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J C Holstege

Publications and source records attributed to J C Holstege.

At least 19 recordsLinked to original sources
PubMed1998

Immunocytochemical localization of GDNF in primary afferents of the lumbar dorsal horn.

Immunocytochemistry was used to identify glial cell line-derived neurotrophic factor (GDNF) in rat spinal cord. Strong GDNF labeling was found in fibers and terminals in laminae I and II (outer) and to a lesser extent in the remaining laminae. A few spinal ganglion cells also contained GDNF. After dorsal root transection GDNF disappeared from the dorsal horn and after dorsal root ligation there was accumulation of GDNF only on the ganglion side of the ligation. These findings demonstrate anterograde transport of GDNF within primary afferent fibers, which constitute the only source of GDNF labeling in the dorsal horn. The strong presence of GDNF in the superficial dorsal horn may indicate that GDNF has a role in pain transmission in the adult rat spinal cord.

Animals↗
PubMed1998

Light microscopic and ultrastructural investigation of the dopaminergic innervation of the ventrolateral outgrowth of the rat inferior olive.

The ventrolateral outgrowth of the inferior olive is involved in the control of compensatory eye movement responses to optokinetic stimuli about the horizontal axis that is perpendicular to the ipsilateral anterior semicircular canal. Combining immunocytochemistry with retrograde tracing of WGA-BSA-gold, we demonstrated in the present study that this olivary subnucleus receives a substantial dopaminergic input, and that the prerubral parafascicular area and its surrounding regions form the sole source of this input. In addition, we investigated the postsynaptic distribution of the dopaminergic terminals in the inferior olive at the ultrastructural level. About a third (32%) of the dopaminergic terminals was found to make synaptic contacts in the olivary neuropil. The majority (81%) of these boutons terminated on cell bodies or extraglomerular dendrites, while the remaining terminals contacted dendritic spines inside glomeruli. In contrast, GABAergic terminals in the inferior olive formed more frequently (66%) synaptic contacts and they terminated more frequently (38%) in glomeruli. Thus, the ventrolateral outgrowth receives a dopaminergic input from the mesodiencephalic junction, and the postsynaptic distribution of this input reveals a characteristic pattern.

Animals↗
PubMed1997

A differential and time-dependent decrease in AMPA-type glutamate receptor subunits in spinal motoneurons after sciatic nerve injury.

After sciatic transection a strong decrease in immunoreactivity occurred, starting at 2 days. After 6, 10, 14, and 20 days survival only 5% of the sciatic motoneurons were strongly labeled for GluR2/3 against 80% in the control situation. From Day 20, GluR2/3 labeling started to increase again, reaching near normal levels at Day 80 after sciatic transection. In contrast, after sciatic crush, the decrease in GluR2/3 labeling in motoneurons was less pronounced and returned to normal in 30 days. In all animals, the GluR1 and GluR4 labeling of motoneurons remained unchanged after sciatic transection or crush. It is concluded that sciatic nerve injury leads to a strong, time-dependent decrease in the expression of GluR2 and 3 subunits in the corresponding motoneurons. As a consequence, AMPA receptors with a different subunit composition may be assembled, leading to a change in the functional properties of these receptors. Moreover, if they lack the GluR2 subunit, they may become calcium permeable.

Animals↗
PubMed1997

Correlating sheet plastinated slices, computed tomography images and magnetic resonance images of the pelvic girdle: a teaching tool.

Sheet plastination is currently used to produce anatomical slices of different body structures, allowing one to study and teach their topography in an anatomically correct state. Correlation with computed tomography (CT) and magnetic resonance imaging (MRI) techniques gives more insight into their anatomy. Using two female cadaver pelvises CT and MRI were performed. One pelvis was used to prepare 2-mm-thick coronal plastinated slices according to the technique described by von Hagens. We found a good overall correlation between plastinated slices, CT and MRI images. This combined approach provides a unique anatomical insight and is a valuable addition to other teaching tools used by medical students, radiologists and anatomists.

Anatomy, Cross-Sectional↗
PubMed1996

Distribution of dopamine immunoreactivity in the rat, cat and monkey spinal cord.

