bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel mechanosensitive channel identified in sensory neurons
Authors: Cho Hawon , Koo Jae Yeon , Kim Sangsung , Park Sung Pyo , Yang Youngduk , Oh Uhtaek
Published: May 2006

Mechanosensitive (MS) channels are ion channels gated by different types of mechanical stimuli. MS channels in sensory neurons are thought to be molecular transducers for somatic sensations such as touch, pressure, proprioception and pain. Previously, we reported that two types of MS channels are present in sensory neurons. These channels are termed low threshold (LT) and high threshold (HT) MS channels based on their pressure threshold for activation. Here, we report another type of MS channel present in sensory neurons. The channel is activated by low pressure applied to a patch (threshold ∼20 mmHg, similar to that in the LT channel). However, because this channel has a smaller single‐channel conductance than that of the LT channel, the newly classified MS channel is now called a low threshold small conductance (LTSC) channel. Unlike the LT channel, which has outwardly rectifying currents, the current–voltage relationship of the LTSC is linear. The LTSC was permeable to monovalent cations and Ca2+, and reversibly blocked by gadolinium, a blocker of MS channels. Unlike the LT channel, the LTSC was sensitized by prostaglandin E2, an inflammatory mediator that is known to sensitize nociceptors to mechanical stimuli. LTSC channels were found mostly in small cultured sensory neurons. Thus, these results suggest that the LTSC is a distinct type of MS channel that is different from the LT and HT channels in sensory neurons, and that LTSCs might play a role in mediating somatosensations, including pain.
Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion
Authors: Grimaldi Piercesare , Rossi Ferdinando
Published: May 2006

Although constitutive neurogenesis exclusively occurs in restricted regions of the adult mammalian brain, resident progenitors can be isolated from many different CNS sites, and neuronal neogeneration can be stimulated in vivo by injury or infusion of growth factors. To ask whether latent compensatory mechanisms, which may be exploited to promote repair processes, are present throughout the CNS, we examined the neurogenic potentialities of the adult rat cerebellum in normal conditions, following injury, and after infusion of growth factors. Degeneration of Purkinje cells was induced by intracerebroventricular administration of the toxin saporin, conjugated to anti‐p75 antibodies. In addition, epidermal growth factor and basic fibroblast growth factor, or FGF8, were infused for 2 weeks to either intact or injured animals. In all conditions, proliferating cells were identified from bromodeoxiurydine (BrdU) incorporation. In the unmanipulated cerebellum there were rare dividing cells, mainly represented by NG2‐positive presumptive oligodendrocyte precursors. Mitotic activity was strongly enhanced in cortical areas with Purkinje cell degeneration, being mostly sustained by microglia, plus minor fractions of NG2‐expressing cells, astrocytes and oligodendrocytes. In contrast, growth factor infusion had a weak effect on both intact and injured cerebella. In all experimental conditions, we never found any BrdU‐positive cells coexpressing distinctive markers for immature or differentiated cerebellar neurons. Therefore, although some progenitor cells reside in the adult cerebellum, the local environment, either intact or injured, does not provide efficient cues to direct their differentiation towards neuronal phenotypes. In addition, neurogenic potentialities cannot be induced or boosted by the application of growth factors which are effective in other CNS regions.
Clearance and prevention of prion infection in cell culture by anti‐PrP antibodies
Authors: Pankiewicz Joanna , Prelli Frances , Sy Man‐Sun , Kascsak Richard J. , Kascsak Regina B. , Spinner Daryl S. , Carp Richard I. , Meeker Harry C. , Sadowski Marcin , Wisniewski Thomas
Published: May 2006

