Neurodevelopmental expression and localization of the cellular prion protein in the central nervous system of the mouseBenvegnù, Stefano; Poggiolini, Ilaria; Legname, Giuseppe
doi: 10.1002/cne.22388pmid: N/A
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by PrPSc, or prion, an abnormally folded form of the cellular prion protein (PrPC). The abundant expression of PrPC in the central nervous system (CNS) is a requirement for prion replication, yet despite years of intensive research the physiological function of PrPC still remains unclear. Several routes of investigation point out a potential role for PrPC in axon growth and neuronal development. Thus, we undertook a detailed analysis of the spatial and temporal expression of PrPC during mouse CNS development. Our findings show regional differences of the expression of PrP, with some specific white matter structures showing the earliest and highest expression of PrPC. Indeed, all these regions are part of the thalamolimbic neurocircuitry, suggesting a potential role of PrPC in the development and functioning of this specific brain system. J. Comp. Neurol. 518:1879–1891, 2010. © 2010 Wiley‐Liss, Inc.
Neurodevelopmental expression and localization of the cellular prion protein in the central nervous system of the mouseBenvegnù, Stefano; Poggiolini, Ilaria; Legname, Giuseppe
doi: 10.1002/cne.22357pmid: 20394048
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by PrPSc, or prion, an abnormally folded form of the cellular prion protein (PrPC). The abundant expression of PrPC in the central nervous system (CNS) is a requirement for prion replication, yet despite years of intensive research the physiological function of PrPC still remains unclear. Several routes of investigation point out a potential role for PrPC in axon growth and neuronal development. Thus, we undertook a detailed analysis of the spatial and temporal expression of PrPC during mouse CNS development. Our findings show regional differences of the expression of PrP, with some specific white matter structures showing the earliest and highest expression of PrPC. Indeed, all these regions are part of the thalamolimbic neurocircuitry, suggesting a potential role of PrPC in the development and functioning of this specific brain system. J. Comp. Neurol. 518:1879–1891, 2010. © 2010 Wiley‐Liss, Inc.
Heat shock protein 25 expression and preferential Purkinje cell survival in the lurcher mutant mouse cerebellumDuffin, C.A.; McFarland, R.; Sarna, J.R.; Vogel, M.W.; Armstrong, C.L.
doi: 10.1002/cne.22309pmid: 20394049
The spatial organization of the mouse cerebellum into transverse zones and parasagittal stripes is reflected during the temporal progression of Purkinje cell death in the Lurcher mutant mouse (+/Lc). Neurodegeneration in the +/Lc mutant is apparent by the second postnatal week and is initially seen in all four transverse zones: the anterior (lobules I–V), central (lobules VI, VII), posterior (lobules VIII, dorsal IX), and nodular (ventral lobule IX and lobule X) zone. However, from postnatal day (P)25–P36, Purkinje cell loss proceeds more rapidly in the anterior zone, followed by the posterior and central zones, and is significantly delayed in the nodular zone. Coronal sections through the +/Lc cerebellum reveal that surviving Purkinje cells are restricted to the paraflocculus/flocculus and the nodular zone and could be detected as late as P146 (∼5 months). Within this region, the pattern of preferentially surviving calbindin‐immunoreactive Purkinje cells reflects the expression of the constitutively expressed small heat shock protein HSP25 in the wild‐type cerebellum. Although the role of constitutively expressed HSP25 in the wild‐type cerebellum is not clear, it appears to play a neuroprotective role in the flocculonodular region of the +/Lc mutant cerebellum as the percentage of surviving Purkinje cells that are HSP25‐immunopositive significantly increases over time. J. Comp. Neurol. 518:1892–1907, 2010. © 2009 Wiley‐Liss, Inc.
