bluuebunny/crossref_metadata_2025 huggingface dataset:
Classic hippocampal sclerosis and hippocampal‐onset epilepsy produced by a single “cryptic” episode of focal hippocampal excitation in awake rats
Authors: Norwood Braxton A. , Bumanglag Argyle V. , Osculati Francesco , Sbarbati Andrea , Marzola Pasquina , Nicolato Elena , Fabene Paolo F. , Sloviter Robert S.
Published: May 2010

In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternative hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30‐minute episodes of perforant pathway stimulation in Sprague–Dawley rats increased granule cell paired‐pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8‐hour episode of reduced‐intensity stimulation in Long–Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal‐onset seizures began 16–25 days postinjury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. J. Comp. Neurol. 518:3381–3407, 2010. © 2010 Wiley‐Liss, Inc.
Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain
Authors: Fu Wenyu , Le Maître Erwan , Fabre Veronique , Bernard Jean‐Francois , David Xu Zhi‐Qing , Hökfelt Tomas
Published: May 2010

Serotonin neurons play a major role in many normal and pathological brain functions. In the rat these neurons have a varying number of cotransmitters, including neuropeptides. Here we studied, with histochemical techniques, the relation between serotonin, some other small‐molecule transmitters, and a number of neuropeptides in the dorsal raphe nucleus (DRN) and the adjacent ventral periaqueductal gray (vPAG) of mouse, an important question being to establish possible differences from rat. Even if similarly distributed, the serotonin neurons in mouse lacked the extensive coexpression of nitric oxide synthase and galanin seen in rat. Although partly overlapping in the vPAG, no evidence was obtained for the coexistence of serotonin with dopamine, substance P, cholecystokinin, enkephalin, somatostatin, neurotensin, dynorphin, thyrotropin‐releasing hormone, or corticotropin‐releasing hormone. However, some serotonin neurons expressed the γ‐aminobutyric acid (GABA)‐synthesizing enzyme glutamic acid decarboxylase (GAD). Work in other laboratories suggests that, as in rat, serotonin neurons in the mouse midline DRN express the vesicular glutamate transporter 3, presumably releasing glutamate. Our study also shows that many of the neuropeptides studied (substance P, galanin, neurotensin, dynorphin, and corticotropin‐releasing factor) are present in nerve terminal networks of varying densities close to the serotonin neurons, and therefore may directly or indirectly influence these cells. The apparently low numbers of coexisting messengers in mouse serotonin neurons, compared to rat, indicate considerable species differences with regard to the chemical neuronatomy of the DRN. Thus, extrapolation of DRN physiology, and possibly pathology, from rat to mouse, and even human, should be made with caution. J. Comp. Neurol. 518:3464–3494, 2010. © 2010 Wiley‐Liss, Inc.
Melatonin receptors in the brain of the European sea bass: An in situ hybridization and autoradiographic study
Authors: Herrera‐Pérez Patricia , Del Carmen Rendón Maria , Besseau Laurence , Sauzet Sandrine , Falcón Jack , Muñoz‐Cueto José A.
Published: May 2010

Melatonin is synthesized in the pineal organ and retina of vertebrates and exhibits a clear nocturnal rhythm of secretion. This hormone influences a number of important physiological processes acting through specific transmembrane G‐protein‐coupled receptors. Recently, we have cloned three different melatonin receptors in sea bass belonging to the MT1, MT2, and Mel1c subtypes. In this paper, we have analyzed the central expression of the MT1 gene by in situ hybridization and compared its distribution with the localization of 2‐[125I]‐iodomelatonin binding sites. In situ hybridization and autoradiographic studies provided consistent results. Melatonin receptors were mainly expressed in visually related areas of the sea bass brain, such as the pretectal area, glomerular complex, optic tectum, torus longitudinalis, and thalamus. A conspicuous expression was also detected in neuroendocrine regions including the ventral telencephalon, preoptic area, and hypothalamus. Furthermore, melatonin receptors were evident in the ganglionic cell layer of the cerebellum. The presence of iodomelatonin binding and/or MT1 mRNA‐expressing cells was also observed in the hindbrain, in particular in the oculomotor and trigeminal nuclei and in the reticular formation. Our results suggest an important role of MT1 in the mediation of melatonin actions in visual/light integration, mechanoreception, somatosensation, eye‐body motor coordination, and integrative and neuroendocrine functions. Remarkable differences in the number and distribution of brain nuclei expressing MT1 mRNAs in sea bass and trout, the only fish species analyzed to date, represent another piece of evidence for differences in the organization of the visual and circadian systems observed between salmoniform and perciform teleosts. J. Comp. Neurol. 518:3495–3511, 2010. © 2010 Wiley‐Liss, Inc.
Cellular and subcellular localization of the neuron‐specific plasma membrane calcium ATPase PMCA1a in the rat brain
Authors: Kenyon Katharine A. , Bushong Eric A. , Mauer Amy S. , Strehler Emanuel E. , Weinberg Richard J. , Burette Alain C.
Published: May 2010

