bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unique 473HD-Chondroitinsulfate Epitope Is Expressed by Radial Glia and Involved in Neural Precursor Cell Proliferation
Authors: von Holst Alexander , Sirko Swetlana , Faissner Andreas
Published: April 2006

Neural stem cells have been documented in both the developing and the mature adult CNSs of mammals. This cell population holds a considerable promise for therapeutical applications in a wide array of CNS diseases. Therefore, universally applicable strategies for the purification of this population to further its cell biological characterization are sought. Here, we report that the unique chondroitin sulfate epitope recognized by the monoclonal antibody 473HD is surface expressed on actively cycling, multipotent progenitor cells of the developing telencephalon with radial glia-like properties. When used for immunopanning, the antibody enriched at least threefold for neural stem/progenitor cells characterized by the ability to self-renew as neurospheres that generated all major neural lineages in differentiation assays. In contrast, the 473HD-depleted cell fraction was mostly devoid of neurosphere-forming cells. The isolation of 473HD-positive adult multipotent progenitors from the subependymal zone of the lateral ventricle wall revealed a substantial overlap with the known adult neural stem cell marker LewisX. When the chondroitin sulfates were removed from immunoselected 473HD-positive neural stem/progenitor cell surfaces by chondroitinase ABC treatment or perturbed by the monoclonal antibody 473HD that recognizes the unique DSD-1 chondroitin sulfate epitope, the generation of neurospheres was significantly reduced. Thus, the 473HD epitope could not only be used for the isolation of multipotent neural progenitors during forebrain development as well as from the adult neurogenic niche but may also constitute a functionally important entity of the neural stem cell niche.
Essential Role of the Hippocampal Formation in Rapid Learning of Higher-Order Sequential Associations
Authors: Ergorul Ceren , Eichenbaum Howard
Published: April 2006

Evidence from studies of amnesia and functional imaging in humans suggest that the medial temporal lobe is involved in the learning of higher-order sequences during acquisition of serial reaction time (SRT) tasks. However, these studies have not clarified whether the hippocampal formation specifically is essential to this type of learning. Here, we developed a rodent model of the SRT task to examine the specific roles of the hippocampal formation in learning first- and second-order conditional sequences. Selective hippocampal formation lesions speeded performance and impaired accuracy on both first- and second-order sequences. Additionally, whereas controls distinguished the sequences based on their complexity alone, animals with hippocampal lesions initially differentiated sequences only by their length. Over multiple sessions, hippocampal rats gradually differentiated sequences by their complexity and not length, similar to control subjects. These findings indicate that the hippocampal formation itself plays an essential role in rapid acquisition of higher-order sequence representations. Extrahippocampal systems can also acquire complex sequential representations, albeit via a gradual learning mechanism.
Associative Memory Stored by Functional Novel Pathway rather than Modifications of Preexisting Neuronal Pathways
Authors: Straub Volko A. , Kemenes Ildiko , O’Shea Michael , Benjamin Paul R.
Published: April 2006

Associative conditioning involves changes in the processing pathways activated by sensory information to link the conditioned stimulus (CS) to the conditioned behavior. Thus, conditioning can recruit neuronal elements to form new pathways for the processing of the CS and/or can change the strength of existing pathways. Using a behavioral and systems level electrophysiological approach on a tractable invertebrate circuit generating feeding in the molluskLymnaea stagnalis, we identified three independent pathways for the processing of the CS amyl acetate used in appetitive conditioning. Two of these pathways, one suppressing and the other stimulating feeding, mediate responses to the CS in naive animals. The effects of these two pathways on feeding behavior are unaltered by conditioning. In contrast, the CS response of a third stimulatory pathway is significantly enhanced after conditioning, becoming an important contributor to the overall CS response. This is unusual because, in most of the previous examples in which naive animals already respond to the CS, memory formation results from changes in the strength of pathways that mediate the existing response. Here, we show that, in the molluscan feeding system, both modified and unmodified pathways are activated in parallel by the CS after conditioning, and it is their integration that results in the conditioned response.
Separate Populations of Receptor Cells and Presynaptic Cells in Mouse Taste Buds
Authors: DeFazio Richard A. , Dvoryanchikov Gennady , Maruyama Yutaka , Kim Joung Woul , Pereira Elizabeth , Roper Stephen D. , Chaudhari Nirupa
Published: April 2006

