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C van der Togt

Publications and source records attributed to C van der Togt.

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Characterization of a directional selective inhibitory input from the medial terminal nucleus to the pretectal nuclear complex in the rat.

The receptive field properties of neurons in the medial terminal nucleus of the accessory optic system (MTN) that project to the ipsilateral nucleus of the optic tract (NOT) and dorsal terminal nucleus (DTN), as identified by antidromic electrical activation, were analysed in the anaesthetized rat. The great majority (88%) of MTN neurons that were antidromically activated from NOT and DTN preferred downward directed movement of large visual stimuli while the remaining cells preferred upward directed stimulus movement. Distinct retrograde tracer injections into the NOT/DTN and the ipsilateral inferior olive (IO) revealed that no MTN neurons project to both targets. MTN neurons projecting to the ipsilateral NOT/DTN were predominantly found in the ventral part of the MTN, whereas those projecting to the IO were found in the dorsal part of the MTN. In situ hybridization for glutamic acid decarboxylase (GAD) mRNA was used as a marker for GABAergic neurons. Up to 98% of MTN neurons retrogradely labelled from the ipsilateral NOT/DTN also expressed GAD mRNA. Earlier studies have shown that MTN neurons that prefer upward directed stimulus movements are segregated from MTN neurons that prefer downward directed stimulus movements. It also has been demonstrated that directionally selective neurons in the NOT/DTN prefer horizontal stimulus movements and receive an inhibitory input from ipsilateral MTN. Our results indicate that this input is mediated by GABAergic cells in the ventral part of MTN, which to a large extent prefer downward directed stimulus movements, and that the great majority of MTN neurons that prefer upward directed stimulus movements project to other targets one of which possibly is the IO.

Animals↗

Functional connectivity within the visual cortex of the rat shows state changes.

The aim of this study was to investigate the dynamics of the horizontal functional connectivity within the visual cortex during spontaneous activity or during visual stimulation. Two arrays of 16 electrodes were inserted in the visual cortex of a rat. From these electrodes a depth profile was obtained of the local spiking activity. The cross-correlations between all electrodes were estimated. Three types of cross-correlation peaks were identified and classified as; 'thin peaks', 'fast waves' and 'slow waves'. Partialization was applied, a mathematical method to reduce the amount of common input in correlations, and its effect on the three types of correlation peaks was studied. Slow waves were found to be the most vulnerable to partialization and thin peaks the least. From these observations it was concluded that the three types of peaks represent synchronous neuronal assemblies of different magnitude; slow waves large, fast waves intermediate and thin peaks assemblies composed of small numbers of neurons. Large changes were observed in the types of cross-correlations and their spatial distribution within the set of interarray combinations of electrodes. These changes were spontaneous, and could not be related to the visual stimulation. Two states were identified; the 'thin-peak' state and the 'slow-wave' state. The 'thin-peak' state is interpreted as occurring at a light level of anaesthesia and is characterized by the presence of thin peaks in all combinations of electrodes. Thin peaks with the largest strength were found in the upper interarray electrode combinations. The 'slow-wave' state is interpreted as occurring at a deep level of anaesthesia and is characterized by the presence of exclusively slow waves, which were limited mostly to the middle and lower interarray combinations of electrodes. Activation of the cortex is thus associated with the appearance of synchrony between small groups of neurons (thin peaks) which, in contrast to the slow-wave state, include the upper layers of the cortex.

Action Potentials↗

The contribution of GABA-mediated inhibition to response properties of neurons in the nucleus of the optic tract in the rat.

The contribution of GABA-mediated inhibition to the generation of directional selectivity of neurons in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic system (DTN) was examined in anaesthetized rats by iontophoretic application of the GABAA receptor antagonist bicuculline methiodide. Spontaneous and visually evoked NOT-DTN cell activities were always increased by bicuculline application. The directional selectivity of NOT-DTN cells to slowly moving whole-field stimuli, expressed as the direction index, was reduced for most neurons. However, the difference between firing rates during stimulus movements in the preferred and in the non-preferred direction did not change systematically. On average, this difference was not significantly affected in the majority of the neurons, although bicuculline more strongly increased the activity during movement in the preferred or non-preferred direction in some of the neurons. These results indicate that directionally selective neurons in the rat NOT-DTN receive GABAergic inhibition which is most likely tonic and independent of the stimulus direction.

Animals↗

Inhibition of neuronal activity in the nucleus of the optic tract due to electrical stimulation of the medial terminal nucleus in the rat.