In the present study, the distribution of dopamine (DA) was identified light microscopically in all segments of the rat, cat, and monkey spinal cord by using immunocytochemistry with antibodies directed against dopamine. Only fibers and (presumed) terminals were found to be immunoreactive for DA. Strongest DA labeling was present in the sympathetic intermediolateral cell column (IML). Strong DA labeling, consisting of many varicose fibers, was found in all laminae of the dorsal horn, including the central canal area (region X), but with the exception of the substantia gelatinosa, which was only sparsely labeled, especially in rat and monkey. In the motoneuronal cell groups DA labeling was also strong and showed a fine granular appearance. The sexually dimorphic cremaster nucleus and Onuf's nucleus (or its homologue) showed a much stronger labeling than the surrounding somatic motoneurons. In the parasympathetic area at sacral levels, labeling was moderate. The remaining areas, like the intermediate zone (laminae VI-VIII), were only sparsely innervated. The dorsal nucleus (column of Clarke) showed the fewest DA fibers, as did the central cervical nucleus, suggesting that cerebellar projecting cells were avoided by the DA projection. In all species, the descending fibers were located mostly in the dorsolateral funiculus, but laminae I and III also contained many rostrocaudally oriented fibers. It is concluded that DA is widely distributed within the spinal cord, with few differences between species, emphasizing that DA plays an important role as one of the monoamines that influences sensory input as well as autonomic and motor output at the spinal level.

Animals↗
PubMed1996

Induction of c-Jun immunoreactivity in spinal cord and brainstem neurons in a transgenic mouse model for amyotrophic lateral sclerosis.

Transgenic mice carrying amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutations develop a motoneuron disease resembling human ALS. c-Jun is a transcription factor frequently induced in injured neurons. In this study we have examined the distribution of c-Jun-immunoreactivity in the brainstem and spinal cord of transgenic SOD1 mice with a glycine 93 alanine (G93A) mutation. In non-transgenic littermates c-Jun immunostaining was predominantly situated in motoneurons. The number of c-Jun immunoreactive motoneuron was reduced in SOD1(G93A) mice due to pronounced loss of motoneurons. In SOD1(G93A) mice, however, c-Jun-immunoreactivity was strongly induced in neurons in the intermediate zone (Rexed's laminae V-VIII and X) of the spinal cord and throughout the brainstem reticular formation. These findings are of interest since increased levels of c-jun also have been found in the intermediate zone of the spinal cord of ALS patients. This c-Jun may be involved in the neurodegenerative processes both in ALS and in motoneuron disease in SOD1(G93A) mice.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Localization of dopamine D2 receptor in rat spinal cord identified with immunocytochemistry and in situ hybridization.

In the present study the distribution of dopamine D2 receptors in rat spinal cord was determined by means of immunocytochemistry using an anti-peptide antibody, directed against the putative third intracellular loop of the D2 receptor and in situ hybridization (ISH) using a [35S]UTP labelled anti-sense riboprobe. With the immunocytochemical technique, labelling was confined to neuronal cell bodies and their proximal dendrites. Strongest labelling was present in the parasympathetic area of the sacral cord and in two sexually dimorphic motor nuclei of the lumbosacral cord, the spinal nucleus of the bulbocavernosus and the dorsolateral nucleus. Moderately labelled cells were present in the intermediolateral cell column, the area around the central canal and lamina I of the dorsal horn. Weak labelling was present in the lateral spinal nucleus and laminae VII and VIII of the ventral horn. Except for the two sexually dimorphic motornuclei of the lumbosacral cord labelled motoneurons were not encountered. With the ISH technique radioactive labelling was present in many neurons, indicating that they contained D2 receptor mRNA. The distribution of these neurons was very similar to the distribution obtained with immunocytochemistry, but with ISH additional labelled cells were detected in laminae III and IV of the dorsal horn, which were never labelled with immunocytochemistry. The present study shows that the D2 receptor is expressed in specific areas of the rat spinal cord. This distribution provides anatomical support for the involvement of D2 receptors in modulating nociceptive transmission and autonomic control. Our data further indicate that D2 receptors are not directly involved in modulating motor functions with the exception, possibly, of some sexual motor functions.

Animals↗
PubMed1995

Inhibitory synaptic inputs to the oculomotor nucleus from vestibulo-ocular-reflex-related nuclei in the rabbit.

