the present study, we investigate the functional properties of NMDA receptors (NMDARs) in the surround of focal lesions with recordings of extracellular field potentials (FPs) in acute slices of rat visual cortex at survival times of 2-6 days. FPs were recorded in cortical layer III lateral to the lesion, while long-term potentiation (LTP) was induced by theta-burst stimulation (TBS) in layer IV. The predominantly AMPA receptor-mediated FPs displayed a significantly enhanced LTP in the surround of the lesion at distances of 2-3.2 mm. The LTP was completely blocked by the NMDAR antagonist D-AP5. Ifenprodil, an antagonist of NMDARs containing the NR2B subunit, only slightly affected the LTP in slices from sham-operated animals, but significantly reduced the LTP in slices from lesioned rats. We quantitatively analysed the proportion of NMDARs containing the NR2B subunit after lesions by applying ifenprodil to pharmacologically isolated NMDAR-FPs. The NR2B antagonist reduced the NMDAR-FPs significantly more strongly at distances of 2.0-3.2 mm from the border of the lesion. This indicates that the early phase of increased synaptic long-term plasticity in the surround of cortical lesions is accompanied by an up-regulation of NMDARs containing the NR2B subunit.

Animals↗
PubMed2004

Probability of transmitter release at neocortical synapses at different temperatures.

The probability of transmitter release at synaptic terminals is one of the key characteristics of communication between nerve cells because it determines both the strength and dynamic properties of synaptic connections. To assess the distribution of the release probabilities at excitatory synapses on supragranular pyramidal cells in rat visual cortex, we have used the MK-801, a blocker of the open N-methyl-d-aspartate (NMDA) receptor-gated channels. With this method, the release probability can be calculated from the time course of the blockade of NMDA-receptor mediated postsynaptic currents in the presence of MK-801. At temperatures >32 degrees C, the distribution of release probabilities covered the range from 0.05 to 0.43 [mean: 0.171 +/- 0.012 (SE), n = 65], being skewed toward low values. When estimated at room temperature (22-25 degrees C), the release probabilities were significantly lower (mean: 0.123 +/- 0.009, n = 54), and almost the whole distribution was restricted to values <0.2. Furthermore, warming from room temperature to >32 degrees C led to a pronounced overshooting increase of the release probability. Taken together, the results of the present study show that release probabilities at synapses formed onto layer 2/3 pyramidal cells in the visual cortex vary significantly, but values >0.3 are rare and the results obtained either at room or variable temperature differ significantly from those made under conditions of constant temperature in the physiological range.

Animals↗
PubMed2004

Nitric oxide synthase in rat visual cortex: an immunohistochemical study.

The aim of the present study was to identify the distribution of two isoforms of the nitric oxide synthase (NOS), the neuronal (nNOS) and the endothelial (eNOS) form, in rat visual cortex. Immunohistochemical localisation of each NOS isoform was studied with three tissue-processing protocols. In the first one, immunohistochemical reactions were made on 30-microm-thick sections with membrane detergents, Triton or Saponin, used to increase the permeability of the tissue for the antibodies. In the second protocol, we excluded these detergents from all solutions to avoid a destruction of the cellular membrane. In the third protocol, we used thin paraffin sections (5 microm thick) to assure delivery of the antibodies to intracellular structures. Our data demonstrate, that both neuronal and endothelial isoforms of the NOS are present in the visual cortex. Among the neurones labelled by the antibodies against eNOS or nNOS, some excitatory cells were definitely present. nNOS immunopositive were neurones and a dense network of fibres, presumably axons. Some of the neurones were heavily labelled in a Golgi-like manner, while others showed only weak labelling. eNOS immunopositivity was found in the blood vessels and in neurones. eNOS positive neurones were much more numerous than nNOS-containing cells, and represent about 60% of the cortical cells. However, with antibodies against eNOS, we never observed neurone-specific cell features. The NOS-containing cells found in our present study represent a possible morphological substrate for production of nitric oxide (NO).

Animals↗
PubMed2004

Time-dependent changes in the expression of the MEF2 transcription factor family during topographic map reorganization in mammalian visual cortex.

