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G K Zupanc

Publications and source records attributed to G K Zupanc.

At least 19 recordsLinked to original sources

Neuronal regeneration in the cerebellum of adult teleost fish, Apteronotus leptorhynchus: guidance of migrating young cells by radial glia.

In contrast to mammals, adult fish exhibit an enormous potential to replace injured brain neurons by newly generated ones. In the present study, the role of radial glia, identified by immunostaining against fibrillary acidic protein (GFAP), was examined in this process of neuronal regeneration. Approximately 8 days after application of a mechanical lesion to the corpus cerebelli in the teleost fish Apteronotus leptorhynchus, the areal density of radial glial fibers increased markedly in the ipsilateral dorsal molecular layer compared to shorter survival times, or to the densities found in the intact brain or in the hemisphere contralateral to the lesion. This density remained elevated throughout the time period of up to 100 days examined. The increase in fiber density was followed approximately 2 days later by a rise in the areal density of young cells, characterized by labeling with the nuclear dye DAPI, in the ipsilateral dorsal molecular layer. Based on this remarkable spatio-temporal correlation, and the frequently observed close apposition of elongated young cells to radial glial fibers, we hypothesize that radial glia play an important role in the guidance of migrating young cells from their proliferation zones to the site of lesion where regeneration takes place.

Age Factors↗

Radial glia-mediated up-regulation of somatostatin in the regenerating adult fish brain.

Adult teleost fish, Apteronotus leptorhynchus, exhibit an enormous regenerative capability after application of mechanical lesions to the dorsalmost subdivision of the cerebellum, the corpus cerebelli. Restoration of the neural tissue is achieved by a cascade of processes, including the guidance of migrating new neurons to the site of injury by radial glial fibers. These fibers are characterised by the expression of immunoreactive glial fibrillary acidic protein and by several morphological features. Within 12 h following the lesion, the fraction of radial glial fibers expressing the neuropeptide somatostatin (SRIF) dramatically increased from approximately 1%, as found in the intact brain, to roughly 27% 12-24 h post-lesion. Subsequently, the percentage of SRIF-expressing radial glial fibers gradually declined, until it reached background levels at about 10 days following the injury. We hypothesise that the expression of SRIF is related to the generation and/or differentiation of the new neurons produced in response to the lesion, rather than to the later guidance of these cells along their migratory pathway.

Animals↗

Differential production of chirping behavior evoked by electrical stimulation of the weakly electric fish, Apteronotus leptorhynchus.

Aperonotus leptorhynchus (Gymnotiformes) produces wave-like electric organ discharges distinguished by a high degree of constancy. Transient frequency and amplitude modulations of these discharges occur both spontaneously and during social interactions, which can be mimicked by external electrical stimulation. The so-called chirps can be divided into four different types. Independent of the type of chirp produced under spontaneous conditions, the fish generate only significant numbers of type-2 chirps under evoked conditions. The rate of production of chirps of this type is largely determined by the frequency relative to the fish's frequency and signal intensity. Frequencies of + 10 Hz of the fish's own discharge frequency most effectively elicit chirps. Type-2 chirps can also be evoked through stimulation at or near the higher harmonic frequencies of the fish's frequency, but the chirp rate decreases with increasing number of the higher harmonic component. Over a certain range, the rate of production of type-2 chirps increases with increasing stimulus intensity. At very high intensities the generation of type-2 chirps is accompanied by the production of a novel type of electrical signal ("abrupt frequency rise") characterized by a frequency increase of approximately 20 Hz and high repetition rates of roughly 10 s(-1). We hypothesize that the different types of electric modulations subserve different behavioral functions.

Animals↗

A comparative approach towards the understanding of adult neurogenesis.

In all vertebrate species examined thus far the production of new neurons in the central nervous system takes place not only during embryogenesis but also in adult life. However, although in mammals this so-called adult neurogenesis appears to be limited to a very few brain regions, in non-mammalian vertebrates new neurons are generated continuously in many regions of the adult central nervous system. This difference makes it particularly interesting to examine adult neurogenesis from a comparative point of view. Such an approach is likely not only to yield new insights into the evolution and function(s) of this phenomenon, but also to facilitate identification of central sites that, although quiescent in vivo, have retained their intrinsic potential to produce new cells during adulthood in mammals.

Aging↗

Adult neurogenesis and neuronal regeneration in the central nervous system of teleost fish.

