Alterations in the motor neuron–renshaw cell circuit in the Sod1G93A mouse modelWootz, Hanna; FitzSimons‐Kantamneni, Eileen; Larhammar, Martin; Rotterman, Travis M.; Enjin, Anders; Patra, Kalicharan; André, Elodie; Van Zundert, Brigitte; Kullander, Klas; Alvarez, Francisco J.
doi: 10.1002/cne.23322pmid: 23508745
Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin‐related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin‐immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN‐IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing. © 2012 Wiley Periodicals, Inc.
WDR1 expression in normal and noise‐damaged Sprague‐Dawley rat cochleaeSong, Jae‐Jin; Adler, Henry J.; Lee, Ho Sun; Jang, Jeong Hun; Park, Min‐Hyun; Lee, Jun Ho; Chang, Sun O; Oh, Seung Ha
doi: 10.1002/cne.23197pmid: 22821633
WD40 repeat protein 1 (WDR1) has been suggested as a protective mechanism or a sign of regeneration in avian cochlea. However, its role in mammalian cochlea has yet to be determined. Hence, we investigated WDR1 expression in sound‐overstimulated Sprague‐Dawley rats. Rats were divided into three groups (the permanent and temporary threshold shift [PTS and TTS] groups and the control group) according to the extent of noise exposure and euthanized immediately, 3, or 7 days after noise exposure for cochlear harvest. Immunocytochemistry localized WDR1 to outer hair cells, Deiter's cells, outer sulcus cells, and Reissner's membrane in the control group, and the PTS and TTS groups exhibited stronger WDR1 expression in the same cochlear regions than the controls. Moreover, WDR1 expression in these noise‐exposed groups was extended to inner hair cells and basal cells of the stria vascularis. The expression of WDR1 in the PTS and TTS groups showed differences in intensity and shifts of localization, based on exposure length and recovery duration. Contrary to the avian cochlea, hair cell regeneration does not naturally occur in the acoustically damaged mammalian cochlea. Therefore, elevated WDR1 expression after acoustic overstimulation in the current experiments may provide a mechanism for protection against noise exposure. J. Comp. Neurol. 521:1470–1481, 2013. © 2012 Wiley Periodicals, Inc.
Delayed and asynchronous ganglionic maturation during cephalopod neurogenesis as evidenced by Sof‐elav1 expression in embryos of Sepia officinalis (Mollusca, Cephalopoda)Buresi, Auxane; Canali, Ester; Bonnaud, Laure; Baratte, Sébastien
doi: 10.1002/cne.23231pmid: 23047428
Among the Lophotrochozoa, centralization of the nervous system reaches an exceptional level of complexity in cephalopods, where the typical molluscan ganglia become highly developed and fuse into hierarchized lobes. It is known that ganglionic primordia initially emerge early and simultaneously during cephalopod embryogenesis but no data exist on the process of neuron differentiation in this group. We searched for members of the elav/hu family in the cuttlefish Sepia officinalis, since they are one of the first genetic markers of postmitotic neural cells. Two paralogs were identified and the expression of the most neural‐specific gene, Sof‐elav1, was characterized during embryogenesis. Sof‐elav1 is expressed in all ganglia at one time of development, which provides the first genetic map of neurogenesis in a cephalopod. Our results unexpectedly revealed that Sof‐elav1 expression is not similar and not coordinated in all the prospective ganglia. Both palliovisceral ganglia show extensive Sof‐elav1 expression soon after emergence, showing that most of their cells differentiate into neurons at an early stage. On the contrary, other ganglia, and especially both cerebral ganglia that contribute to the main parts of the brain learning centers, show a late extensive Sof‐elav1 expression. These delayed expressions in ganglia suggest that most ganglionic cells retain their proliferative capacities and postpone differentiation. In other molluscs, where a larval nervous system predates the development of the definitive adult nervous system, cerebral ganglia are among the first to mature. Thus, such a difference may constitute a cue in understanding the peculiar brain evolution in cephalopods. J. Comp. Neurol. 521:1482–1496, 2013. © 2012 Wiley Periodicals, Inc.