Studies of the pathways involved in the vestibulo-ocular reflex have suggested that the projection from the superior vestibular nucleus to the ipsilateral oculomotor nucleus is inhibitory, whereas the medial vestibular nucleus, the abducens nucleus and the contralateral superior vestibular nucleus most likely exert excitatory effects on oculomotor neurons. In order to determine directly the termination pattern and the neurotransmitter of these afferents, we studied their input to the oculomotor nucleus in the rabbit at the light microscopic level with the use of anterograde tracing of Phaseolus vulgaris-leucoagglutinin combined with retrograde tracing of horseradish peroxidase from the extraocular muscles, and at the ultrastructural level with the use of anterograde tracing of wheatgerm-agglutinated horseradish peroxidase combined with GABA and glycine postembedding immunocytochemistry. The general ultrastructural characteristics of the neuropil and the types of boutons observed in the rabbit oculomotor nuclei are in general agreement with the descriptions for the oculomotor complex of other mammals. The superior vestibular nucleus projected bilaterally to the superior rectus and inferior oblique subdivisions, and ipsilaterally to the inferior rectus and medial rectus subdivision; the medial vestibular nucleus projected bilaterally to the medial rectus, inferior oblique, inferior rectus and superior rectus subdivisions with a strong contralateral predominance. The abducens nucleus projected contralaterally to the medial rectus subdivision. More than 90% of all the anterogradely labeled terminals from the ipsilateral superior vestibular nucleus were GABAergic. These terminals were characterized by flattened vesicles and symmetric synapses, and they contacted somata, as well as proximal and distal dendrites of motoneurons. All terminals derived from the medial vestibular nucleus the abducens nucleus and the contralateral superior vestibular nucleus were non-GABAergic. These non-GABAergic terminals showed spherical vesicles and asymmetric synapses, and they contacted predominantly distal dendrites. None of the anterogradely labeled terminals from the studied vestibular nuclei or abducens nucleus were glycinergic. The present study provides the first direct anatomical evidence that most, if not all, of the synaptic input from the superior vestibular nucleus to the ipsilateral oculomotor nucleus is GABAergic, and that the medial rectus subdivision is included in the termination area. Furthermore, it confirms that the projections from the medial vestibular nucleus, the abducens nucleus and the contralateral superior vestibular nucleus are exclusively non-GABAergic.

Animals↗
PubMed1994

GABA and glycine frequently colocalize in terminals on cat spinal motoneurons.

In this ultrastructural study the colocalization of gamma-amino butyric acid (GABA) and glycine in terminals within cat lumbar motoneuronal cell groups was investigated and the frequency of this colocalization was determined. For this purpose the post-embedding immunogold technique was applied on serial sections, using antibodies directed against either GABA or glycine. Analysis of all labelled terminals in a random area of cat motoneuronal cell groups showed that 25 +/- 5% were labelled for GABA only, 29 +/- 6% were labelled for glycine only and 46 +/- 9% were labelled for both GABA and glycine, meaning that nearly two out of every three GABA-labelled terminals were also labelled for glycine and vice versa. Based on these results and on other data suggesting a high frequency of colocalization, it is concluded that in cat motoneuronal cell groups colocalization of GABA and glycine is the rule rather than the exception.

Animals↗
PubMed1993

Colocalization of GABA and glycine in the rabbit oculomotor nucleus.

In the present study we examined the possible colocalization of the inhibitory neurotransmitters glycine and GABA in the oculomotor nucleus of the rabbit. Serial sections were processed alternately for glycine and GABA postembedding immuno-cytochemistry. Ultrastructural analysis revealed that all terminals that showed glycine-positive immunoreactivity were also GABA positive; up to 5% of the GABA-positive terminals were also glycine positive.

Animals↗
PubMed1991

A glycinergic projection from the ventromedial lower brainstem to spinal motoneurons. An ultrastructural double labeling study in rat.

