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Effect of telencephalon ablation on the reinforcing and eliciting properties of species-specific events in Betta splendens.

In male Betta splendens, aggressive behavior is drastically attenuated following telencephalon ablation. Because instrumental training and Pavlovian conditioning experiments with intact fish have suggested that associative factors may play an important role in the performance of agonistic behaviors, the effect of ablation on instrumental learning and Pavlovian conditioning was studied. In Experiment 1, ablation had no effect on the learning of the instrumental tunnel-swimming response reinforced by mirror presentation (i.e., viewing a conspecific), although the mirror presentations in yoked-control groups elicited fewer responses in ablates than in normal and sham-operated control fish. Yoked controls further established that instrumental responding was maintained by the reinforcement contingency and was not merely the result of increased motor activity. Experiment 2 studied Pavlovian conditioning of the components of the agonistic display. Unconditioned fin erection, gill erection, and tail beating (i.e., unconditioned responses, URs) to the mirror US all were less frequent in ablates than in normals or shams. Of these, only gill cover erection showed evidence of true conditioning (i.e., conditioned responses; CRs) in which responses to the conditioned stimulus (CS) are due to the pairings of CS and US (unconditioned stimulus). However, ablates suffered no impairment of conditioned gill erections. Ablates performed fewer fin erections to the CS; however, fin erection responses were not due to CS-US pairings but were attributable to pseudoconditioning. These results are related to hypotheses postulating the involvement of learning mechanisms in ablation-produced deficits and normal aggressive behavior.

Aggression↗

Programmed cell death in the developing human telencephalon.

Programmed cell death (PCD) in the form of apoptosis is recognized as one of the central events in the development of the central nervous system. To study the time of onset, extent and distribution of PCD in the human telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With the formation of the cortical plate at 7-8 g.w. , TUNEL(+) nuclei were seen in all developmental layers of the cortical anlage, as well as in the subcortical regions such as the ganglionic eminence and the internal capsule. The proliferative zones (the ventricular zone, the subventricular zone and the ganglionic eminence) contained the majority of all apoptotic nuclei observed in each specimen. However, the apoptotic index was highest in the subplate zone and in layer I. Double-labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cells probably start dying around midgestation. The onset of labelling of microglial cells and apoptotic nuclei were synchronous, indicating the involvement of microglia in PCD. In conclusion, two distinct types of PCD were observed during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probably not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal-target connectivity.

Apoptosis↗

Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis.

Neurons of the mammalian CNS are thought to originate from progenitors dividing at the apical surface of the neuroepithelium. Here we use mouse embryos expressing GFP from the Tis21 locus, a gene expressed throughout the neural tube in most, if not all, neuron-generating progenitors, to specifically reveal the cell divisions that produce CNS neurons. In addition to the apical, asymmetric divisions of neuroepithelial (NE) cells that generate another NE cell and a neuron, we find, from the onset of neurogenesis, a second population of progenitors that divide in the basal region of the neuroepithelium and generate two neurons. Basal progenitors are most frequent in the telencephalon, where they outnumber the apically dividing neuron-generating NE cells. Our observations reconcile previous data on the origin and lineage of CNS neurons and show that basal, rather than apical, progenitors are the major source of the neurons of the mammalian neocortex.

Aging↗

Qualitative behavior of spontaneous potentials from explants of 15 day chick embryo telencephalon in vitro.

The apparatus and technique used in the preparation and observation of explants of brain tissue capable of producing spontaneous potentials in vitro are described. The magnitude and pattern of spontaneous potentials from explants of telencephalon of 15 day chick embryos (measured using external bare platinum electrodes) and some aspects of their "normal" behavior during 12 days in vitro are also described. No change was noted in these potentials with change of amplifiers, recorders, or electrodes. The response of the potentials to change in temperature and proportionate composition of the atmosphere around the explant was such as to suggest that the potentials arise as a result of a living process. The changes brought about by the administration of anesthetics, strychnine, brucine, and barbiturates were those that might be anticipated in a normal functional activity of the central nervous system. It is concluded that these potentials are a true physiological phenomenon and arise from living cells of the central nervous system.