Removal of retinal input from a restricted region of adult mammalian visual cortex leads to a substantial reorganization of the retinotopy within the lesion projection zone (LPZ) of primary visual cortex (area 17). Little is known about the molecular mechanisms underlying such cortical plasticity. We investigated whether small but homonymous central retinal lesions induced differences in gene expression patterns between central area 17, the LPZ, vs. peripheral area 17 of the adult cat. Systematic differential mRNA display screening revealed higher levels for the mRNA encoding the transcription factor MEF2A in the LPZ. Semi-quantitative PCR confirmed this dependency of mef2A mRNA expression on visual eccentricity in area 17 of animals with retinal lesions in contrast to normal animals. Western blotting experiments extended these data to the protein level and to two other members of the MEF2 transcription factor family, i.e. MEF2C and MEF2D. Quantitative analysis of the Western blotting experiments further revealed a post-lesion survival time-dependent change in expression for all three MEF2 family members. The lesion effect was maximal at 3 days and 1 month post-lesion, but only minor at 2 weeks post-lesion. Interestingly, complete removal of retinal input from area 17 by surgery did not significantly alter the expression of the MEF2 transcription factors, excluding a definite correlation between neuronal activity and MEF2A expression levels. MEF2A immunocytochemistry confirmed both qualitatively and quantitatively the Western blotting observations in all animal models. Together, our findings identified a brain plasticity-related expression pattern for the MEF2 transcription factor family in adult mammalian neocortex.

Animals↗
PubMed2004

The role of the magnocellular pathway in serial deployment of visual attention.

Normal human visual function often demands detection of a target among a number of other objects cluttering the scene, such as when searching for a known face in a crowd. In these and similar tasks, the search performed is a serial one, with an attentional spotlight scanning the objects of the scene. We have investigated whether one of the afferent channels in vision, the colour-blind magnocellular pathway, is essential in such serial searches. We did this by using items that were isoluminant with the background but of a different colour, for which the magnocellular cells would be blind. The search in these conditions required much longer reaction times than when even a very small luminance contrast (2%) was added to the items. Because such luminance contrasts can be detected only by magnocellular cells and not by neurons of the other channels (parvocellular and koniocellular), the magnocellular pathway appears vitally important for serial search. In contrast, in a feature search task, which does not require allocation of attentional resources, the search was as efficient with isoluminance as when luminance contrast was added to the items.

Analysis of Variance↗
PubMed2003

Extracellular GABA concentrations in area 17 of cat visual cortex during topographic map reorganization following binocular central retinal lesioning.

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of mammals, plays an important role in cortical reorganization following sensory deprivation, by regulating the level of cortical inhibition and gating changes in receptive field size and synaptic efficacy. In cats it has been shown that 2 weeks after the induction of binocular retinal lesions, GABAergic inhibition, as determined by immunocytochemistry, is decreased in the deafferented region of area 17, whereas 3 months post-lesion, normal GABAergic control is restored within the cortical scotoma. In this study we used in vivo microdialysis to investigate the extracellular GABA concentrations 1-2 months post-lesion, in the sensory-deprived and remote, non-deprived region of area 17. Data were collected at those sample times and sites for which the extracellular glutamate concentrations had been determined in a previous investigation to elucidate the role of this excitatory neurotransmitter in cortical reorganization. As for glutamate, we observed significantly increased extracellular GABA concentrations in non-deprived area 17, whereas in deafferented area 17, extracellular GABA concentrations were comparable to those observed in normal, control subjects. These data suggest that 1-2 months post-lesion the deafferented cortex behaves like normal visual cortex, in contrast to remote, non-deprived cortex. Notwithstanding the increase in extracellular GABA concentration of 134%, the parallel increase in glutamate concentration of 269% could give rise to a net increase in excitability in remote area 17. We therefore suggest that LTP-like mechanisms, and thereby cortical reorganization, might still be facilitated, while possible excessive hyperexcitability is balanced by the moderately increased GABAergic control.

Animals↗
PubMed2003

A computerized image analysis system for quantitative analysis of cells in histological brain sections.

We propose a reliable method for automatic counting of cells in brain sections labeled with different antibodies (against NeuN, parvalbumin, GABA and c-Fos) and in Nissl-staining. Images of stained sections are converted to binary images by thresholding. Clusters of 'ON pixels' (value of 1) corresponding to cell bodies are selected based on size. The parameters of the algorithm (intensity range and cluster-size) are adjusted for different methods of staining according to expert knowledge. The automatic cell counting method (ACCM) provides correct counting results, as demonstrated by a comparison of computational results with counts gained by human experimenters and with a commercially available image analysis system. On the basis of ACCM counts, small and perhaps physiologically relevant differences in the number of labeled cells can be revealed, as demonstrated here for the GABAergic system following electrical stimulation.

Algorithms↗