In the present study it was determined whether glycine was present in the descending brainstem projections to spinal motoneurons in the rat. For this purpose injections of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) were made in the ventromedial part of the lower brainstem at the levels of the rostral inferior olive and the caudal facial nucleus. After perfusion, WGA-HRP histochemistry was performed, followed by the postembedding immunogold technique with an antibody against glycine. Electron microscopical examination of the lumbar motoneuronal cell groups showed that 15% of the WGA-HRP labeled terminals, derived from the ventromedial reticular formation, were also labeled for glycine. The majority (91%) of these double labeled terminals were of the F-type (containing many flattened vesicles), while the remaining 9% were of the S-type (containing mostly spherical vesicles). Many of the double labeled terminals established a synapse, mostly with proximal and distal dendrites. The present data, combined with our previous findings that 40% of the projections from the same ventromedial brainstem area to lumbar motoneurons contained gamma-aminobutyric acid (GABA), indicate that over 50% of these brainstem projections contain GABA and/or glycine, exerting a direct inhibitory effect on spinal motoneurons. The possibility that the glycinergic fibers within these projections play an important role in producing muscle atonia during rapid eye movement (REM) sleep is discussed.

Animals↗
PubMed1991

Ultrastructural aspects of the coeruleo-spinal projection.

Few studies have focussed on the ultrastructure of the coeruleo-spinal projection. In rat the projections from the area of the locus coeruleus (LC) and subcoeruleus (SC) to lumbar motoneuronal cell groups exhibited two different types of terminals: E-type terminals, containing many very small vesicles and S-type terminals, containing many spherical vesicles and an occasional dense-cored vesicle. These findings are in agreement with data indicating the existence of a noradrenergic (NA) and a non-NA projection from the area of the LC and SC to the spinal cord. A study on dopamine-beta-hydroxylase (D beta H)-immunoreactive terminals in lumbar motoneuronal cell groups showed that they contained several granular vesicles, which were not found in the E- and S-type terminals. Only a few immunoreactive terminals exhibited a synaptic specialization in a single, thin section. A low incidence of synaptic junctions was also found for the E-type terminals, but not for the S-type. Based on this and other data, it is suggested that the E-type terminal is NA, while the S-type may contain a non-NA transmitter, possibly acetylcholine. A low incidence of synaptic junctions in single, thin sections may indicate the presence of non-synaptic NA terminals, but direct evidence from serial-section analysis is not available. In the superficial dorsal horn, terminals derived from the area of the LC and SC were identified at the ultrastructural level in two studies, one using the anterograde degeneration technique in opossum, the other (presented in this chapter) using WGA-HRP anterograde tracing in rat. It was found in both studies that most of the labeled structures were small axons (mostly unmyelinated), while few terminals were labeled. They contained mostly spherical vesicles and, according to the degeneration study, a variable number of dense-cored vesicles. The labeled terminals appeared to make regular synaptic contacts mostly with small dendrites and occasionally with spines. They were not present in glomeruli or engaged in presynaptic arrangements. A study on NA terminals showed similar results, although large granular vesicles were not observed and fewer synapses were seen. On the few data available at present it is concluded that in the spinal superficial dorsal horn, most terminals derived from the area of the LC and SC are NA and establish conventional synapses. However, a non-NA component cannot be excluded.

Animals↗
PubMed1991

Vasopressin immunoreactive fibers and neurons in the dorsal pontine tegmentum of the rat, monkey and human.

It is now well established that extensive extrahypothalamic vasopressin (VP) systems exist in the rat, monkey and human brain. There are marked differences between species, but in each case VP nuclei provide dense afferents to the dorsal pontine tegmentum. Here VP may play a role in the mechanisms exerted by the locus coeruleus (LC) neurons, possibly both as a neurotransmitter and as a neuromodulator. Although we are aware of some properties of VP systems, e.g., gonadal steroid dependency in the rat, major gaps characterize our knowledge of its anatomy. With regard to the interaction of VP with the LC in the brainstem of mammals some of the questions which stand out are: (1) Is VP really being biosynthesized and transported by LC cells and, if not, what is its function within these cells? (2) Is there a structural difference between male and female LC neurons in the rat as a consequence of the sex-dimorphic VP innervation? (3) What is the origin of VP afferents in the dorsal pontine tegmentum of the (non)human primate and are these afferents also controlled by gonadal steroids? Research strategies to answer these questions will provide us with information to resolve some of the current inconsistencies about the anatomy and the function of the VP and LC systems in the brain.

Afferent Pathways↗
PubMed1991

Ultrastructural evidence for GABAergic brain stem projections to spinal motoneurons in the rat.