Animals↗

Complementary distribution of collagen type IV and the epidermal growth factor receptor in the rat embryonic telencephalon.

We previously identified an interaction between collagen type IV and the EGF receptor that regulates the differentiation of a limbic cortical phenotype in vitro (Ferri and Levitt, 1995). In the present study, we map the expression of the EGF receptor and collagen type IV in the embryonic telencephalon of the rat. At embryonic day (E) II, the earliest age examined, both proteins are coexpressed throughout the ventricular zone in the cerebral wall; this zone remains immunoreactive throughout corticogenesis (E14-E19). The cells comprising the subventricular zone are the most intensely immunoreactive for the EGF receptor, although little collage type IV is detected in this region. In contrast, postmitotic neurons that leave the proliferative zones are negative for the receptor. Moreover, during the peak of neuronal migration, the intermediate zone lacks collagen type IV immunoreactivity. Neurons that settle in the cortical plate once again exhibit EGF receptor immunoreactivity; this same zone is devoid of collagen type IV. By E19, coexpression of both proteins is evident only in the rostral extension of the subventricular zone, the pathway of migrating cells leading to the olfactory bulb. The temporal and spatial overlap of the EGF receptor and collage type IV in the cortical progenitor pool in vivo indicates that these molecules may participate in the initial decisions of neuronal differentiation. Their modified distribution during cortical maturation suggests a changing role for both proteins.

Animals↗

ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation.

Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame duplications/insertions leading to expansions of polyalanine tracts in ARX, were found in nine familial and one sporadic case of MR. In contrast to other genes involved in XLMR, ARX expression is specific to the telencephalon and ventral thalamus. Notably there is an absence of expression in the cerebellum throughout development and also in adult. The absence of detectable brain malformations in patients suggests that ARX may have an essential role, in mature neurons, required for the development of cognitive abilities.

Adolescent↗

A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon.

Zebrafish embryos homozygous for the masterblind (mbl) mutation exhibit a striking phenotype in which the eyes and telencephalon are reduced or absent and diencephalic fates expand to the front of the brain. Here we show that mbl(-/-) embryos carry an amino-acid change at a conserved site in the Wnt pathway scaffolding protein, Axin1. The amino-acid substitution present in the mbl allele abolishes the binding of Axin to Gsk3 and affects Tcf-dependent transcription. Therefore, Gsk3 activity may be decreased in mbl(-/-) embryos and in support of this possibility, overexpression of either wild-type Axin1 or Gsk3beta can restore eye and telencephalic fates to mbl(-/-) embryos. Our data reveal a crucial role for Axin1-dependent inhibition of the Wnt pathway in the early regional subdivision of the anterior neural plate into telencephalic, diencephalic, and eye-forming territories.

Animals↗

Two glutamate decarboxylase forms corresponding to the mammalian GAD65 and GAD67 are expressed during development of the chick telencephalon.

The gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamate decarboxylase (GAD) was studied during development of the chick telencephalon. By means of reverse-phase HPLC analysis, we showed that GABA indeed accumulates during embryogenesis, whereas the levels of glutamate, the substrate for GAD, are more or less unchanged up to later developmental stages. The enzyme activity increased approximately 25-fold from embryonic day 3 to embryonic day 17. Immunoblotting data revealed that two GAD proteins, of approximately 65 and 67 kDa, were present during the period investigated. Furthermore, Northern blot analysis with probes obtained from rat cDNA sequences, as well as a chicken-specific probe for GAD65 generated by means of reverse transcriptase-polymerase chain reaction (RT-PCR), strengthened the interpretation that the chick embryo expresses genes corresponding to GAD65 and GAD67. The rat probes recognized transcript sizes of 3.9 kb (GAD65) and 5.6 kb (GAD67), sizes which are different from those of the rat brain (Erlander et al., Neuron, 7, 91-100, 1991). Sequencing of the RT-PCR products revealed a high level of homology (82% at the nucleotide level) between the mammalian and chick GAD65 genes. Taken together, these findings suggest that the chick embryo expresses two GAD genes during embryogenesis. The functional properties of each gene product remain to be investigated.