In contrast to mammals, teleost fish exhibit an enormous potential to produce new neurons in the adult central nervous system and to replace damaged neurons by newly generated ones. In the gymnotiform fish Apteronotus leptorhynchus, on average, 100,000 cells, corresponding to roughly 0.2% of the total population of cells in the adult brain, are in S-phase within any 2-h period. As in all other teleosts examined thus far, many of these cells are produced in specific proliferation zones located at or near the surface of ventricular, paraventricular, and cisternal systems, or in areas that are likely derived from proliferation zones located at ventricular surfaces during embryonic development. The majority of cells born in such proliferation zones migrate within the first few weeks following their generation to specific target areas. In the cerebellum, where approximately 75% of all brain cells are born during adulthood, cells originate from the molecular layers of the corpus cerebelli and the valvula cerebelli partes lateralis and medialis, as well as from the eminentia granularis pars medialis. From these proliferation zones, the young cells migrate to the associated granule cell layers or to the eminentia granularis pars posterior, respectively. In the course of their migration, the young cells appear to be guided by radial glial fibers. Upon arrival at their target region, approximately 50% of the young cerebellar cells undergo apoptosis. The remaining cells survive for the rest of the fish's life, thus contributing to permanent brain growth. At least some cells differentiate into granule cell neurons. The potential to produce new neurons, together with the ability to guide the young cells to their target areas by radial glial fibers and to eliminate damaged cells through apoptosis, also forms the basis for the enormous regenerative capability of the central nervous system of Apteronotus, as demonstrated in the cerebellum and spinal cord. A factor involved in the cerebellar regeneration appears to be somatostatin, as the expression of this neuropeptide is up-regulated in a specific spatio-temporal fashion following mechanical lesions. Besides its involvement in neuronal regeneration adult neurogenesis in Apteronotus, and possibly teleost fish in general, appears to play a role in providing central neurons to match the growing number of sensory and motor elements in the periphery, and to establish the neural substrate to accommodate behavioral plasticity.

Aging↗

Up-regulation of somatostatin after lesions in the cerebellum of the teleost fish Apteronotus leptorhynchus.

Following application of mechanical lesions to the corpus cerebelli, a cerebellar subdivision, in adult individuals of the teleost fish Apteronotus leptorhynchus, the pattern of expression of the neuropeptide somatostatin was examined by employing immunohistochemical techniques. In the intact corpus cerebelli, only a very few cells displayed somatostatin-like immunoreactivity. This number dramatically increased in the area of the lesion within the granule cell layer 1 day following the injury and peaked after 2 days, when the normalized total number of somatostatin-positive cells was approximately 50 times higher than the mean number of labeled cells found after 3, 6, and 12 h of survival. Between 5 and 10 days of post-lesioning survival time, this number abruptly declined and returned to background levels at 17 and 25 days. Confocal microscopy revealed three cell types, presumably corresponding to granule cell neurons, astrocytes and microglia, which all displayed a similar temporal pattern of somatostatin expression. It is hypothesized that somatostatin is involved in regulation of the genesis and/or development of new neurons which are produced in response to injuries and which replace damaged cells at the site of the lesion.

Animals↗

Cell proliferation after lesions in the cerebellum of adult teleost fish: time course, origin, and type of new cells produced.

In contrast to mammals, fish exhibit an enormous capacity to replace damaged neurons following injuries to the adult central nervous system. As the mechanisms controlling this so-called neuronal regeneration are unknown, we have, in the present study, examined the role of cell proliferation in this process. Lesions were applied to one subdivision of the cerebellum, the corpus cerebelli, in the teleost fish Apteronotus leptorhynchus. Proliferative activity was monitored through incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine into replicating DNA. Cerebellar lesions induce high proliferative activity especially in areas in close vicinity to the injury, although the number of cells produced is also increased in other regions of the corpus cerebelli. Many of the cells generated in these areas become, after migration, specifically incorporated at the site of the lesion. The vast majority of them is dividing between 1 and 10 days following the lesion, with the maximum proliferative activity occurring at 5 days. Remarkably, also cells dividing 2 days prior to applying a lesion participate, at a significant number, in the regenerative process. Combination of 5-bromo-2'-deoxyuridine labeling with retrograde tract-tracing techniques demonstrated that at least some of the new cells that replace damaged neurons are cerebellar granule cells. This ability to generate new neurons, together with the previously described occurrence of apoptosis to remove damaged cells, is likely to form the basis for the enormous capacity of teleost fish to perform neuronal regeneration.