Regulation of intracellular calcium is crucial both for proper neuronal function and survival. By coupling ATP hydrolysis with Ca2+ extrusion from the cell, the plasma membrane calcium‐dependent ATPases (PMCAs) play an essential role in controlling intracellular calcium levels in neurons. In contrast to PMCA2 and PMCA3, which are expressed in significant levels only in the brain and a few other tissues, PMCA1 is ubiquitously distributed, and is thus widely believed to play a “housekeeping” function in mammalian cells. Whereas the PMCA1b splice variant is predominant in most tissues, an alternative variant, PMCA1a, is the major form of PMCA1 in the adult brain. Here, we use immunohistochemistry to analyze the cellular and subcellular distribution of PMCA1a in the brain. We show that PMCA1a is not ubiquitously expressed, but rather is confined to neurons, where it concentrates in the plasma membrane of somata, dendrites, and spines. Thus, rather than serving a general housekeeping function, our data suggest that PMCA1a is a calcium pump specialized for neurons, where it may contribute to the modulation of somatic and dendritic Ca2+ transients. J. Comp. Neurol. 518:3169–3183, 2010. © 2010 Wiley‐Liss, Inc.
Similarities and differences in the forebrain expression of Lhx1 and Lhx5 between chicken and mouse: Insights for understanding telencephalic development and evolution
Authors: Abellán Antonio , Vernier Baptiste , Rétaux Sylvie , Medina Loreta
Published: May 2010

We compared expression of the paralogous LIM‐homeodomain genes Lhx1 and Lhx5 in the developing rostral forebrain of mouse and chicken. Both genes are expressed in similar patterns in the septum, preoptic region, and related areas of the basal telencephalon, including the medial septum/diagonal band nuclei and the medial extended amygdala. In the septum, the expression of Lhx5 and Lhx1 appears to be specifically related to the pallial septum and its derivatives in mouse and chicken, and may produce the glutamatergic neurons observed in the diagonal band/medial septum nuclei. The preoptic area expresses both Lhx1 and Lhx5 in mouse and chicken, and appears to produce γ‐aminobutyric acid (GABA)ergic, glutamatergic, and cholinergic cells for the preoptic region and basal telencephalon. In addition, in mouse and chicken Lhx5 is expressed in two extratelencephalic domains that appear to contribute Lhx5‐expressing cells to the basal telencephalon, including the supraoptoparaventricular hypothalamic domain and the eminentia thalami. In contrast, there are striking differences in the pallial expression of Lhx1 and Lhx5 between mouse and chicken. Both genes are expressed in Cajal‐Retzius cells, and Lhx5 is also present in most pallial sources of Cajal‐Retzius cells (including the cortical hem and retrobulbar area) and in the olfactory bulbs in the mouse. In contrast, putative Cajal‐Retzius cells, the retrobulbar area, and the olfactory bulb of chicken do not express the paralog genes cLhx1/cLhx5. Moreover, the cortical hem—although it expresses cLhx5—is very tiny in chicken. We discuss the consequences of these differences in Lhx1/Lhx5 expression between mouse and chicken for pallial/cortical evolution. J. Comp. Neurol. 518:3512–3528, 2010. © 2010 Wiley‐Liss, Inc.
Evaluation of inputs to rat primary auditory cortex from the suprageniculate nucleus and extrastriate visual cortex
Authors: Smith Philip H. , Manning Karen A. , Uhlrich Daniel J.
Published: May 2010

Evidence indicates that visual stimuli influence cells in the primary auditory cortex. To evaluate potential sources of this visual input and how they enter into the circuitry of the auditory cortex, we examined axonal terminations in the primary auditory cortex from nonprimary extrastriate visual cortex (V2M, V2L) and from the multimodal thalamic suprageniculate nucleus (SG). Gross biocytin/biotinylated dextran amine (BDA) injections into the SG or extrastriate cortex labeled inputs terminating primarily in superficial and deep layers. SG projects primarily to layers I, V, and VI while V2M and V2L project primarily to layers I and VI, with V2L also targeting layers II/III. Layer I inputs differ in that SG terminals are concentrated superficially, V2L are deeper, and V2M are equally distributed throughout. Individual axonal reconstructions document that single axons can 1) innervate multiple layers; 2) run considerable distances in layer I; and 3) run preferentially in the dorsoventral direction similar to isofrequency axes. At the electron microscopic level, SG and V2M terminals 1) are the same size regardless of layer; 2) are non‐γ‐aminobutyric acid (GABA)ergic; 3) are smaller than ventral medial geniculate terminals synapsing in layer IV; 4) make asymmetric synapses onto dendrites/spines that 5) are non‐GABAergic and 6) are slightly larger in layer I. Thus, both areas provide a substantial feedback‐like input with differences that may indicate potentially different roles. J. Comp. Neurol. 518:3679–3700, 2010. © 2010 Wiley‐Liss, Inc.
Recovery of viscerosensory innervation from the dorsal root ganglia of the adult rat following capsaicin‐induced injury
Authors: Gallaher Zachary R. , Larios Rose Marie , Ryu Vitaly , Sprunger Leslie K. , Czaja Krzysztof
Published: May 2010

