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U T Eysel

Publications and source records attributed to U T Eysel.

At least 19 recordsLinked to original sources

Effect of sensory deafferentation on immunoreactivity of GABAergic cells and on GABA receptors in the adult cat visual cortex.

To investigate the effects of sensory deafferentation on the cortical GABAergic circuitry in adult cats, glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) immunoreactivity and GABA receptor binding were studied in the visual cortex of normal cats and compared with cats that had received restricted binocular central lesions of the retina and had survived for 2 weeks postlesion in a normal visual environment. In the visual cortex of lesioned cats, two changes were observed in the number of GAD-immunoreactive elements in the regions affected by the retinal lesions: the number of GAD-positive puncta decreased, whereas that of GAD-immunoreactive somata increased. In contrast, no detectable changes were measured in the number of GABA-immunopositive somata or puncta. At the receptor level, we observed no differences in either the laminar distribution or the affinity of cortical GABAA and GABAB receptors labeled with [3H]-muscimol and [3H]-baclofen, respectively, in the lesioned versus normal cats. We present the hypothesis that sensory deafferentation in these adult cats (1) leads to a reduction of cortical GABAergic inhibition in the deafferented region, and (2) that this decreased inhibition may permit changes in efficiency of synapses and (3) that these changes may represent a first stage of events underlying the retinotopic reorganization preceeding the structural changes.

Afferent Pathways

Possible enhancement of GABAergic inputs to cat dorsal lateral geniculate relay cells by serotonin.

The possible enhancement of inhibitory inputs to relay cells of the dorsal lateral geniculate nucleus (dLGN) by serotonin (5-HT) was studied during blockade of GABAA-receptor mediated inhibition with bicuculline (BICU). Visually induced spike activity of single units was recorded during simultaneous micro-iontophoretic application of BICU or 5-HT. All 28 relay cells studied were disinhibited by BICU and strongly inhibited by 5-HT. The responses during BICU or 5-HT were on average statistically different from the controls (p < 0.01, Student's t-test). The inhibition by 5-HT could be almost totally abolished by the simultaneous application of BICU and responses during the combined application of both substances were only slightly different from those obtained during BICU alone (p < 0.3).

Animals

Transient immunohistochemical labelling of rat retinal axons during Wallerian degeneration by a monoclonal antibody to neurofilaments.

Immunohistochemical labelling with the monoclonal antibody SMI32 to non-phosphorylated epitopes on neurofilament proteins of high molecular weight class was low in rat central optic fibers of controls. After unilateral transection of optic nerve, a strong, transient increase of labelling with SMI32 occurred in degenerating fibers of optic tract at 2 and 4 days, which then declined at 8 and remained low at 21 days. Consequently, immunostaining with SMI32 may serve as a positive marker for degenerating fibers in rat optic system.

Animals

Immunohistochemical staining for glial fibrillary acidic protein (GFAP) after deafferentation or ischemic infarction in rat visual system: features of reactive and damaged astrocytes.

Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is standard for visualization of reactive astrocytes in tissue sections, whereas various forms of astrocytic damage remain to be described in detail. In this study we tested differences in GFAP labeling in reactive astrocytes and in glial cells damaged by ischemia and edema. Studies were performed in the anatomically well defined visual system of rat. Basic staining patterns for GFAP were established in subcortical visual nuclei and visual cortex. In the first model, deafferentation of visual centers was performed by unilateral optic nerve lesion, and characteristic changes of GFAP labeling in reactive astrocytes were studied at 0.5, 1, 1.5, 2, 4, 8 and 21 days after lesion. Initial changes were seen in the deafferented superior colliculus at 1 day after deafferentation with a diffuse increase and stellate types of reactive cells formed at 2-8 days. In the second model, small ischemic infarcts were produced in the visual cortex of rats using the method of photochemically-induced thrombosis. GFAP labeling with a polyclonal antiserum was massively enhanced in the infarct at 4 hr. Characteristic morphological changes in damaged astrocytes were seen which were also identified in experiments with simulated global ischemia. In the surround of the infarct, swelling of astrocytes also caused increased labeling. At 3-4 days infarction typical reactive astrocytes surrounded the lesioned area. In conclusion, these immunohistochemical studies on GFAP in rat visual system allow for the following classifications. (a) Normal astrocytes vary in labeling at different anatomical localizations. (b) Reactive astrocytes show enhanced labeling and larger cell-size within an interval of 1-2 days after lesion. (c) Astrocytes damaged by ischemia reveal increased labeling of disintegrating cellular elements within hours after a lesion. (d) Swollen astrocytes undergo enhanced labeling in areas with vasogenic edema.