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Corticotropin releasing factor in the brain of the gymnotiform fish, Apteronotus leptorhynchus: immunohistochemical studies combined with neuronal tract tracing.

The expression of corticotropin-releasing factor (CRF) has been studied by immunohistochemistry in the brain of the gymnotiform fish, Apteronotus leptorhynchus. Labeled somata were found exclusively in the posterior subdivision of the nucleus preopticus periventricularis and in the hypothalamus anterioris, where these cells form a continuous cluster of neurons. Combination of anti-peptide immunohistochemistry with an in vitro tract-tracing technique confirmed that at least some of these neurons project to the pituitary. Additional terminal fields were present in the following areas of the telencephalon and the diencephalon: ventral subdivision of the ventral telencephalon, supracommissural subdivision of the ventral telencephalon, anterior subdivision of the nucleus preopticus periventricularis, inferior subdivision of the nucleus recessus lateralis, central posterior/prepacemaker nucleus, hypothalamus dorsalis and lateralis, medial subdivision 2 of the nucleus recessus lateralis, and in the region between the dorsal edge of the nucleus tuberis anterior on the one side and both the glomerular nucleus and the central nucleus of the inferior lobe on the other side. It is likely that the projection of CRF-expressing neurons of the posterior subdivision of the nucleus preopticus periventricularis/hypothalamus anterioris to the pituitary provides, similarly as in other fishes, the neural substrate for the activation of the hypothalamo-pituitary adrenal axis through CRF. In addition to this function, CRF may be involved in the regulation of several other processes, including neural control of communicatory behavior exerted by neurons of the central posterior/prepacemaker nucleus.

Animals↗

Molecular cloning and pharmacological characterization of a somatostatin receptor subtype in the gymnotiform fish Apteronotus albifrons.

The actions of the various forms of somatostatin (SRIF), including those of the tetradecapeptide SRIF(14), are mediated by specific receptors. In mammals, five subtypes of SRIF receptors, termed sst(1-5), have been cloned. Using a combination of reverse transcriptase-polymerase chain reaction and genomic library screening in the gymnotiform fish Apteronotus albifrons, a gene encoding the first-known nonmammalian SRIF receptor has been isolated. The deduced amino acid sequence displays 59% identity with the human sst(3) receptor protein; hence, the gene is termed "Apteronotus sst(3)." The predicted protein consists of 494 amino acid residues exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. A signal corresponding to the Apteronotus sst(3) receptor was detected in brain after amplification of poly(A)(+)-RNA by reverse transcriptase-polymerase chain reaction, but not by Northern blot analysis or in situ hybridization, suggesting a low level of expression. Membranes prepared from CCL39 cells stably expressing the Apteronotus sst(3) receptor gene bound [(125)I][Leu(8),d-Trp(22), (125) I-Tyr(25)]SRIF(28) with high affinity and in a saturable manner (B(max) = 4470 fmol/mg protein; pK(D) = 10.5). SRIF(14) and various synthetic SRIF receptor agonists produced a dose-dependent inhibition of radioligand binding, with the following rank order of potency: SRIF(14) approximately SRIF(28) > BIM 23052 > octreotide > BIM 23056. Under low stringency conditions, an Apteronotus sst(3) probe hybridized to multiple DNA fragments in HindIII or EcoRI digests of A. albifrons DNA, indicating that the Apteronotus sst(3) receptor is a member of a larger family of Apteronotus SRIF receptors.

Amino Acid Sequence↗

Characterisation of the fish sst3 receptor, a member of the SRIF1 receptor family: atypical pharmacological features.

