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D van der Kooy

Publications and source records attributed to D van der Kooy.

At least 19 recordsLinked to original sources
PubMed1992

Cortical and striatal structure and connectivity are altered by neonatal hemidecortication in rats.

The cortical cytoarchitecture, cortical thickness, corticostriatal connections, cortical dendritic arborization, and striatal patch-matrix compartmentalization were compared in rats with neonatal (1 day of age) or adult hemidecortication. Neonatal hemidecortication produced few changes in cytoarchitecture of the remaining hemisphere and did not preclude the development of a patch-matrix compartmentalization in either striatum. There was a significant modification of contralateral cortical-striatal connections, however, as there were extensive crossed connections from layer II/III of the prefrontal cortex in the neonatal hemidecorticates, which contrasts with connections from layer V in the normal brain. Adult hemidecorticates had no crossed corticostriatal connections. Neonatal hemidecortication also led to an increase in cortical thickness relative to adult operates or controls and the neonatal hemidecorticates, and led to an increase in dendritic arborization in layer II/III pyramidal cells of the somatosensory and motor cortex but not in the visual or temporal cortex. The results suggest that the behavioral sparing of sensorimotor and some prefrontal functions after neonatal hemidecortication could be supported, in part, by the anatomical changes in the prefrontal and sensorimotor connectivity and dendritic arborization.

Animals↗
PubMed1992

Embryonic lesions of the substantia nigra prevent the patchy expression of opiate receptors, but not the segregation of patch and matrix compartment neurons, in the developing rat striatum.

Unilateral lesions of the substantia nigra on embryonic day 19 prevent the development of the normal patchy distribution of opiate receptors in the ipsilateral rat striatum. Independent, early and permanent labelling of patch compartment neurons in the same brains on embryonic day 14 with [3H]thymidine revealed that the substantia nigra lesions did not prevent the aggregation of early born neurons into patches, but rather blocked the normal expression of one phenotype (dense opiate receptor binding) of these patches. Thus, early nigrostriatal connections may not be critical for the fundamental patch/matrix compartmentation of the striatum, but may be important in the maturation of phenotypic markers of these compartments.

Animals↗
PubMed1992

Lesions of the tegmental pedunculopontine nucleus: effects on the locomotor activity induced by morphine and amphetamine.

One of the important questions in the neurobiology of motivation asks how the incentive impact of stimuli acting on the limbic system of the forebrain are ultimately translated into action and approach behavior. Bilateral ibotenic acid lesions of the tegmental pedunculopontine nucleus (TPP) (a brainstem output of the limbic system that receives neuronal input from limbic forebrain and midbrain sites identified as primary sites for psychoactive drug reward) have been shown previously to block the acquisition, but not the retention, of morphine and amphetamine conditioned place preferences in formerly drug-naive rats. These results suggest a deficit in the processing of the unconditioned rewarding effects of these drugs. The TPP projects to widespread parts of the brain and spinal cord involved in various somatomotor responses. Thus, we investigated the role of the TPP in morphine- and amphetamine-induced locomotion as assessed in an open field. We report that TPP lesions blocked the locomotor excitation, as well as the conditioned hyperactivity, produced by amphetamine. TPP lesions also blocked the conditioned increase in locomotion, but not the catalepsy, produced by morphine. TPP lesions were behaviorally specific in that the analgesic properties of morphine in a tail-flick test were not attenuated, nor did the lesions affect the locomotion induced by naloxone-precipitated withdrawal in morphine-dependent animals. We suggest that the neural circuits mediating the acute rewarding effects of drug stimuli acting at forebrain sites exit the limbic system in the TPP region of the brainstem, where motivation gains access to (or is isomorphic with) motor systems that initiate approach and exploration.

Amphetamine↗
PubMed1992

Saccharin's rewarding, conditioned reinforcing, and memory-improving properties: mediation by isomorphic or independent processes?

Unconditioned reward and conditioned reinforcing effects may reflect an isomorphic motivational process because increased conditioned reinforcing effects were seen with increased amounts of saccharin consumed in taste and place conditioning. Reinforcing effects in place conditioning leveled off as saccharin unconditioned consumption reached maximum amounts of approximately 140 mg/rat. Posttrial consumption, but not intraperitoneal injection, of saccharin significantly enhanced conditioned place and taste preferences as well as conditioned taste aversions. Saccharin's memory-improving effects in both aversive and appetitive conditioning suggest a process separate from the reward-reinforcement process. Independent of effects on blood glucose, the motivational property of saccharin's sweet taste undergoes differential central processing to mediate reward-reinforcement versus memory improvement processes.