Animals

EEG-dependent modulation of response dynamics of cat dLGN relay cells and the contribution of corticogeniculate feedback.

Single unit recordings were made extracellularly from the dorsal lateral geniculate nucleus (dLGN) in the anaesthetized and paralysed cat. The impulse rates of phasic (peak) and tonic components of visual responses to stimulation of the receptive field center by a flashing spot were determined during different states of the EEG, during local cortical cooling and during micro-iontophoretic application of the excitatory amino acid receptor agonists, quisqualate (QUIS) and N-methyl-D-aspartate (NMDA). Typically, visual responses were phasic during low frequency/high amplitude EEG patterns, resembling slow wave sleep (SWS). During high frequency EEG patterns (non-SWS) visual responses of X- and Y-cells exhibited a prominent tonic response component. This tonic component could be clearly reduced during ipsilateral cortical cooling in the non-SWS state. QUIS or NMDA, applied in order to mimic corticofugal activity, augmented the tonic response component, most efficiently during SWS EEG. The effects did not differ significantly for X- and Y-cells. During non-SWS EEG Y-cells exhibited a tonic response component similar to X-cells, but because of their higher peak rates the responses of Y-cells were on average more phasic than those of X-cells. Our results indicate that state-dependent changes in CNS activity modulate dL'GN responsiveness in part via the corticogeniculate feedback, and that predominantly the tonic response component is modulated.

Animals

Immunohistochemical changes of neuronal calcium-binding proteins parvalbumin and calbindin-D-28k following unilateral deafferentation in the rat visual system.

The neuron-specific calcium-binding proteins, parvalbumin and calbindin-D-28k, were studied in the subcortical visual system of normal and unilaterally deafferented albino rats. Immunohistochemistry with monoclonal antibodies was used on vibratome sections through optic tract (OT), dorsal lateral geniculate nucleus (dLGN), olivary pretectal nucleus (OPN), and superior colliculus (SC). In controls, OT stained strongly for parvalbumin and weakly for calbindin-D-28k. The dLGN contained a plexus of parvalbumin-positive fibers. In dLGN, calbindin-D-28k-antibodies showed strong labeling of some neurons with long dendrites and weak staining of the cytoplasm in other neurons. In OPN, parvalbumin stained a ring of neurons and terminals in the shell region, whereas calbindin-D-28k was contained in medial cell populations. In SC, parvalbumin was contained in fibers, terminals, and neurons throughout the visual layer. Calbindin-D-28k showed a laminar distribution of neurons with a predominance in deep portions of superficial grey matter and in ventral portions of stratum opticum. Following unilateral deafferentation induced by optic nerve section, retinal axons showed immunohistochemical changes related to Wallerian degeneration and target neurons reacted by changes of calcium-binding proteins. Parvalbumin and calbindin-D-28k immunostaining decreased during Wallerian degeneration of OT. In the deafferented dLGN, immunohistochemical labeling for calbindin-D-28k declined in strongly stained neurons from 4 to 21 days after lesion. Measurement of dendritic length per number of cells or per area of dLGN showed a significant decline for the contralateral side at 4, 8, and 21 days (ANOVA, P less than 0.05). In deafferented OPN, terminal-like staining for parvalbumin decreased and neuronal labeling was enhanced. In deafferented SC, the neuronal and dendritic staining for parvalbumin increased beginning from Day 1 on and persisting at Day 21, whereas fibers and terminal-like elements decreased in staining. Measurement of parvalbumin-positive neurons per area of SC showed a significant increase of labeling in the contralateral side from Day 1 to Day 21 (ANOVA, P less than 0.05). These studies show that cellular responses to deafferentation of visual neurons involve a regulation of calcium-binding proteins. The decline in staining for calbindin-D-28k in dLGN may relate to reduced retinal afferent activity. The progressive cellular changes in parvalbumin staining may be related to unmasking of intrinsic neurons after removal of parvalbumin-containing, afferent fibers and terminals. Additionally, the changes of parvalbumin labeling in SC neurons may reflect a plastic reorganization of local circuits known to occur in rat SC in response to deafferentation.