Taste buds are aggregates of 50–100 cells, only a fraction of which express genes for taste receptors and intracellular signaling proteins. We combined functional calcium imaging with single-cell molecular profiling to demonstrate the existence of two distinct cell types in mouse taste buds. Calcium imaging revealed that isolated taste cells responded with a transient elevation of cytoplasmic Ca2+to either tastants or depolarization with KCl, but never both. Using single-cell reverse transcription (RT)-PCR, we show that individual taste cells express either phospholipase C β2 (PLCβ2) (an essential taste transduction effector) or synaptosomal-associated protein 25 (SNAP25) (a key component of calcium-triggered transmitter exocytosis). The two functional classes revealed by calcium imaging mapped onto the two gene expression classes determined by single-cell RT-PCR. Specifically, cells responding to tastants expressed PLCβ2, whereas cells responding to KCl depolarization expressed SNAP25. We demonstrate this by two methods: first, through sequential calcium imaging and single-cell RT-PCR; second, by performing calcium imaging on taste buds in slices from transgenic mice in which PLCβ2-expressing taste cells are labeled with green fluorescent protein. To evaluate the significance of the SNAP25-expressing cells, we used RNA amplification from single cells, followed by RT-PCR. We show that SNAP25-positive cells also express typical presynaptic proteins, including a voltage-gated calcium channel (α1A), neural cell adhesion molecule, synapsin-II, and the neurotransmitter-synthesizing enzymes glutamic acid decarboxylase and aromatic amino acid decarboxylase. No synaptic markers were detected in PLCβ2 cells by either amplified RNA profiling or by immunocytochemistry. These data demonstrate the existence of at least two molecularly distinct functional classes of taste cells: receptor cells and synapse-forming cells.
Tubulin-Mediated Binding of Human Immunodeficiency Virus-1 Tat to the Cytoskeleton Causes Proteasomal-Dependent Degradation of Microtubule-Associated Protein 2 and Neuronal Damage
Authors: Aprea Susanna , Del Valle Luis , Mameli Giuseppe , Sawaya Bassel E. , Khalili Kamel , Peruzzi Francesca
Published: April 2006

One of the hallmarks of human immunodeficiency virus (HIV)-1 associated pathology in the CNS is deterioration of neuronal processes. Although there is mounting evidence of neuronal toxicity and cell death induced by the HIV-1 transactivating factor Tat, the molecular events linked directly to its detrimental effect on neuronal cells remain unclear. In this study, we used rat embryonic cortical neurons and demonstrated that Tat causes rapid degradation of microtubule-associated protein 2 (MAP2) and the collapse of cytoskeletal filaments. The mechanism of Tat action on MAP2 stability involved Tat-mediated translocation of the proteasome to the site of microtubule filaments. Immunohistochemical analysis of clinical samples from patients with HIV encephalopathy further revealed a significant decrease in MAP2 with predominant cytoplasmic 20S in cortical neurons near microglial nodules. These findings indicate a novel mechanism for the action of Tat on neuronal cells. It involves proteasome-mediated MAP2 degradation and may account for the loss of MAP2 and neuronal damage observed in the brain of AIDS patients with neurological dysfunctions.
Impaired Sequential Egocentric and Allocentric Memories in Forebrain-Specific–NMDA Receptor Knock-Out Mice during a New Task Dissociating Strategies of Navigation
Authors: Rondi-Reig Laure , Petit Géraldine H. , Tobin Christine , Tonegawa Susumu , Mariani Jean , Berthoz Alain
Published: April 2006

The hippocampus is considered to play a role in allocentric but not in egocentric spatial learning. How does this view fit with the emerging evidence that the hippocampus and possibly related cortical areas are necessary for episodic-like memory, i.e., in all situations in which events need to be spatially or sequentially organized? Are NMDA receptor-dependent mechanisms crucial for the acquisition of spatiotemporal relationships? To address this issue, we used knock-out (KO) mice lacking hippocampal CA1 NMDA receptors and presenting a reduction of these receptors in the deep cortical layers (NR1-KO mice). A new task (the starmaze) was designed, allowing us to distinguish allocentric and sequential-egocentric memories. NR1-KO mice were impaired in acquiring both types of memory. Our findings suggest that memories composed of multiple spatiotemporal events require intact NMDA receptors-dependent mechanisms in CA1 and possibly in the deep cortical layers.
Requirement of Akt to Mediate Long-Term Synaptic Depression inDrosophila
Authors: Guo Hui-Fu , Zhong Yi
Published: April 2006

Drosophilalarval neuromuscular junction (NMJ) is a well established preparation enabling quantitative analyses of synaptic physiology at identifiable synapses. Here, we report the first characterization of synaptic long-term depression (LTD) at theDrosophilaNMJ. LTD can be reliably induced by specific patterns of tetanic stimulation, and the level of LTD depends on both stimulus frequency and Ca2+concentration. We provide evidence that LTD is likely a result of presynaptic changes. Through screening of targeted mutants with defects in memory or signal transduction pathways, we found that LTD is strongly reduced in theaktmutants. This defect can be rescued by acutely induced expression of the normalakttransgene, suggesting that altered LTD is not attributable to developmental abnormalities and that Akt is critical for the induction of LTD. Our study also indicates that the molecular mechanisms of LTD are distinct from that of short-term synaptic plasticity, becauseaktmutants showed normal short-term facilitation and posttetanic potentiation, whereas LTD was unaffected in mutants that exhibit defective short-term synaptic plasticity, such asdunceandrutabaga. The characterization of LTD allows genetic analysis of the molecular mechanisms of long-term synaptic plasticity inDrosophilaand provides an additional assay for studying functions of genes pertaining to synaptic and behavioral plasticity.
Semaphorin-1a Functions as a Guidance Receptor in theDrosophilaVisual System
Authors: Cafferty Patrick , Yu Li , Long Hong , Rao Yong
Published: April 2006