Animals↗
PubMed1992

A single brain stem substrate mediates the motivational effects of both opiates and food in nondeprived rats but not in deprived rats.

Drug-naive and morphine-dependent rats both preferred places paired with morphine over unfamiliar neutral places. Morphine-dependent, but not naive, rats avoided places paired with the lack of morphine (i.e., withdrawal). Food-sated and food-deprived rats both preferred places paired with food over unfamiliar neutral places. Food-deprived, but not sated, rats avoided places paired with the lack of food (i.e., hunger). Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the morphine- and food-conditioned place preferences in drug-naive and food-sated rats, respectively. TPP lesions failed to block morphine- and food-conditioned place preferences as well as morphine withdrawal-conditioned and hunger-conditioned place aversions in morphine-dependent and food-deprived rats, respectively. These results suggest that separate neural mechanisms subserve deprivation- and non-deprivation-induced motivation.

Animals↗
PubMed1992

Chronic exposure to morphine does not alter the neural tissues subserving its acute rewarding properties: apparent tolerance is overshadowing.

Drug-naive, but not morphine-dependent, rats preferred places paired with morphine (2 mg/kg) over unfamiliar neutral places. Both drug-naive and morphine-dependent rats preferred places paired with higher doses of morphine (20 mg/kg) over unfamiliar places. Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the conditioned place preferences produced by both 2 and 20 mg/kg morphine in drug-naive rats but not the preferences produced by 20 mg/kg morphine in dependent rats. When morphine-dependent animals received withdrawal-alleviating doses of morphine (20 mg/kg) 3.5 hr before pairing one environment with 2 mg/kg morphine, they showed morphine-conditioned place preferences that were abolished by TPP lesions. The apparent behavioral tolerance to the TPP-mediated rewarding effects may have resulted from overshadowing by separate withdrawal-related motivational mechanisms.

Animals↗
PubMed1992

Neurobiology of motivation: double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals.

Separate brain manipulations double dissociate two motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation.

Animals↗
PubMed1992

Visceral targets specify calcitonin gene-related peptide and substance P enrichment in trigeminal afferent projections.

Rat trigeminal ganglion projections to a visceral target (intracranial blood vessels) are enriched in calcitonin gene-related peptide (CGRP) and substance P (Sub P) compared to trigeminal ganglion projections to a cutaneous target (the forehead skin). We asked if transplants of a novel visceral target (fetal stomach antrum tissue) into the path of the neonatal rat trigeminal frontal nerve projection to forehead skin would induce neuronal CGRP and Sub P enrichment. By postnatal day (P) 25, the percentage of nerves containing CGRP increased from 14-15% in the control trigeminal projection to forehead skin to 20-31% (in different experiments) in the trigeminal projection to transplanted stomach antrum. The percentage of Sub P-containing neurons increased from 10% in the control forehead skin projection to 22% in the trigeminal projection to stomach transplants over the same time period. The number of neurons in the trigeminal frontal nerve projection to stomach antrum transplants was not significantly different from the number of frontal neurons projecting to control forehead skin. We suggest that respecification of trigeminal neurons to the CGRP and Sub P phenotype, not selective survival of CGRP- and Sub P-positive afferents, is the mechanism by which stomach antrum induces enrichment of CGRP and Sub P. A subpopulation of rat trigeminal neurons with cutaneous forehead skin projections also sends a transient axon collateral projection to a visceral target (the cerebral arteries) during early postnatal development. Postnatal maintenance of an axonal projection to a cutaneous target (forehead skin) may be incompatible with a neuron also maintaining a visceral collateral to the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

A unique tubulin antiserum attenuates the rate of poleward chromosome movement in anaphase.