Afferent Pathways

Cellular organization of reciprocal patchy networks in layer III of cat visual cortex (area 17).

There is no direct information available concerning the exact spatial characteristics of long-range axons and their relationship with the patchy phenomena observed after extracellular injection of retrograde tracers. In the present study, using the recently introduced neuronal tracer biocytin, we demonstrate by detailed three-dimensional reconstruction of 10 pyramidal cells in layer III, that their clustered axonal terminals form a specific patchy network in layers II and III. The reconstructed network occupied an area of 6.5 x 3.5 mm parallel to the cortical surface elongated in an anteroposterior direction. The average centre-to-centre distance between patches within the network was 1.1 mm. On average, the axonal field of each of the 10 pyramidal cells contained a total of 417 boutons at four to eight distinct sites (patches), and in each patch, an average of 79 boutons was provided by the same cell. The identified connections between the patches were predominantly reciprocal. Detailed analyses have shown that many pyramidal cells of the network are directly interconnected so that each of them can receive one to four, chiefly axospinous, contacts onto the distal segment of its apical and basal dendrites from the axon of another pyramidal cell belonging to a different patch labelled from the same injection site. We hypothesize that the possible functional role of the network is to link remote sites with similar physiological characteristics, such as orientation preference, supporting the model of Mitchison and Crick [(1982) Proc. natn. Acad. Sci. U.S.A. 79, 3661-3665].

Animals

GABA-induced inactivation of functionally characterized sites in cat visual cortex (area 18): effects on orientation tuning.

Microiontophoresis of the inhibitory transmitter GABA was used to reversibly inactivate small sites of defined orientation specificity at a horizontal distance of some 600 microns from single cells recorded in area 18 of cat visual cortex, and the effects on orientation tuning were studied. The receptive fields of cells at the recording and inactivation sites overlapped extensively. During the inactivation of sites where the orientation preference differed by 45 degrees or more from that of a recorded cell ("cross-orientation" sites), 65% of 54 cells tested showed significant broadening of orientation tuning, with a mean increase in tuning width (measured at half the maximum response) of 93%, and an almost fourfold increase in the relative response to the orientation orthogonal to the optimum, compared with the response to the optimum; four cells essentially lost their orientation tuning. Broadening of tuning reflected an increase in response to nonoptimal orientations and was reversible upon termination of GABA application. The effects on orientation tuning typically peaked within 10-15 min of the onset of GABA iontophoresis with 50-100 nA ejecting currents, and could not be replicated by inactivating sites where the orientation preference was similar to that of a recorded cell; when the orientation preference at the inactivation sites was within 22.5 degrees of that of a recorded cell ("iso-orientation" sites), only 3 of 22 cells showed significant broadening of tuning, and in these cases, the effects were relatively weak (mean increase in tuning width of 39% and a negligible change in the relative response to the orientation orthogonal to the optimum). The effect of inactivating "iso-orientation" sites consisted primarily in an increase in response magnitude. The difference in the magnitude of the effects on orientation tuning elicited by inactivating "cross-orientation" and "iso-orientation" sites was highly statistically significant. Additionally, inactivation of "cross-orientation" or "iso-orientation" sites elicited differential effects on orientation tuning in 10 of the 13 cells in which direct comparisons were made. It is argued that the observed broadening of tuning was due to the loss of a "cross-orientation" inhibitory input, which normally sharpens orientation tuning by suppressing responses to nonoptimal orientations.