In the present ultrastructural study in the rat, it was determined whether GABA was present in projections descending from the ventromedial reticular formation of the lower brain stem to motoneuronal cell groups in the lumbar spinal cord. For this purpose, the anterograde transport of WGA-HRP was combined with the postembedding immunogold technique for GABA, with the advantage that both markers could be visualized simultaneously in a single terminal. In 4 rats, WGA-HRP was injected in the ventromedial part of the brain stem reticular formation at levels between the rostral inferior olive and the caudal part of the facial nucleus. Vibratome sections were cut from the lumbar spinal cord, reacted for WGA-HRP, and processed for electron microscopy. Ultrathin sections containing the lateral motoneuronal cell groups were cut and treated following the immunogold technique using a polyclonal antibody directed against GABA. It was found that nearly 40% of the terminal profiles that were labeled with WGA-HRP reaction products from the ventromedial brain stem were also labeled for GABA (double labeled). Most of the double-labeled terminals (81%) were F-type (containing many flattened vesicles), 12% were G-type (containing many granular vesicles), and 7% were S-type (containing many spherical vesicles). The majority of the double-labeled terminals contacted proximal dendrites. It is argued that the descending GABAergic projection produces a general inhibitory effect on spinal motoneurons, counteracting the general facilitation produced by the serotonergic projection derived from the same brain stem area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Intracellular labeling of neurons in the medial accessory olive of the cat: II. Ultrastructure of dendritic spines and their GABAergic innervation.

In order to describe the morphology of dendritic spines of identified neurons in the cat inferior olive together with their gamma-aminobutyric acid (GABA) synaptic input, a technique was used combining intracellular labeling of horseradish peroxidase with postembedding gold-immunocytochemistry. With this technique physiologically identified olivary cells were reconstructed with the light microscope, and the horseradish peroxidase reaction product and immunogold labeling were subsequently examined in serial sections at the ultrastructural level. In addition, a degenerating neuron was observed, resulting in a triple labeling in single ultrathin sections. Quantitative and three-dimensional analysis showed that the dendritic spines were composed of long, thin stalks ending in one or more spine heads. The spines of cells located in the caudal half of the medial accessory olive (type I cells, characterized by dendrites which run away from the soma) were found to be less complex than those of cells located rostrally in this olivary subnucleus (type II cells, characterized by dendrites which tend to turn back towards the soma). Most, if not all, of the spines of both cell types were located within glomeruli. On average, the spines within individual glomeruli originated from 6 different dendrites (with a maximum of 8). Different spines within the same glomerulus were never derived from different dendrites of the same olivary neuron, but single spines frequently gave rise to several spine heads, which could be located either within different glomeruli or inside a single glomerulus. The glomerular spine heads originating from the same spine were rarely located near one another. All spines and most of the spine heads were contacted by both GABAergic and non-GABAergic terminals. Most of the GABAergic terminals contained pleomorphical vesicles and displayed symmetric synapses whereas the non-GABAergic terminals showed usually round to oval vesicles and asymmetric synapses.

Animals↗
PubMed1990

Intracellular labeling of neurons in the medial accessory olive of the cat: III. Ultrastructure of axon hillock and initial segment and their GABAergic innervation.

The gamma-aminobutyric acid (GABA) synaptic input of identified axons in the cat inferior olive was studied by use of combination of intracellular labeling with horseradish peroxidase and postembedding gold-immunocytochemistry. With this technique olivary cells were physiologically identified and light microscopically reconstructed, and the horseradish peroxidase reaction product and the immunogold labeling were subsequently simultaneously visualized for electron microscopic investigation with the use of serial ultrathin sections. The axons of cell type I (characterized by dendrites which radiate away from the cell body) originated from the soma, whereas those of type II neurons (characterized by dendritic trees which curve back towards the soma) were derived from a primary dendrite. The axons of olivary neurons stand out by the length of their axon hillock (up to 21 microns) and initial segment (up to 40 microns). The hillock forms various spiny appendages which were located within glomeruli together with dendritic spines of other olivary neurons. Axonal spines of type II neurons were more numerous and complex looking than those of type I. The axonal spines, the shaft of the axon hillock, and the transition between the hillock and initial segment were primarily innervated by GABAergic terminals (65%) but non-GABAergic terminals (35%) were present as well. The terminals apposed to the axons of type I neurons contacted mainly the axonal shafts, whereas most of the terminals adjacent to the axons of type II neurons established synaptic contacts with the axonal spines. The initial segments were largely devoid of synaptic input. Distally, the initial segment acquired a myelin sheath.

Animals↗