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Biomedical subjects

K Braun

Publications and source records attributed to K Braun.

At least 73 records · Page 4Linked to original sources

Organization of the dorsocaudal neostriatal complex: a retrograde and anterograde tracing study in the domestic chick with special emphasis on pathways relevant to imprinting.

In the forebrain of domestic chicks, a network of distinct regions is crucially involved in auditory and visual filial imprinting. Among these areas, a distinct part of the dorsocaudal neostriatal complex (dNC complex), termed neostriatum dorsocaudale (Ndc), was recently discovered by its enhanced metabolic activity during the presentation of auditory and visual imprinting stimuli. Since there is evidence that the dNC complex consists of several distinct functional subareas, we investigated the neural connections of different parts of the dNC complex by retro- and anterograde pathway tracing. Special emphasis was put on the connections of the dNC complex with other imprinting relevant regions in the rostral telencephalon, such as the mediorostral neostriatum/hyperstriatum ventrale (MNH) and the intermediate and medial part of the hyperstriatum ventrale (IMHV). By anterograde and multiple retrograde pathway tracing, we found that the dNC complex may at least be subdivided into three major constituents. The most medial part of the dNC complex, termed neostriatum dorsale (Nd), is characterized by strong reciprocal connections with the neostriatal part of the MNH and by its auditory related inputs, including those from the output layers L1 and L3 of field L, and the shell region of the thalamic n. ovoidalis. The Ndc, which occupies the central aspects of the dNC complex, is mainly characterized by reciprocal connections with the ectostriatal belt (Ep) and the adjacent neostriatum (N). Furthermore, Nd and Ndc receive strong thalamic input from the n. dorsolateralis posterior (DLP), both project to the IMHV, and both are reciprocally connected with the archistriatum intermedium (AI). The most lateral aspect of the dNC complex, termed Ndl, is characterized by afferents from the neostriatum frontale, pars trigeminalis (NFT), and by the lack of a thalamic input. Results indicate that the dNC complex comprises distinct subregions, which are characterized by their specific afferents from parasensory areas of different sensory modalities. These different subregions may be integral components of a general pattern of sensory processing in the avian telencephalon. The strong interconnections between Nd, Ndc, and MNH as well as IMHV may constitute essential parts of auditory and visual imprinting circuits.

Animals↗

Developing an integrated information system for specialized addiction treatment agencies.

This article outlines the development of an integrated information system for specialized alcohol and drug treatment agencies in Ontario, Canada. The system is being developed following a strategic planning process involving provincial funding ministries and coalitions of service providers. An overview of the system's development is provided and the implementation of one subcomponent, a client-tracking system, is described. Some challenges to the implementation of this component are identified.

Alcoholism↗

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.

OBJECTIVES: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection. BACKGROUND: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis. METHODS: In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies. RESULTS: Mean troponin T serum concentrations were identical in control subjects (23.2 +/- 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 +/- 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 +/- 1.8 ng/liter; grade 2: 33.2 +/- 2.7 ng/liter; grade 3A: 54.6 +/- 6.5 ng/liter; grade 3B and 4: 105.4 +/- 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings. CONCLUSIONS: The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection.

Acute Disease↗

TNFalpha-mediated cell death is independent of cdc25A.

Tumor necrosis factor (TNFs) have been shown to be synthesized by ovarian carcinomas, and may therefore affect tumor cells in an autocrine manner. Therefore, we investigated the effects of recombinant TNFs on ovarian carcinoma cells N.1 and examined expression of the proto-oncogenes c-myc and cdc25A which are known to play a prominent role in apoptosis. TNFalpha elicited apoptosis in N.1 cells within 72 h which was shown by typical morphological changes, DNA fragmentation and signature type cleavage of poly(ADP-ribose) polymerase into a 89 kDa proteolytic peptide. TNFalpha-induced apoptosis was accompanied by constitutive c-Myc expression, although the mRNA level of phosphatase cdc25A was suppressed within 24 h of TNFalpha treatment and the protein level decreased after 48 h. Cdc25A tyrosine phosphatase is an activator of the cdk2-cyclin E complex which allows for cell cycle progression. As expected, we found TNFalpha-mediated Cdc25A down-regulation to inhibit Cdk2 activity. Cdc25A suppression was related to TNFalpha-induced apoptosis but not to a TNFalpha-induced G0 arrest because cyclin D1 expression was unaffected and the gene gas6 (growth arrest specific 6) was not induced. Arresting cells by treatment with genistein prevented TNFalpha-triggered apoptosis and inhibited c-myc expression. TNFalpha-induced apoptosis is not accompanied by cell cycle arrest which may be due to constitutive c-Myc expression, although Cdc25A and Cdk2 activity is also down-regulated. High c-Myc and low Cdc25A activity might present conflicting signals to the cell cycle machinery which are incompatible with cell survival.