Capsaicin is a neurotoxin selective for C‐ and Aδ‐type neurons. Systemic treatment with capsaicin is known to reduce this subpopulation in the dorsal root ganglia (DRG) of neonatal rats. To better understand the effects of capsaicin on adult afferent fibers, we examined DRG neurons retrogradely labeled by an i.p. injection of Fast Blue (FB) administered 3, 30, or 60 days after systemic capsaicin treatment (125 mg/kg i.p.). FB labeling in the 12th and 13th thoracic DRG was dramatically reduced 3 and 30 days post capsaicin (50% and 35% of control, respectively). However, the number of retrogradely labeled neurons rose to 65% of control by 60 days post capsaicin. In addition to FB labeling, we quantified the immunoreactivity of NR1, the obligatory N‐methyl‐D‐aspartate receptor subunit, and Nav1.8, a DRG‐specific sodium channel, in FB‐labeled neurons as well as mRNA levels for both proteins in the 5th and 6th lumbar DRG. NR1 immunoreactivity and mRNA expression followed a pattern of early reduction and subsequent partial restoration similar to FB labeling. Nav1.8 immunoreactivity and mRNA expression dropped to approximately 50% of control at 3 days post capsaicin but completely recovered by 60 days. These data strongly support the conclusion that restoration of spinal afferent projections and signaling occurs in adult rats following capsaicin‐induced damage. J. Comp. Neurol. 518:3529–3540, 2010. © 2010 Wiley‐Liss, Inc.
Analysis of morphological features of thalamocortical neurons from the ventroposterolateral nucleus of the cat
Authors: Zomorrodi Reza , Ferecskó Alex S. , Kovács Krisztina , Kröger Helmut , Timofeev Igor
Published: May 2010

Morphological features of the dendritic arborization can affect neuronal responses and thus the input‐output function of a particular neuron. In this study, morphological data of eight fully reconstructed thalamocortical (TC) neurons from the ventroposterolateral (VPL) nucleus of adult cats have been analyzed. We examined several geometrical and topological parameters, which have been previously shown to have a high impact on the neuron firing pattern and propagation of signals in the dendritic tree. In addition to well‐known morphological parameters such as number of dendritic trees (8.3 ± 1.5) and number of branching points (80–120), we investigated the distribution of dendritic membrane area, branching points, geometrical ratio, asymmetry index, and mean path length for all subtrees of the TC neurons. We demonstrate that due to extensive branching in proximal and middle dendritic sections, the maximum value of the dendritic area distribution is reached at 120–160 μm from the soma. Our analysis reveals that TC neurons are highly branched cells and their dendritic branching pattern does not follow Rall's 3/2 power rule; average values at proximal vs. distal dendritic sections were different. We also found that the dendritic branching pattern of each subtree of the cell had a wide range in symmetry index, whereas the mean path length did not show a large variation through the dendritic arborizations. J. Comp. Neurol. 518:3541–3556, 2010. © 2010 Wiley‐Liss, Inc.
Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis
Authors: Hegarty Deborah M. , Tonsfeldt Karen , Hermes Sam M. , Helfand Helen , Aicher Sue A.
Published: May 2010

Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene‐related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple‐labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations. J. Comp. Neurol. 518:3557–3569, 2010. © 2010 Wiley‐Liss, Inc.
Ascending general visceral sensory pathways from the brainstem to the forebrain in a cichlid fish, Oreochromis (Tilapia) niloticus
Authors: Yoshimoto Masami , Yamamoto Naoyuki
Published: May 2010

Fiber connections of the general visceral sensory centers in the brainstem were studied with tract‐tracing methods in a percomorph teleost, tilapia Oreochromis niloticus. General visceral afferents of the vagal nerve from abdominal viscera terminated bilaterally in the commissural nucleus of Cajal (NCC) and area postrema (AP). The NCC and AP projected bilaterally to the secondary general visceral nucleus (SVN), four diencephalic nuclei (the preglomerular general visceral nucleus [pVN], nucleus of the lateral recess, posterior thalamic nucleus, and lateral tuberal area), preoptic area, and ventral telencephalon (supracommissural, dorsal, and ventral parts) in addition to the glossopharyngeal and vagal lobes and medullary reticular formation. Injections to the SVN resulted in labeled terminals in the forebrain structures that receive fibers from the primary centers and additionally in the diffuse nucleus of the inferior lobe, lateral torus, and inferior subdivision of lateral torus. The present study suggests that the ascending general visceral projections arising from the brainstem centers in teleosts are quite similar to those in mammals and birds. Descending pathways were also notable. In addition to descending projections from the SVN and medullary structures to the primary centers, long descending pathways to the SVN, NCC, and AP were found to originate from the pVN, nucleus of the lateral recess, posterior thalamic nucleus, and preoptic area. The SVN was found to receive fibers from the ventral telencephalon as well. Therefore, the present study indicates that most of the general visceral structures in the forebrain are reciprocally connected with the brainstem centers. J. Comp. Neurol. 518:3570–3603, 2010. © 2010 Wiley‐Liss, Inc.
cGMP‐dependent cone photoreceptor degeneration in the cpfl1 mouse retina
Authors: Trifunović Dragana , Dengler Katja , Michalakis Stylianos , Zrenner Eberhart , Wissinger Bernd , Paquet‐Durand François
Published: May 2010