The evolutionarily conserved Semaphorin family proteins are well known axon guidance ligands that mediate both attractive and repulsive responses in invertebrates and vertebrates. In this study, we show that theDrosophilaSemaphorin-1a (Sema1a), a transmembrane Semaphorin, is required cell autonomously in adult photoreceptor (R-cell) axons for the establishment of an appropriate topographic termination pattern in the optic lobe. Loss ofsema1adisrupts the association of neighboring R-cell growth cones leading to defects in local termination pattern, whereas overexpression ofsema1ainduces the hyper-fasciculation of R-cell axons. The function of Sema1a in R-cell axon guidance absolutely requires its cytoplasmic domain. We propose that Sema1a functions as a receptor in regulating R-cell axon guidance in theDrosophilavisual system.
Effects of Musical Experience on Different Components of MEG Responses Elicited by Sequential Piano-Tones and Chords
Authors: Kuriki Shinya , Kanda Satoshi , Hirata Yoshihiro
Published: April 2006

Magnetoencephalographic (MEG) studies have revealed enhancement of neural activity of the N1m response of auditory evoked fields in long-term trained musicians, reflecting neuroplastic modification of the representation of the auditory cortex. In contrast, the amplitude of the P2 response of auditory evoked potentials is modified by musical experience, with no alteration of N1. Here, we performed a comprehensive MEG study using stimulation of successive musical-instrument tones to examine how the neural activities of different MEG responses are modified in long-term experienced musicians who commenced musical lessons at ages of ∼5 years and had continued to practice. The dipole moment of the P2m response occurring at 160–180 ms was significantly enlarged in musicians compared with that in individuals who had not received musical lessons. The enlargement was found for the dipole moment of N1m occurring at 100–120 ms in a restricted condition but not for the moment of P1m at 50–60 ms. Furthermore, the dipole moment of P2m for successive stimuli, normalized by the moment for the first stimulus, was significantly larger for chord tones than single tones and was significantly larger in the musicians than controls. These results suggest that the P2m response is susceptible to be modified by musical training in a period of neural maturation, with a short refractory period of neural activity for the auditory input of composite tones. The P2m activity may be specialized to the processing of multifrequency sounds, such as musical timbre consisting of abundant harmonics.
Estimation of the Timing of Human Visual Perception from Magnetoencephalography
Authors: Amano Kaoru , Goda Naokazu , Nishida Shin'ya , Ejima Yoshimichi , Takeda Tsunehiro , Ohtani Yoshio
Published: April 2006

To explore the timing and the underlying neural dynamics of visual perception, we analyzed the relationship between the manual reaction time (RT) to the onset of a visual stimulus and the time course of the evoked neural response simultaneously measured by magnetoencephalography (MEG). The visual stimuli were a transition from incoherent to coherent motion of random dots and an onset of a chromatic grating from a uniform field, which evoke neural responses in different cortical sites. For both stimuli, changes in median RT with changing stimulus strength (motion coherence or chromatic contrast) were accurately predicted, with a stimulus-independent postdetection delay, from the time that the temporally integrated MEG response crossed a threshold (integrator model). In comparison, the prediction of RT was less accurate from the peak MEG latency, or from the time that the nonintegrated MEG response crossed a threshold (level detector model). The integrator model could also account for, at least partially, intertrial changes in RT or in perception (hit/miss) to identical stimuli. Although we examined MEG–RT relationships mainly for data averaged over trials, the integrator model could show some correlations even for single-trial data. The model predictions deteriorated when only early visual responses presumably originating from the striate cortex were used as the input to the integrator model. Our results suggest that the perceptions for visual stimulus appearances are established in extrastriate areas [around MT (middle temporal visual area) for motion and around V4 (fourth visual area) for color] ∼150–200 ms before subjects manually react to the stimulus.
Control of Mammalian Cochlear Amplification by Chloride Anions
Authors: Santos-Sacchi Joseph , Song Lei , Zheng Jiefu , Nuttall Alfred L.
Published: April 2006

Chloride ions have been hypothesized to interact with the membrane outer hair cell (OHC) motor protein, prestin on its intracellular domain to confer voltage sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that transmembrane chloride movements via the lateral membrane conductance of the cell,GmetL, could serve to underlie cochlear amplification in the mammal. Here, we report on experimental manipulations of chloride-dependent OHC motor activityin vitroandin vivo.In vitro, we focused on the signature electrical characteristic of the motor, the nonlinear capacitance of the cell. Using the well known ototoxicant, salicylate, which competes with the putative anion binding or interaction site of prestin to assess level-dependent interactions of chloride with prestin, we determined that the resting level of chloride in OHCs is near or below 10 mm, whereas perilymphatic levels are known to be ∼140 mm. With this observation, we sought to determine the effects of perilymphatic chloride level manipulations of basilar membrane amplification in the living guinea pig. By either direct basolateral perfusion of the OHC with altered chloride content perilymphatic solutions or by the use of tributyltin, a chloride ionophore, we found alterations in OHC electromechanical activity and cochlear amplification, which are fully reversible. Because these anionic manipulations do not impact on the cation selective stereociliary process or the endolymphatic potential, our data lend additional support to the argument that prestin activity dominates the process of mammalian cochlear amplification.
Opioid Receptors in the Nucleus Accumbens Regulate Attentional Learning in the Blocking Paradigm
Authors: Iordanova Mihaela D. , McNally Gavan P. , Westbrook R. Frederick
Published: April 2006