Prion diseases are transmissible and invariably fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrPC) into a self‐replicating and proteinase K (PK)‐resistant conformer, scrapie PrP (PrPSc). Humoral immunity may significantly prolong the incubation period and even prevent disease in murine models of prionoses. However, the mechanism(s) of action of anti‐PrP monoclonal antibodies (Mabs) remain(s) obscure. The murine neuroblastoma N2a cell line, infected with the 22L mouse‐adapted scrapie strain, was used to screen a large library of Mabs with similar binding affinities to PrP, to identify those antibodies which could clear established infection and/or prevent infection de novo. Three Mabs were found capable of complete and persistent clearing of already‐infected N2a cells of PrPSc. These antibodies were 6D11 (generated to PK‐resistant PrPSc and detecting PrP residues 93–109), and 7H6 and 7A12, which were raised against recombinant PrP and react with neighbouring epitopes of PrP residues 130–140 and 143–155, respectively. Mabs were found to interact with PrPSc formation both on the cell surface and after internalization in the cytosol. Treatment with Mabs was not associated with toxicity nor did it result in decreased expression of PrPC. Both preincubation of N2a cells with Mabs prior to exposure to 22L inoculum and preincubation of the inoculum with Mabs prior to infecting N2a cells resulted in a significant reduction in PrPSc levels. Information provided in these studies is important for the rational design of humoral immune therapy for prion infection in animals and eventually in humans.
Self‐Regulatory Dysfunctions in Personality Disorders: The Role of Poor Self‐Monitoring and Mindreading
Authors: Dimaggio Giancarlo , Nicolò Giuseppe , Popolo Raffaele , Semerari Antonio , Carcione Antonino
Published: May 2006

To understand how persons self‐regulate, we need, as Cervone, Shadel, Smith, and Fiori (2006) assert, to refer to personality science, with which it is possible to identify the multifarious psychological elements and processes helping or hindering action programming, overcoming difficulties, and error correction. Personality disorder research and personality science itself demonstrate that dysfunctions in two skills—self‐monitoring and mindreading—worsen self‐regulation and lead individuals to fail chronically to achieve goals in the social domain. Here we describe how poor self‐reflection and biased mindreading impair self‐regulation in personality disorders and other clinical conditions and make some suggestions about how to tackle them in psychotherapy.
Personality Science and Self‐Regulation: Personal Projects as Integrative Units
Authors: Little Brian R.
Published: May 2006

Cervone, Shadel, Smith, and Fiori (2006) make a strong case for enhancing theoretical coherence in the study of self‐regulation by examining recent advances in personality science. I extend their line of argument, reframe their philosophical reminders and strategically shift their suggestions. My goal is to provide an augmented base from which personality science and self‐regulation research and practice can derive mutual benefit. Consensus seems to be emerging that personality science can be usefully conceptualised as a multi‐tier structure, each floor of which focuses on different units of analysis. I focus on Tier I (trait units) and Tier II (PAC units (personal action constructs)). I suggest that Tier II is the home of both the social cognitive theorists and social ecological theorists and that they seem to have colluded to ignore each other. I use Cervone et al.'s timely article as a stimulant to do some renovation work on this floor. Focusing on personal projects I suggest that they provide an integrative function for personality science that augments the contributions of their close neighbors doing CAPS and KAPA research. By some minor renovations we find ourselves able to speak to the narrative theorists in the loft above and even to the trait theorists below. The resulting conversational potential, I suggest, is salutary for both personality science and the study of self‐regulation.
Eco‐dependency in Latin America
Authors: Barton Jonathan R.
Published: May 2006

This article develops an argument around the perpetuation of socioeconomic development models based on non‐renewable natural resource exploitation, weak management and regulation of renewables and the deterioration in environmental quality across different natural resources. It concludes that the structural constraints pointed out during the 1940–80 period by thedependentistas(advocates of the various theorizations of dependency) and to a lesser extent thecepalistastructuralists (policy analysts at the United Nations Economic Commission for Latin America and the Caribbean) were alive and well in Latin America in the period 1980–2000. A theoretical case is made for the political economy reading of dependency into the realm of natural resources and environmental issues. It is argued that Latin American history and the region’s more contemporary insertion into the global political economy has been determined by its use of natural resources and ongoing degradation of diverse environments. The conclusions emphasize the importance of responding to this historical condition, recognizing the concerns of the structuralists of the 1940s and 1950s and the threats highlighted by thedependentistasin the 1970s, but through the lens of contemporary changes.
Involvement of the Cyclic AMP‐Responsive Element Binding Protein Gene Transcription Factor in Genetic Preference for Alcohol Drinking Behavior
Authors: Pandey Subhash C. , Mittal Navdha , Lumeng Lawrence , Li Ting‐Kai
Published: May 2006