Apoptosis↗

The spacing effect depends on an encoding deficit, retrieval, and time in working memory: evidence from once-presented words.

The spacing effect in list learning occurs because identical massed items suffer encoding deficits and because spaced items benefit from retrieval and increased time in working memory. Requiring the retrieval of identical items produced a spacing effect for recall and recognition, both for intentional and incidental learning. Not requiring retrieval produced spacing only for intentional learning because intentional learning encourages retrieval. Once-presented words provided baselines for these effects. Next, massed and spaced word pairs were judged for matches on their first three letters, forcing retrieval. The words were not identical, so there was no encoding deficit. Retrieval could and did cause spacing only for the first word of each pair; time in working memory, only for the second.

Humans↗

Deregulated expression of CDK2- or CDK3-associated kinase activities enhances c-Myc-induced apoptosis.

Activation of high ectopic levels of c-Myc in serum-deprived Rat1-MycER cells by 4-hydroxytamoxifen induces both proliferation and apoptosis. To further elucidate the role of G1 cyclin-dependent kinases (CDKs) in the process of Myc-induced apoptosis, we generated Rat1-MycER cells stably overexpressing CDK2 or CDK3. Ectopic expression of these CDKs in Myc-overexpressing cells was accompanied by upregulation of the specific kinase activities. Whereas neither high ectopic CDK2 nor CDK3 alone induced apoptosis in serum-deprived Rat1 cells, both CDKs markedly elevated the incidence of Myc-induced apoptosis. It was shown earlier that in Rat1-MycER cells, which are resistant to tumor necrosis factor-alpha (TNF) when grown in high serum concentrations, the addition of TNF with the concomitant activation of Myc resulted in apoptotic cell death. Here, we show that neither CDK2 nor CDK3 induces susceptibility to the cytotoxic action of TNF in Rat1 cells. However, both molecules heavily elevated the incidence of apoptosis induced by TNF together with Myc. It has earlier been reported that Myc-induced apoptosis in serum-deprived Rat1 fibroblasts is inhibited by specific cytokines, such as platelet-derived growth factor (PDGF). Here, we demonstrate that PDGF-mediated protection from Myc-induced apoptosis is almost lost in Rat1 cells overexpressing CDK2 or CDK3. These apoptotic effects of CDK2 or CDK3 are not accompanied by alterations of proliferation parameters, such as DNA distribution, time the cells spend in each phase of the cell cycle, thymidine incorporation into DNA, or cell size analyzed during Myc-induced apoptosis. However, we found CDK3 to deregulate E2F-dependent transcription. In this report, we provide evidence for a not yet described property of CDK2 or CDK3 besides their activity in promoting proliferation: these G1-CDKs can promote apoptosis by interfering with the cell's response to survival factors.

Animals↗

Working in addictions treatment services: some views of a sample of service providers in Ontario.

Respondents in a survey of specialized addiction treatment providers indicated a strong commitment to the addictions field. In a multivariate analysis, intention to stay in the addictions field was positively related to a measure of attitudes toward staying or leaving, to age, involvement in an addictions studies program, working in a residential service, and job satisfaction. Intention to stay was negatively related to education and working in a nonresidential setting. Attention to factors that create positive attitudes to the addictions field, especially among younger, more educated people and those working in nonresidential services, is necessary to ensure a healthy future for addictions treatment.

