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Forebrain
Kinds of Forebrain Terms modified by Forebrain Selected AbstractsRole of Wake-Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep-Promoting Effects of EthanolALCOHOLISM, Issue 6 2010Mahesh M. Thakkar Background:, Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol-induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? Methods:, To address these questions, we performed 3 experiments in Sprague,Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol-induced sleep. Results:, Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. Conclusion:, These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol. [source] Effects of Ethanol on Extracellular Levels of Adenosine in the Basal Forebrain: An In Vivo Microdialysis Study in Freely Behaving RatsALCOHOLISM, Issue 5 2010Rishi Sharma Background:, Adenosine is implicated to play a pivotal role in mediating many neuronal responses to ethanol. While in vitro studies performed in cell culture have demonstrated that acute ethanol exposure increases extracellular adenosine levels, this effect has not been demonstrated, in vivo, in the brain. We performed an in vivo microdialysis study to examine the effects of local ethanol perfusion on extracellular levels of adenosine in the basal forebrain (BF). Methods:, Under sterile conditions and using a standard surgical protocol, adult male Sprague,Dawley rats were implanted with unilateral microdialysis guide cannula targeted toward the BF. Following postoperative recovery, the microdialysis probe was inserted. After allowing at least 12 to 16 hours for probe insertion recovery, the experiment was begun. Artificial cerebrospinal fluid (aCSF) was perfused (0.7 ,l/min) for 80 minutes, and 4 × 20-minute pre-ethanol baseline samples were collected. Subsequently, 30, 100, and 300 mM doses of ethanol were perfused. Each ethanol dose was perfused for 80 minutes, and 4 × 20-minute samples were collected. Finally, aCSF was perfused, and 4 × 20 postethanol samples were collected. Adenosine in the microdialysate was separated and measured with HPLC coupled with an UV detector. On completion, the animals were euthanized, brain removed and processed for histology. Results:, Local ethanol perfusion in the BF produced a significant increase in extracellular adenosine with the highest dose of 300 mM ethanol producing a 4-fold increase. Cresyl violet (Nissl) staining did not indicate any toxic damage in the area surrounding the probe tip. Choline acetyltransferase immunohistochemistry revealed that all microdialysis probe sites were localized in the BF. Conclusion:, Our study is the first to demonstrate that ethanol acts directly in the brain to increase extracellular adenosine. [source] Consequential Apoptosis in the Cerebellum Following Injury to the Developing Rat ForebrainBRAIN PATHOLOGY, Issue 3 2006Deanna L. Taylor In focal brain lesions, alterations in blood flow and cerebral metabolism can be detected in brain areas remote from the primary injury. The cellular consequences of this phenomenon, originally termed diaschisis, are not fully understood. Here, we report that in two distinct models of forebrain injury, neuronal death in the cerebellum, a site distant to the primary injury, results as consequence of neuronal loss in the forebrain. Fourteen-day-old rats were subjected to unilateral forebrain injury, achieved by either hypoxia-ischemia (right carotid artery ligation and hypoxia) or direct needle injury to brain tissue. At defined times after injury, the presence of apoptosis was investigated by cell morphology, in situ end labeling, electron microscopy and poly-ADP-ribose polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia-ischemia increased apoptosis in the internal granular and Purkinje cell layers of the cerebellum, a site distant to that of the primary injury. The number of apoptotic cells in the cerebellum was significantly related to cell death in the hippocampus. Similarly, direct needle injury to the forebrain resulted in extensive apoptotic cell death in the cerebellum. These results emphasize the intimate relationship between defined neuronal populations in relatively distant brain areas and suggest a cellular basis for diaschisis. [source] Activation of the basal forebrain by the orexin/hypocretin neuronesACTA PHYSIOLOGICA, Issue 3 2010E. Arrigoni Abstract The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurones promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurones may promote arousal by exciting cortically projecting neurones of the BF. Orexin fibres synapse on BF cholinergic neurones and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurones, induces cortical release of acetylcholine and promotes wakefulness. The orexin neurones also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurones that project to the cortex. Cholinergic neurones were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurones that project to the cortex seem to comprise at least two populations with some directly excited by orexin-A that may represent wake-active, GABAergic neurones, whereas others did not respond to orexin-A but were inhibited by dynorphin and may be sleep-active, GABAergic neurones. This evidence suggests that the BF is a key site through which orexins activate the cortex and promote behavioural arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. [source] Characterization of sleep,wake patterns in a novel transgenic mouse line overexpressing human prepro-orexin/hypocretinACTA PHYSIOLOGICA, Issue 3 2010K. A. Mäkelä Abstract Aim:, Orexin/hypocretin peptides are expressed in the lateral hypothalamus and involved in the regulation of autonomic functions, energy homeostasis and arousal states. The sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and occurrence of sudden rapid eye movement (REM) sleep, is associated with a loss of orexin neurones. Our study investigated the effects of orexins on sleep,wake patterns in a novel transgenic mouse line overexpressing the human prepro-orexin (hPPO) gene under the control of its endogenous promoter. Methods:, Orexin overexpression was investigated by PCR, Southern and Western blotting as well as immunohistochemistry. Polysomnographic recordings were performed for analyses of sleep,wake patterns and for electroencephalographic activity during 24 h baseline and during and after 6 h of sleep deprivation (SD). Results:, Transgenic hPPO mice had increased expression of human prepro-orexin (hPPO) and orexin-A in the hypothalamus. Transgene expression decreased endogenous orexin-2 receptors but not orexin-1 receptors in the hypothalamus without affecting orexin receptor levels in the basal forebrain, cortex or hippocampus. Transgenic mice compared with their wild type littermates showed small but significant differences in the amount of waking and slow wave sleep, particularly during the light,dark transition periods, in addition to a slight reduction in REM sleep during baseline and during recovery sleep after SD. Conclusion:, The hPPO-overexpressing mice show a small reduction in REM sleep, in addition to differences in vigilance state amounts in the light/dark transition periods, but overall the sleep,wake patterns of hPPO-overexpressing mice do not significantly differ from their wild type littermates. [source] Epigenetic regulation in neural stem cell differentiationDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2010Berry Juliandi The central nervous system (CNS) is composed of three major cell types , neurons, astrocytes, and oligodendrocytes , which differentiate from common multipotent neural stem cells (NSCs). This differentiation process is regulated spatiotemporally during the course of mammalian development. It is becoming apparent that epigenetic regulation is an important cell-intrinsic program, which can interact with transcription factors and environmental cues to modulate the differentiation of NSCs. This knowledge is important given the potential of NSCs to produce specific CNS cell types that will be beneficial for clinical applications. Here we review recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NSC fate during CNS development, with a particular focus on the developing mammalian forebrain. [source] FGF19-FGFR4 signaling elaborates lens induction with the FGF8-L-Maf cascade in the chick embryoDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2005Hitomi Kurose The fibroblast growth factor (FGF) family is known to be involved in vertebrate eye development. However, distinct roles of individual FGF members during eye development remain largely elusive. Here, we show a detailed expression pattern of Fgf19 in chick lens development. Fgf19 expression initiated in the forebrain, and then became restricted to the distal portion of the optic vesicle abutting the future lens placode, where FGF receptor 4 (Fgfr4), a receptor for FGF19, was expressed. Fgf8, a positive regulator for L-Maf, was expressed in a portion of the optic vesicle. To examine the role of FGF19 signaling during early eye development, Fgf19 was misexpressed near the presumptive lens ectoderm; however, no alteration in the expression of lens marker genes was observed. Conversely, a secreted form of FGFR4 was misexpressed to inhibit an FGF19 signal, resulting in the induction of L-Maf expression. To further define the relationship between L-Maf and Fgf19, L-Maf misexpression was performed, resulting in ectopic induction of Fgf19 expression by Hamburger and Hamilton's stage 12/13. Furthermore, misexpression of Fgf8 induced Fgf19 expression in addition to L-Maf. These results suggest that FGF19-FGFR4 signaling plays a role in early lens development in collaboration with FGF8 signaling and L-Maf transcriptional system. [source] An olig2 reporter gene marks oligodendrocyte precursors in the postembryonic spinal cord of zebrafishDEVELOPMENTAL DYNAMICS, Issue 12 2007Hae-Chul Park Abstract Continuous production of new neurons and glia in adult mammals occurs within specialized proliferation zones of the forebrain. Neural cell proliferation and neurogenesis is more widespread in adult amphibians, reptiles, and fish but the identity of neural stem cell populations in these organisms has not been fully described. We investigated expression of a reporter gene driven by olig2 regulatory DNA at postembryonic stages in zebrafish. We show that olig2 expression marks a discrete population of spinal cord radial glia in larvae and adults that divide continuously. olig2+ radial glia have hallmarks of stem cells and their divisions appear to be asymmetric, producing new oligodendrocytes but not neurons or astrocytes. Developmental Dynamics 236:3402,3407, 2007. © 2007 Wiley-Liss, Inc. [source] Differential expression of CaMK-II genes during early zebrafish embryogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2007Sarah C. Rothschild Abstract CaMK-II is a highly conserved Ca2+/calmodulin-dependent protein kinase expressed throughout the lifespan of all vertebrates. During early development, CaMK-II regulates cell cycle progression and "non-canonical" Wnt-dependent convergent extension. In the zebrafish, Danio rerio, CaMK-II activity rises within 2 hr after fertilization. At the time of somite formation, zygotic expression from six genes (camk2a1, camk2b1, camk2g1, camk2g2, camk2d1, camk2d2) results in a second phase of increased activity. Zebrafish CaMK-II genes are 92,95% identical to their human counterparts in the non-variable regions. During the