Background:Cyclic adenosine 3′,5′‐monophosphate (cAMP)‐responsive element binding (CREB) protein is a gene transcription factor that can integrate the signals mediated via the cAMP second messenger cascade at the gene expression level, which then controls neuronal functions.

Methods:To examine if the protein kinase A → CREB signaling cascade is involved in genetic alcohol drinking preference, different measures of CREB were determined in various brain structures of alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rats.

Results:We show here that CRE‐DNA binding activity is significantly decreased in the amygdala but not in the cortex, hippocampus, or striatum of P rats compared with NP rats. The levels of total CREB and phosphorylated CREB protein in the amygdala are significantly lower in P rats compared with NP rats. On the other hand, levels of the α‐isoform of the catalytic subunit of protein kinase A protein, and basal as well as cAMP‐stimulated protein kinase A activity are similar in the amygdala of both P and NP rats.

Conclusions:Because P and NP rats are genetically bred for high and low alcohol drinking behavior, respectively, these results suggest the possibility that decreased expression of CREB protein in the amygdala may be associated with the high alcohol drinking behavior of P rats.
Michaelis‐Menten Elimination Kinetics of Acetate in Rabbit
Authors: Fujimiya Tatsuya , Li Yu‐Jiang , Uemura Koichi , Ohbora Yumiko
Published: May 2006

Background: Acetate redistribution from hepatic to peripheral tissues was reported during ethanol metabolism when saturating conditions were reached for acetate metabolism. Because this redistribution cannot be clarified by linear kinetics, elimination kinetics of acetate was studied in the rabbit.

Methods: A sodium‐acetate solution in physiological saline (0.5 and 1.0 g/kg of body weight) was injected as an intravenous bolus. The blood acetate profile was measured by headspace gas chromatography.

Results: Blood acetate disappeared rapidly. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve and the mean residence time increased with an increasing dose amount. These increases suggested a capacity‐limited elimination of acetate. Simultaneous multilines fitting after two acetate doses was used to estimate the pharmacokinetic model by the application of minimum Akaike's information criterion estimation. As a result, the blood acetate concentration‐time curve was best described by a two‐compartment open model with Michaelis‐Menten elimination kinetics. The Vmax value was approximately two times larger than that of ethanol obtained by using the same compartment model. The Km value (1.5 mM) was almost the same as that of ethanol and corresponded to blood acetate levels during ethanol oxidation that had been reported to be approximately 2 mM.

Conclusion: The elimination of acetate obeys nonlinear kinetics, which can clarify the saturation of acetate metabolism.
Use of Colonic Luminal Pressure to Predict Outcome After Surgical Treatment of Strangulating Large Colon Volvulus in Horses
Authors: MATHIS STEPHANIE C. , SLONE DONNIE E. , LYNCH TIMOTHY M. , HUGHES FAITH E. , CLARK CAROL K.
Published: May 2006

Objective—To evaluate the relationship of colonic luminal pressure (CLP) measurements to outcome in horses with large colon volvulus (LCV) after either manual correction or large colon resection and anastomosis (LCRA).

Study Design—Retrospective study.

Animals—Horses (n=57) that had LCV.

Methods—Records for horses with LCV (March 1997–December 2003) were reviewed. Inclusion criteria were strangulating LCV proximal to the cecocolic ligament (>270°), recorded CLP, and successful recovery from anesthesia. CLP measurements and survival/mortality rates were compared between horses that had manual correction (M) or LCRA (R).

Results—Of 57 horses, 27 had M and 30 had LCRA. For group M, CLP measurements had a sensitivity of 0.60 and specificity of 0.77 for predicting survival, whereas for group R, sensitivity was 0.50 and specificity was 0.54.