Amino Acid Sequence↗

Multiple isoforms of the tumor protein p73 are expressed in the adult human telencephalon and choroid plexus and present in the cerebrospinal fluid.

p73, a homolog of the p53 tumor suppressor, codes for full-length transactivating (TA) and N-terminally truncated (DeltaN) isoforms, with pro- and anti-apoptotic activities, respectively. We examined the expression of the main p73 isoforms in adult human and mouse telencephalon and choroid plexus by immunohistochemistry on paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal fluid (CSF), using antibodies against different protein domains. Cortical neurons expressed TAp73 predominantly in the cytoplasm and DeltaNp73 mainly in the nucleus, with partial overlap in the cytoplasm. Highest expression was found in the hippocampus. IB showed an array of TAp73 variants in adult human cortex and hippocampus. IB of human choroid plexus and CSF using TAp73-specific antibodies revealed the presence of a approximately 90-kDa protein whose molecular weight was reduced after N-deglycosylation, suggesting that glycosylated TAp73 is exported into the CSF. In the mouse, high expression of TAp73 was also detected in the subcommissural organ (SCO), an ependymal gland absent in adult humans. TAp73 colocalized with anti-fibra-Reissner-antibody (AFRU), which is a marker of Reissner's fiber, the secreted SCO product. p73-deficient mice had generalized cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size reduction of the choroid plexus. However, the SCOs were apparently unaltered and continued to secrete Reissner's fiber. Our findings point to complex and widespread p73 activities in the maintenance of adult cortical neurons and in brain homeostasis. TAp73 in the CSF may play important roles in the maintenance of the adult ventricular wall as well as in the development of the proliferating neuroepithelium.

Adolescent↗

Secreted factors from ventral telencephalon induce the differentiation of GABAergic neurons in cortical cultures.

It is widely believed that the pyramidal cells and interneurons of the cerebral cortex are distinct in their origin, lineage and genetic make up. In view of these findings, the current thesis is that the phenotype determination of cortical neurons is primarily directed by genetic mechanisms. Using in vitro assays, the present study demonstrates that secreted factors from ganglionic eminence (GE) of the ventral telencephalon have the potency to induce the differentiation of a subset of cortical neurons towards gamma-aminobutyric acid (GABA)ergic lineage. Characterization of cortical cultures that were exposed to medium derived from GE illustrated a significant increase in the number of GABA-, calretinin- and calbindin-positive neurons. Calcium imaging together with pharmacological studies showed that the application of exogenous medium significantly elevated the intracellular calcium transients in cortical neurons through the activation of ionotropic glutamate receptors. The increase in GABA+ neurons appeared to be associated with the elevated calcium activity; treatment with blockers specific for glutamate receptors abolished both the synchronized transients and reduced the differentiation of GABAergic neurons. Such studies demonstrate that although intrinsic mechanisms determine the fate of cortical interneurons, extrinsic factors have the potency to influence their neurochemical differentiation and contribute towards their molecular diversity.

Animals↗

Development and maintenance of the neuronal cytoskeleton in aggregated cell cultures of fetal rat telencephalon and influence of elevated K+ concentrations.

Serum-free aggregating cell cultures of fetal rat telencephalon were examined by biochemical and immunocytochemical methods for their development-dependent expression of several cytoskeletal proteins, including the heavy- and medium-sized neurofilament subunits (H-NF and M-NF, respectively); brain spectrin; synapsin I; beta-tubulin; and the microtubule-associated proteins (MAPs) 1, 2, and 5 and tau protein. It was found that with time in culture the levels of most of these cytoskeletal proteins increased greatly, with the exceptions of the particular beta-tubulin form studied, which remained unchanged, and MAP 5, which greatly decreased. Among the neurofilament proteins, expression of M-NF preceded that of H-NF, with the latter being detectable only after approximately 3 weeks in culture. Furthermore, MAP 2 and tau protein showed a development-dependent change in expression from the juvenile toward the adult form. The comparison of these developmental changes in cytoskeletal protein levels with those observed in rat brain tissue revealed that protein expression in aggregate cultures is nearly identical to that in vivo during maturation of the neuronal cytoskeleton. Aggregate cultures deprived of glial cells, i.e., neuron-enriched cultures prepared by treating early cultures with the antimitotic drug cytosine arabinoside, exhibited pronounced deficits in M-NF, H-NF, MAP 2, MAP 1, synapsin I, and brain spectrin, with increased levels of a 145-kDa brain spectrin breakdown product. These adverse effects of glial cell deprivation could be reversed by the maintenance of neuron-enriched cultures at elevated concentrations of KCl (30 mM). This chronic treatment had to be started at an early developmental stage to be effective, a finding suggesting that sustained depolarization by KCl is able to enhance the developmental expression and maturation of the neuronal cytoskeleton.