The first cloned non-mammalian somatostatin (somatostatin release-inhibiting factor = SRIF) receptor previously obtained from the teleost fish Apteronotus albifrons and generically named somatostatin receptor 3 (fsst3), was stably expressed and characterised in Chinese hamster lung fibroblast (CCL39) cells. Radioligand binding studies were performed with four radioligands selective for SRIF receptors in CCL39 cells expressing the fsst3 receptors; [125I]LTT-SRIF28 ([Leu8, D-Trp22, 125I-Tyr25]-SRIF28), [125I]Tyr10-cortistatin, [125I]CGP 23996, and [125I]Tyr3-octreotide labelled the fsst3 receptor with high affinity (pKd values: 10.47, 10.87, 9.59 and 9.57) and in a saturable manner, but defined different Bmax values; 4500, 4000, 3400 and 1500 fmol/mg, respectively. The affinities of SRIF peptides and analogues determined for fsst3 receptors displayed the following rank order of potency: seglitide = SRIF25 > SRIF14 = SRIF28 > cortistatin 14 > BIM 23014 > RC160 = L361,301 = octreotide > or = BIM 23052 > or = L362,855 > CGP23996 > BIM 23056 > BIM 23030 = cycloantagonist > SRIF22. The pharmacological profiles determined with [125I]LTT-SRIF28, [125I]CGP 23996 and [125I]Tyr10-cortistatin correlated highly significantly (r = 0.96-0.99), whereas [125I]Tyr3-octreotide binding was rather divergent (r = 0.78-0.81). Further, [125I]Tyr3-octreotide- and [125I]CGP 23996-labelled sites showed higher affinity for the various peptides than [125I]LTT-SRIF28 and [125I]Tyr10-cortistatin-labelled sites, although there were exceptions. [125I]LTT-SRIF28-binding to fsst3 receptors and human sst1-5 receptors was compared; the fsst3 binding profile correlated better with the hsst5- than with the hsst3 receptor profile. SRIF inhibited potently forskolin-stimulated adenylate cyclase activity in fsst3 transfected CCL39 cells; this effect was blocked by pertussis toxin, suggesting coupling of the fsst3 receptor to Gialpha and/or Goalpha. [125I]LTT-SRIF28 binding was detected in fish brain, liver, heart, spleen, and stomach, but not in gut. The pharmacological profile of [125I]LTT-SRIF28-labelled sites in brain, but not in liver, correlated significantly with the recombinant fsst3 receptor, in agreement with expression of the fsst3 receptor gene found by RT-PCR in the brain. However, biphasic binding curves obtained with two SRIF-analogues in brain, as well as the distinct pharmacological profile of the liver SRIF receptor, suggest the existence of several yet to be defined SRIF receptor subtypes in fish. The present data demonstrate that the recombinantly expressed fsst3 receptor has a pharmacological profile compatible with that of a SRIF1 receptor, although the rank order of affinity of fsst3 is closer to that of hsst5 than hsst3 receptors, as may be found when comparing very distantly related species. The fsst3 receptor expressed in CCL39 cells, is negatively coupled to adenylate cyclase activity via pertussis toxin-sensitive G-proteins, like mammalian sst3 receptors. Radioligand binding performed with fish tissue suggests the presence of a native sst3 receptor in brain as well as other yet to be defined SRIF receptor subtypes.

Adenylyl Cyclases↗

Neurogenesis, cell death and regeneration in the adult gymnotiform brain.

Gymnotiform fish, like all teleosts examined thus far, are distinguished by their enormous potential for the production of new neurons in the adult brain. In Apteronotus leptorhynchus, on average 10(5) cells, corresponding to approximately 0.2 % of the total population of cells in the adult brain, are in S-phase within any period of 2 h. At least a portion of these newly generated cells survive for the rest of the fish's life. This long-term survival, together with the persistent generation of new cells, leads to a continuous growth of the brain during adulthood. Zones of high proliferative activity are typically located at or near the surface of the ventricular, paraventricular and cisternal systems. In the central posterior/ prepacemaker nucleus, for example, new cells are generated, at very high rates, in areas near the wall of the third ventricle. At least some of these cells differentiate into neurons, express immunoreactivity against the neuropeptide somatostatin and migrate into more lateral areas of this complex. Approximately 75 % of all new brain cells are generated in the cerebellum. In the corpus cerebelli and the valvula cerebelli, they are produced in the molecular layers, whereas in the eminentia granularis the newborn cells stem from proliferation zones in the pars medialis. Within the first few days of their life, these cells migrate towards specific target areas, namely the associated granule cell layers. At least some of them develop into granule neurons. The high proliferative activity is counterbalanced by apoptosis, a mechanism that resembles the processes known from embryonic development of the vertebrate brain. Apoptosis also appears to be used as an efficient mechanism for the removal of cells damaged through injury in the brain of adult Apteronotus leptorhynchus. Since apoptosis is not accompanied by the side effects known from necrosis, this 'clean' type of cell death may, together with the enormous proliferative activity in the brain, explain, at least partially, the tremendous capability of teleost fish to replace damaged neurons with newly generated ones. One factor that appears to play a major role in the generation of new cells and in their further development is the neuropeptide somatostatin. In the caudal cerebellum of the gymnotiform brain, somatostatin-binding sites are expressed, at extremely high densities, at sites corresponding to the areas of origin, migration and differentiation of the newborn cells. This pattern of expression resembles the expression pattern in the rat cerebellum, where somatostatin immunoreactivity and somatostatin-binding sites are transiently expressed at the time when the granule cells of the cerebellum are generated. Moreover, after mechanical lesions of the corpus cerebelli, the expression of somatostatin-like immunoreactivity is tremendously increased in several cell types (presumably astrocytes, microglia and granule cell neurons) near the path of the lesion; the time course of this expression coincides with the temporal pattern underlying the recruitment of new cells incorporated at the site of the lesion.