Fear learning depends on prediction error, or the discrepancy between the actual and expected outcome of a conditioning trial. These experiments used blocking and unblocking designs to study the role of opioid receptors in the nucleus accumbens (Acb) in predictive fear learning. Previous fear conditioning to a context blocked later fear conditioning to a conditioned stimulus (CS) in that context. Fear learning proceeded normally (i.e., unblocking occurred) if the CS signaled a more intense footshock than was used during previous context conditioning. Blocking and unblocking were mediated by Acb opioid receptors. Acb microinjections of a nonselective opioid receptor agonist prevented blocking, whereas a nonselective antagonist prevented unblocking. Examination of the associative mechanism for blocking and unblocking revealed that Acb opioid receptors mediate indirect predictive learning by controlling learned variations in attention. μ-Opioid and κ-opioid receptors contribute to this learned regulation of attention because Acb microinjections of a μ-opioid receptor agonist impaired, whereas a κ-opioid receptor agonist facilitated, blocking. Acb microinjections of a μ-opioid receptor antagonist also prevented unblocking. Microinjections of a δ-opioid receptor agonist or antagonist were without effect on blocking and unblocking. Our data show that the Acb mediates attentional selection between competing predictors of motivationally significant events to enable learning about the best predictor of such events at the expense of worse predictors. During fear learning, Acb μ-opioid receptors upregulate attention to conditioned stimuli that are predictive of shock, whereas κ-opioid receptors downregulate attention to conditioned stimuli that are redundant or noninformative predictors of shock.
Medial Frontal Cortex Activity and Loss-Related Responses to Errors
Authors: Taylor Stephan F. , Martis Brian , Fitzgerald Kate D. , Welsh Robert C. , Abelson James L. , Liberzon Israel , Himle Joseph A. , Gehring William J.
Published: April 2006

Making an error elicits activity from brain regions that monitor performance, especially the medial frontal cortex (MFC). However, uncertainty exists about whether the posterior or anterior/rostral MFC processes errors and to what degree affective responses to errors are mediated in the MFC, specifically the rostral anterior cingulate cortex (rACC). To test the hypothesis that rACC mediates a type of affective response, we conceptualized affect in response to an error as a reaction to loss and amplified this response with a monetary penalty. While subjects performed a cognitive interference task during functional magnetic resonance imaging, hemodynamic activity in the rACC was significantly greater when subjects lost money as a result of an error compared with errors that did not lead to monetary loss. A significant interaction between the incentive conditions and error events demonstrated that the effect was not merely attributable to working harder to win (or not lose) money, although an effect of motivation was noted in the mid-MFC. Activation foci also occurred in similar regions of the posterior MFC for error and interference processing, which were not modulated by the incentive conditions. However, at the level of the individual subject, substantial functional variability occurred along the MFC during error processing, including foci in the rostral/anterior extent of the MFC not appearing in the group analysis. The findings support the hypothesis that the rostral extent of the MFC (rACC) processes loss-related responses to errors, and individual differences may account for some of the reported variation of error-related foci in the MFC.
Persistent Responses to Brief Stimuli: Feedback Excitation among Brainstem Neurons
Authors: Li Wen-Chang , Soffe Stephen R. , Wolf Ervin , Roberts Alan
Published: April 2006

The ability of brief stimuli to trigger prolonged neuronal activity is a fundamental requirement in nervous systems, common to motor responses and short-term memory. Bistable membrane properties and network feedback excitation have both been proposed as suitable mechanisms to sustain such persistent responses. There is now good experimental evidence for membrane bistability. In contrast, the long-standing hypotheses based on positive feedback excitation have yet to be supported by direct evidence for mutual excitatory connections between appropriate neurons. In young frog tadpoles (Xenopus), we show that a small region of caudal hindbrain and rostral spinal cord is sufficient to generate prolonged swimming in response to a brief stimulus. We used paired whole-cell patch recordings to identify hindbrain neurons in this region that actively excite spinal neurons to drive sustained swimming. We show directly that some of these hindbrain neurons make reciprocal excitatory connections with each other. We use a population model of the hindbrain network to illustrate how feedback excitation can provide a robust mechanism to generate persistent responses. Our recordings provide direct evidence for feedback excitation among neurons within a network that drives a prolonged response. Its presence in a lower brain region early in development suggests that it is a basic feature of neuronal network design.
Low Doses of Memantine Disrupt Memory in Adult Rats
Authors: Creeley Catherine , Wozniak David F. , Labruyere Joanne , Taylor George T. , Olney John W.
Published: April 2006

