Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuliKronenberg, Golo; Reuter, Katja; Steiner, Barbara; Brandt, Moritz D.; Jessberger, Sebastian; Yamaguchi, Masahiro; Kempermann, Gerd
doi: 10.1002/cne.10945pmid: 14624480
To study how adult hippocampal neurogenesis might originate from the proliferation of stem or progenitor cells in vivo, we have used transgenic mice expressing green fluorescent protein (GFP) under the nestin promoter to identify these cells. Having described an astrocyte‐like type 1 cell with low proliferative activity, a characteristic morphology, vascular end feet, and passive electrophysiological properties, we focused here on the large population of nestin‐GFP‐expressing type 2 cells, which lack all these features. Type 2 cells were highly proliferative and showed signs suggestive of their involvement in the neuronal lineage. They could be subclassified by the absence (type 2a) or presence (type 2b) of a coexpression of the early neuronal marker doublecortin. A third type of proliferating cells was doublecortin positive but nestin‐GFP negative (type 3). We believe that type 2a, 2b, and 3 cells mirror a marker progression during earliest neuronal development. This view is supported by the increasing coexpression of the early granule cell‐specific marker Prox‐1. The low proliferative activity of type 1 cells showed little change over time or under “neurogenic interventions,” such as a challenge by environmental complexity (ENR) or voluntary physical activity (RUN). However, RUN led to a significant increase of type 2 cells labeled with the proliferation marker bromodeoxyuridine (BrdU). ENR did not cause increased cell proliferation or an increased number of BrdU‐labeled type 2 cells, but both ENR and RUN resulted in more newly generated cells lacking nestin‐GFP immunoreactivity and expressing Prox‐1. These findings allow us to break down what was broadly perceived as “proliferation” in earlier experiments into the relative contribution of several cell types, representing the earliest steps of neuronal development. J. Comp. Neurol. 467:455–463, 2003. © 2003 Wiley‐Liss, Inc.
Isoform‐specific distribution of the plasma membrane Ca2+ ATPase in the rat brainBurette, Alain; Rockwood, Julia M.; Strehler, Emanuel E.; Weinberg, Richard J.
doi: 10.1002/cne.10933pmid: 14624481
Regulation of cytoplasmic calcium is crucial both for proper neuronal function and cell survival. The concentration of Ca2+ in cytoplasm of a neuron at rest is 10,000 times lower than in the extracellular space, pointing to the importance of the transporters that extrude intracellular Ca2+. The family of plasma membrane calcium‐dependent ATPases (PMCAs) represent a major component of the Ca2+ regulatory system. However, little information is available on the regional and cellular distribution of these calcium pumps. We used immunohistochemistry to investigate the distribution of each of the four PMCA isoforms (PMCA1–4) in the rat brain. Each isoform exhibited a remarkably precise and distinct pattern of distribution. In many cases, PMCA isoforms in a single brain structure were differentially expressed within different classes of neurons, and within different subcellular compartments. These data show that each isoform is independently organized and suggest that PMCAs may play a more complex role in calcium homeostasis than generally recognized. J. Comp. Neurol. 467:464–476, 2003. © 2003 Wiley‐Liss, Inc.
Autonomic and motor neuron death is progressive and parallel in a lumbosacral ventral root avulsion model of cauda equina injuryHoang, Thao X.; Nieto, Jaime H.; Tillakaratne, Niranjala J.K.; Havton, Leif A.
doi: 10.1002/cne.10928pmid: 14624482
Injuries to the cauda equina of the spinal cord result in autonomic and motor neuron dysfunction. We developed a rodent lumbosacral ventral root avulsion injury model of cauda equina injury to investigate the lesion effect in the spinal cord. We studied the retrograde effects of a unilateral L5–S2 ventral root avulsion on efferent preganglionic parasympathetic neurons (PPNs) and pelvic motoneurons in the L6 and S1 segments at 1, 2, 4, and 6 weeks postoperatively in the adult male rat. We used Fluoro‐Gold–prelabeling techniques, immunohistochemistry, and quantitative stereologic analysis to show an injury‐induced progressive and parallel death of PPNs and motoneurons. At 6 weeks after injury, only 22% of PPNs and 16% of motoneurons remained. Furthermore, of the neurons that survived at 6 weeks, the soma volume was reduced by 25% in PPNs and 50% in motoneurons. Choline acetyltransferase (ChAT) protein was expressed in only 30% of PPNs, but 80% of motoneurons remaining at 1 week postoperatively, suggesting early differential effects between these two neuronal types. However, all remaining PPNs and motoneurons were ChAT positive at 4 weeks postoperatively. Nuclear condensation and cleaved caspase‐3 were detected in axotomized PPNs and motoneurons, suggesting apoptosis as a contributing mechanism of the neural death. We conclude that lumbosacral ventral root avulsions progressively deplete autonomic and motor neurons. The findings suggest that early neuroprotection will be an important consideration in future attempts of treating acute cauda equina injuries. J. Comp. Neurol. 467:477–486, 2003. © 2003 Wiley‐Liss, Inc.