Morphologically, a GABAergic connection between the medial terminal nucleus of the accessory optic system and the nucleus of the optic tract, two primary visual nuclei involved in the optokinetic reflex, has been demonstrated. In this study it was investigated if the medial terminal nucleus forms an inhibitory input to movement direction selective units in the nucleus of the optic tract. Neurons in the nucleus of the optic tract were visually stimulated with moving large random square patterns in their preferred and non-preferred direction, and their activity was recorded extracellularly. Concomitantly, bipolar electrical stimulation was applied to the medial terminal nucleus and its effect was studied on the visual responses of units in the nucleus of the optic tract. Units in the nucleus of the optic tract were strongly inhibited during electrical stimulation of the medial terminal nucleus. The role of GABA in mediating this inhibition was investigated by applying bicuculline, a GABAA receptor antagonist, iontophoretically to the recorded units in the nucleus of the optic tract. However, although average spike rate levels of units in the nucleus of the optic tract increased with bicuculline, bicuculline did not reduce inhibition invoked by electrical stimulation of the medial terminal nucleus. A possible explanation for this observation is that this inhibition is GABAB receptor mediated.

Animals↗

Segregation of direction selective neurons and synaptic organization of inhibitory intranuclear connections in the medial terminal nucleus of the rat: an electrophysiological and immunoelectron microscopical study.

A combined electrophysiological and morphological investigation of the medial terminal nucleus (MTN) in the rat was undertaken, aimed at a better understanding of the relationship between structure and function in this nucleus. The locations of upward and downward direction selective units in the MTN were documented with extracellular electrophysiological recording. By means of tracer experiments, with Phaseolus vulgaris-leucoagglutinin, biocytin, and cholera toxin subunit B-horseradish peroxidase, the internal connections of the MTN, its retinal afferents, and the projection neurons to the inferior olive were visualized. Terminals originating from the retina and from internal connections were characterized at the ultrastructural level. Their termination pattern on cells in the MTN, including identified inferior olive projection neurons, were determined. Additionally, postembedding GABA immunocytochemistry was performed to identify GABAergic elements. From reconstructions of the positions of electrophysiologically recorded units in the MTN, a local segregation between upward and downward direction selective units was revealed. Upward direction selective units were found in the dorsal part and ventromedially, whereas downward direction selective units were found ventral and laterally in the MTN. The MTN receives optic fibers via two separate routes which, based on their trajectory, presumably terminate in different parts of the MTN: the inferior fascicle of the accessory optic tract in the dorsal part, and the posterior fiber bundle of the superior fascicle in the ventral part of the MTN. A correspondence has been found between the segregation of direction selective units and the areas in the MTN where the retinal fibers from the two pathways distribute. It is, therefore, proposed that the inferior fasciculus conveys upward direction selectivity and the posterior fiber bundle downward direction selectivity, and that the two fiber bundles terminate segregated in the MTN. After anterograde tracing from the eye, retinal terminals were found evenly distributed throughout the MTN. They are characterized as GABA negative R-type terminals. After retrograde tracing from the inferior olive, identified MTN-inferior olive projection neurons were found in the dorsal MTN and medially in the ventral MTN. Their location in the MTN suggests that MTN-inferior olive projection neurons are upward direction selective. MTN-inferior olive projection neurons are large non-GABAergic cells, with a variable form. A majority of both F- and R-type terminals were found to make synaptic contacts on the dendrites of MTN cells. MTN-inferior olive projection neurons did not differ from other neurons in this respect.

Animals↗

Variation in form and axonal termination in the nucleus of the optic tract of the rat: the medial terminal nucleus input on neurons projecting to the inferior olive.

The nucleus of the optic tract (NOT) and the medial terminal nucleus (MTN) are two primary visual nuclei that take part in circuits sustaining the optokinetic reflex. The morphology of rat NOT cells projecting to the inferior olive (NOT-IO neurons) and their terminal input, specifically terminals originating from the MTN, have been studied in the rat at the light and electron microscopical level. This has been done by means of combined retrograde tracing from the inferior olive and anterograde tracing from the MTN to the NOT. The area containing MTN terminal fibers and the area occupied by NOT-IO neurons has been found to match. This matched distribution provides a more detailed description of the NOT, with possible functional implications. Identified NOT-IO neurons demonstrate considerable variability in their dendritic branching pattern and have been found to include all neuronal cell types described for the NOT. The dendritic branching pattern of NOT-IO cells could be related to the orientation and distribution of the NOT's major afferent fiber systems. NOT-IO neurons receive a variable MTN and retinal input onto their somata, comparable to other cells in the NOT. With exception of the superficial part of the NOT, NOT-IO neurons with the most MTN terminals were found dorsally in areas containing large numbers of MTN terminals. In conclusion, although NOT-IO neurons are uniform with respect to their receptive field properties, they vary considerably with respect to the shape of the cell body, dendritic branching pattern, and terminal input. This means that morphological characteristics of NOT-IO neurons have no predictive value with regard to their receptive field properties.

Animals↗

GABAergic neurons and circuits in the pretectal nuclei and the accessory optic system of mammals.