first three days of development, alternative splicing yields at least 20 splice variants, many of which are unique. Whole-mount in situ hybridization reveals that camk2g1 comprises the majority of maternal expression. All six genes are expressed strongly in ventral regions at the 18-somite stage. Later, camk2a1 is expressed in anterior somites, heart, and then forebrain. Camk2b1 is expressed in somites, mid- and forebrain, gut, retina, and pectoral fins. Camk2g1 appears strongly along the midline and then in brain, gut, and pectoral fins. Camk2g2 is expressed early in the midbrain and trunk and exhibits the earliest retinal expression. Camk2d1 is elevated early at somite boundaries, then epidermal tissue, while camk2d2 is expressed in discrete anterior locations, steadily increasing along either side of the dorsal midline and then throughout the brain, including the retina. These findings reveal a complex pattern of CaMK-II gene expression consistent with pleiotropic roles during development. Developmental Dynamics 236:295,305, 2007. © 2006 Wiley-Liss, Inc. [source] The zebrafish bHLH PAS transcriptional regulator, single-minded 1 (sim1), is required for isotocin cell developmentDEVELOPMENTAL DYNAMICS, Issue 8 2006Jennifer L. Eaton Abstract A wide range of physiological and behavioral processes, such as social, sexual, and maternal behaviors, learning and memory, and osmotic homeostasis are influenced by the neurohypophysial peptides oxytocin and vasopressin. Disruptions of these hormone systems have been linked to several neurobehavioral disorders, including autism, Prader-Willi syndrome, affective disorders, and obsessive-compulsive disorder. Studies in zebrafish promise to reveal the complex network of regulatory genes and signaling pathways that direct the development of oxytocin- and vasopressin-like neurons, and provide insight into factors involved in brain disorders associated with disruption of these systems. Isotocin, which is homologous to oxytocin, is expressed early, in a simple pattern in the developing zebrafish brain. Single-minded 1 (sim1), a member of the bHLH-PAS family of transcriptional regulatory genes, is required for terminal differentiation of mammalian oxytocin cells and is a master regulator of neurogenesis in Drosophila. Here we show that sim1 is expressed in the zebrafish forebrain and is required for isotocin cell development. The expression pattern of sim1 mRNA in the embryonic forebrain is dynamic and complex, and overlaps with isotocin expression in the preoptic area. We provide evidence that the role of sim1 in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals. Developmental Dynamics 235:2071,2082, 2006. © 2006 Wiley-Liss, Inc. [source] Ontogeny of tyrosine hydroxylase mRNA expression in mid- and forebrain: Neuromeric pattern and novel positive regionsDEVELOPMENTAL DYNAMICS, Issue 3 2005Faustino Marín Abstract Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines and, thus, critical in determining the catecholaminergic phenotype. In this study, we have examined the expression of TH mRNA by in situ hybridization in the embryonic mouse forebrain and midbrain and have mapped its localization according to the neuromeric pattern. We find that early in embryonic development, 10 to 12 days post coitum (dpc), TH mRNA is expressed in ample continuous regions of the neuroepithelium, extending across several neuromeres. However, from 12.5 dpc onward, the expression becomes restricted to discrete regions, which correspond to the dopaminergic nuclei (A8 to A15). In addition to these nuclei previously described, TH mRNA is also observed in regions that do not express this enzyme according to immunohistochemical studies. This difference in relation to protein expression pattern is consequent with the known posttranscriptional regulation of TH expression. The most representative example of a novel positive region is the conspicuous mRNA expression in both medial and lateral ganglionic eminences. This result agrees with reports describing the capacity of striatal stem cells (that is, located at the lateral ganglionic eminence) to become dopaminergic in vitro. Other regions include the isthmic mantle layer and the early floor plate of the midbrain,caudal forebrain. On the whole, the expression map we have obtained opens new perspectives for evolutionary/comparative studies, as well as for therapeutic approaches looking for potentially dopaminergic cells. Developmental Dynamics 234:709,717, 2005. © 2005 Wiley-Liss, Inc. [source] Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous systemDEVELOPMENTAL DYNAMICS, Issue 3 2005Carles Gaston-Massuet Abstract Zic genes comprise a family of transcription factors, characterized by the presence of a zinc-finger domain containing two cysteines and two histidines (C2-H2). Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention. We studied the expression of Zic4 by in situ hybridization during mouse embryogenesis. Zic4 mRNA was first detected at low intensity at embryonic day (E) 9 and, by E10.5, expression was up-regulated in the dorsal midline of the forebrain with a strong, expanded expression domain at the boundary between the diencephalon and telencephalon, the septum, and the lamina terminalis. The choroid plexus of the third ventricle expresses Zic4, as does the dorsal part of the spinal neural tube, excluding the roof plate. The dorsal sclerotome and the dorsomedial lip of the dermomyotome also express Zic4 whereas dorsal root ganglia are negative. At E12.5, Zic4 continues to be expressed in the midline of the forebrain and in the dorsal spinal neural tube. Postnatally, Zic4 is expressed in the granule cells of the postnatal day 2 cerebellum, and in the periventricular thalamus and anterior end of the superior colliculus. We conclude that Zic4 has an expression pattern distinct from, but partly overlapping with, other members of the Zic gene family. Developmental Dynamics 233:1110,1115, 2005. © 2005 Wiley-Liss, Inc. [source] Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain developmentDEVELOPMENTAL DYNAMICS, Issue 2 2005Daniel W. Seufert Abstract Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development. We verified that xArx is expressed in the prospective diencephalon, as the forebrain is patterned and specified during neural plate stages. Expression spreads into the ventral and medial telencephalon as development proceeds through neural tube and tadpole stages. Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia. Additionally, there is a delay in expression of many molecular markers of brain and retinal development. However, expression of some markers, dlx5 and wnt8b, was enhanced in xArx -injected embryos. Loss-of-function experiments indicated that xArx was necessary for normal forebrain development. Expansion of wnt8b expression depended on xArx function as a transcriptional repressor, whereas ectopic expression of dlx5, accompanied by development of ectopic otic structures, depended on function of Arx as a transcriptional activator. These results suggest that Arx acts as a bifunctional transcriptional regulator in brain development. Developmental Dynamics 232:313,324, 2005. © 2004 Wiley-Liss, Inc. [source] Expression of a novel zebrafish zinc finger gene, gli2b, is affected in Hedgehog and Notch signaling related mutants during embryonic developmentDEVELOPMENTAL DYNAMICS, Issue 2 2005Zhiyuan Ke Abstract Gli zinc-finger proteins are known as downstream mediators of the evolutionary conserved Hedgehog pathway. In zebrafish, gli2 functions differently from Gli2 in mammals. This difference could be due to the gli2 duplication in teleosts evolution and partial redundancy between two duplicated genes. Here, we report a novel zebrafish gli2 -like cDNA. Its structure, genetic location, and distinct expression pattern in the central nervous system suggested that this gene might represent a second gli2 of teleosts, and we named it gli2b. gli2b was expressed in the neural keel, excluding the forebrain,midbrain boundary, while gli2 expression complemented this pattern. After 24 hours postfertilization, several specific domains of gli2b expression were observed in the lateral and medial hindbrain and hypothalamus. In mutants affecting the Hedgehog and Notch signaling pathways, gli2b expression was either disrupted or extended in different regions. Developmental Dynamics 232:479,486, 2005. © 2005 Wiley-Liss, Inc. [source] Phenotypic analyses of mouse embryos with ubiquitous expression of Oct4: Effects on mid,hindbrain patterning and gene expressionDEVELOPMENTAL DYNAMICS, Issue 1 2005Verónica Ramos-Mejía Abstract Oct4 is a transcription factor that has been associated with pluripotency and fate determination in the initial cell lineages of mammals. On the other hand, Pou2, the ortholog of Oct4 in zebrafish, serves additional later functions during brain development acting as a differentiation switch. In mice, Oct4 is expressed throughout the neural plate of embryos until embryonic day (E) 8.0. In this study, we produced transgenic mouse embryos that ubiquitously express Oct4 and analyzed the consequences during development. We show that, at E8.0, a higher dosage of Oct4 in the neuroectoderm is sufficient to transiently alter mid,hindbrain patterning and produced a strong up-regulation of Pax2, indicating that Oct4 can regulate this gene in vivo. After E9.5, ectopic Oct4 in this region produced cell death and affected the development of the forebrain, suggesting that, at these later stages, Oct4 down-regulation is necessary for normal development to proceed. The phenotype of the transgenic embryos was also accompanied with an increase of Fgf8 expression in several of its endogenous domains, suggesting the possibility that Oct4 can participate in the regulation of expression of this ligand. Our observations support the hypothesis that Oct4, like zebrafish Pou2, has a conserved function during early brain patterning in mouse. Developmental Dynamics 232:180,190, 2005. © 2004 Wiley-Liss, Inc. [source] Zinc finger gene fez - like functions in the formation of subplate neurons and thalamocortical axonsDEVELOPMENTAL DYNAMICS, Issue 3 2004Tustomu Hirata Abstract fez - like (fezl) is a forebrain-expressed zinc finger gene required for the formation of the hypothalamic dopaminergic and serotonergic (monoaminergic) neurons in zebrafish. To reveal its function in mammals, we analyzed the expression of the mouse orthologue of fezl and generated fezl -deficient mice by homologous recombination. Mouse fezl was expressed specifically in the forebrain from embryonic day 8.5. At mid-gestation, fezl expression was detected in subdomains of the forebrain, including the dorsal telencephalon and ventral diencephalon. Unlike the zebrafish fezl mutant too few, the fezl -deficient mice displayed normal development of hypothalamic monoaminergic neurons, but showed abnormal "hyperactive" behavior. In fezl,/, mice, the thalamocortical axons (TCA) were reduced in number and aberrantly projected to the cortex. These mutants had a reduced number of subplate neurons, which are involved in guiding the TCA from the dorsal thalamus, although the subplate neurons were born normally. These results suggest that fezl is required for differentiation or survival of the subplate neurons, and reduction of the subplate neurons in fezl -deficient mice leads to abnormal development of the TCA, providing a possible link between the transcriptional regulation of forebrain development and hyperactive behavior. Developmental