An antiserum against tubulin, NS20, was previously shown to specifically attenuate both fast axonal transport in vivo (Johnston, K. M. et al., Brain Res. 385, 38-45 (1986)) and in vitro (Johnston, K. M. et al., Cell Motil. Cytoskel. 7, 110-115 (1987)) and flagellar motility (Goldsmith, M. et al., Cell Motil. Cytoskel. 20, 249-262 (1991)). We hypothesized that NS20 blocked motility by binding to a multifunctional motor binding domain on the microtubules (MTs), or axonemes. Here we have examined the effect of microinjecting NS20, at metaphase, into dividing PtK2 cells. Plotting chromosome separation (CS) as a function of time, we report here that CS rates for anaphase A (chromosome-to-pole movement) were reduced by approximately 50% relative to uninjected controls. CS rates for anaphase B (spindle pole elongation) were unaffected by the NS20 antiserum. The inhibition of CS rate during anaphase A by NS20 was significantly greater than the inhibition caused by a control antitubulin serum (PC5). Two possible mechanisms underlying NS20's inhibition of CS during anaphase A were considered. NS20 could block the binding of a kinetochore-associated motor to kinetochore MTs (kMTs) or, alternatively, NS20 could stabilize kMTs against depolymerization. Our results favor the first alternative. In a cold-induced depolymerization assay, NS20 had no selective stabilizing effect on MTs. Moreover, we show that NS20 can selectively block the binding of a well characterized MT-associated motor (kinesin) to MTs, in vitro. These results suggest that NS20 may be defining a unique tubulin binding domain common to the motors underlying vesicle transport, flagellar motility, and chromosome movements during anaphase A.

Anaphase↗
PubMed1992

Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain.

The early development of the mammalian forebrain involves the massive proliferation of the ventricular zone cells lining the lateral ventricles. A remnant of this highly proliferative region persists into adult life, where it is known as the subependymal layer. We examined the proliferation kinetics and fates of the mitotically active cells in the subependyma of the adult mouse. The medial edge, the lateral edge, and the dorsolateral corner of the subependymal layer of the rostral portion of the lateral ventricle each contained mitotically active cells, but the dorsolateral region had the highest percentage of bromodeoxyuridine (BrdU)-labeled cells per unit area. Repeated injections of BrdU over 14 hr revealed a proliferation curve for the dorsolateral population with a growth fraction of 33%, indicating that 33% of the cells in this subependymal region make up the proliferating population. The total cell cycle time in this population was approximately 12.7 hr, with an S-phase of 4.2 hr. To examine the fate of these proliferating cells, we injected low concentrations of a replication-deficient, recombinant retrovirus directly into the lateral ventricles of adult mice for uptake by mitotically active subependymal cells. Regardless of the survival time postinjection (10 hr, 1 d, 2 d, or 8 d), the number of retrovirally labeled cells per clone remained the same (1 or 2 cells/clone). This suggests that one of the progeny from each cell division dies. Moreover, the clones remained confined to the subependyma and labeled cells were not seen in the surrounding brain tissue. Thus, while 33% of the dorsolateral subependymal cells continue to proliferate in adult life, the fate of the postmitotic progeny is death.

Animals↗
PubMed1991

Pattern formation in the striatum: neurons with early projections to the substantia nigra survive the cell death period.

During the early postnatal period the striatum undergoes significant cell death. The specificity and regulation of this regressive event may be particularly interesting in the light of recent findings demonstrating that a developmentally organized compartmental architecture exists in the striatum. The striatum can be divided into two complementary and phenotypically distinct compartments, the patches and the matrix. In the adult, these two striatal compartments can be distinguished on the basis of their anatomy and a series of compartment-specific biochemical and hodological markers. We have previously demonstrated that the neurons within the patch and matrix compartments become postmitotic and make connections with the substantia nigra at distinct and sequential developmental times. The majority of patch neurons become postmitotic between embryonic days 12 and 15 and make a striatonigral connection prenatally. In contrast, a majority of matrix neurons become postmitotic between embryonic days 17 and 20 and do not form an efferent connection to the substantia nigra until the first postnatal week. Here we investigated whether either neuronal birthdate or time of making an efferent projection correlates with a neuron's probability of surviving the cell death period. We found that both the patch and matrix compartments undergo their entire cell death period by the end of the first postnatal week. During this period approximately 30% of striatal neurons are subject to cell death, regardless of striatal compartment. Neuronal counts within the striatal patch compartment suggest that both early born neurons (embryonic day 13) and early projecting neurons (to the substantia nigra) are preferentially spared. However, their considerable overlap (i.e., most early born neurons also have a nigral projection) prevents assessment of which feature is critical for survival. In contrast, there are small, but mostly separate, populations of early born and early projecting neurons within the matrix compartment. Quantitative analysis of these two distinct populations suggests that while early projection neurons within the matrix are spared, the early born matrix neurons lacking an early nigral projection undergo significant cell death. This proposal is further supported by the observation that the percentage of early born neurons in both the patch and matrix compartments that also have an early nigral projection increases from postnatal day 2 to 17. This finding suggests that among the early born striatal neurons in both compartments, those that do not project to the nigra selectively die during the cell death period. Together these results support the hypothesis that completion of an early projection to the substantia nigra gives neurons an advantage for surviving the cell death period.