Animals

Neuronal dysfunction at the border of focal lesions in cat visual cortex.

Traditional concepts assume that traumatic or ischemic brain lesions are surrounded by regions with depressed neuronal function. More recently hyperactivity gained increasing attention as excitotoxic mechanisms become effective at certain stages of neuronal injury. Single cell recordings in the surrounding of small focal lesions in the cat visual cortex revealed both types of functional pathology 1-30 days after lesioning. A rim of suppressed neurons surrounded a completely silent core. Cells further away from the lesion showed bursts and long lasting hyperactivity with extremely high discharge rates. Consequently, the volume of disturbed tissue was considerably larger than the region of initial cell death. This halo of dysfunction may be important for neurological symptoms evoked by cortical lesions.

Animals

Retinogeniculate transmission by NMDA and non-NMDA receptors in the cat.

The contributions of N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptors to retinogeniculate transmission were investigated in the cat. The EAA antagonists 2-amino-5-phosphonovaleric acid (APV) and kynurenic acid (KYN) were used to block the NMDA receptors and all EAA receptors, respectively. Antagonistic effects on the visual response were assessed with single On/Off stimuli of 2 s duration or repetitive flicker stimulation (5 Hz) with a light spot projected onto the receptive field center. With APV, the NMDA response could be almost completely abolished but the visual response to repetitive stimulation was reduced on average by only 34%. Initial (transient) components of the single flash response were attenuated on average by 23%, the residual (sustained) component by 48%. With KYN the responses to NMDA, quisqualate (QUIS) and glutamate (GLU) were abolished or strongly reduced as was the visual response to flicker (mean 58%) and single flash stimulation (mean transient 73%, sustained 90%). Prolonged iontophoretic applications of the agonists GLU, QUIS and NMDA revealed receptor desensitization or competitive interactions with the naturally released transmitter in a dose-dependent manner. When the responses to any of the 3 agonists declined during continuous application, superimposed visual responses were clearly reduced in amplitude. Visual response amplitudes were also reduced when superimposed on steady state QUIS responses but unchanged in amplitude when superimposed on steady state NMDA responses. In conclusion, non-NMDA as well as NMDA receptors seem to participate in cat retinogeniculate transmission. Non-NMDA receptors appear to be most important for the initial component but can also maintain the visual response, while the NMDA receptors seem to be more effective during the later component of the response.

2-Amino-5-phosphonovalerate

Axial responses in visual cortical cells: spatio-temporal mechanisms quantified by Fourier components of cortical tuning curves.

The responses of 81 cells from area 17 in paralysed and anaesthetized cats were studied with moving spots and moving bars of different lengths. Tuning curves were measured and plotted as polar-plots. The strongest response of visual cortical cells to a moving bar occurs when the stimulus trajectory crosses the long axis of the receptive field (Hubel and Wiesel 1962). The optimal orientation for a moving and a flashing bar are identical, so that this response-type has been called the orientational component. For a moving spot, however, in most cases the strongest response occurs for motion along the receptive field long axis (axial component). Thus, the axial and orientational components are orthogonal (Wörgötter and Eysel 1989). It is shown that orientational and axial components can display direction selectivity and for short bar stimuli a superposition of the two orthogonal components is demonstrated. Such a superposition in general, resulted in a polar-plot with four peaks 90 degrees apart from each other (four-symmetrical polar-plot). Polar-plots with three or two response peaks were also found; the actual number of response peaks depending on the direction selectivity of the components. In many cells pure axial responses could be elicited with a light spot which stimulates only motion dependent mechanisms. Thus, it was concluded that temporal facilitation is strongly involved in the generation of axial responses. Fourier analysis of polar-plots (SDO-analysis, Wörgötter and Eysel 1987; Wörgötter et al. 1990) was applied to determine the tuning strengths of the different components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Correlations between directional and orientational tuning of cells in cat striate cortex.