Memantine, a drug recently approved for treatment of Alzheimer’s disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptor-mediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose that we found, contrary to previous reports, produces locomotor disturbances severe enough to preclude testing for learning and memory effects. We then determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts both memory and locomotor behaviors. Rats treated with these doses performed at control-like levels in learning a hole-board task but were significantly impaired in demonstrating what they had learned when tested 24 h later. This impairment of memory retention was not state dependent in that it was demonstrable regardless of whether the rats were or were not exposed to memantine on the day of retention testing. We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment.
Random Wiring in the Midget Pathway of Primate Retina
Authors: Jusuf Patricia R. , Martin Paul R. , Grünert Ulrike
Published: April 2006

The present study addresses the questions of how topographically organized neuronal populations are connected, and whether there is anatomical evidence for color-selective wiring in retinal pathways for red–green color vision. The connectivity of OFF midget bipolar and OFF midget ganglion cells was studied in the peripheral retina of dichromatic (“red–green color blind”) and trichromatic (“color normal”) marmosets (Callithrix jacchus). Midget bipolar cells were identified immunohistochemically. Midget ganglion cells were retrogradely labeled from the lateral geniculate nucleus and photofilled. Comparable results were obtained from all retinas studied. Between 3 and 16 bipolar terminals converge onto each ganglion cell. Nearly all bipolar terminals investigated show regions of colocalization (areas of presumed synaptic contacts) with ganglion cell dendrites. This contact area makes up ∼14% of the axon surface area for a typical midget bipolar cell. The output from individual midget bipolar axons is often shared between midget ganglion cells so that, on average, <70% of the axon terminal area of a midget bipolar cell shows overlap with the dendritic field of a given midget ganglion cell. We conclude that there is no morphological evidence of red–green color selectivity in the connections between midget bipolar and midget ganglion cell mosaics. Furthermore, the results suggest that convergence is based on local interactions between axons and dendrites rather than cell-by-cell recognition between members of each mosaic.
Long-Term Effects of Brief Acute Stress on Cellular Signaling and Hippocampal LTP
Authors: Ahmed Tariq , Frey Julietta U. , Korz Volker
Published: April 2006

In a previous study, we reported that a brief exposure to swim stress transforms an electrically induced, protein synthesis-independent early long-term potentiation (early LTP) into a protein synthesis-dependent late LTP [“reinforcement of LTP” in the hippocampal dentate gyrus (DG)] (Korz and Frey, 2003). This transformation depends on activation of mineralocorticoid receptors (MRs) by corticosterone, and on intact basolateral amygdala (BLA) function. Here, we demonstrate that a brief swim experience results in lasting changes in levels of hippocampal cellular signaling molecules that are known to be involved in the induction of late LTP. Within the DG, MRs were rapidly upregulated, whereas glucocorticoid receptor (GR) levels were elevated with a 3 h delay. Levels of phosphorylated mitogen-activated protein kinase 2 (pMAPK2) and p38 MAPK, as well as phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMKII) were enhanced shortly after swim stress and remained elevated until 24 h, whereas levels of phosphorylated cAMP response element-binding protein (pCREB) remained unchanged. MR and GR were upregulated with a longer delay within the CA1 region, whereas levels of pMAPK2 and p38MAPK were rapidly increased, but the former returned to basal levels after 3 h. Levels of pCREB and pCaMKII were maintained in an enhanced state after swim stress. DG-LTP reinforcement requires a serotonergic but not dopaminergic heterosynaptic receptor activation that probably mediates the BLA-dependent modulation of LTP under stress. Thus, molecular alterations induced by specific stress resemble late LTP-related molecular changes. These changes, in interaction with stress-specific heterosynaptic processes, may support the transformation of early LTP into late LTP. The results contribute to the understanding of the rapid consolidation of cellular and possibly systemic memories triggered by stress.
Pathological Changes in Dopaminergic Nerve Cells of the Substantia Nigra and Olfactory Bulb in Mice Transgenic for Truncated Human α-Synuclein(1–120): Implications for Lewy Body Disorders
Authors: Tofaris George K. , Garcia Reitböck Pablo , Humby Trevor , Lambourne Sarah L. , O’Connell Mark , Ghetti Bernardino , Gossage Helen , Emson Piers C. , Wilkinson Lawrence S. , Goedert Michel , Grazia Spillantini Maria
Published: April 2006

Dysfunction of the 140 aa protein α-synuclein plays a central role in Lewy body disorders, including Parkinson’s disease, as well as in multiple system atrophy. Here, we show that the expression of truncated human α-synuclein(1–120), driven by the rat tyrosine hydroxylase promoter on a mouse α-synuclein null background, leads to the formation of pathological inclusions in the substantia nigra and olfactory bulb and to a reduction in striatal dopamine levels. At the behavioral level, the transgenic mice showed a progressive reduction in spontaneous locomotion and an increased response to amphetamine. These findings suggest that the C-terminal of α-synuclein is an important regulator of aggregationin vivoand will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders and multiple system atrophy.
Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain
Authors: Bertolino Alessandro , Blasi Giuseppe , Latorre Valeria , Rubino Valeria , Rampino Antonio , Sinibaldi Lorenzo , Caforio Grazia , Petruzzella Vittoria , Pizzuti Antonio , Scarabino Tommaso , Nardini Marcello , Weinberger Daniel R. , Dallapiccola Bruno
Published: April 2006

Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158allele and the DAT 3′ variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.
Spike-Timing Codes Enhance the Representation of Multiple Simultaneous Sound-Localization Cues in the Inferior Colliculus
Authors: Chase Steven M. , Young Eric D.
Published: April 2006

To preserve multiple streams of independent information that converge onto a neuron, the information must be re-represented more efficiently in the neural response. Here we analyze the increase in the representational capacity of spike timing over rate codes using sound localization cues as an example.

The inferior colliculus receives convergent input from multiple auditory brainstem nuclei, including sound localization information such as interaural level differences (ILDs), interaural timing differences (ITDs), and spectral cues. Virtual space techniques were used to create stimulus sets varying in two sound-localization parameters each. Information about the cues was quantified using a spike distance metric that allows one to separate contributions to the information arising from spike rate and spike timing.

Spike timing enhances the representation of spectral and ILD cues at timescales averaging 12 ms. ITD information, however, is carried by a rate code. Comparing responses to frozen and random noise shows that the temporal information is mainly attributable to phase locking to temporal stimulus features, with an additional first-spike latency component. With rate-based codes, there is significant confounding of information about two cues presented simultaneously, meaning that the cues cannot be decoded independently. Spike-timing-based codes reduce this confounded information. Furthermore, the relative representation of the cues often changes as a function of the time resolution of the code, implying that information about multiple cues can be multiplexed onto individual spike trains.
Controlling the Gain of Rod-Mediated Signals in the Mammalian Retina
Authors: Dunn Felice A. , Doan Thuy , Sampath Alapakkam P. , Rieke Fred
Published: April 2006

Effective sensory processing requires matching the gain of neural responses to the range of signals encountered. For rod vision, gain controls operate at light levels at which photons arrive rarely at individual rods, light levels too low to cause adaptation in rod phototransduction. Under these conditions, adaptation within a conserved pathway in mammalian retina maintains sensitivity as light levels change. To relate retinal signals to behavioral work on detection at low light levels, we measured how background light affects the gain and noise of primate ganglion cells. To determine where and how gain is controlled, we tracked rod-mediated signals across the mouse retina. These experiments led to three main conclusions: (1) the primary site of adaptation at low light levels is the synapse between rod bipolar and AII amacrine cells; (2) cellular noise after the gain control is nearly independent of background intensity; and (3) at low backgrounds, noise in the circuitry, rather than rod noise or fluctuations in arriving photons, limits ganglion cell sensitivity. This work provides physiological insights into the rich history of experiments characterizing how rod vision avoids saturation as light levels increase.
Cholinergic Modulation of Synaptic Transmission and Postsynaptic Excitability in the Rat Gracilis Dorsal Column Nucleus
Authors: Fernández de Sevilla David , Rodrigo-Angulo Margarita , Nuñez Angel , Buño Washington
Published: April 2006

Somatosensory information, conveyed through the gracilis nucleus (GN), is regulated by descending corticofugal (CF) glutamatergic fibers. In addition, the GN receives cholinergic inputs with still unclear source and functional significance. Using both thein vitroslice and intracellular recording with sharp and patch electrodes andin vivoextracellular single-unit recordings, we analyzed the effects of activation of cholinergic receptors on synaptic, intrinsic, and functional properties of rat GN neurons. The cholinergic agonist carbamilcholine-chloride [carbachol (CCh); 1–10 μm]in vitro(1) induced presynaptic inhibition of EPSPs evoked by both dorsal column and CF stimulation, (2) increased postsynaptic excitability, and (3) amplified the spike output of GN neurons. The inhibition by atropine (1 μm) and pirenzepine (10 μm) of all presynaptic and postsynaptic effects of CCh suggests actions through muscarinic M1receptors. The above effects were insensitive to nicotinic antagonists. We searched the anatomical origin of the cholinergic projection to the GN throughout the hindbrain and forebrain, and we found that the cholinergic fibers originated mainly in the pontine reticular nucleus (PRN). Electrical stimulation of the PRN amplified sensory responses in the GNin vivo, an effect prevented by topical application of atropine. Our results demonstrate for the first time that cholinergic agonists induce both presynaptic and postsynaptic effects on GN neurons and suggest an important regulatory action of inputs from cholinergic neuronal groups in the pontine reticular formation in the functional control of somatosensory information flow in the GN.
Seizures Accelerate Functional Integration of Adult-Generated Granule Cells
Authors: Overstreet-Wadiche Linda S. , Bromberg Daniel A. , Bensen AeSoon L. , Westbrook Gary L.
Published: April 2006