Animals↗
PubMed1991

Conserved beta-tubulin binding domain for the microtubule-associated motors underlying sperm motility and fast axonal transport.

An antiserum against tubulin, NS20, has been previously shown to inhibit anterograde and retrograde axonal transport by 50% in vivo and in vitro. We report here that Protein A purified NS20 antibodies also attenuate sperm motility by 50% in demembranated sea urchin sperm. This inhibition is absorbed out by preincubating the NS20 antibodies with a biochemically purified porcine microtubule preparation, with recombinant Trypanosoma beta- (but not alpha-) tubulin and most specifically, with a 37 amino acid (a.a.) synthetic peptide corresponding to a domain near (but not including) the porcine beta-tubulin C terminus. Furthermore, addition of this beta-tubulin peptide alone is sufficient to attenuate motility by 50% in demembranated sperm, indicating that this critical 37a.a. NS20 antigen is a motor binding domain. Together, the results suggest that at least two phenotypically distinct forms of microtubule-based motility, axonal transport and flagellar beating, are homologous at the fundamental level of the microtubule domains (the beta-tubulin peptide and we suggest a distinct but similarly located alpha-tubulin domain) mediating the attachment of tubulin-associated motors.

Amino Acid Sequence↗
PubMed1991

Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci.

Mutations in either the dominant white-spotting (W) or Steel (Sl) loci of the mouse lead to coat color, primordial germ cell and hematopoietic defects. Consistent with the cell autonomous and microenvironmental nature of W and Sl mutations, respectively, it has recently been shown that W encodes the c-kit receptor tyrosine kinase while Sl encodes a ligand for this receptor. Previous in situ hybridization analysis has shown that both c-kit and steel are expressed in the embryo in anatomical sites known to be affected by W and Sl mutations and in various tissues in which no corresponding phenotype has been described. To investigate the possible involvement of the Kit transduction pathway in developmental processes, we compared the patterns of expression of c-kit and steel in wild-type embryos and in embryos homozygous for severe (lethal) and mild (viable) alleles at the W and Sl loci. In addition, we analyzed the patterns of expression of both genes in adult wild-type and mutant gonads and brain. Both c-kit and steel are contiguously expressed in a wide variety of anatomical locations in both the developing embryo and in the adult. In adult gonads, steel is expressed in the follicular cells of the ovary and in Sertoli cells of the testis, the layers that immediately surround the c-kit expressing germ cells. In adult brain, the complementary patterns are particularly striking in the olfactory bulb, cerebral cortex, hippocampus region and cerebellum. steel expression in brain is probably restricted to neurons in certain areas, while c-kit is expressed in neurons and in some glial cells. Severe mutations in the W or Sl loci result in dramatic reduction or absence of c-kit positive cells in lineages known to be affected by these mutations. In contrast, these mutations do not affect the number or histological organization of c-kit positive cells in the embryonic peripheral or central nervous systems, nor is the number or organization of c-kit positive cells detectably altered in Wv/Wv or Sld/Sld adult brain. Taken together, these results suggest that the Kit signaling pathway is not obligatory for the viability and/or migration of most c-kit expressing cells either because of functional redundancy with another signaling pathway or because the Kit pathway is involved in post-developmental processes of mature cells.

Animals↗
PubMed1990

Separate blood and brain origins of proliferating cells during gliosis in adult brains.