Animals↗

Localization and quantification of melatonin receptors in the diencephalon and posterior telencephalon of the sheep brain.

In an attempt to better understand the mechanisms by which melatonin controls neuroendocrine activity, we tried to define with accuracy the brain areas where the density of melatonin receptors is the highest in sheep and to establish their characteristics. The specific labelling of 125I-melatonin was first revealed by autoradiography on brain sections of the posterior telencephalon and diencephalon in three ewes. The extent and position of the five structures where the binding was found to be the highest (i.e., the pars verticalis and pars horizontalis of the nucleus tractus diagonalis, the septal area, the bed nucleus of the stria terminalis, and the ventromedial hypothalamic area) were then accurately defined by image analysis. In comparison to the landmarks given by image analysis, photographs of coronal sections of another ewe permitted the accurate definition of the limits of the structures to be punched in a second step. In six ewes, each of the five structures previously identified were punched from frozen coronal sections and binding of 125I-melatonin to membrane preparations was studied individually by Scatchard analysis. The correlation coefficient between the B/F ratio and binding (B) was in the range of 0.96-0.98, indicating that a precise quantification was possible in these different structures. The Bmax was the highest in the bed nucleus of the stria terminalis, the septal area, and the ventromedial hypothalamic area (1.38, 1.25, and 0.95 fmol/mg protein, respectively). All Kd values were less than 10 pM and the Hill coefficient was close to 1, indicating the presence of a single class of receptor to 125I-melatonin. These results indicate the reliability of a method used to measure with accuracy low concentrations of melatonin receptors in brain structures. In addition, the ventromedial hypothalamic area was found to be rich in melatonin receptors. This region is known to be involved in the central gonadotrope control in sheep.

Animals↗

Connections of the nurse shark's telencephalon.

The extrinsic connections of the telencephalon of the nurse shark are very largely crossed and in this respect differ from those identified in all other vertebrate species so far examined. Studies with Nauta and Fink-Heimer methods have revealed telencephalic projections to the contralateral thalamus and optic tectum as well as to ipsilateral brainstem and rostral spinal cord.

Animals↗

Electrophysiological identification of a visual area in shark telencephalon.

Optic nerve stimulation in the shark evokes short-latency telencephalic field potentials localized to the ipsilateral, posterior central nucleus. Such a well-defined visual area in elasmobranch telencephalon further challenges classical formulations of forebrain evolution. Moreover, its ipsilateral representation confirms recent evidence for a crossed thalamotelencephalic visual projection.

Animals↗

Glutamate and regulation of proliferation in the developing mammalian telencephalon.

Increasing evidence suggests that classical neurotransmitters play an important morphogenetic role during development of the mammalian central nervous system. Using in vitro and in vivo models, we have previously identified a role for the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors in the proliferation of striatal progenitors. Here, we compare the roles of ionotropic glutamate receptors in the proliferation of either striatal or cortical progenitors. In culture, glutamate receptor activation promoted proliferation of both striatal and cortical neuroblasts. However, cortical and striatal neuroblasts responded to distinct ionotropic receptors. Cortical cultures were sensitive to AMPA/KA receptor blockade, whereas striatal neuroblast proliferation was altered by NMDA antagonists. In vivo, BrdU uptake in the proliferative ventricular zone was reduced in embryos following acute administration of ionotropic glutamate receptor antagonists. In keeping with in vitro observations, proliferation in cortical and striatal ventricular regions was reduced, respectively, by either AMPA/KA or NMDA receptor blockade. We also determined whether forebrain-derived progenitors expanded as neurospheres in the presence of growth factors show similar ionotropic glutamatergic responses. Cells in neither dorsal nor ventral telencephalon-derived neurospheres showed altered proliferation following exposure to either class of ionotropic glutamate receptor antagonist. Together, these findings suggest that glutamate influences the proliferation of forebrain neuronal progenitors, but not more primitive populations represented in multipotential progenitors expanded in vitro. The effects on neuroblast proliferation in different forebrain domains are heterogeneous and are mediated by distinct subclasses of ionotropic glutamate receptors.