In humans and experimental animals, structural and functional changes in neural circuits can accompany the development of epilepsy. In the dentate gyrus, seizures enhance adult neurogenesis, but it is unclear to what extent newborn granule cells participate in seizure-induced synaptic reorganization. During the first weeks of their existence, mouse newborn granule cells labeled with enhanced green fluorescent protein have only short dendrites that lack excitatory input. We report that pilocarpine-induced seizures accelerated the morphological development of labeled granule cells, causing their dendrites to extend through the molecular layer. In whole-cell recordings 5–16 d after seizure induction, perforant-path stimulation now evoked glutamatergic input to newborn granule cells. These synaptic responses were mediated by monosynaptic as well as recurrent polysynaptic input. Thus, seizures facilitated functional integration of adult-generated granule cells. One month later, subsequent generations of newborn cells also showed alterations in dendrite morphology, suggesting persistent effects of seizures on granule cell maturation. The sensitivity of newborn granule cells to seizures could contribute to hyperexcitability during the latent period.
Aging-Dependent Alterations in Synaptic Plasticity and Memory in Mice That Overexpress Extracellular Superoxide Dismutase
Authors: Hu Daoying , Serrano Faridis , Oury Tim D. , Klann Eric
Published: April 2006

Oxidative damage caused by reactive oxygen species (ROS) has been proposed to be critically involved in several pathological manifestations of aging, including cognitive dysfunction. ROS, including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. Therefore, we reasoned that the role that ROS and antioxidant enzymes play in modulating neuronal processes varies over the lifespan of an animal. We examined hippocampal long-term potentiation (LTP) and memory-related behavioral performance in transgenic mice overexpressing extracellular superoxide dismutase (EC-SOD) and their wild-type littermates at different ages. We found that aged EC-SOD transgenic mice exhibited enhanced hippocampal LTP, better cerebellum-dependent motor learning, and better hippocampus-dependent spatial learning compared with their wild-type littermates. We also found that EC-SOD overexpression impaired contextual learning, but the impairment was decreased in the aged transgenic mice. At the molecular level, aged EC-SOD transgenic mice had lower superoxide levels, a decrease in protein carbonyl levels, and a decrease in p38 and extracellular signal-regulated kinase 2 phosphorylation compared with aged wild-type mice. Our findings suggest that elevated levels of superoxide contribute to aging-related impairments in hippocampal LTP and memory, and that these impairments can be alleviated by overexpression of EC-SOD. We conclude that there is an age-dependent alteration in the role of superoxide in modulating synaptic plasticity and learning and memory.
Espaço social urbano e doença mental: um estudo de área ecológica
Authors: Almeida Filho Naomar de , Santana Vilma Souza
Published: April 2006

A hipótese de uma correlação positiva entre densidade demográfica e níveis de psicopatologia foi testada, a partir de um estudo de área ecológica realizado em um setor de baixa renda da Região Metropolitana de Salvador-BA. Taxas de prevalência de doença mental em adultos e em crianças, além de níveis de sintomatologia psiquiátrica, coletadas por área, através de um inquérito transversal, com uma amostra representativa de 1 549 adultos e 848 crianças, foram tomadas como indicadores da variável dependente. Densidade externa e densidade interna, tempo de residência urbana e renda média per capita, medidas por meio de coleta direta na mesma amostra, foram utilizadas como variáveis independentes. A análise de regressão múltipla revelou que apenas renda exercia um efeito significante, porém no sentido oposto ao previsto, sobre as equações de todas as variáveis dependentes. O incremento no R², que variou de 15 a 71%, deveu-se principalmente a variáveis não incluídas nas hipóteses, como média de idade, número de residentes por família e proporção de migrantes. As hipóteses deste estudo, em resumo, são refutadas pelos seus resultados, devendo-se interpretar tais achados basicamente em termos das suas objeções metodológicas.
Variação sazonal das trocas gasosas, turgescência relativa do tronco e produtividade em dois cultivares de seringueira em Votuporanga, SP, Brasil
Authors: Conforto Elenice de Cássia , Cavalcante Juliane Ribeiro , Pessoa José Dalton Cruz , Moreno Rogério Manoel Biagi , Mattoso Luiz Henrique Capparelli
Published: April 2006

Alguns pesquisadores têm enfocado a influência dos fatores agrometeorológicos e fisiológicos sobre a produtividade da seringueira, mas a magnitude destas relações ainda não é totalmente conhecida. Assim, no presente estudo, investigou-se a possível relação entre alguns parâmetros fisiológicos e a produção de dois cultivares de seringueira, PB 235 e GT 1, cultivados em Votuporanga, Estado de São Paulo, durante o período seco e úmido de 2000-2001. A produção total do período foi de 4.550,5 kg/ha, dos quais PB 235 respondeu por 59,9%, com produção 12,6% maior que a de GT 1 no período seco e 29,8 % no período úmido. Os valores da taxa fotossintética variaram entre 2,19 e 3,46 µmol m-2s-1 para GT 1, e entre 2,31 e 3,93 µmol m-2s-1 para PB 235; a transpiração variou entre 0,66 e 1,88 mmol m-2s-1 e 0,78 e 1,77 mmolm-2s-1, respectivamente; e, a condutância estomática, entre 0,021 e 0,041 molm-2s-1 e 0,021 e 0,043 mol m-2s-1, respectivamente. A ausência de recuperação noturna da turgescência do caule durante o período seco, em ambos os cultivares, poderia justificar a variação da produtividade, que foi mais intensa em PB 235, provavelmente decorrente do significativo decréscimo da taxa fotossintética e da eficiência da carboxilação neste período.
Effect of Spring Application of a Paper Mill Soil Conditioner on Corn Yield
Authors: Curnoe William E. , Irving David C. , Dow Charles B. , Velema George , Unc Adrian
Published: April 2006