Ultrastructural localization of high‐affinity choline transporter in the rat anteroventral thalamus and ventral tegmental area: Differences in axon morphology and transporter distributionHolmstrand, Ericka C.; Asafu‐Adjei, Josephine; Sampson, Allan R.; Blakely, Randy D.; Sesack, Susan R.
doi: 10.1002/cne.22310pmid: 20394050
The high‐affinity choline transporter (CHT) is a protein integral to the function of cholinergic neurons in the central nervous system (CNS). We examined the ultrastructural distribution of CHT in axonal arborizations of the mesopontine tegmental cholinergic neurons, a cell group in which CHT expression has yet to be characterized at the electron microscopic level. By using silver‐enhanced immunogold detection, we compared the morphological characteristics of CHT‐immunoreactive axon varicosities specifically within the anteroventral thalamus (AVN) and the ventral tegmental area (VTA). We found that CHT‐immunoreactive axon varicosities in the AVN displayed a smaller cross‐sectional area and a lower frequency of synapse formation and dense‐cored vesicle content than CHT‐labeled profiles in the VTA. We further examined the subcellular distribution of CHT and observed that immunoreactivity for this protein was predominantly localized to synaptic vesicles and minimally to the plasma membrane of axons in both regions. This pattern is consistent with the subcellular distribution of CHT displayed in other cholinergic systems. Axons in the AVN showed significantly higher levels of CHT immunoreactivity than those in the VTA and correspondingly displayed a higher level of membrane CHT labeling. These novel findings have important implications for elucidating regional differences in cholinergic signaling within the thalamic and brainstem targets of the mesopontine cholinergic system. J. Comp. Neurol. 518:1908–1924, 2010. © 2010 Wiley‐Liss, Inc.
PDF receptor expression reveals direct interactions between circadian oscillators in drosophilaIm, Seol Hee; Taghert, Paul H.
doi: 10.1002/cne.22311pmid: 20394051
Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment‐dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4‐mediated rescue of pdfr phenotypes using a UAS‐PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a ∼70‐kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non‐pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF‐expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non‐neuronal cells that resides at the base of the eye. J. Comp. Neurol. 518:1925–1945, 2010. © 2009 Wiley‐Liss, Inc.
Hypoglossal motor neurons display a reduced calcium increase after axotomy in mice with upregulated parvalbuminPaizs, Melinda; Engelhardt, József I.; Katarova, Zója; Siklós, László
doi: 10.1002/cne.22312pmid: 20394052
Motor neurons that exhibit differences in vulnerability to degeneration have been identified in motor neuron disease and in its animal models. The oculomotor and hypoglossal neurons are regarded as the prototypes of the resistant and susceptible cell types, respectively. Because an increase in the level of intracellular calcium has been proposed as a feature amplifying degenerative processes, we earlier studied the calcium increase in these motor neurons after axotomy in Balb/c mice and demonstrated a correlation between the susceptibility to degeneration and the intracellular calcium increase, with an inverse relation with the calcium buffering capacity, characterized by the parvalbumin or calbindin‐D28k content. Because the differential susceptibility of the cells might also be attributed to their different cellular environments, in the present experiments, with the aim of verifying directly that a higher calcium buffering capacity is indeed responsible for the enhanced resistance, motor neurons were studied in their original milieu in mice with a genetically increased parvalbumin level. The changes in intracellular calcium level of the hypoglossal and oculomotor neurons after axotomy were studied electron microscopically at a 21‐day interval after axotomy, during which time no significant calcium increase was detected in the hypoglossal motor neurons, the response being similar to that of the oculomotor neurons. The hypoglossal motor neurons of the parental mice, used as positive controls, exhibited a transient, significant elevation of calcium. These data provide more direct evidence of the protective role of parvalbumin against the degeneration mediated by a calcium increase in the acute injury of motor neurons. J. Comp. Neurol. 518:1946–1961, 2010. © 2009 Wiley‐Liss, Inc.