Adult↗

Localization of dopamine D1 receptors and dopaminoceptive neurons in the chick forebrain.

The distributions of dopamine D1 receptors, dopaminoceptive neurons, and catecholaminergic fibers were investigated in the forebrain of the domestic chick by using D1 receptor autoradiography and immunohistochemical detection of D1 receptor protein (D1rp), the dopamine- and cAMP-regulated phosphoprotein DARPP-32, and tyrosine hydroxylase (TH). Particular attention was paid to two forebrain regions, the mediorostral neostriatum/ hyperstriatum ventrale (MNH) and neostriatum dorsocaudale (Ndc), which have been shown to be crucially involved in filial imprinting. In general, there was a good, but not complete, correlation between the immunohistochemical pattern of DARPP-32 positive perikarya and the distribution of D1 receptors. Both, DARPP-32 positive neurons as well as D1 receptors were highly enriched in the striatal part of the basal ganglia including the lobus parolfactorius (LPO) and paleostriatum augmentatum. High to moderate densities were observed in the outer rind of the pallium. Low to moderate densities were found in the belt regions of primary sensory areas, whereas densities in the respective core regions were generally low. Labeling in the MNH and Ndc was heterogeneous. Whereas the neostriatal part of MNH displayed both, moderate DARPP-32 immunostaining and moderate D1 receptor densities, the hyperstriatal part showed also moderate D1 receptor densities but was only weakly labeled by DARPP-32. The rostral part of the Ndc was among the most intensely DARPP-32 labeled areas of the pallium, its caudal part revealed only moderate DARPP-32 immunostaining. By using D1 receptor autoradiography, a homogeneous labeling throughout the rostrocaudal extension of the Ndc was found. Double-labeling experiments with antibodies to DARPP-32 and TH revealed that TH positive fibers in the MNH, Ndc, and LPO were often closely related to DARPP-32 positive perikarya. At the ultrastructural level, both immunoreaction for D1rp and DARPP-32 in the MNH and Ndc were primarily found to be associated with postsynaptic elements. Whereas D1rp immunoreactivity was enriched at postsynaptic densities or in their vicinity, reaction product for DARPP-32 was present throughout the perikaryal cytoplasm, dendrites, and dendritic spines. These results indicate that DARPP-32 as well as D1 receptors in the avian forebrain reveal a distribution that is substantially similar to that of mammals.

Animals↗

Agonist antibody and Fas ligand mediate different sensitivity to death in the signaling pathways of Fas and cytoplasmic mutants.

We have produced three forms of human Fas: full-length Fas, Fas with a C-terminal deletion, and a chimera between extracellular Fas and the intracellular domain of the tumor necrosis factor receptor I p55 subunit. We transfected cell lines with these constructs to compare the relative capacity of antibody agonists and the physiological Fas ligand (FasL) to stimulate death. With two agonistic antibodies, the chimera is 100- to 1000-fold more sensitive to induction of death than the full-length Fas. The C-terminal deletion mutant also shows greatly enhanced death in comparison to the wild-type receptor. In contrast, when FasL is used to trigger the Fas pathway, wild-type Fas and the deletion mutant are similarly sensitive, whereas the chimera is 100-fold less susceptible to ligand-mediated killing than Fas. This demonstrates that antibody agonists and natural ligand can stimulate different signaling pathways and emphasizes the limitations of defining physiologically important signaling pathways solely by antibody agonists.

Animals↗

Changes of neuronal responsiveness in the mediorostral neostriatum/hyperstriatum after auditory filial imprinting in the domestic chick.