Use of paper mill residuals as soil amendment on farmland is believed to have a beneficial impact on crop yields and soil quality. The objective of our study was to evaluate the effect of spring applying Domtar Soil Conditioner (SC) (pulp and paper mill waste water treatment residue) to a sandy soil in eastern Ontario, Canada. The effects of SC on corn (Zea mays L.) yields, N concentrations in plants, and post‐harvest levels in soil of NO3, P, K, Mg, organic matter (OM), and pH were investigated. The experimental design was a randomized complete block with five treatments, replicated four times. The treatments included two SC rates (15 and 25 Mg ha−1 dry matter: SC15 and SC25), 150 kg ha−1 NH4NO3–N (N150), a composite SC and mineral fertilizer treatment (15 Mg ha−1 dry matter SC and 75 kg ha−1 NH4NO3–N: SC15N75), and a control. The experiment was repeated annually from 1997 to 2001. Addition of SC the spring before planting increased grain yield by 2360 kg ha−1 for SC15 and by 2908 kg ha−1 for SC25 vs. the control. When N was also added (SC15N75), the average increase vs. the control was 3406 kg ha−1. More total N was measured in the corn plants from the plots amended with SC than the control. The SC amendments temporarily increased soil OM but did not increase NO3–N leaching risk. Annual spring application of SC improved corn yield but had little impact on soil nutrient levels, OM, and pH.
Tillage and Phosphorus Management Effects on Crop Production in Soils with Phosphorus Stratification
Authors: Schwab Gregory J. , Whitney David A. , Kilgore Gary L. , Sweeney Daniel W.
Published: April 2006

Reduced‐ and no‐tillage seedbed preparation methods coupled with broadcast P applications lead to an accumulation of available P in the surface 0‐ to 5‐cm soil layer and a depletion of available P deeper in the profile. A 3‐yr study determined the effects of tillage and fertilizer P management on P uptake and grain yield for P‐stratified soils. Tillage practices were moldboard plow (once at the start of the study followed by reduced tillage), reduced tillage (disk followed by field cultivation), and no‐tillage. Four P management methods were imposed: (i) no P; (ii) 20 kg P ha−1 applied as a surface broadcast; (iii) 20 kg ha−1 applied as a banded starter, 5 cm to the side and 5 cm below the seed; or (iv) 20 kg ha−1 applied in a deep placed band, 13 to 15 cm on 0.7‐m centers. The one‐time moldboard plowing produced higher early season dry matter yields for corn (Zea mays L.), wheat (Triticum aestivum L.), and soybean [Glycine max (L.) Merr.] compared with the no‐tillage system, but tillage effects on final grain yield were inconsistent. Subsurface placement of P generally increased P uptake and grain yield of corn and sorghum [Sorghum bicolor (L.) Moench], but had little effect on grain yield of soybean. Results indicate that subsurface applications of P fertilizers should be considered if soil test P is highly stratified within the surface 0‐ to 15‐cm layer and the 15‐cm composite is medium or below for available P.
Tillage × Maize Hybrid Interactions
Authors: Duiker Sjoerd W. , Haldeman James F. , Johnson David H.
Published: April 2006

Continuous maize (Zea mays L.) yields may be depressed with no‐tillage (NT) compared with conventional chisel and disking systems (CD). Shallow or deep in‐row tillage (ST and DT, respectively) may help alleviate this yield reduction, whereas some hybrids may be better adapted to NT. We therefore evaluated five maize hybrids with NT, ST, DT, and CD from 2002 to 2004 on a Hagerstown silt loam (fine, mixed, semiactive, mesic Typic Hapludalf) in southeastern Pennsylvania. Residue cover, penetration resistance, bulk density, and soil temperature were measured as well as maize emergence, mid‐season height, and yield. Residue cover varied in the order NT > ST and DT > CD. Bulk density and penetration resistance in NT were higher than in ST, DT, and CD to the depth of tillage. In 2002, the average soil temperature during the first month after planting varied in the order NT < ST and DT < CD, but did not vary between tillage systems in 2004. Emergence was slower in NT than the other tillage systems in 2002 only. Emergence varied between hybrids, but there was no tillage × hybrid interaction. Mid‐season maize height was not lower in NT than the other tillage systems. Tillage systems did not affect yield, and there was no tillage × hybrid interaction for yield, although some hybrids yielded better than others. The study suggests continuous maize yields with NT will be similar to tilled systems on well‐drained soils in the northeastern USA and that tillage system is not important for hybrid selection.