Animals↗

Apoptosis after injuries in the cerebellum of adult teleost fish.

In contrast to mammals, all teleost fish examined thus far exhibit an enormous potential to regenerate not only neuronal processes (axonal regeneration), but even whole neurons (neuronal regeneration) after injuries in the central nervous system. By application of lesions to one subdivision of the cerebellum, the corpus cerebelli, the role of apoptosis in neuronal regeneration was examined in the gymnotiform fish, Apteronotus leptorhynchus. Apoptotic cells were identified by examination of cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) reaction, an in situ technique employed for detection of nuclear DNA fragmentation. Additional evidence for the apoptotic nature of dying cells was obtained through analysis of morphologies displayed at both the light microscopic and the ultrastructural level. The first TUNEL-positive cells at the site of the lesion appeared as rapidly as 5 min following mechanical damage of the tissue. Thirty minutes after stab wound lesion, their number reached maximum levels. Starting with 2 days of postlesioning survival time, a gradual decline in the number of TUNEL-positive cells was evident, until this process reached background levels 20 days after the lesion. We hypothesize that apoptosis is used in A. leptorhynchus as an efficient mechanism for the removal of cells damaged through injury in the central nervous system. Since apoptosis is not accompanied by the side-effects known from necrosis (which is predominant after injuries in the mammalian central nervous system), this "clean" type of cell death may, at least partially, explain the tremendous regenerative capability of teleosts.

Animals↗

An in vitro technique for tracing neuronal connections in the teleost brain.

The availability of neuronal tract-tracing techniques has been fundamental to the development of the neurosciences. While most of the previously described methods are performed in vivo, in the present paper, detailed protocols are reported for tracing neuronal connections in an in vitro preparation. This technique, tested in various neural systems of the teleost brain, allows precise application of tracer substance(s) under visual control. After the isolation of the brain, the tissue is kept alive by superfusion with oxygenated artificial cerebrospinal fluid in a slice chamber. Neuronal connections are traced by the application of crystals of biocytin or dextran-tetramethylrhodamine to the region of interest. Following intracellular transport over 8-18 h, the tissue is fixed and processed histochemically for visualization of structures filled with the tracer substance. This method can readily be modified for double labelling. Step-by-step procedures are outlined for (a) the simultaneous detection of two tracer substances in the same tissue sample, (b) the combination of tract tracing with the immunohistochemical identification of various biochemical markers such as 'classical' transmitters and neuropeptides, and (c) the visualization of both traced structures and mitotically active cells labelled with the thymidine analogue 5-bromo-2'-deoxyuridine. By exhibiting a high degree of efficiency, the described in vitro tract-tracing technique represents also a significant contribution towards a reduction of living animals in neurobiological experimentation.

Animals↗

A distinct population of neurons in the central posterior/prepacemaker nucleus project to the nucleus preopticus periventricularis in the weakly electric gymnotiform fish, Apteronotus leptorhynchus.

The central posterior/prepacemaker nucleus of weakly electric gymnotiform fish is a cell cluster in the dorsal thalamus involved in neural control of electric behaviors. By employing anterograde and retrograde tract-tracing techniques, we examined the neural connection between this complex and the preoptic area in Apteronotus leptorhynchus. Unilateral application of biocytin restricted to the region defined by the somata of the central posterior/prepacemaker nucleus revealed a network of fibers and terminals bilaterally in the anterior and posterior subdivisions of the nucleus preopticus periventricularis. Application of biocytin to the nucleus preopticus periventricularis demonstrated that these fibers arise from a small population of cell bodies located predominantly in the central and medial portions of the central posterior/prepacemaker nucleus. These somata were distinguished from the remaining cells in this complex not only by their pattern of connectivity, but also by their position within the cluster and by the relatively large size. The projection from the central posterior/prepacemaker nucleus to the nucleus preopticus periventricularis may provide a feedback loop complementing a recently described connection projecting from the preoptic area to the central posterior/prepacemaker nucleus with one synaptic link in the preglomerular nucleus.