Two classes of GABAergic cell bodies have been described. They probably can be divided into GABAergic local interneurons and GABAergic projection neurons. GABAergic cell bodies receive few terminals which is in contrast to non-GABAergic somata, which receive many synaptic contacts. GABAergic dendrites that originate from GABAergic cell bodies, however, receive numerous terminals, both GABAergic and nonGABAergic. It can therefore be concluded that somatic inhibition is not present on GABAergic neurons, but does occur on nonGABAergic neurons. Furthermore, dendrites traverse large parts of the NOT/DTN forming a complex network that enables sampling and integration from a wide area. The projection to the IO is not GABAergic itself, but cells projecting to the IO receive a substantial GABAergic input, that probably originates in part from the MTN. Further investigation on the distribution of this input over a completely identified neuron would provide the quantitative data that are required to verify the above mentioned hypothesis. A GABAergic projection that originates in the pretectal nuclei is directed towards the superficial layers of the SC in the cat (Appell and Behan, 1990) and rat (Van der Want et al., 1991). A second GABAergic projection derives from the pretectum and reaches the LGN (Cucchiaro et al., 1991). Whether this projection originates from the same GABAergic cell bodies that project to the SC and the LGN or is derived from different populations remains to be determined. The ultrastructural studies of the NOT/DTN complex have shown that GABAergic terminals with different morphological characteristics are present and that the GABA positive F and P terminals are widely distributed over somata and the adjacent neuropil. The P terminals probably originate from dendrites of GABAergic interneurons while the F types originate from GABAergic projection and interneurons (Van der Want and Nunes Cardozo, 1988). One of these sources is located in the MTN differ from the intrinsic GABAergic terminals with respect to their relation to R terminals. GABAergic MTN terminals were never observed to receive R terminal input. This is in contrast with other GABAergic terminals which frequently do receive direct contact from R terminals. Within glomeruli triadic arrangements, formed by a single retinal terminal, a dendritic profile and second axonal profile dendritic profile and second axonal profile synapsing with the dendrite, were frequently encountered in the OPN (Campbell and Lieberman, 1985), but only occasionally in the NOT/DTN (Nunes Cardozo and Van der Want, 1987).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Medial terminal nucleus terminals in the nucleus of the optic tract contain GABA: an electron microscopical study with immunocytochemical double labeling of GABA and PHA-L.

In this study the medial terminal nucleus (MTN) projection to the nucleus of the optic tract (NOT) was investigated in pigmented rats at the light and electron microscopical levels with a new combination of techniques. MTN terminals were anterogradely labeled with Phaseolus vulgaris-leucoagglutinin (PHA-L). Preembedding immunocytochemistry, followed by gold intensification, was used to visualize PHA-L. Postembedding immunocytochemistry with 15 nm immunogold particles was carried out to demonstrate the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Both PHA-L and GABA labeling can be easily discriminated at the electron microscopical level even when present in the same neuronal profiles. Light microscopically MTN-NOT fibers proved to have several branches with many varicosities. MTN terminals were found concentrated in terminal fields. Electron microscopically, it was shown that MTN boutons display characteristics resembling F-type terminals, i.e., terminals with dark mitochondria, pleomorphic vesicles, and symmetrical synapses. All NOT afferents originating from the MTN contained GABA and made multiple contacts exclusively with GABA negative NOT somata and dendrites. These results indicate the existence of a strong and direct inhibitory input onto GABA negative projection neurons in the NOT. This substantiates earlier physiological and morphological reports. It was further demonstrated that the location and organization of MTN terminals in the neuropil differ from that of the retinal input: MTN terminals are largely separated from retinal terminals. MTN terminal fields contain large amounts of GABA positive F terminals in contrast to retinal terminal areas. MTN terminals take part in irregularly shaped agglomerations of terminals, which contain many F terminals and dendritic processes and are surrounded by a glial sheet. Retinal terminals are found grouped together in small circular arrangements contacting a central dendrite.

Animals↗

Post-fixation horseradish peroxidase tracing in rat fetus and pups.

Horseradish peroxidase (HRP) has been shown to be applicable to fixed tissue in tracing projections in adult animals. This technique has several advantages in studying short projections in difficult attainable brain areas, especially with fetuses in utero. We have used this method to trace developing fibers (e.g., vestibulo-cerebellar connections) in rat fetuses and pups. It has been possible to make discrete and precise injections in any location. The quality of labeling by this method is distinctly related to the grade of fixation. Fixation grade determines how well HRP is anchored inside fibers and cell bodies. In optimally fixed preparations fibers and cell bodies are intensively stained with HRP up to over 3 mm from the center of an injection site. HRP is probably only taken up by damaged fibers so that the amount of fibers labeled is determined by the extent of the lesion caused by the injection pipette.

Animals↗

Gangliosides restore the specificity of afferent projection patterns in spinal cord explants chronically exposed to tetrodotoxin.

Sensory afferent projection patterns within organotypic explants of fetal mouse spinal cord-dorsal root ganglia (SC-DRG) were mapped out histologically using an HRP-staining method. Cultures grown in tetrodotoxin-containing medium with added gangliosides, in contrast to those grown without the addition of these compounds, showed preferential DRG innervation of the dorsal half of the cord. It therefore appears that gangliosides can compensate for the absence of functional activity during the development of selective innervation patterns.

Animals↗