Simple (N = 284) and complex cells (N = 125) in the central projection area (0-5 degrees eccentricity) of the striate cortex of cats were stimulated with moving light bars and the responses to different directions of movement were recorded and plotted as polar-plots. Fourier analysis was applied to polar plots (SDO-analysis, Wörgötter and Eysel 1987; Wörgötter et al. 1990) to determine the general sensitivity (S) of the cells to visual stimulation, the directional (D) and orientational (O) tuning strength as well as preferred direction (PD) and preferred orientation (PO). Statistical distributions of the S, D and O parameters were determined for simple and complex cells of the cortical layers II-VI. Simple cells were more strongly tuned for direction and orientation than complex cells, whereas complex cells had a greater general sensitivity to visual stimulation. Directional tuning was significantly stronger in layer VI than in layer IV simple cells, otherwise no differences were detected between these two layers. We found that cells with large D and small O components are generally rare. The D and O components were plotted against each other to determine any possible correlation between the tuning strengths. The correlations were statistically significant for simple and complex cells but the correlation coefficients were very small (r less than 0.3). It is suggested that only a very weak coupling between directional and orientational tuning exists, preferentially in the deeper layer simple cells.

Animals

Influence of GABA-induced remote inactivation on the orientation tuning of cells in area 18 of feline visual cortex: a comparison with area 17.

We have investigated the effect of iontophoretically applying the inhibitory transmitter gamma-aminobutyric acid (GABA) through four pipettes, each located at a horizontal distance of some 500-600 microns from the recording site, on the orientation tuning of cells in areas 17 and 18 of the cat visual cortex for moving the stationary flash-presented bar stimuli. Forty-five of 74 cells tested in area 18 (61%) showed a significant (greater than 25%) increase in orientation tuning width (at half the maximum response) during GABA application, which reflected an increase in response to non-optimal orientations. The mean orientation tuning width of these cells increased by 79%, and the ratio of responses to the orientation orthogonal to the optimum and to the optimum increased from 0.16 to 0.46. The results were similar to those from area 17, in which 36 of 54 cells (66%) showed significant broadening of orientation tuning during GABA application, with a 90% increase in mean tuning width and an increase in the relative response to the orientation orthogonal to the optimum from 0.17 to 0.42. The distributions of cells in areas 17 and 18 with respect to the magnitude of GABA-induced effects on orientation tuning width were not significantly different (mean increase in tuning width: area 17, 102%; area 18, 87%). Although most cells were tested only with moving bars, comparable effects of remote GABA application on orientation tuning were observed when stationary flash-presented bars were used. Of 11 cells thus tested in area 18, seven showed significantly broader tuning during GABA application, with a 132% increase in mean tuning width. In some 25% of cells in each area which showed a significant effect of GABA application on orientation tuning the response to at least one non-optimal orientation exceeded, during GABA application, the response to the previous optimum. There was essentially no correlation between the changes in orientation tuning and changes in the level of spontaneous activity or in the response to the optimum orientation during GABA application. Thus, an increase in the general excitability of recorded cells or the loss of an unspecific inhibitory input cannot account for the effects of GABA application on orientation tuning. Remote GABA application presumably inactivated cells with different preferred orientations from that of the recorded cell. It is thus argued that the observed broadening of orientation tuning during GABA application reflected the loss of an inhibitory input tuned to non-optimal orientations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Anatomical correlations between soma size, axon diameter, and intraretinal length for the alpha ganglion cells of the cat retina.

