Localization of TrkC to Schwann cells and effects of neurotrophin‐3 signaling at neuromuscular synapsesHess, Darren M.; Scott, Marion O.; Potluri, Srilatha; Pitts, Elizabeth Vernon; Cisterni, Claire; Balice‐Gordon, Rita J.
doi: 10.1002/cne.21163pmid: 17278135
Neurotrophins and their receptors, the Trks, are differentially expressed among the cell types that make up neuromuscular and other synapses, but the function and directionality of neurotrophin signaling at synapses are poorly understood. Here we demonstrate, via immunostaining, Western blotting, and RT‐PCR analyses, that TrkC, the receptor for neurotrophin‐3 (NT3), is expressed by mouse perisynaptic and myelinating Schwann cells from birth through adulthood and is unaltered after denervation. Analyses of transgenic mice in which the NT3 coding sequence is replaced by lacZ showed that NT3 is expressed in motor neurons and Schwann cells during perinatal development, but not in adult mice. In muscle, NT3 is expressed by intrafusal muscle fibers within spindles, as has been previously reported. Surprisingly, NT3 is also expressed in extrafusal muscle fibers during perinatal life and in adults. Genetic approaches were used to explore the roles of NT3 and TrkC signaling at neuromuscular synapses. Overexpression of NT3 in muscle fibers during development resulted in an increased number of perisynaptic Schwann cells at neuromuscular synapses, without altering synaptic size, suggesting that muscle‐derived NT3 might act as a mitogen or trophic factor for Schwann cells. Conditional deletion of NT3 from motor neurons did not alter the number of Schwann cells or other aspects of neuromuscular synaptic structure, suggesting that motor‐neuron‐derived NT3 is not required for normal development of perisynaptic Schwann cells or synapses. Together, these results demonstrate that NT3 expression is developmentally regulated in skeletal muscle and may modulate the number of Schwann cells at neuromuscular synapses. J. Comp. Neurol. 501:465–482, 2007. © 2007 Wiley‐Liss, Inc.
Cadherin expression in the developing mouse olfactory systemAkins, Michael R.; Benson, Deanna L.; Greer, Charles A.
doi: 10.1002/cne.21270pmid: 17278136
Although odor receptors have been implicated in establishing the topography of olfactory sensory neurons (OSNs) in the olfactory bulb (OB), it is likely other molecules are also involved. The cadherins (CDHs) are a large family of cell adhesion molecules that mediate cell:cell interactions elsewhere in the central nervous system. However, their distribution and role in the olfactory system have remained largely unexplored. We previously demonstrated that intracellular binding partners of cadherins, the catenins, have unique spatiotemporal patterns of expression in the developing olfactory system. To further our understanding of cadherin function within the developing olfactory system, we now report on the localization of 11 classical cadherins—CDH1, 2, 3, 4, 5, 6, 8, 10, 11, 13, and 15. We demonstrate the expression of all but CDH5 and CDH15 in neuronal and/or glial cells in primary olfactory structures. CDH1 and CDH2 are expressed by OSNs; CDH2 expression closely parallels that seen for γ‐catenin in OSN axons. CDH3 and CDH11 are expressed by olfactory ensheathing glia, which surround OSN axons in the outer OB. CDH2, CDH4, and CDH6 are expressed within neuropil. CDH2, CDH4, CDH6, CDH8, CDH10, CDH11, and CDH13 are expressed by projection neurons within the main and accessory OBs. We conclude that cadherin proteins in the developing olfactory system are positioned to underlie the formation of the odorant map and local circuits within the OB. J. Comp. Neurol. 501:483–497, 2007. © 2007 Wiley‐Liss, Inc.
Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and agingBeramendi, Ana; Peron, Samantha; Casanova, Gabriela; Reggiani, Carlo; Cantera, Rafael
doi: 10.1002/cne.21253pmid: 17278125
The neuromuscular junction (NMJ) of Drosophila melanogaster has been established as a productive model for the study of synaptogenesis, synaptic plasticity, vesicle recycling, and other synaptic functions in embryos and larvae. It also has potential for the study of long‐term plasticity during adult life and degenerative processes associated with aging. Here we provide a detailed description of the morphology and ultrastructure of the NMJ on abdominal dorsal longitudinal muscles throughout adult life from eclosion to senescence. In contrast to the case in the larva, the predominant type of terminals in these muscles in the adult fly consists of only two or three branches with tightly packed synaptic boutons. We observed qualitative and quantitative changes as mean bouton size increased gradually during adulthood, and the largest boutons were present in the old fly. The length of nerve branches first increased and thereafter decreased gradually during most of adult life. Branch diameter also decreased progressively, but branch number did not change. The subsynaptic reticulum became progressively thinner, and “naked” boutons were found in old flies. Ultrastructural traits gave indications of an age‐associated increment in autophagy, larger synaptic vesicles, and impaired endocytosis. We propose that NMJ aging in the fly correlates with impaired endocytosis and membrane dynamics. This view finds a functional correlate in flies carrying a temperature‐sensitive mutation in shibire that reversible blocks endocytosis; age significantly reduces the time required for complete paralysis and increases the time of recovery, thus confirming the age‐dependent alteration in vesicle dynamics. J. Comp. Neurol. 501:498–508, 2007. © 2007 Wiley‐Liss, Inc.
Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathwaySun, Xia; Xia, Qiang; Lai, Chun‐Hong; Shum, Daisy Kwok‐Yan; Chan, Ying‐Shing; He, Jufang
doi: 10.1002/cne.21249pmid: 17278128
To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos‐labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a γ‐aminobutyric acid type A (GABAA) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos‐labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos‐labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM‐injected cortex showed a significantly higher number of Fos‐labeled neurons than the contralateral IC. However, no difference in the number of Fos‐labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC. J. Comp. Neurol. 501:509–525, 2007. © 2007 Wiley‐Liss, Inc.
Differential distribution of the MeCP2 splice variants in the postnatal mouse brainDragich, Joanna M.; Kim, Yong‐Hwan; Arnold, Arthur P.; Schanen, N. Carolyn
doi: 10.1002/cne.21264pmid: 17278130
Mutations in the gene encoding methyl CpG binding protein 2 (MeCP2) are the primary cause of the neurodevelopmental disorder Rett syndrome (RTT). Mecp2‐deficient mice develop a neurological phenotype that recapitulates many of the symptoms of RTT, including postnatal onset of the neurological deficits. MeCP2 has two isoforms, MeCP2e1 and MeCP2e2, with distinct amino termini, which are generated by alternative splicing. We examined the distribution of the Mecp2 splice variants in the postnatal mouse brain by in situ hybridization and found regional and age‐related differences in transcript abundance. In newborn mice, signals for total Mecp2 and the Mecp2e2 transcripts were widely distributed, with overlapping expression patterns throughout the brain. Expression of the Mecp2e2 splice variant became largely restricted to nuclei within the dorsal thalamus (DT) and cortical layer V in juvenile animals, a pattern that was maintained into adulthood. In contrast, the total Mecp2 riboprobe only weakly labeled the DT and cortical layer V in juvenile and adult animals, although it heavily labeled surrounding brain regions, suggesting that Mecp2e1 is the predominant transcript outside the thalamus. Quantitative real‐time PCR was used to measure Mecp2e1 and Mecp2e2 abundance in the diencephalon of adult mice, demonstrating significantly more Mecp2e2 in the DT than in the hypothalamus, which is in agreement with the Mecp2e2 in situ hybridization. The differential distribution of the Mecp2e1 and Mecp2e2 transcripts indicates regional and developmental regulation of Mecp2 splicing in the postnatal mouse brain. J. Comp. Neurol. 501:526–542, 2007. © 2007 Wiley‐Liss, Inc.
Vestibular neurons in the rat contain imidazoleacetic acid‐ribotide, a putative neurotransmitter involved in blood pressure regulationMartinelli, Giorgio P.; Friedrich, Victor L.; Prell, George D.; Holstein, Gay R.
doi: 10.1002/cne.21271pmid: 17278132
A substantial body of research has led to the recognition that the vestibular system participates in blood pressure modulation during active movements and changes in posture, and that this modulation is effected at least partly by the caudal vestibular nuclei. The I‐4 isomer of imidazoleacetic acid‐ribotide (IAA‐RP) is a putative neurotransmitter/modulator that is thought to be an endogenous regulator of general sympathetic drive, particularly systemic blood pressure. The present study employed immunofluorescence and light and electron microscopic immunocytochemistry to visualize IAA‐RP in the vestibular nuclei of adult male rats. The results demonstrate IAA‐RP immunolabeling of subpopulations of vestibular neurons in the descending nucleus and the caudal half of the medial nucleus, with scattered immunostained vestibular neurons also present more rostrally. On the basis of double immunofluorescence staining for IAA‐RP and calbindin, many of these ribotide‐immunoreactive neurons appear to be innervated by cerebellar Purkinje cell afferents. Ultrastructural observations in the caudal vestibular nuclei confirm the IAA‐RP immunolocalization in cell bodies and dendritic processes, and in some myelinated axons and presynaptic boutons. The regional distribution of IAA‐RP immunoreactivity corresponds to the location of vestibular neurons involved in autonomic functions. The presence of IAA‐RP in those neurons suggests that they participate specifically in vestibulo‐autonomic regulation of blood pressure. The localization of immunostain in processes and terminals suggests that vestibulo‐autonomic activity is subject to local feedback control. Overall, the observations offer a chemoanatomic basis for understanding the vestibular side effects commonly experienced by patients treated with clonidine and other imidazoline‐related drugs. J. Comp. Neurol. 501:568–581, 2007. © 2007 Wiley‐Liss, Inc.