Dynamics 230:546,556, 2004. © 2004 Wiley-Liss, Inc. [source] Characterization of the plasticity-related gene, Arc, in the frog brainDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2010Lisa A. Mangiamele Abstract In mammals, expression of the immediate early gene Arc/Arg3.1 in the brain is induced by exposure to novel environments, reception of sensory stimuli, and production of learned behaviors, suggesting a potentially important role in neural and behavioral plasticity. To date, Arc has only been characterized in a few species of mammals and birds, which limits our ability to understand its role in modifying behavior. To begin to address this gap, we identified Arc in two frog species, Xenopus tropicalis and Physalaemus pustulosus, and characterized its expression in the brain of P. pustulosus. We found that the predicted protein for frog Arc shared 60% sequence similarity with Arc in other vertebrates, and we observed high Arc expression in the forebrain, but not the midbrain or hindbrain, of female túngara frogs sacrificed at breeding ponds. We also examined the time-course of Arc induction in the medial pallium, the homologue of the mammalian hippocampus, in response to a recording of a P. pustulosus mating chorus and found that accumulation of Arc mRNA peaked 0.75 h following stimulus onset. We found that the mating chorus also induced Arc expression in the lateral and ventral pallia and the medial septum, but not in the striatum, hypothalamus, or auditory midbrain. Finally, we examined acoustically induced Arc expression in response to different types of mating calls and found that Arc expression levels in the pallium and septum did not vary with the biological relevance or acoustic complexity of the signal. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 813,825, 2010 [source] Evidence for neural stem cells in the medaka optic tectum proliferation zones,DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2010Alessandro Alunni Abstract Few adult neural stem cells have been characterized in vertebrates. Although teleosts continually generate new neurons in many regions of the brain after embryogenesis, only two types of neural stem cells (NSCs) have been reported in zebrafish: glial cells in the forebrain resembling mammalian NSCs, and neuroepithelial cells in the cerebellum. Here, following our previous studies on dividing progenitors (Nguyen et al. [1999]: J Comp Neurol 413:385,404.), we further evidenced NSCs in the optic tectum (OT) of juvenile and adult in the medaka, Oryzias latipes. To detect very slowly cycling progenitors, we did not use the commonly used BrdU/PCNA protocol, in which PCNA may not be present during a transiently quiescent state. Instead, we report the optimizations of several protocols involving long subsequent incubations with two thymidine analogs (IdU and CldU) interspaced with long chase times between incubations. These protocols allowed us to discriminate and localize fast and slow cycling cells in OT of juvenile and adult in the medaka. Furthermore, we showed that adult OT progenitors are not glia, as they express neither brain lipid-binding protein (BLBP) nor glial fibrillary acidic protein (GFAP). We also showed that expression of pluripotency-associated markers (Sox2, Musashi1 and Bmi1) colocalized with OT progenitors. Finally, we described the spatio-temporally ordered population of NSCs and progenitors in the medaka OT. Hence, the medaka appears as an invaluable model for studying neural progenitors that will open the way to further exciting comparative studies of neural stem cells in vertebrates. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 693,713, 2010 [source] The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrainDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2010Dino P. Leone Abstract Progenitor cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing forebrain give rise to neurons and glial cells, and are characterized by distinct morphologies and proliferative behaviors. The mechanisms that distinguish VZ and SVZ progenitors are not well understood, although the homeodomain transcription factor Cux2 and Cyclin D2, a core component of the cell cycle machinery, are specifically involved in controlling SVZ cell proliferation. Rho GTPases have been implicated in regulating the proliferation, differentiation, and migration of many cell types, and one family member, Cdc42, affects the polarity and proliferation of radial glial cells in the VZ. Here, we show that another family member, Rac1, is required for the normal proliferation and differentiation of SVZ progenitors and for survival of both VZ and SVZ progenitors. A forebrain-specific loss of Rac1 leads to an SVZ-specific reduction in proliferation, a concomitant increase in cell cycle exit, and premature differentiation. In Rac1 mutants, the SVZ and VZ can no longer be delineated, but rather fuse to become a single compact zone of intermingled cells. Cyclin D2 expression, which is normally expressed by both VZ and SVZ progenitors, is reduced in Rac1 mutants, suggesting that the mutant cells differentiate precociously. Rac1-deficient mice can still generate SVZ-derived upper layer neurons, indicating that Rac1 is not required for the acquisition of upper layer neuronal fates, but instead is needed for the normal regulation of proliferation by progenitor cells in the SVZ. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 659,678, 2010 [source] Transient expression of serotonin 5-HT4 receptors in the mouse developing thalamocortical projectionsDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2010Erin R. Slaten Abstract The serotonin 5-HT4 receptor (5-HT4 -R) is an unusually complex G-protein coupled receptor that is likely to play important roles in brain development and that may underlie the comorbidity of central and peripheral abnormalities in some developmental disorders. We studied the expression of 5-HT4 -Rs in the developing mouse forebrain at embryonic days 13, 15, 17, and at postnatal days 3 and 14 by using immunohistochemistry, tract tracing, and quantitative RT-PCR. The developing thalamocortical projections transiently expressed 5-HT4 -Rs in the embryonic brain and the 5-HT4 -R expression in the forebrain changed from axonal to somatic around birth. From embryonic days 13,17, the forebrain mRNA levels of the 5-HT4(a) -R and 5-HT4(b) -R splice variants increased nine- and fivefold, respectively, whereas the levels of the 5-HT4(e) -R and 5-HT4(f) -R variants remained relatively low throughout the studied period of embryonic development. These results suggest that during development 5-HT4 -R expression undergoes a dynamic regulation and that this regulation may be important for the normal development of sensory and limbic processing. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010. [source] The development of stimulus-specific auditory responses requires song exposure in male but not female zebra finchesDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2010Kristen K. Maul Abstract Juvenile male zebra finches develop their song by imitation. Females do not sing but are attracted to males' songs. With functional magnetic resonance imaging and event-related potentials we tested how early auditory experience shapes responses in the auditory forebrain of the adult bird. Adult male birds kept in isolation over the sensitive period for song learning showed no consistency in auditory responses to conspecific songs, calls, and syllables. Thirty seconds of song playback each day over development, which is sufficient to induce song imitation, was also sufficient to shape stimulus-specific responses. Strikingly, adult females kept in isolation over development showed responses similar to those of males that were exposed to songs. We suggest that early auditory experience with songs may be required to tune perception toward conspecific songs in males, whereas in females song selectivity develops even without prior exposure to song. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010 [source] Developmental shifts in gene expression in the auditory forebrain during the sensitive period for song learningDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2009Sarah E. London Abstract A male zebra finch begins to learn to sing by memorizing a tutor's song during a sensitive period in juvenile development. Tutor song memorization requires molecular signaling within the auditory forebrain. Using microarray and in situ hybridizations, we tested whether the auditory forebrain at an age just before tutoring expresses a different set of genes compared with later life after song learning has ceased. Microarray analysis revealed differences in expression of thousands of genes in the male auditory forebrain at posthatch day 20 (P20) compared with adulthood. Furthermore, song playbacks had essentially no impact on gene expression in P20 auditory forebrain, but altered expression of hundreds of genes in adults. Most genes that were song-responsive in adults were expressed at constitutively high levels at P20. Using in situ hybridization with a representative sample of 44 probes, we confirmed these effects and found that birds at P20 and P45 were similar in their gene expression patterns. Additionally, eight of the probes showed male,female differences in expression. We conclude that the developing auditory forebrain is in a very different molecular state from the adult, despite its relatively mature gross morphology and electrophysiological responsiveness to song stimuli. Developmental gene expression changes may contribute to fine-tuning of cellular and molecular properties necessary for song learning. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Myosin-II negatively regulates minor process extension and the temporal development of neuronal polarityDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2009K.M. Kollins Abstract The earliest stage in the development of neuronal polarity is characterized by extension of undifferentiated "minor processes" (MPs), which subsequently differentiate into the axon and dendrites. We investigated the role of the myosin II motor protein in MP extension using forebrain and hippocampal neuron cultures. Chronic treatment of neurons with the myosin II ATPase inhibitor blebbistatin increased MP length, which was also seen in myosin IIB knockouts. Through live-cell imaging, we demonstrate that myosin II inhibition triggers rapid minor process extension to a maximum length range. Myosin II activity is determined by phosphorylation of its regulatory light chains (rMLC) and mediated by myosin light chain kinase (MLCK) or RhoA-kinase (ROCK). Pharmacological inhibition of MLCK or ROCK increased MP length moderately, with combined inhibition of these kinases resulting in an additive increase in MP length similar to the effect of direct inhibition of myosin II. Selective inhibition of RhoA signaling upstream of ROCK, with cell-permeable C3 transferase, increased both the length and number of MPs. To determine whether myosin II affected development of neuronal polarity, MP differentiation was examined in cultures treated with direct or indirect myosin II inhibitors. Significantly, inhibition of myosin II, MLCK, or ROCK accelerated the development of neuronal polarity. Increased myosin II activity, through constitutively active MLCK or RhoA, decreased both the length and number of MPs and, consequently, delayed or abolished the development of neuronal polarity. Together, these data indicate that myosin II negatively regulates MP extension, and the developmental time course for axonogenesis. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Distribution of progesterone receptor immunoreactivity in the midbrain and hindbrain of postnatal ratsDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2008Princy S. Quadros Abstract Nuclear steroid hormone receptors are powerful transcription factors and therefore have the potential to influence and regulate fundamental processes of neural development. The expression of progesterone receptors (PR) has been described in the developing forebrain of rats and mice, and the mammalian brain may be exposed to significant amounts of progesterone, either from maternal sources and/or de novo synthesis of progesterone from cholesterol within the brain. The present study examined the distribution of PR immunoreactive (PRir) cells within the midbrain and hindbrain of postnatal rats. The results demonstrate that PR is transiently expressed within the first 2 weeks of life in specific motor, sensory and reticular core nuclei as well as within midbrain dopaminergic cell groups such as the substantia nigra and the ventral tegmental area. Additionally, robust PRir was observed in cells of the lower rhombic lip, a transient structure giving rise to precerebellar nuclei. These results suggest that progestins and progesterone receptors may play a fundamental role in the postnatal development of numerous midbrain and hindbrain nuclei, including some areas implicated in human disorders. Additionally, these findings contribute to the increasing evidence that steroid hormones and their receptors influence neural development in a wide range of brain areas, including many not typically associated with reproduction or neuroendocrine function. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Social experience organizes parallel networks in sensory and limbic forebrainDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Eun-Jin Yang Abstract Successful social behavior can directly influence an individual's reproductive success. Therefore, many organisms readily modify social behavior based on past experience. The neural changes induced by social experience, however, remain to be fully elucidated. We hypothesize that social modulation of neural systems not only occurs at the level of individual nuclei, but also of functional networks, and their relationships with behavior. We used the green anole lizard (Anolis carolinensis), which displays stereotyped, visually triggered social behaviors particularly suitable for comparisons of multiple functional networks in a social context, to test whether repeated aggressive interactions modify behavior and metabolic activity in limbic,hypothalamic and sensory forebrain regions, assessed by quantitative cytochrome oxidase (a slowly accumulating endogenous metabolic marker) histochemistry. We found that aggressive interactions potentiate aggressive behavior, induce changes in activities of individual nuclei, and organize context-specific functional neural networks. Surprisingly, this experiential effect is not only present in a limbic,hypothalamic network, but also extends to a sensory forebrain network directly relevant to the behavioral expression. Our results suggest that social experience modulates organisms' social behavior via modifying sensory and limbic neural systems in parallel both at the levels of individual regions and networks, potentially biasing perceptual as well as limbic processing. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Immediate early gene (ZENK, Arc) expression in the auditory forebrain of female canaries varies in response to male song qualityDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2005Stefan Leitner Abstract In male songbirds, the song control pathway in the forebrain is responsible for song production and learning, and in females it is associated with the perception and discrimination of male song. However, experiments using the expression of immediate early genes (IEGs) reveal the activation of brain regions outside the song control system, in particular the caudomedial nidopallium (NCM) and the caudomedial mesopallium (CMM). In this study on female canaries, we investigate the role of these two regions in relation to playback of male songs of different quality. Male canaries produce elaborate songs and some contain syllables with a more complex structure (sexy syllables) that induce females to perform copulation solicitation displays (CSD) as an invitation to mate. Females were first exposed to playback of a range of songs of different quality, before they were finally tested with playback of songs containing either sexy or nonsexy syllables. We then sectioned the brains and used in situ hybridization to reveal brain regions that express the IEGs ZENK or Arc. In CMM, expression of ZENK mRNA was significantly higher in females that last heard sexy syllables compared to those that last heard nonsexy syllables, but this was not the case for NCM. Expression of Arc mRNA revealed no differences in either CMM or NCM in both experimental groups. These results provide evidence that in female canaries CMM is involved in female perception and discrimination of male song quality through a mechanism of memory reconsolidation. The results also have further implications for the evolution of complex songs by sexual selection and female choice. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 [source] Syllable repertoire and the size of the song control system in captive canaries (Serinus canaria)DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2004Stefan Leitner Abstract In songbirds, there is considerable interest in relationships between song structure and the size of the song control system in the forebrain. In male canaries, earlier studies have reported that repertoire size increased with age, and positive correlations were obtained between repertoire size and the volume of song control nuclei such as high vocal center (HVC). Here we investigate whether age has an effect upon both the song structure and the morphology of two song control nuclei [HVC and robustus archistriatalis (RA)] that are important in song production. We recorded songs from an aviary population of 1- and 2-year-old male domesticated canaries. We found that repertoire size, number of sexually attractive (sexy) syllables, and size of song nuclei did not differ between 1- and 2-year-old males. Neither did we find significant correlations between syllable repertoire size and the size of the song control nuclei. However, HVC size was positively correlated with the proportion of sexy syllables in the repertoires of 2-year-old males. Some older males may enhance vocal performance by modifying the control of syllables rather than by increasing repertoire size or neural space. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 21,27, 2004 [source] Female canaries that respond and discriminate more between male songs of different quality have a larger song control nucleus (HVC) in the brainDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2002Stefan Leitner Abstract In male songbirds the song control pathway in the forebrain is responsible for song production and learning. In most species, females do not sing and have smaller nuclei in the song control pathway. Although the function of the pathway in females is assumed to be associated with the perception of male song, there is little direct evidence to support this view. In this study on female canaries, we investigate the role of two key nuclei in the song control pathway (HVC and lMAN) in relation to playback of male song. Male canaries produce elaborate songs that function to attract and stimulate females. The songs are constructed from smaller units called syllables, and special syllables with a more complex structure (sexy syllables) are known to induce females to perform copulation solicitation displays (CSD) as an invitation to mate. By using computer-edited experimental songs, we first show that females discriminate between songs by producing significantly more CSD to those containing sexy syllables. We then sectioned the brains and used in situ hybridization to reveal song nuclei containing androgen receptors. We report positive correlations between the size of HVC and both total CSD response and the amount of discrimination between sexy and nonsexy songs. We found no such relationships between these measures and the size of lMAN. These results provide some evidence to support the view that, in female canaries HVC is involved in female perception and discrimination of male song. The results also have implications for the evolution of complex male songs by sexual selection and female choice. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 294,301, 2002 [source] Changes in mid-to-late latency auditory evoked reponses in the chicken during neural maturationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2010Rebbekah Atkinson Abstract Utilizing the special advantages offered by the protracted maturation of neural circuits in chicken forebrain this study investigates the functional consequence of maturation using auditory evoked response potentials (AERPs) in behaving animals. Repeated measures AERP recordings were undertaken between weeks 1 and 8 posthatch. Quantitative analysis revealed a significant decrease in amplitude of the positive AERP component and a decrease in latency of the negative AERP component with maturation. AERPs were also utilized to investigate perturbed maturation via the induction of chemically induced hypothyroidism. Results from this study showed that the induction of late onset hypothyroidism produces measurable effects on the chicken AERP consistent with perturbation in maturation of neuronal circuits and synapses. This suggests that AERPs may be useful noninvasive functional measures of brain maturation that can be used to study the effects of endogenous or exogenous factors on brain maturation in the chicken. Since human brain also exhibits a protracted maturation period the availability of a well-characterized animal model for protracted brain maturation provides an opportunity to identify molecules, genes and environmental factors that are important in the regulation of maturation. The protracted maturation of neuronal circuits observed in chicken forebrain offers such a model. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 52: 24,34, 2010 [source] The cortex in multidimensional space: where do cortical areas come from?DEVELOPMENTAL SCIENCE, Issue 2 2001Marcy A. Kingsbury The concept of a cortical ,area' as a discrete phylogenetic, developmental and computational unit is evaluated. Evidence including the comparative organization of the forebrain in vertebrates, the organization of cortex in different mammals, the scaling of the areas of the isocortex in mammals, and the early molecular differentiation of the cortex all suggest a special status for the primary sensory cortical areas, particularly the visual cortex. Furthermore, the overlapping gradients of early molecular expression and the patterning of cortical structure and connectivity by thalamic input suggest a new view of cortical organization that is different from the traditional view of a developmentally mosaic cortex; this view proposes that distinct cortical areas arise combinatorily from the multiple overlapping processes imposed upon the developing cortex. [source] | |||||||||||||||||||||||||||||||