Inherited retinal degeneration affecting both rod and cone photoreceptors constitutes one of the leading causes of blindness in the developed world. Such degeneration is at present untreatable, and the underlying neurodegenerative mechanisms are unknown, even though certain genetic causes have been established. The rd1 mouse is one of the best characterized animal models for rod photoreceptor degeneration, whereas the cpfl1 mouse is a recently discovered model for cone cell death. Because both animal models are affected by functionally similar mutations in the rod and cone phosphodiesterase 6 genes, respectively, we asked whether the mechanisms of photoreceptor degeneration in these two mouse lines share common pathways. In the present study, we followed the temporal progression of photoreceptor degeneration in the cpfl1 retina, correlated it with specific metabolic markers, and compared it with the wild‐type and the rd1 situation. Similar to corresponding rd1 observations, cpfl1 cone photoreceptor cell death was associated with an accumulation of cyclic guanosine monophosphate (cGMP), activity of calpains, and phosphorylation of vasodilator‐stimulated protein (VASP). Cone degeneration progressed rapidly, with a peak in cell death around postnatal day 24. Furthermore, cpfl1 cone photoreceptor migration during early postnatal development was delayed significantly compared with the corresponding wild‐type retina. The finding that rod and cone photoreceptor degeneration was associated with the same metabolic markers suggests that in both cell types similar degenerative mechanisms are active. This raises the possibility that equivalent neuroprotective strategies may be used to prevent both rod and cone photoreceptor degeneration. J. Comp. Neurol. 518:3604–3617, 2010. © 2010 Wiley‐Liss, Inc.
Morphological patterns of the postcentral sulcus in the human brain
Authors: Zlatkina Veronika , Petrides Michael
Published: May 2010

The morphological structure of the postcentral sulcus and its variability were investigated in 40 structural magnetic resonance images of the human brain registered to the Montreal Neurological Institute (MNI) proportional stereotaxic space. This analysis showed that the postcentral sulcus is not a single sulcus, but rather a complex of sulcal segments separated by gyri, which merge their banks at distinct locations. Most of these gyri are submerged deep within the sulcus and can be observed only by examining the depth of the sulcus, although a small proportion may be observed from the surface of the brain. In the majority of the examined cerebral hemispheres (73.75%), the postcentral sulcus is separated into two or three segments or, less frequently, into four or five segments (12.5%), or it remains continuous (13.75%). Examination of the in‐depth relationship between the postcentral sulcus and the intraparietal sulcus revealed that these two sulci may appear to join on the surface of the brain but they are in fact always separated by a gyrus in the cortical depth. In 32.5% of the examined hemispheres, a dorsoventrally oriented sulcus, the transverse postcentral sulcus, is located anterior to the postcentral sulcus on the lower part of the postcentral gyrus. Systematic examination of the morphology of the postcentral sulcus in the proportional stereotaxic space that is used in functional neuroimaging studies is the first step toward the establishment of anatomical–functional correlations in the anterior parietal lobe. J. Comp. Neurol. 518:3701–3724, 2010. © 2010 Wiley‐Liss, Inc.
Estrogen configures sexual dimorphism in the preoptic area of C57BL/6J and ddN strains of mice
Authors: Orikasa Chitose , Sakuma Yasuo
Published: May 2010

Immunohistochemistry using a calbindin D28k antibody revealed a marked sex difference in neuronal distribution in the central portion of the medial preoptic area in C57BL/6J and ddN strains of mice when the animals were sacrificed on D65 (D1 = the day of birth). Male mice had a distinct ellipsoidal cell aggregate, whereas females lacked such a structure. This sex difference was not observed in Nissl‐stained sections. Co‐localization of calbindin D28k and the neuron‐specific nuclear protein NeuN confrmed that the cells in the aggregate were neurons. The aggregates were larger in males than in females in both strains. When observed on D65, males orchidectomized on D1 had smaller aggregates. However, daily injections of 2 μg estradiol benzoate through D1–D5 as well as a single injection of 100 μg testosterone propionate on D1 enlarged the aggregates in females, but a single injection of 100 μg dihydrotestosterone on D1 had no effect on the female phenotype. Similar endocrine manipulations had no effects in adult animals of both sexes. Thus, the calbindin‐immunoreactive cell aggregates in the preoptic area of C57BL/6J and ddN mice are homologous to the sexually dimorphic nucleus of the rat preoptic area in terms of the morphology and sex steroid‐dependent organization. J. Comp. Neurol. 518:3618–3629, 2010. © 2010 Wiley‐Liss, Inc.
Fiber pathways and cortical connections of preoccipital areas in rhesus monkeys
Authors: Yeterian E.H. , Pandya D.N.
Published: May 2010