Ipsilateral representation of oral structures in human anterior parietal somatosensory cortex and integration of inputs across the midlineDisbrow, Elizabeth A.; Hinkley, Leighton B.N.; Roberts, Timothy P.L.
doi: 10.1002/cne.10935pmid: 14624483
Anterior parietal somatosensory areas 3a, 3b, 1, and 2 generally contain cells with receptive fields that are on the contralateral body. However, inputs from midline structures such as the mouth must be uniquely integrated across the midline. This hypothesis is supported by studies of these fields from nonhuman primates that demonstrate ipsilateral representations of oral structures. We used magnetoencephalography (MEG) to examine the cortical representations of the lips and tongue in humans and to examine the time course of interaction of bilateral inputs from these structures. Ipsilateral activation was observed in response to tactile stimulation of the upper lip in 69% of cases, the lower lip in 85% of cases, and the tongue in 88% of cases. In the contralateral hemisphere, the map of oral structures tended to be in agreement with that from nonhuman primates, although variation was large and source locations were not statistically significantly different from each other. There were no differences in latency of activation for ipsi‐vs. contralateral responses (about 30 msec), and cortical sources from ipsi‐and contralateral stimulation tended to be located together. Differential activation for bilateral vs. unilateral stimulation occurred later than activation in S1, around 110 msec, and was localized to the upper bank of the Sylvian sulcus. Our findings indicate that, unlike nonhuman primates, humans have an ipsilateral representation of the lips in 3b/1, possibly related to the precise manipulation necessary for the articulation of speech. The distinct pattern of differential activation for uni‐vs. bilateral stimulation suggests a unique neural mechanism of integration across the midline for inputs from the mouth. J. Comp. Neurol. 467:487–495, 2003. © 2003 Wiley‐Liss, Inc.
Cloning of the zebra finch androgen synthetic enzyme CYP17: A study of its neural expression throughout posthatch developmentLondon, Sarah E.; Boulter, Jim; Schlinger, Barney A.
doi: 10.1002/cne.10936pmid: 14624484
Male zebra finches develop a robust neural song system that supports singing, but females have a minimal song circuit and do not sing. Estrogens masculinize the song circuit and are especially potent during the first 3 weeks of posthatch development. The gonads do not seem to supply the masculinizing steroids, implying that another tissue synthesizes steroids. Evidence suggests that the brain is capable of synthesizing neurosteroids, which in developing zebra finches may be required for song system differentiation. Aromatase, the enzyme that synthesizes estrogen from androgen, is equally abundant in male and female brains. To investigate further the potential for neurosteroidogenesis in the zebra finch brain, we cloned and examined the expression of 17α‐hydroxylase/17,20 lyase (CYP17), the enzyme that synthesizes the androgenic substrate for aromatase. We used Northern blots, reverse transcription‐polymerase chain reaction, and in situ hybridization to show that CYP17 is transcribed in developing and adult brains. CYP17 is transcribed at developmental stages and in brain areas potentially important to aspects of the developing song system, although no sex difference was detected in mRNA levels. Our results support the hypothesis that neurosteroids may act to influence brain organization and function in the zebra finch. J. Comp. Neurol. 467:496–508, 2003. © 2003 Wiley‐Liss, Inc.
Developmental segregation in the efferent projections to auditory hair cells in the gerbilRontal, Daniel A.; Echteler, Stephen M.
doi: 10.1002/cne.10931pmid: 14624485
The auditory receptor epithelium of mammals receives efferent innervation from neurons within and surrounding the superior olivary complex of the brainstem (Warr [1975] J. Comp. Neurol. 161:159–181). Disruption of this pathway during early postnatal life, when olivocochlear axons are forming their final connections with auditory hair cells and nerve fibers, can lead to profound and permanent hearing impairments (Walsh et al. [1998] J. Neurosci. 18:3859–3869). Identification of the possible causes for this deterioration in auditory function requires a better understanding of the normal developmental interactions that occur between efferent axons and their target cells within the cochlea. To provide such information, we labeled developing efferent fibers at a constant location within the gerbil cochlea by using the fluorescent carbocyanine dye 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindo‐carbocyanine perchlorate (DiI). The terminal arbors of these neurons were then reconstructed by using digital confocal microscopy. By postnatal day (P) 2, the efferent arbors associated with inner hair cells (IHCs) and outer hair cells (OHCs) displayed distinctly different morphologies closely resembling those described for adult animals (Brown [1987] J. Comp. Neurol. 260:605–619). Unlike their mature counterparts, however, P2 efferent axons frequently branched to contact both types of auditory hair cells. Unexpectedly, between P4 and P6, both IHC and OHC efferent axons produced additional branches that crossed the tunnel of Corti to invade the OHC zone. By P8, all of these supernumerary connections were eliminated, yielding completely segregated efferent pathways to IHCs and OHCs. J. Comp. Neurol. 467:509–520, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of mGluR1α and mGluR5 immunolabeling in primate prefrontal cortexMuly, E. Chris; Maddox, Marcelia; Smith, Yoland
doi: 10.1002/cne.10937pmid: 14624486
Metabotropic glutamate receptors (mGluRs) mediate important modulatory glutamatergic influences throughout the brain. However, the specific localization and functions of group I mGluR subtypes (mGluR1α and mGluR5) in cortical neurotransmission are not well known, particularly in primates. To address this issue, we used immunoelectron microscopy to compare the subcellular localizations of mGluR1α and mGluR5 in the prefrontal cortex of macaque monkeys. Both receptor subtypes were found in a variety of subcellular compartments, including spines, dendrites, preterminal axons, axon terminals, and glia; however, quantitative differences were found in the relative abundance of labeled elements for each receptor. The mGluR1α‐immunoreactive (‐IR) elements were overwhelmingly the spines and dendrites, with labeled terminals, axons, and glia seen more rarely. The mGluR5‐IR elements were also mostly spines and dendrites, but the proportion of labeled unmyelinated axons, terminals, and glia was higher than for mGluR1α‐IR elements. Double labeling with SMI‐32 and parvalbumin confirmed that both receptors were found in pyramidal cell and interneuron dendrites. The localization of mGluR1α to pyramidal cells in primate cortex contrasts with reports that mGluR1α is found almost exclusively in interneurons in rodent cortex. By using double labeling, we found no evidence for mGluR1α or mGluR5 in dopaminergic afferents to prefrontal cortex. The data presented here provide an anatomical substrate for a differential role of mGluR1α and mGluR5 in post‐and presynaptic actions of glutamate in primate prefrontal cortex. They further suggest differences in the cortical distribution of group I mGluRs between primates and rodents. J. Comp. Neurol. 467:521–535, 2003. © 2003 Wiley‐Liss, Inc.