Retinal ganglion cells within the same region of the retina may have different lengths of axon before reaching the optic disc depending on the route they take with respect to the temporal raphe. We have investigated whether there is a correlation between soma and intraretinal axon diameter and how these parameters relate to intraretinal axon length on both sides of the cat temporal raphe. Retinas were wholemounted and alpha-cell somata and fibers stained with a modified neurofibrillar method. Moving peripherally from the area centralis along the raphe there was a progressively increasing difference between the intraretinal axon lengths for nearly adjacent cells across the raphe, which reached a maximum of 4-5 mm at the retinal periphery. Cells on the nasal aspect of the raphe had shorter axons than did adjacent cells on the temporal aspect of the raphe. Comparison of soma diameter samples across the raphe showed there was no clear trend between soma diameter and intraretinal length. Replotting the raphe and sample areas on a cell density map indicated that differences in soma diameter could be attributed to ganglion-cell density differences between the sampled areas. Examination of the stained cells revealed that within the initial length of the axon there was a region showing a reduction of axon diameter (diameter less than 1 micron), which varied in length from cell to cell. The axon was, therefore, divided into three segments: the portion of axon prior to thinning (A), the thin segment itself (B), and the part of the axon after the thin segment (C). The diameter of each segment (A,B,C) and the lengths of the first and second segments (A,B) were significantly correlated with soma diameter (P less than 0.001). From measurements of the axon diameter of segment C, it was concluded that alpha-cell axons continue to increase in diameter along their path towards the optic disc. The present report indicates that alpha-cell soma size, when going from the area centralis to the periphery along the raphe, reaches a plateau and then declines within more peripheral retinal locations in spite of increasing intraretinal axon length. Thus, there is no positive correlation between soma or axon diameter and intraretinal axon length. The anatomical findings are discussed in relation to previous reports of retinal development and complementary conduction times within intraretinal and extraretinal visual pathways.

Animals

Influence of retinal lesions on grating acuity of the cat.

Grating acuity was investigated behaviorally in the cat. Retinal lesions of increasing diameter centered on the area centralis were made by photocoagulations in one eye, while the intact eye was used as control. Lesion size evaluated from fundus photographs was precisely correlated with the anatomical lesion size measured in retinal whole mounts. Grating acuity improved with increasing grating area in cats with intact retinae and after small (less than 3 degrees diameter) retinal lesions but not after large lesions (greater than 4 degrees diameter). Overall, grating acuity clearly decreased when lesions became larger than 4 degrees in diameter. The acuity-eccentricity relationship closely fits the cutoff frequency of brisk sustained cells at the corresponding eccentricities.

Animals

GABA-induced remote inactivation reveals cross-orientation inhibition in the cat striate cortex.

We investigated the contributions of lateral intracortical connections to the orientation tuning of area 17 cells using micro-iontophoresis of the inhibitory transmitter gamma-aminobutyric acid (GABA) to inactivate small cortical sites in the vicinity of a recorded cell. GABA was ejected from an array of micropipettes each with an average horizontal distance of 500 microns from the recording site. Of 54 cells tested, 33 showed a reduction and 3 a loss of orientation selectivity due to an increase in responses to non-optimal orientations during GABA inactivation. The response to the optimal orientation remained constant in more than half of the cells and increased or decreased in others. Given that a complete cycle of orientations occupies a tangential distance of 1000 microns, the observed broadening of orientation tuning is presumably due to GABA-mediated inactivation of inhibitory interneurones with different preferred orientations from those of their target cell.

Animals

Axis of preferred motion is a function of bar length in visual cortical receptive fields.

The responses of 82 simple cells and 41 complex cells in area 17 of anesthetized and paralysed cats were examined with light bars of different length. For 84% of the simple cells and 66% of the complex cells the preferred axis of orientation of a stationary flashing long bar (orientational selectivity) and the preferred axis of movement of a small spot were parallel. As a consequence, the axis of maximal response to a moving light spot was mostly orthogonal to the optimal axis of a moving bar. Thus, a single cell responds to two perpendicular axes of preferred movement one for a long bar and one for a light spot, respectively. For both axes independent direction preferences could be distinguished. Additional preferred axes of movement between the two orthogonal extremes could be found with moving bars of intermediate lengths. This can be explained by the fact that cells with a pronounced response to a moving spot showed a strong tendency for intermediate bar length to elicit responses consisting of a superposition of both components. Therefore, decreasing bar length resulted in a gradual rotation of the preferred direction of movement from orthogonal to parallel with respect to the orientational axis, rather than to a mere widening of the tuning curve. Accordingly, the change in orientation selectivity with decreasing bar length is a regular transition from the orientation dependent response to a response type that depends only on the movement axis of the spot. Thus, in a simple model, the resulting response characteristic can be interpreted as an average of both components weighted according to the length of the stimulus.

Animals