An understanding of visual function at the cerebral cortical level requires detailed knowledge of anatomical connectivity. Cortical association pathways and terminations of preoccipital visual areas were investigated in rhesus monkeys by using the autoradiographic tracing technique. Medial and adjacent dorsomedial preoccipital regions project via the occipitofrontal fascicle to the frontal lobe (dorsal area 6, and areas 8Ad, 8B, and 46); via the dorsal portion of the superior longitudinal fascicle (SLF) to dorsal area 6, area 9, and the supplementary motor area; and via the cingulate fascicle to area 24. In addition, medial and dorsomedial preoccipital areas send projections to parietal (areas PGm, PEa, PG‐Opt, and POa) and superior temporal (areas MST and MT) regions. In contrast, connections from the dorsolateral, annectant, and ventral preoccipital regions are conveyed via the inferior longitudinal fascicle (ILF) to the parietal lobe (areas POa and IPd), superior temporal sulcus (areas MT, MST, FST, V4t, and IPa), inferotemporal region (areas TEO and TE1–TE3), and parahippocampal gyrus (areas TF, TH, and TL). The central‐lateral preoccipital region projects via an ILF‐SLF pathway to frontal area 8Av. The preoccipital areas also have caudal connections to occipital areas V1, V2, and V3. Finally, preoccipital regions are interconnected via different intrinsic pathways. These findings provide further insight into the nature of preoccipital fiber pathways and the connectional organization of the visual system. J. Comp. Neurol. 518:3725–3751, 2010. © 2010 Wiley‐Liss, Inc.
Expression and light sensitivity of clock genes Per1 and Per2 and immediate‐early gene c‐fos within the retina of early postnatal Wistar rats
Authors: Matějů Kristýna , Sumová Alena , Bendová Zdeňka
Published: May 2010

Mammalian retina contains a circadian clock that is composed of components similar to those of the master circadian clock within the suprachiasmatic nuclei of the hypothalamus. The aim of the present study was to elucidate whether, when, and where the transcripts of the clock genes Per1 and Per2 and the immediate early gene c‐fos are spontaneously expressed and/or induced by light in the newborn rat retina. At postnatal day 1 (P1), P3, P5, and P10, Wistar rat pups were released into constant darkness, and a 30‐minute light pulse was administered during the subjective day or during the first or second part of subjective night. Gene expression was determined 30 minutes, 1 hour, 2 hours, and 4 hours after the light pulse by in situ hybridization followed by emulsion autoradiography. Endogenous expression of Per1 was detected in the neuroblastic retina, and Per2 expression was detected in the inner part of the neuroblastic retina from birth. Light pulses induced c‐fos expression in ganglion cells from P1. Until P5, the cells were localized in the dorsal part of the retina, but, at P10, they were already distributed across the entire retinal circumference. Light pulses also induced the expression of c‐fos and Per1 in the retinal pigment epithelium until P3, but not afterward. Expression of the Per2 gene was not photoresponsive until P10. These data demonstrate that the rat retina is light‐sensitive immediately after birth. During early postnatal development, the spatial distribution of spontaneous and light‐induced gene expression within the retinal layers changes gradually. J. Comp. Neurol.518:3630–3644, 2010. © 2010 Wiley‐Liss, Inc.
Distribution of mRNAs encoding transforming growth factors‐β1, ‐2, and ‐3 in the intact rat brain and after experimentally induced focal ischemia
Authors: Vincze Csilla , Pál Gabriella , Wappler Edina A. , Szabó Éva R. , Nagy Zoltán G. , Lovas Gábor , Dobolyi Arpád
Published: May 2010

Transforming growth factors‐β1 (TGF‐β1), ‐2, and ‐3 form a small group of related proteins involved in the regulation of proliferation, differentiation, and survival of various cell types. Recently, TGF‐βs were also demonstrated to be neuroprotective. In the present study, we investigated their distribution in the rat brain as well as their expression following middle cerebral artery occlusion. Probes were produced for all types of TGF‐βs, and in situ hybridization was performed. We demonstrated high TGF‐β1 expression in cerebral cortex, hippocampus, central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular nucleus, substantia nigra, brainstem reticular formation and motoneurons, and area postrema. In contrast, TGF‐β2 was abundantly expressed in deep cortical layers, dentate gyrus, midline thalamic nuclei, posterior hypothalamic area and mamillary body, superior olive, areas of monoaminergic neurons, spinal trigeminal nucleus, dorsal vagal complex, cerebellum, and choroid plexus, and a high level of TGF‐β3 mRNA was found in cerebral cortex, hippocampus, basal amygdaloid nuclei, lateral septal nucleus, several thalamic nuclei, arcuate and supramamillary nuclei, superior colliculus, superior olive, brainstem reticular formation and motoneurons, area postrema, and inferior olive. Focal brain ischemia induced TGF‐βs with markedly different expression patterns. TGF‐β1 was induced in the penumbral region of cortex and striatum, whereas TGF‐β2 and ‐β3 were induced in different layers of the ipsilateral cortex. The expression of the subtypes of TGF‐βs in different brain regions suggests that they are involved in the regulation of different neurons and bind to different latent TGF‐β binding proteins. Furthermore, they might have subtype‐specific functions following ischemic attack. J. Comp. Neurol. 518:3752–3770, 2010. © 2010 Wiley‐Liss, Inc.
Oncomodulin identifies different hair cell types in the mammalian inner ear
Authors: Simmons Dwayne D. , Tong Benton , Schrader Angela D. , Hornak Aubrey J.
Published: May 2010