Conclusion—In our LCV population, elevated CLP measurements had poor accuracy for predicting outcome in horses after surgical correction, especially after LCRA.

Clinical Relevance—CLP measurements based on a single hospital population of horses with LCV should be used with caution for other hospital populations of LCV. CLP may be only one of many variables needed for predicting outcome of horses with strangulating LCV, especially after LCRA.
Clinical Evaluation of the CRIF 4.5/5.5 System for Long‐Bone Fracture Repair in Cattle
Authors: GAMPER SIMONE , STEINER ADRIAN , NUSS KARL , OHLERTH STEFANIE , FÜRST ANTON , FERGUSON JAMES G. , AUER JOERG A. , LISCHER CHRISTOPH
Published: May 2006

Objective— To report clinical evaluation of the clamp rod internal fixator 4.5/5.5 (CRIF 4.5/5.5) in bovine long‐bone fracture repair.

Study Design— Retrospective study.

Animals— Cattle (n=22) with long‐bone fractures.

Methods— Records for cattle with long‐bone fractures repaired between 1999 and 2004 with CRIF 4.5/5.5 were reviewed. Quality of fracture repair, fracture healing, and clinical outcome were investigated by means of clinical examination, medical records, radiographs, and telephone questionnaire.

Results— Successful long‐term outcome was achieved in 18 cattle (82%); 4 were euthanatized 2–14 days postoperatively because of fracture breakdowns. Two cattle had movement of clamps on the rod. Moderate to severe callus formation was evident in 11 cattle 6 months postoperatively.

Conclusions— Movement of clamps on the rod was recognized as implant failure unique to the CRIF. This occurred in cattle with poor fracture stability because of an extensive cortical defect. The CRIF system may not be ideal to treat metacarpal/metatarsal fractures because its voluminous size makes skin closure difficult, thereby increasing the risk of postoperative infections.

Clinical Relevance— CRIF cannot be recommended for repair of complicated long‐bone fractures in cattle.
Partial Prostatectomy Using Nd:YAG Laser for Management of Canine Prostate Carcinoma
Authors: L'Eplattenier Henry F. , Van Nimwegen Sebastiaan A. , Van Sluijs Frederik J. , Kirpensteijn Jolle
Published: May 2006

Objective—To report a technique for partial prostatectomy by laser dissection and to evaluate outcome and complications in dogs with prostate carcinoma (PCA).

Study Design—Experimental and clinical case series.

Animals—Four normal dogs and 8 dogs with PCA.

Methods—Subcapsular partial prostatectomy, sparing the urethra and the dorsal aspect of the prostatic capsule, using Nd:YAG laser dissection to remove the prostatic parenchyma and control hemorrhage was performed in 4 normal dogs and subsequently in 8 dogs with histologically confirmed PCA. Additional treatment of PCA dogs included local application of interleukin‐2 and systemic administration of meloxicam. Prostate size, complications, and survival time were recorded. Laser‐associated thermal damage to surrounding tissue was evaluated by histology.

Results—In normal dogs, no damage to the dorsal prostatic capsule or urethra was detected. In PCA dogs, median survival was 103 days (range, 5–239 days). Three dogs died from complications within 16 days, whereas 5 (median survival, 183 days; range, 91–239 days) had improvement or resolution of clinical signs. Urinary incontinence did not occur.

Conclusion—Laser assisted subcapsular partial prostatectomy can be performed in dogs with PCA without development of postoperative incontinence.