Fiber connections of the corpus glomerulosum pars rotunda, with special reference to efferent projection pattern to the inferior lobe in a percomorph teleost, tilapia (Oreochromis niloticus)Yang, Chun‐Ying; Xue, Hao‐Gang; Yoshimoto, Masami; Ito, Hironobu; Yamamoto, Naoyuki; Ozawa, Hitoshi
doi: 10.1002/cne.21261pmid: 17278137
Fiber connections of the corpus glomerulosum pars rotunda (GR) in a teleost, tilapia Oreochromis niloticus, were studied by biotinylated dextran amine injections into the GR and inferior lobe. After tracer injections into the GR, major groups of labeled somata were found bilaterally in the cortical nucleus and ipsilaterally in the nucleus intermedius. Numerous labeled terminals were found ipsilaterally in the central nucleus, nucleus of lateral recess, and diffuse nucleus (NDLI) of the inferior lobe. Some other connections were also elucidated in the present study, although these were less abundant. Notably, efferent projections to the inferior lobe were not evenly distributed within each lobar nucleus. Labeled terminals were confined to the cell body zone of central nucleus and the outer cell‐sparse layer of the nucleus of lateral recess. The rostrolateral portion of NDLI and ventrolateral portion of middle to caudal NDLI received few GR fibers, the rostromedial portion of NDLI a moderate density of fibers, and the rest of the nucleus numerous fibers. These different portions of the NDLI, to some extent, also differed in other afferent and efferent connections, suggesting regional specialization of the nucleus. Furthermore, restricted injections to the lobar nuclei suggest different efferent projections of the component cells of the GR: large and small cells. The large cells project only to the central nucleus, whereas the small cells project to the NDLI and nucleus of lateral recess. Therefore, the two types of GR cells appear to constitute parallel pathways from the pretectum to the inferior lobe. J. Comp. Neurol. 501:582–607, 2007. © 2007 Wiley‐Liss, Inc.
Noradrenergic axon terminals contact gastric preautonomic neurons in the paraventricular nucleus of the hypothalamus in ratsBalcita‐Pedicino, J.J.; Rinaman, L.
doi: 10.1002/cne.21267pmid: 17278138
Hypothalamic neural activity is modulated by viscerosensory signals that are carried in large part by noradrenergic (NA) inputs to the paraventricular nucleus of the hypothalamus (PVN). The present study examined the ultrastructural relationship of NA axon varicosities with the somata and dendrites of identified gastric preautonomic PVN neurons in adult male rats. NA varicosities were visualized by immunoperoxidase labeling of dopamine beta hydroxylase (DbH), and gastric preautonomic PVN neurons were identified by immunogold labeling of pseudorabies virus (PRV) transported retrogradely and transneuronally from injection sites in the stomach wall. Among 1,136 DbH‐positive varicosities identified within the parvocellular PVN in four rats, approximately 36% formed either a close apposition or a synaptic contact with a somatic or dendritic profile. The majority of identified contacts between DbH‐ and PRV‐positive profiles were classified as close appositions that lacked clear synaptic specializations. Approximately 65% of identified synaptic contacts between DbH‐ and PRV‐positive profiles were classified as symmetric (Gray's type II) synapses. DbH‐positive terminals formed close appositions and synaptic contacts with dendritic and somatic compartments of PRV‐positive neurons, although dendrites were contacted nearly five times more often than somata. These findings invite continued work to delineate the functional role of NA signaling pathways in conveying interoceptive signals to preautonomic PVN neurons under normal and pathophysiological conditions. J. Comp. Neurol. 501:608–618, 2007. © 2007 Wiley‐Liss, Inc.
Purkinje cell compartmentation as revealed by Zebrin II expression in the cerebellar cortex of pigeons (Columba livia)Pakan, Janelle M.P.; Iwaniuk, Andrew N.; Wylie, Douglas R.W.; Hawkes, Richard; Marzban, Hassan
doi: 10.1002/cne.21266pmid: 17278140
Purkinje cells in the cerebellum express the antigen zebrin II (aldolase C) in many vertebrates. In mammals, zebrin is expressed in a parasagittal fashion, with alternating immunopositive and immunonegative stripes. Whether a similar pattern is expressed in birds is unknown. Here we present the first investigation into zebrin II expression in a bird: the adult pigeon (Columba livia). Western blotting of pigeon cerebellar homogenates reveals a single polypeptide with an apparent molecular weight of 36 kDa that is indistinguishable from zebrin II in the mouse. Zebrin II expression in the pigeon cerebellum is prominent in Purkinje cells, including their dendrites, somata, axons, and axon terminals. Parasagittal stripes were apparent with bands of Purkinje cells that strongly expressed zebrin II (+ve) alternating with bands that expressed zebrin II weakly or not at all (−ve). The stripes were most prominent in folium IXcd, where there were seven +ve/−ve stripes, bilaterally. In folia VI–IXab, several thin stripes were observed spanning the mediolateral extent of the folia, including three pairs of +ve/−ve stripes that extended across the lateral surface of the cerebellum. In folium VI the zebrin II expression in Purkinje cells was stronger overall, resulting in less apparent stripes. In folia II–V, four distinct +ve/−ve stripes were apparent. Finally, in folia I (lingula) and X (nodulus) all Purkinje cells strongly expressed zebrin II. These data are compared with studies of zebrin II expression in other species, as well as physiological and neuroanatomical studies that address the parasagittal organization of the pigeon cerebellum. J. Comp. Neurol. 501:619–630, 2007. © 2007 Wiley‐Liss, Inc.