Somatostatin interneurons delineate the inner part of the external plexiform layer in the mouse main olfactory bulbLepousez, Gabriel; Csaba, Zsolt; Bernard, Véronique; Loudes, Catherine; Videau, Catherine; Lacombe, Joelle; Epelbaum, Jacques; Viollet, Cécile
doi: 10.1002/cne.22317pmid: 20394054
Neuropeptides play a major role in the modulation of information processing in neural networks. Somatostatin, one of the most concentrated neuropeptides in the brain, is found in many sensory systems including the olfactory pathway. However, its cellular distribution in the mouse main olfactory bulb (MOB) is yet to be characterized. Here we show that ≈95% of mouse bulbar somatostatin‐immunoreactive (SRIF‐ir) cells describe a homogeneous population of interneurons. These are restricted to the inner lamina of the external plexiform layer (iEPL) with dendritic field strictly confined to the region. iEPL SRIF‐ir neurons share some morphological features of Van Gehuchten short‐axon cells, and always express glutamic acid decarboxylase, calretinin, and vasoactive intestinal peptide. One‐half of SRIF‐ir neurons are parvalbumin‐ir, revealing an atypical neurochemical profile when compared to SRIF‐ir interneurons of other forebrain regions such as cortex or hippocampus. Somatostatin is also present in fibers and in a few sparse presumptive deep short‐axon cells in the granule cell layer (GCL), which were previously reported in other mammalian species. The spatial distribution of somatostatin interneurons in the MOB iEPL clearly outlines the region where lateral dendrites of mitral cells interact with GCL inhibitory interneurons through dendrodendritic reciprocal synapses. Symmetrical and asymmetrical synaptic contacts occur between SRIF‐ir dendrites and mitral cell dendrites. Such restricted localization of somatostatin interneurons and connectivity in the bulbar synaptic network strongly suggest that the peptide plays a functional role in the modulation of olfactory processing. J. Comp. Neurol. 518:1976–1994, 2010. © 2010 Wiley‐Liss, Inc.
Language‐related Cntnap2 gene is differentially expressed in sexually dimorphic song nuclei essential for vocal learning in songbirdsPanaitof, S. Carmen; Abrahams, Brett S.; Dong, Hongmei; Geschwind, Daniel H.; White, Stephanie A.
doi: 10.1002/cne.22318pmid: 20394055
Multiple studies, involving distinct clinical populations, implicate contactin associated protein‐like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language. J. Comp. Neurol. 518:1995–2018, 2010. © 2010 Wiley‐Liss, Inc.
Netrin 1 provides a chemoattractive cue for the ventral migration of GnRH neurons in the chick forebrainMurakami, Shizuko; Ohki‐Hamazaki, Hiroko; Watanabe, Keisuke; Ikenaka, Kazuhiro; Ono, Katsuhiko
doi: 10.1002/cne.22319pmid: 20394056
Hypothalamic gonadotropin‐releasing hormone (GnRH) neurons originate in the olfactory placode and migrate to the forebrain during embryonic development. We found that GnRH neurons migrated in two different modes in the chick medial telencephalon: they initially underwent axophilic migration in association with a subset of olfactory fibers in a dorsocaudal direction. This was followed by ventrally directed tangential migration to the basal forebrain. Since many of the ventrally migrating GnRH neurons did not follow distinct fiber fascicles, it is proposed that diffusible guidance molecules played a role in this migratory process. A long‐range diffusible factor, netrin 1, was expressed in the lower part of the commissural plate and the subpallial septum, but not along the axophilic migratory route of GnRH neurons. Failure of ventrally directed migration of GnRH neurons and their misrouting to the dorsomedial forebrain was induced by misexpression of netrin 1 in the dorsocaudal part of the septum near the top of the commissural plate, which is where the migration of GnRH neurons changed to a ventral direction. In such cases, a subset of olfactory fibers also extended, but close contact between aberrant fibers and misrouted GnRH neurons did not exist. A coculture experiment demonstrated that netrin 1 exerts an attractive effect on migrating GnRH neurons. These results provide evidence that netrin 1 acts as chemoattractant to migrating GnRH neurons at the dorsocaudal part of the septum and has the potential to regulate the ventral migration of GnRH neurons to the ventral septum and the preoptic area. J. Comp. Neurol. 518:2019–2034, 2010. © 2010 Wiley‐Liss, Inc.