Auditory filial imprinting in the domestic chick is an established experimental model for investigating basic mechanisms of learning-related synaptic plasticity. In in vivo electrophysiological studies, we analysed whether imprinting alters the responsiveness of neurons to acoustic imprinting stimuli in the mediorostral neostriatum/hyperstriatum ventrale. We compared the response characteristics of neurons in the mediorostral neostriatum/hyperstriatum ventrale in freely behaving or anesthetized acoustically imprinted, non-imprinted (naive controls) and passive control chicks (stimulus-exposed) during presentation of either the imprinting stimulus or an unfamiliar discrimination stimulus. In acoustically imprinted chicks, the multiunit activity in anesthetized chicks and the fast Fourier transform power spectrum in freely behaving chicks in the mediorostral neostriatum/hyperstriatum ventrale were significantly changed during playback of the learned stimulus in comparison to spontaneous activity and compared to the activity during playback of the unfamiliar discrimination stimulus. In anesthetized non-imprinted and passive control chicks, the multiunit activity showed slightly enhanced activity during playback of either the imprinting or the discrimination stimulus in comparison to spontaneous activity. However, in both control groups there were no significant differences between the responses towards the imprinting and the discrimination stimuli. These results indicate that neurons in the mediorostral neostriatum/hyperstriatum ventrale change their responsiveness towards learned, behaviorally relevant stimuli during auditory filial imprinting.

Acoustic Stimulation↗

Distinct activation of monoaminergic pathways in chick brain in relation to auditory imprinting and stressful situations: a microdialysis study.

In the forebrain of the domestic chick (Gallus gallus domesticus), an area termed the mediorostral neostriatum/hyperstriatum ventrale is strongly involved in emotional learning paradigms such as acoustic filial imprinting. Furthermore, the involvement of the mediorostral neostriatum/hyperstriatum ventrale in stressful situations, such as social separation, has been demonstrated in 2-deoxyglucose studies. The aim of the present study was to examine whether quantitative changes of dopamine, serotonin and their metabolites occur during auditory filial imprinting and during social separation. Using in vivo microdialysis in tone-imprinted and in naive, control chicks, we compared the extracellular levels of homovanillic acid, a metabolite of dopamine, and 5-hydroxyindoleacetic acid, a metabolite of serotonin, during the presentation of the imprinting tone. A small, but statistically significant, decrease of extracellular homovanillic acid levels was found in the mediorostral neostriatum/hyperstriatum ventrale of imprinted chicks compared to control animals, whereas changes of 5-hydroxyindoleacetic acid were not detected. In a second experiment, we investigated the levels of homovanillic acid and 5-hydroxyindoleacetic acid in the mediorostral neostriatum/hyperstriatum ventrale of socially reared chicks during different stress situations, such as handling or separation from their cage mates. Handling induced a significant increase of homovanillic acid and 5-hydroxyindoleacetic acid, while social separation resulted in a significant increase of 5-hydroxyindoleacetic acid and only a slight increase of homovanillic acid. Despite considerable inter-individual variability, the increase of distress vocalizations (duration of distress calls) after social separation displayed a good correlation to the increased 5-hydroxyindoleacetic acid levels in all animals analysed. These results provide the first evidence that the physiological response of the mediorostral neostriatum/hyperstriatum ventrale related to different emotional conditions after acoustic imprinting and during stressful situations is, at least in part, mediated by dopaminergic and/or serotonergic pathways. Furthermore, the results from the present study indicate a distinct activation of dopaminergic and serotonergic pathways in relation to the behavioural situation and the associated changes of emotional status.

Acoustic Stimulation↗

Role of the dorso-caudal neostriatum in filial imprinting of the domestic chick: a pharmacological and autoradiographical approach focused on the involvement of NMDA-receptors.

Newly hatched domestic chicks were either acoustically imprinted on 400 Hz tone pulses or visually imprinted on a rotating red light. Compared to naive control animals, both groups of imprinted chicks expressed significantly enhanced stimulus evoked 2-fluoro-2-deoxyglucose (2-FDG) uptake in circumscribed areas of the dorso-caudal neostriatum (Ndc). This enhanced excitability after imprinting seems not to be related to changes of NMDA-receptor densities as measured by quantitative receptor autoradiography. However, pharmacological blockade of NMDA-receptors in the dorso-caudal neostriatum leads to a marked suppression of stimulus-evoked 2-FDG uptake in the dorso-caudal neostriatum and also in the interconnected imprinting relevant forebrain area, medio-rostral neostriatum/hyperstriatum ventrale (MNH). Furthermore, chicks which received bilateral Ndc injections of the competitive NMDA antagonist DL-2-amino-5-phosphono valeric acid (APV) during the imprinting experiments showed a dose-dependent decrease of imprinting success compared to vehicle-injected controls. These results indicate that the dorso-caudal neostriatum may represent a polysensory associative brain region in which visual and acoustic features of imprinting objects may be integrated. The activation in this area evoked by the imprinting stimulus during and after imprinting is critically dependent on NMDA-receptor activation, which appears to be required for this learning process.