Properties of the ON bistratified ganglion cell in the rabbit retinaHoshi, Hideo; Tian, Lian‐Ming; Massey, Stephen C.; Mills, Stephen L.
doi: 10.1002/cne.23237pmid: 23047654
The identity of the types of different neurons in mammalian retinae is now close to being completely known for a few mammalian species; comparison reveals strong homologies for many neurons across the order. Still, there remain some cell types rarely encountered and inadequately described, despite not being rare in relative frequency. Here we describe in detail an additional ganglion cell type in rabbit that is bistratified with dendrites in both sublaminae, yet spikes only at light onset and has no response bias to the direction of moving bars. This ON bistratified ganglion cell type is most easily distinguished by the unusual behavior of its dendritic arbors. While dendrites that arborize in sublamina b terminate at that level, those that ascend to arborize in sublamina a do not normally terminate there. Instead, when they reach the approximate radius of the dendrites in sublamina b, they dive sharply back down to ramify in sublamina b. Here they continue to course even further away from the soma at the same level as the branches wholly contained in sublamina b, thereby forming an annulus of secondary ON dendrites in sublamina b. This pattern of branching creates a bistratified dendritic field of approximately equal area in the two sublaminae initially, to which is then added an external annulus of dendrites only in sublamina b whose origin is entirely from processes descending from sublamina a. It is coupled to a population of wide‐field amacrine cells upon which the dendrites of the ganglion cell often terminate. J. Comp. Neurol. 521:1497–1509, 2013. © 2012 Wiley Periodicals, Inc.
3D model of frequency representation in the cochlear nucleus of the CBA/J mouseMuniak, Michael A.; Rivas, Alejandro; Montey, Karen L.; May, Bradford J.; Francis, Howard W.; Ryugo, David K.
doi: 10.1002/cne.23238pmid: 23047723
The relationship between structure and function is an invaluable context with which to explore biological mechanisms of normal and dysfunctional hearing. The systematic and topographic representation of frequency originates at the cochlea, and is retained throughout much of the central auditory system. The cochlear nucleus (CN), which initiates all ascending auditory pathways, represents an essential link for understanding frequency organization. A model of the CN that maps frequency representation in 3D would facilitate investigations of possible frequency specializations and pathologic changes that disturb frequency organization. Toward this goal, we reconstructed in 3D the trajectories of labeled auditory nerve (AN) fibers following multiunit recordings and dye injections in the anteroventral CN of the CBA/J mouse. We observed that each injection produced a continuous sheet of labeled AN fibers. Individual cases were normalized to a template using 3D alignment procedures that revealed a systematic and tonotopic arrangement of AN fibers in each subdivision with a clear indication of isofrequency laminae. The combined dataset was used to mathematically derive a 3D quantitative map of frequency organization throughout the entire volume of the CN. This model, available online (http://3D.ryugolab.com/), can serve as a tool for quantitatively testing hypotheses concerning frequency and location in the CN. J. Comp. Neurol. 521:1510–1532, 2013. © 2012 Wiley Periodicals, Inc.
Phylogeny and expression divergence of metabotropic glutamate receptor genes in the brain of zebrafish (Danio rerio)Haug, Marion F.; Gesemann, Matthias; Mueller, Thomas; Neuhauss, Stephan C.F.