The response of the brain to injury involves the accumulation of a large number of proliferating cells at the site of damage. Neither the identity nor the origin of these cells is unequivocally established. We have investigated this proliferative response after unilateral kainic acid lesions in the striatum of adult mice by labeling with tritiated thymidine (3H-thy) or bromodeoxyuridine (Brdu) to identify cells passing through S-phase. Labeled cells were seen only ipsilaterally in coronal section and extended laterally from the subependymal zone lining the lateral ventricle, through the striatal kainic acid injection site and into the cortex. The maximum proliferative response, after a single pulse of 3H-thy administered 4 h before sacrifice, was seen 6 days post-lesion close to the injection site. The proliferating cells were not astrocytes, as neither 3H-thy- nor Brdu-labeled cells were double-labeled with antisera to glial fibrillary acidic protein after the lesion. Animals given 3H-thy on day 3 post-lesion and then sacrificed on days 4, 5 or 6 post-lesion showed cumulative increases in the number of proliferating cells at the injection site with no increases in the surrounding tissue. We hypothesized that this reflected the presence of 2 sources of labeled cells: (1) an exogenous population of blood cells coming in through the broken blood-brain barrier and accumulating at the injection site and (2) endogenous cells (microglia) which are normally quiescent in the adult but proliferate in response to injury. By irradiating adult mice (900 rads) we attempted to selectively remove the blood stem cell precursors which gave rise to the proposed exogenous source of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mechanisms of striatal pattern formation: conservation of mammalian compartmentalization.

The striatum is composed of two neuroanatomically and neurochemically defined compartments, termed the patches and matrix. We compared this compartmentalization of the striatum in sections from the rat, rhesus monkey and human, in terms of (1) total striatal area, (2) the ratio of patch to matrix areas, (3) the number of patches and (4) the cross-sectional area of individual patches. Dense mu-opiate receptor binding and immunohistochemical staining for enkephalin were used as histochemical markers for the patch compartment and heavy immunostaining for calcium binding protein was used as a matrix marker. Analysis of coronal sections revealed that a relatively constant ratio of 15% patch to 85% matrix area is maintained in each species. The numbers of patches also remain relatively constant across species, despite a 19-fold increase in total striatal area from rat to human. The constant ratio of patch to matrix areas is maintained by an increase in the size of the individual patches. We hypothesize that the maintenance of a 15% patch to 85% matrix ratio in the striata of different mammalian species occurs through proportionate changes in the length of striatal neurogenesis and the numbers of striatal precursors in the ventricular zone, whereas the maintenance of average patch number is proposed to be a function of reciprocal connections with the substantia nigra and adhesive factors that are specific to patch cells.

Animals↗
PubMed1990

Neuronal lineages in chimeric mouse forebrain are segregated between compartments and in the rostrocaudal and radial planes.

On the basis of neuronal phenotypes and the mode of development of the mammalian forebrain, the cerebral cortex can be subdivided into deep versus superficial layers, and the striatum into patch versus matrix compartments. Interspecific chimeric Mus musculus----Mus caroli mice were used to determine the contribution of lineage to cellular position within these forebrain compartments. Statistical analysis revealed evidence of both spatial and compartmental lineage segregation. A significant difference in genotype ratio depending on chimeric specimen was observed between areas (regardless of compartment) that were separated by greater than 300 microns in the rostrocaudal plane. Differences were observed between early-born (striatal patch and deep cortex) versus late-born (striatal matrix and superficial cortex) neurons, but not between neurons of cortex as a whole versus neurons of striatum as a whole. The difference between early- and late-born neurons was primarily due to the difference between deep and superficial cortical neurons. On a finer scale of analysis, differences in genotype ratios were seen between radially aligned deep versus superficial cortical compartments, in both the neuronal and glial populations. This evidence is consistent with an early positional and compartmental segregation of forebrain progenitor cells.

Analysis of Variance↗
PubMed1990

Discriminative properties of morphine that modulate associations between tastes and lithium chloride.

Wistar rats learned to withhold consumption of a target solution when morphine preceded presentation of the target solution and lithium chloride (LiCl) and to consume the same target solution when saline preceded the presentation of the solution. After this serial feature discrimination training, morphine did not block the formation of a Pavlovian association between saccharin and LiCl but did suppress consumption of familiar tap water. After Pavlovian conditioning, morphine blocked the formation of an association between saccharin and LiCl but did not suppress consumption of a familiar tap water solution. The roles of morphine and saline can be interchanged. It appears that the morphine discriminative stimulus is calling up a representation of neither the conditioned stimulus nor the unconditional stimulus alone, but rather a modified representation of some aspect of their association.

Animals↗