Animals↗

Neurons of the posterior subdivision of the nucleus preopticus periventricularis project to the preglomerular nucleus in the weakly electric fish, Apteronotus leptorhynchus.

By using an in vitro tract-tracing technique, the neural connections between two diencephalic cell groups, the posterior subdivision of the nucleus preopticus periventricularis (PPp) and the preglomerular nucleus (PG), was examined in the weakly electric gymnotiform fish Apteronotus leptorhynchus. Neurons of the PPp project to one area within PG, the ventromedial cell group of the medial subdivision of the preglomerular nucleus (PGm-vmc). Axons of these cells reach the ipsilateral PGm-vmc via the basic hypothalamic tract, while collaterals decussate via the postoptic commissure to innervate the contralateral PGm-vmc. We hypothesize that those neurons within PPp that project to the PGm-vmc are homologous to neurons of the medial preoptic area of mammals. As part of an elaborate circuit, PPp and PG may participate, as in mammals, in the control of complex social behavior patterns.

Animals↗

The preglomerular nucleus of gymnotiform fish: relay station for conveying information between telencephalon and diencephalon.

The preglomerular nucleus of teleost fishes, believed to be a lateral part of the posterior tuberculum in the diencephalon, receives input from several sensory areas. By employing an in vitro technique, the pattern of connectivity between this cell group and the telencephalon has been explored through retrograde and anterograde tracing in the gymnotiform fish Apteronotus leptorhynchus. Neurons of the preglomerular nucleus project to the following telencephalic areas: central division of dorsal forebrain, dorsal subdivision of dorsolateral telencephalon, posterior subdivision of dorsolateral telencephalon, dorsal posterior telencephalon, and probably, also subdivision 2 of dorsomedial telencephalon. Experiments in which tracer application was restricted to the lateral subdivision of the preglomerular nucleus, or in which tracer substance was placed into various regions of the telencephalon revealed a differential projection pattern of cells in the lateral and the medial subdivision of the preglomerular nucleus. Neurons in the central division of the dorsal forebrain, the dorsal posterior telencephalon, and likely, also in the subdivision 2 of the dorsomedial telencephalon and the ventricular zone of the intermediate subdivision of the ventral telencephalon project back to the preglomerular nucleus. Thus, a major function of the preglomerular nucleus appears to be to act as a relay station for conveying information between diencephalon and telencephalon.

Animals↗

Expression of somatostatin in neurons of the central posterior/prepacemaker nucleus projecting to the preglomerular nucleus: immunohistochemical evidence for a non-synaptic function.

In the diencephalon of the weakly electric gymnotiform fish Apteronous leptorhynchus, part of the central posterior/prepacemaker nucleus innervates the preglomerular nucleus. A minor population of these neurons expresses immunoreactivity against somatostatin, as has been shown by combining peptide immunohistochemistry with an in vitro tract-tracing technique. In contrast to the expectation, however, this neuropeptide does not appear to be transported along the axons to the projection site, as somatostatin-like immunoreactivity could not be detected in the preglomerular nucleus. It is, therefore, likely that somatostatin expressed in these neurons exerts a non-synaptic function in the region of the central posterior/prepacemaker nucleus itself.

Animals↗

Long-term survival of postembryonically born cells in the cerebellum of gymnotiform fish, Apteronotus leptorhynchus.

The gymnotiform fish Apteronotus leptorhynchus is, like all teleosts examined thus far, distinguished by its enormous potential for the production of new neurons in the adult brain. In the cerebellum, cells are generated continuously and at high rate in discrete proliferation zones. From there, they migrate into specific target areas comprised of granule cell layers in the four cerebellar subdivisions. The long-term fate of these cells was followed through labelling with 5-bromo-2'-deoxyuridine. Employment of survival times of up to 440 days after the administration of this thymidine analogue revealed that the newborn cells survive for extremely long periods of time, spanning most of the fish's adult life, without exhibiting a decline in their number. This long-term survival, together with the permanent addition of new cells to the population of older cells, forms the basis for the continuous growth of the cerebellum during adulthood.

Animals↗