Internal structure of the nucleus rotundus revealed by mapping cadherin expression in the embryonic chicken visual systemBecker, Tanja; Redies, Christoph
doi: 10.1002/cne.10954pmid: 14624487
The nucleus rotundus is the largest nucleus of the avian thalamus. It is an important center of visual information processing and conveys information from the optic tectum to the ectostriatum in the telencephalon. The nucleus rotundus is generally believed to contain internal divisions processing information on color, form, motion, and looming of visual objects. The detailed arrangement of these internal divisions is unclear. Here, we map the expression of four classic cadherins (N‐cadherin, R‐cadherin, cadherin‐6B, and cadherin‐7), which are markers for specific functional gray matter divisions and their fiber connections in the vertebrate brain. Results show that each cadherin is expressed by one coherent part of the nucleus rotundus that is connected to other brain structures by fiber tracts expressing the same subtype of cadherin. Overall, the expression of the four cadherins encompasses almost the entire nucleus rotundus. The four cadherin‐expressing parts show different degrees of overlap. For example, the cadherin‐6B part and the cadherin‐7 part overlap extensively, whereas the R‐cadherin part and the cadherin‐6B part show little overlap and are partially complementary. Regions with shallow gradients of cadherin expression alternate with regions that show relatively abrupt changes in cadherin expression. At some points, changes of cadherin expression are also arranged in a pinwheel‐like fashion, alternating between clockwise and counterclockwise orientations. In general, these results are reminiscent of the organization of functional modules in the mammalian visual cortex. It is speculated that each domain of cadherin expression corresponds to a functional domain, which processes a specific stimulus feature. J. Comp. Neurol. 467:536–548, 2003. © 2003 Wiley‐Liss, Inc.
Persistence of graded EphA/Ephrin‐A expression in the adult frog visual systemBach, Helene; Feldheim, David A.; Flanagan, John G.; Scalia, Frank
doi: 10.1002/cne.10941pmid: 14624488
Many studies have demonstrated the involvement of the EphA family of receptor tyrosine kinases and their ligands, ephrin‐A2 and ‐A5, in the development of the temporonasal axis of the retinotectal/collicular map, but the role of these molecules in optic nerve regeneration has not been well studied. Noting that the characteristic gradients of the EphA/ephrin‐A family that are expressed topographically in the retina and tectum of embryonic chicks and mice tend to disappear after birth, we took as our starting point an analysis of EphA and ephrin‐A expression in leopard frogs (Rana pipiens and utricularia), species capable of regenerating the retinotectal map as adults. For the EphA family to be involved in the regeneration, one would expect these topographic gradients to persist in the adult or, if downregulated after metamorphosis, to be reexpressed after optic nerve injury. Using EphA3 receptor and ephrin‐A5 ligand alkaline phosphatase in situ affinity probes (RAP and LAP, respectively) in whole‐mount applications, we report that reciprocally complementary gradients of RAP and LAP binding persist in the optic tract and optic tectum of postmetamorphic frogs, including mature adults. EphA expression in temporal retinal axons in the optic tract was significantly reduced after nerve section but returned during regeneration. However, ephrin‐A expression in the tectal parenchyma was not significantly elevated by either eye removal, with degeneration of optic axons, or during regeneration of the retinotectal projection. Thus, the present study has demonstrated a persisting expression of EphA/ephrin‐A family members in the retinal axons and tectal parenchyma that may help guide regenerating fibers, but we can offer no evidence for an upregulation of ephrin‐A expression in conjunction with optic nerve injury. J. Comp. Neurol. 467:549–565, 2003. © 2003 Wiley‐Liss, Inc.