doi: 10.1002/cne.23240pmid: 23047810
Glutamate, the most abundant excitatory neurotransmitter of the central nervous system, modulates synaptic transmission and neuronal excitability via metabotropic glutamate receptors (mGluRs). These receptors are essential components for diverse cognitive functions and they represent potential drug targets for the treatment of a number of neurological and psychiatric disorders. Here we describe the phylogenetic relation and mRNA distribution of zebrafish mGluRs. In comparison to the eight mglurs present in the mammalian genome, we identified 13 different mglur genes in the zebrafish genome. In situ hybridization experiments in zebrafish revealed widespread expression patterns for the different mglurs in the central nervous system, implicating their significance in diverse neuronal functions. Prominent mglur expression is found in the olfactory bulb, the optic tectum, the hypothalamus, the cerebellum, and the retina. We show that expression pattern of paralogs generated by the teleost‐specific whole genome duplication is overlapping in some brain regions but complementary in others, suggesting sub‐ and/or neofunctionalization in the latter. Group I mglurs are similarly expressed in brain areas of both larval and adult zebrafish, suggesting that their functions are comparable during these stages. J. Comp. Neurol. 521:1449–1469, 2013. © 2012 Wiley Periodicals, Inc.
Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutantsWang, Bei; Long, Jason E.; Flandin, Pierre; Pla, Ramon; Waclaw, Ronald R.; Campbell, Kenneth; Rubenstein, John L.R.
doi: 10.1002/cne.23242pmid: 23042297
Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and ‐2 have distinct interactions with Dlx1 and ‐2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development. J. Comp. Neurol. 521:1561–1584, 2013. © 2012 Wiley Periodicals, Inc.
Ephrin‐B2 reverse signaling is required for topography but not pattern formation of lateral superior olivary inputs to the inferior colliculusWallace, Matthew M.; Kavianpour, Sarah M.; Gabriele, Mark L.
doi: 10.1002/cne.23243pmid: 23042409
Graded and modular expressions of Eph‐ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin‐B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin‐B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild‐type and ephrin‐B2lacZ/+ mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin‐B2lacZ/+ mutants. By the onset of hearing, both wild‐type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin‐B2lacZ/+ mice lack a reliable topography in LSO‐IC projections, suggesting that fully functional ephrin‐B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin‐B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience. J. Comp. Neurol. 521:1585–1597, 2013. © 2012 Wiley Periodicals, Inc.
Anatomical and electrophysiological mechanisms for asymmetrical excitatory propagation in the rat insular cortex: In vivo optical imaging and whole‐cell patch‐clamp studiesAdachi, Kazunori; Fujita, Satoshi; Yoshida, Atsushi; Sakagami, Hiroshi; Koshikawa, Noriaki; Kobayashi, Masayuki
doi: 10.1002/cne.23246pmid: 23124629
The insular cortex (IC) integrates limbic information from the amygdala and hypothalamic nucleus to multimodal sensory inputs, including visceral, gustatory, and somatosensory information. However, the functional framework of excitation in the IC is still unknown. We performed optical imaging and single pyramidal neuronal staining using a whole‐cell patch‐clamp technique in urethane‐anesthetized rats to elucidate the precise anatomical and physiological features of IC pyramidal neurons, which regulate cortical information processing via their horizontal connections. Optical imaging revealed that electrical stimulation of the granular (GI) or dysgranular (DI) IC elicited characteristic excitatory propagations along the rostrocaudal axis parallel to the rhinal fissure, with a preference toward the rostral direction. Spatial patterns of the dendrites and axons of layer II/III pyramidal cells in the DI/GI support these functional features of excitation; for example, rostrocaudal axonal arbors tend to extend with a rostral directional preference. The mean length of the axons from the soma to the farthest site rostrally was ∼50% longer than that of the caudal length. Pyramidal cells in the DI/GI exhibited spontaneous membrane oscillation in the UP and DOWN states. Similarly to the evoked signals obtained by optical imaging, repetitive electrical stimulation of the caudal IC ∼1 mm away from the recorded cells (five pulses at 50 Hz) induced the summation of evoked excitatory postsynaptic potentials during the DOWN state and profound inhibitory postsynaptic potentials during the UP state. Clarification of the excitation feature with its cellular basis provides new clues about the functional mechanisms of the asymmetric propagation of neural activities in the IC. J. Comp. Neurol. 521:1598–1613, 2013. © 2012 Wiley Periodicals, Inc.