The tight regulation of Ca2+ is essential for inner ear function, and yet the role of Ca2+ binding proteins (CaBPs) remains elusive. By using immunofluorescence and reverse transcriptase‐polymerase chain reaction (RT‐PCR), we investigated the expression of oncomodulin (Ocm), a member of the parvalbumin family, relative to other EF‐hand CaBPs in cochlear and vestibular organs in the mouse. In the mouse cochlea, Ocm is found only in outer hair cells and is localized preferentially to the basolateral outer hair cell membrane and to the base of the hair bundle. Developmentally, Ocm immunoreactivity begins as early as postnatal day (P) 2 and shows preferential localization to the basolateral membrane and hair bundle after P8. Unlike the cochlea, Ocm expression is substantially reduced in vestibular tissues at older adult ages. In vestibular organs, Ocm is found in type I striolar or central hair cells, and has a more diffuse subcellular localization throughout the hair cell body. Additionally, Ocm immunoreactivity in vestibular hair cells is present as early as E18 and is not obviously affected by mutations that cause a disruption of hair bundle polarity. We also find Ocm expression in striolar hair cells across mammalian species. These data suggest that Ocm may have distinct functional roles in cochlear and vestibular hair cells. J. Comp. Neurol. 518:3785–3802, 2010. © 2010 Wiley‐Liss, Inc.
Clathrin assembly proteins AP180 and CALM in the embryonic rat brain
Authors: Schwartz Catherine M. , Cheng Aiwu , Mughal Mohamed R. , Mattson Mark P. , Yao Pamela J.
Published: May 2010

Clathrin‐coated vesicles are known to play diverse and pivotal roles in cells. The proper formation of clathrin‐coated vesicles is dependent on, and highly regulated by, a large number of clathrin assembly proteins. These assembly proteins likely determine the functional specificity of clathrin‐coated vesicles, and together they control a multitude of intracellular trafficking pathways, including those involved in embryonic development. In this study, we focus on two closely related clathrin assembly proteins, AP180 and CALM (clathrin assembly lymphoid myeloid leukemia protein), in the developing embryonic rat brain. We find that AP180 begins to be expressed at embryonic day 14 (E14), but only in postmitotic cells that have acquired a neuronal fate. CALM, on the other hand, is expressed as early as E12, by both neural stem cells and postmitotic neurons. In vitro loss‐of‐function studies using RNA interference (RNAi) indicate that AP180 and CALM are dispensable for some aspects of embryonic neurogenesis but are required for the growth of postmitotic neurons. These results identify the developmental stage of AP180 and CALM expression and suggest that each protein has distinct functions in neural development. J. Comp. Neurol. 518:3803–3818, 2010. © 2010 Wiley‐Liss, Inc.
Seasonal changes in aromatase and androgen receptor, but not estrogen receptor mRNA expression in the brain of the free‐living male song sparrow, Melospiza melodia morphna
Authors: Wacker Douglas W. , Wingfield John C. , Davis Jason E. , Meddle Simone L.
Published: May 2010

Free‐living male song sparrows experience three annually repeating life history stages associated with differential expression of sex steroid‐dependent reproductive and aggressive behavior. In the breeding stage, they display reproductive and aggressive behavior and have elevated circulating testosterone levels. During molt, males show little or no aggression and no reproductive behavior, and have basal levels of circulating testosterone. In the non‐breeding stage, they display high levels of aggression and no reproductive behavior, and have basal levels of circulating testosterone. In order to understand more fully the neural regulation of seasonal aggressive and reproductive behavior, birds were collected during all three life history stages, and levels of neural aromatase, androgen receptor (AR), and estrogen receptor α (ERα) and β (ERβ) mRNA expression were measured. Breeding males had the highest levels of aromatase expression in both the preoptic area (POA) and medial preoptic area/medial bed nucleus of the stria terminalis (mPOA/BSTm), and the highest AR expression levels in the POA, consistent with the well‐established role these regions play in the regulation of male reproductive behavior. Aromatase expression in the ventromedial nucleus of the hypothalamus (VMH) was higher during breeding and non‐breeding compared with molt, suggesting that the VMH may play a role in the estrogen‐dependent regulation of aggression in this species. AR expression also varied in medial HVC and pvMSt, a newly described periventricular region in the medial striatum. ERα and ERβ mRNA expression did not vary seasonally in any brain region examined, suggesting that estrogen‐dependent changes in behavior are mediated by differences in neural estrogen synthesis. J. Comp. Neurol. 518:3819–3835, 2010. © 2010 Wiley‐Liss, Inc.
Identification of μ‐ and κ‐opioid receptors as potential targets to regulate parasympathetic, sympathetic, and sensory neurons within rat intracardiac ganglia
Authors: Mousa Shaaban A. , Shaqura Mohammed , Schäper Jörn , Huang Wei , Treskatsch Sascha , Habazettl Helmut , Abdul‐Khaliq Hashim , Schäfer Michael
Published: May 2010