Animals↗

A new interpretation on the homology of the teleostean telencephalon based on hodology and a new eversion model.

Various hypotheses regarding the homology of the teleostean telencephalon with that of other vertebrates have been proposed to date. However, a firm conclusion on this issue has yet to be drawn. We propose here a new hypothesis with a new eversion model. Our hodological data and the analysis of dorsal telencephalic organization in adult cyprinids suggest that: (1) the area dorsalis pars posterior corresponds to the lateral pallium; (2) ventral region of area dorsalis pars lateralis to the medial pallium; (3) pars medialis, dorsal region of pars lateralis, pars dorsalis, and pars centralis of the area dorsalis to the dorsal pallium, and (4) nucleus taenia to the ventral pallium. We propose in a three dimensional model that the eversion process occurs not only dorsolaterally but also caudolaterally. We consider that the caudally directed component dominates for ventral zones of the pallium, or the lateral and ventral pallia; and the periventricular surface of these zones shift caudally, laterally, and then rostrally in teleosts with pronounced telencephalic eversion. This new model fits well with the putative homology based on hodology and the organization of telencephalic divisions in the adult brain.

Animals↗

Developmental expression of glial fibrillary acidic protein and glutamine synthetase in serum-free aggregating cell cultures of fetal rat telencephalon.

Serum-free aggregating cell cultures of fetal rat telencephalon were examined by a combined biochemical and double-labeling immunocytochemical study for the developmental expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). It was found that these two astroglial markers are co-expressed at different developmental stages in vitro. During the phase of cellular maturation (i.e. between days 14 and 34), GFAP levels and GS activity increase rapidly and in parallel. At the same time, the number of immunoreactive cells increase while the long and thick processes staining in early cultures gradually disappear. The present results demonstrate that in this particular cell culture system only one type of astrocytes develops which expresses both GFAP and GS and which attains a relatively high degree of maturation.

Animals↗

Area dorsalis pars lateralis of the telencephalon in a teleost (Sebastiscus marmoratus) can be divided into dorsal and ventral regions.

Area dorsalis pars lateralis was shown to be subdivided into a dorsal region and a ventral region by a shallow groove on the telencephalic surface. In the dorsal region, three layers were distinguished by Nissl staining; a surface layer I, a middle layer II, and a deep layer III. Although a three-layered structure was also observed in the ventral region, it was not as clear as that in the dorsal region. Cells in area dorsalis pars lateralis were classified by Golgi-Cox staining into 5 types; small cells, horizontal cells, pyriform cells, inverted cells, and multipolar cells. The distribution of zinc was examined by the Neo-Timm method and found to be present in layers I and II and weakly in layer III of the dorsal region but not in layers I and II of the ventral region. The presence of zinc in synaptic terminals in the dorsal region was verified by analytical electron microscopy. Following separate and localized injections of horseradish peroxidase into dorsal and ventral regions, some different fiber connections were revealed. Both dorsal and ventral regions had reciprocal connections with ipsilateral area dorsalis pars centralis, area ventralis pars supracommissuralis, area ventralis pars dorsalis, area ventralis pars posterior, nucleus prethalamicus, and had afferent connections from area ventralis pars lateralis, area ventralis pars intermedia, raphe nuclei, and locus ceruleus. Only the dorsal region, however, received projections from contralateral area dorsalis pars centralis, ipsilateral area dorsalis pars dorsalis, area dorsalis pars medialis, and area dorsalis pars posterior and sent fibers to the inferior lobe, nucleus paracommissuralis, and optic tectum. Although area dorsalis pars lateralis had been thought to be a homogeneous region of the primary visual area of the telencephalon, histochemistry of zinc and fiber connections of the region indicates that the area is subdivided into two regions: dorsal and ventral.

Animals↗