2-Amino-5-phosphonovalerate↗

Early auditory filial learning in degus (Octodon degus): behavioral and autoradiographic studies.

Degu mothers (Octodon degus) utter specific maternal calls during nursing which presumably stimulate and reinforce suckling. Pups from surgically muted mothers show a reduced gain of body weight during postnatal development compared to pups from normally vocalizing mothers. Our behavioral studies suggest that the pups have to learn the meaning of the maternal calls during the first two weeks of life. Two-week-old pups from normally vocalizing mothers expressed a preference for the maternal call in a behavioral discrimination test, in contrast to pups from surgically muted mothers. Investigation of brain activities using the 2-[14C]fluoro-deoxyglucose (2-FDG) method revealed that pups from normal mothers display a significantly higher 2-FDG uptake in precentral medial, anterior cingulate cortex and a slight, non-significant increase in the prelimbic cortex and orbital PFC upon presentation of the maternal call, compared to pups from muted mothers, for which the maternal call was unfamiliar and meaningless. These prefrontal cortical areas are known to be involved in associative learning processes and our data suggest that they are involved in the association between the maternal call and the positive emotional situation during nursing.

Acoustic Stimulation↗

Organization of the dopaminergic innervation of forebrain areas relevant to learning: a combined immunohistochemical/retrograde tracing study in the domestic chick.

The mediorostral neostriatum/hyperstriatum ventrale (MNH) and neostriatum dorsocaudale (Ndc) of the domestic chick are crucially involved in auditory filial imprinting, whereas the lobus parolfactorius (LPO) seems to be involved in the emotional modulation of behavior. Because there is evidence that MNH and Ndc are akin to higher association areas in mammals, the present study evaluates the dopaminergic and thalamic input to these areas, as well as to the avian caudate/putamen homologue LPO, by using retrograde pathway tracing, together with dopamine (DA) and tyrosine hydroxylase (TH) immunohistochemistry. By combining DA immunohistochemistry with retrograde fluorescent tracing, we demonstrated that dopaminergic afferents to the MNH and Ndc arise mainly from the area ventralis, whereas the main dopaminergic input to the LPO arises from the substantia nigra. The main thalamic input to the MNH and LPO arises from the dorsal thalamic nuclei, n. dorsomedialis anterior and n. dorsolateralis anterior, whereas the thalamic input to the Ndc arises from the n. dorsolateralis posterior and n. subrotundus. Furthermore, there are reciprocal intratelencephalic connections between distinct parts of the neostriatum caudale and the mediorostral neostriatum. DA-immunoreactive (ir) fibers are present at moderate densities in the MNH and Ndc and at high densities in the LPO. At the ultrastructural level, DA- and TH-ir axon terminals in the MNH and Ndc form predominantly symmetric synaptic contacts with dendritic shafts, which are often situated in close vicinity to unstained terminals. These results indicate that the general organization of dopaminergic afferents to the chick telecephalon is similar to that of the mesotelencephalic dopaminergic subsystems in mammals such as the mesostriatal and mesolimbocortical DA system.

Animals↗

Development of dopamine receptors in the forebrain of the domestic chick in relation to auditory imprinting. An autoradiographic study.