Recent interest has been focused on the opioid regulation of heart performance; however, specific allocation of opioid receptors to the parasympathetic, sympathetic, and sensory innervations of the heart is scarce. Therefore, the present study aimed to characterize such specific target sites for opioids in intracardiac ganglia, which act as a complex network for the integration of the heart's neuronal in‐ and output. Tissue samples from rat heart atria were subjected to RT‐PCR, Western blot, radioligand‐binding, and double immunofluorescence confocal analysis of μ (M)‐ and κ (K)‐opioid receptors (ORs) with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene‐related peptide (CGRP), and substance P (SP). Our results demonstrated MOR‐ and KOR‐specific mRNA, receptor protein, and selective membrane ligand binding. By using immunofluorescence confocal microscopy, MOR and KOR immunoreactivity were colocalized with VAChT in large‐diameter parasympathetic principal neurons, with TH‐immunoreactive small intensely fluorescent (SIF) cells, and on nearby TH‐IR varicose terminals. In addition, MOR and KOR immunoreactivity were identified on CGRP‐ and SP‐IR sensory neurons throughout intracardiac ganglia and atrial myocardium. Our findings show that MOR and KOR are expressed as mRNA and translated into specific receptor proteins on cardiac parasympathetic, sympathetic, and sensory neurons as potential binding sites for opioids. Thus, they may well play a role within the complex network for the integration of the heart's neuronal in‐ and output. J. Comp. Neurol. 518:3836–3847, 2010. © 2010 Wiley‐Liss, Inc.
Calcium‐binding protein immunoreactivity characterizes the auditory system of Gekko gecko
Authors: Yan Kai , Tang Ye‐Zhong , Carr Catherine E.
Published: May 2010

Geckos use vocalizations for intraspecific communication, but little is known about the organization of their central auditory system. We therefore used antibodies against the calcium‐binding proteins calretinin (CR), parvalbumin (PV), and calbindin‐D28k (CB) to characterize the gecko auditory system. We also examined expression of both glutamic acid decarboxlase (GAD) and synaptic vesicle protein (SV2). Western blots showed that these antibodies are specific to gecko brain. All three calcium‐binding proteins were expressed in the auditory nerve, and CR immunoreactivity labeled the first‐order nuclei and delineated the terminal fields associated with the ascending projections from the first‐order auditory nuclei. PV expression characterized the superior olivary nuclei, whereas GAD immunoreactivity characterized many neurons in the nucleus of the lateral lemniscus and some neurons in the torus semicircularis. In the auditory midbrain, the distribution of CR, PV, and CB characterized divisions within the central nucleus of the torus semicircularis. All three calcium‐binding proteins were expressed in nucleus medialis of the thalamus. These expression patterns are similar to those described for other vertebrates. J. Comp. Neurol. 518:3409–3426, 2010. © 2010 Wiley‐Liss, Inc.
Architecture of cannabinoid signaling in mouse retina
Authors: Shu‐Jung Hu Sherry , Arnold Andy , Hutchens Jacqueline M. , Radicke Josh , Cravatt Benjamin F. , Wager‐Miller Jim , Mackie Ken , Straiker Alex
Published: May 2010

Cannabinoid receptors and their ligands constitute an endogenous signaling system that is found throughout the body, including the eye. This system can be activated by Δ9‐tetrahydrocannabinol, a major drug of abuse. Cannabinoids offer considerable therapeutic potential in modulating ocular immune and inflammatory responses and in regulating intraocular pressure. The location of cannabinoid receptor 1 (CB1) in the retina is known, but recently a constellation of proteins has been identified that produce and break down endocannabinoids (eCBs) and modulate CB1 function. Localization of these proteins is critical to defining specific cannabinoid signaling circuitry in the retina. Here we show the localization of diacylglycerol lipase‐α and ‐β (DGLα/β), implicated in the production of the eCB 2‐arachidonoyl glycerol (2‐AG); monoacylglycerol lipase (MGL) and α/β‐hydrolase domain 6 (ABHD6), both implicated in the breakdown of 2‐AG; cannabinoid receptor‐interacting protein 1a (CRIP1a), a protein that may modulate CB1 function; and fatty acid amide hydrolase (FAAH) and N‐acylethanolamine‐hydrolyzing acid amidase (NAAA), which have been shown to break down the eCB anandamide and related acyl amides. Our most prominent finding was that DGLα is present in postsynaptic type 1 OFF cone bipolar cells juxtaposed to CB1‐containing cone photoreceptor terminals. CRIP1a is reliably presynaptic to DGLα, consistent with a possible role in cannabinoid signaling, and NAAA is restricted to retinal pigment epithelium, whereas DGLβ is limited to retinal blood vessels. These results taken together with previous anatomical and functional studies define specific cannabinoid circuitry likely to modulate eCB signaling at the first synapse of the retina as well as in the inner plexiform layer. J. Comp. Neurol. 518:3848–3866, 2010. © 2010 Wiley‐Liss, Inc.
Progranulin expression in the developing and adult murine brain
Authors: Petkau Terri L. , Neal S.J. , Orban P.C. , MacDonald J.L. , Hill A.M. , Lu G. , Feldman H.H. , Mackenzie I.R.A. , Leavitt B.R.
Published: May 2010

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative condition characterized by focal degeneration of the frontal and temporal lobes of the brain. Autosomal dominantly inherited mutations of the progranulin gene (GRN) have been identified as the cause of a subset of cases of familial FTLD. In order to better understand the function of progranulin in the central nervous system (CNS), we have assessed the spatiotemporal expression pattern of both the murine progranulin gene (Grn) and the protein (Grn) by using transgenic knock‐in mice expressing a reporter gene from the Grn locus and by immunohistochemistry, respectively. We compared Grn expression with a panel of established markers for distinct neuronal developmental stages and specific cell lineages at time points ranging from embryonic day 13.5 through to the mature adult. We find that Grn is expressed in both neurons and microglia within the CNS, but that it shows a different developmental expression pattern in each cell type. Grn expression in neurons increases as the cells mature, whereas expression in microglia varies with the cells' state of activation, being specifically upregulated in microglia in response to excitotoxic injury. Our results suggest that progranulin plays distinct roles in neurons and microglia, both of which likely contribute to overall neuronal health and function. J. Comp. Neurol. 518:3931–3947, 2010. © 2010 Wiley‐Liss, Inc.
Suppression of fibrotic scar formation promotes axonal regeneration without disturbing blood‐brain barrier repair and withdrawal of leukocytes after traumatic brain injury
Authors: Yoshioka Nozomu , Hisanaga Shin‐Ichi , Kawano Hitoshi
Published: May 2010

The fibrotic scar containing type IV collagen (Col IV) formed in a lesion site is considered as an obstacle to axonal regeneration, because intracerebral injection of 2,2′‐dipyridyl (DPY), an inhibitor of Col IV triple‐helix formation, suppresses fibrotic scar formation in the lesion site and promotes axonal regeneration. To determine the role of the fibrotic scar on the healing process of injured central nervous system (CNS), the restoration of blood‐brain barrier (BBB) and withdrawal of inflammatory leukocytes were examined in mice subjected to unilateral transection of the nigrostriatal dopaminergic pathway and intracerebral DPY injection. At 5 days after injury, destruction of BBB represented by leakage of Evans blue (EB) and widespread infiltration of CD45‐immunoreactive leukocytes was observed around the lesion site, whereas reactive astrocytes increased surrounding the BBB‐destroyed area. By 2 weeks after injury, the region of EB leakage and the diffusion of leukocytes were restricted to the inside of the fibrotic scar, and reactive astrocytes gathered around the fibrotic scar. In the DPY‐treated lesion site, formation of the fibrotic scar was suppressed (84% decrease in Col IV‐deposited area), reactive astrocytes occupied the lesion center, and areas of both EB leakage and leukocyte infiltration decreased by 86%. DPY treatment increased the number of regenerated dopaminergic axons by 2.53‐fold. These results indicate that suppression of fibrotic scar formation does not disturb the healing process in damaged CNS, and suggest that this strategy is a reliable tool to promote axonal regeneration after traumatic injury in the CNS. J. Comp. Neurol. 518:3867–3881, 2010. © 2010 Wiley‐Liss, Inc.
Distribution of hypophysiotropic thyrotropin‐releasing hormone (TRH)‐synthesizing neurons in the hypothalamic paraventricular nucleus of the mouse
Authors: Kádár Andrea , Sánchez Edith , Wittmann Gábor , Singru Praful S. , Füzesi Tamás , Marsili Alessandro , Larsen P. Reed , Liposits Zsolt , Lechan Ronald M. , Fekete Csaba
Published: May 2010

Hypophysiotropic thyrotropin‐releasing hormone (TRH) neurons, the central regulators of the hypothalamic‐pituitary‐thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non‐hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double‐ and triple‐labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitoneally with the retrograde tracer Fluoro‐Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid‐level of the PVN, primarily in the compact part. In this part of the PVN, TRH neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co‐localization of TRH and cocaine‐ and amphetamine‐regulated transcript (CART) were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid‐level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid‐level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats. J. Comp. Neurol. 518:3948–3961, 2010. © 2010 Wiley‐Liss, Inc.
Neural architecture of the primary gustatory center of Drosophila melanogaster visualized with GAL4 and LexA enhancer‐trap systems
Authors: Miyazaki Takaaki , Ito Kei
Published: May 2010

Gustatory information is essential for animals to select edible foods and avoid poisons. Whereas mammals detect tastants with their taste receptor cells, which convey gustatory signals to the brain indirectly via the taste sensory neurons, insect gustatory receptor neurons (GRNs) send their axons directly to the primary gustatory center in the suboesophageal ganglion (SOG). In spite of this relatively simple architecture, the precise structure of the insect primary gustatory center has not been revealed in enough detail. To obtain comprehensive anatomical knowledge about this brain area, we screened the Drosophila melanogaster GAL4 enhancer‐trap strains that visualize specific subsets of the gustatory neurons as well as putative mechanosensory neurons associated with the taste pegs. Terminals of these neurons form three branches in the SOG. To map the positions of their arborization areas precisely, we screened newly established LexA::VP16 enhancer‐trap strains and obtained a driver line that labels a large subset of peripheral sensory neurons. By double‐labeling specific and landmark neurons with GAL4 and LexA strains, we were able to distinguish 11 zones in the primary gustatory center, among which 5 zones were identified newly in this study. Arborization areas of various known GRNs on the labellum, oesophagus, and legs were also mapped in this framework. The putative mechanosensory neurons terminate exclusively in three zones of these areas, supporting the notion of segregated primary centers that are specialized for chemosensory and mechanosensory signals associated with gustatory sensation. J. Comp. Neurol. 518:4147–4181, 2010. © 2010 Wiley‐Liss, Inc.