The rostro-medial neostriatum/hyperstriatum ventrale (MNH) and the neostriatum dorsocaudale (Ndc) are forebrain regions which play a role in auditory filial imprinting. Both regions receive a distinct dopaminergic input from the mesencephalon and we were interested to investigate if the dopaminergic system, which is known to play a role in associative learning processes and neuronal plasticity is involved in auditory imprinting. Using ligand autoradiography we studied the distribution and density of dopamine receptors (D1 and D2 type) in the forebrain of socially isolated chicks during the first postnatal week and compared these data with the values of age-matched imprinted chicks. D1- and D2-receptors were present in the chick forebrain on the day of hatching and they showed in general, the same distribution until postnatal day 7. Between days 0 and 2 the D2-receptor density increased significantly in the lobus parolfactorius and paleostriatum augmentatum while for D1-receptor density no significant changes were detectable. The receptor densities in the investigated forebrain regions did not differ significantly between imprinted and control chicks. These results suggest that auditory imprinting does not induce alterations of dopamine receptor density, however, more subtle changes can not be excluded. The presented detailed data about the developmental profile of dopamine receptors within distinct brain regions is a further step towards a more specific interpretation of behavioral effects of dopamine receptor agonists or antagonists at different postnatal ages.

Acoustic Stimulation↗

Influence of the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid on auditory filial imprinting in the domestic chick.

Newly hatched domestic chicks were injected uni- or bilaterally into the imprinting relevant forebrain region mediostral neostriatum/ hyperstriatum ventrale (MNH) with different concentrations (1, 3, 12.5, 50 nmol) of the competitive NMDA antagonist DL-5-amino-5- phosphonovaleric acid (APV) prior to exposure to the imprinting stimulus (400-Hz tone pulses). In both APV-injected experimental groups there was a dose-dependent decrease of imprinting rates compared to that seen in controls, suggesting an APV-induced blockade of the learning process. In order to find out how the injected APV interferes with the stimulus-evoked enhanced metabolic activity in imprinting-relevant brain regions and to gain information about the spatial extent of its physiological effect, 2-fluorodeoxyglucose (2-FDG) experiments were performed. Chronically APV-treated chicks which failed in the imprinting tests showed similarly low 2-FDG uptake in imprinting relevant areas as naive untreated controls, further suggesting that no learning process has occurred in these animals. In imprinted chicks acute APV injections into the MNH led to a suppression of the stimulus-evoked 2-FDG uptake in this region. This pharmacologically induced reduction extended beyond the MNH region to adjacent regions. Furthermore, unilateral injections into the MNH always resulted in a bilateral reduction of 2-FDG uptake in this area. The results suggest that NMDA-mediated mechanisms in restricted telecephalic areas such as the MNH play a crucial role in the process of auditory filial imprinting.

2-Amino-5-phosphonovalerate↗

Localization of the neural calcium-binding protein VILIP (visinin-like protein) in neurons of the chick visual system and cerebellum.

The visinin-like protein (VILIP) is a member of a recently discovered family of calcium sensors specifically expressed in neurons. Family members contain four potential calcium-binding domains commonly referred to as "EF-hand motifs". VILIP interacts in a calcium-dependent manner with the actin-based neuronal cytoskeleton and modulates the phosphorylation of G-protein-coupled receptors, i.e., rhodopsin, in vitro. Here, we have used antisera against VILIP to study its distribution in the chick brain. Immunostaining of subsets of neurons is observed throughout the brain. Generally, the distribution of VILIP coincides well with the distribution of VILIP transcripts as detected previously by in situ hybridization. The most intense expression is detected in the visual system and the cerebellum. In the visual system, neurons of the nuclei of the ascending tecto-fugal pathway are stained, as are the pretectal, isthmic, and oculomotor nuclei. VILIP immunoreactivity is found in cell bodies, dendrites, and synaptic structures. Thus, VILIP appears to be an excellent marker for the characterization of neurons of the visual pathway. In the cerebellum, VILIP immunoreactivity is detected in deep cerebellar nuclei and in a subset of granule cells, Golgi type II cells, basket cells, and stellate cells, whereas it is completely absent from Purkinje cells. Intense punctate staining in the molecular layer suggests that VILIP is transported from deep cerebellar nuclei and from granule cells to the glutamatergic climbing-fiber and parallel-fiber synapses, respectively, both of which terminate on Purkinje-cell dendrites. The localization of VILIP in these presynaptic terminals has been confirmed at the electron-microscopic level.

Animals↗