Clinical Relevance—Subcapsular partial prostatectomy is a potential palliative treatment for PCA in dogs and may lead to the resolution of clinical signs for several months.
INSTRUMENTAL AND SENSORY EVALUATION OF TEXTURAL CHANGES DURING ROASTING OF CASHEW KERNELS
Authors: WANLAPA APINUN , JINDAL V.K.
Published: May 2006

Textural changes in cashew kernels roasted in hot‐air oven at controlled temperatures in the range of 140–180C for 30–120 min were studied using both instrumental and sensory evaluations. The Kramer shear force decreased exponentially, whereas the color lightness index and the total color difference exhibited linear relationships with roasting time at all temperatures. The changes in sensory parameters such as acceptability, appearance and taste were adequately described by third‐degree polynomials. The optimum roasting conditions for cashew kernels based on hedonic sensory evaluations were determined to be 140C–33.3 min, 160C–11.2 min and 180C–5.7 min, and resulted in similar values of Kramer shear force and color lightness index estimated from the developed models. The instrumental measurements could be used for monitoring the roasting process to produce optimally roasted cashew kernels.
Local Signals From Beyond the Receptive Fields of Striate Cortical Neurons
Authors: Müller James R. , Metha Andrew B. , Krauskopf John , Lennie Peter
Published: May 2006

We examined in anesthetized macaque how the responses of a striate cortical neuron to patterns inside the receptive field were altered by surrounding patterns outside it. The changes in a neuron's response brought about by a surround are immediate and transient: they arise with the same latency as the response to a stimulus within the receptive field (this argues for a source locally in striate cortex) and become less effective as soon as 27 ms later. Surround signals appeared to exert their influence through divisive interaction (normalization) with those arising in the receptive field. Surrounding patterns presented at orientations slightly oblique to the preferred orientation consistently deformed orientation tuning curves of complex (but not simple) cells, repelling the preferred orientation but without decreasing the discriminability of the preferred grating and ones at slightly oblique orientations. By reducing responsivity and changing the tuning of complex cells locally in stimulus space, surrounding patterns reduce the correlations among responses of neurons to a particular stimulus, thus reducing the redundancy of image representation.
Cerebellar Responses Evoked by Nociceptive Leg Withdrawal Reflex as Revealed by Event-Related fMRI
Authors: Dimitrova A. , Kolb F. P. , Elles H.-G. , Maschke M. , Forsting M. , Diener H. C. , Timmann D.
Published: May 2006

The aim of the present study was to examine nociceptive leg withdrawal reflex–related areas in the human cerebellum using event-related functional brain imaging (fMRI). Knowledge about cerebellar areas involved in unconditioned limb withdrawal reflex control has some relevance in understanding data of limb withdrawal reflex conditioning studies. Sixteen healthy adult subjects participated. Nociceptive leg withdrawal reflexes were evoked by electrical stimulation of the left tibial nerve behind the medial malleolus. An event-related fMRI paradigm was applied with a total of 30 stimuli being delivered pseudorandomly during 500 consecutive MR scans. Surface electromyographic (EMG) recordings were performed from the left anterior tibial muscle. Only trials with significant reflex EMG activity were used as active events in fMRI statistical analysis. The specified contrasts compared the active event condition with rest. Leg withdrawal reflex–related areas were located within the vermis, paravermis, and lateral posterior cerebellar hemispheres bilaterally. Vermal and paravermal areas in lobules III/IV in the anterior lobe and in lobule VIII in the posterior lobe agree with the cerebellar representation of climbing and mossy fiber hindlimb afferents and voluntary leg movements. They are likely related to efferent modulation of the leg withdrawal reflex and/or sensory processing of afferent inputs from the reflex and/or the noxious stimulus. Additional activation within vermal lobule VI and hemispheral lobules VI/Crus I may be related to other pain-related processes (e.g., facial grimacing, fear, and startlelike reactions).
From Rule to Response: Neuronal Processes in the Premotor and Prefrontal Cortex
Authors: Wallis Jonathan D. , Miller Earl K.
Published: May 2006

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: “same” or “different.” The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.
Rapid Olfactory Processing Implicates Subcortical Control of an Olfactomotor System
Authors: Johnson Bradley N. , Mainland Joel D. , Sobel Noam
Published: May 2006

Sniffs are modulated in response to odor content. Higher concentrations of odor induce lesser-volume sniffs. This phenomenon implicates a neural feedback mechanism that measures sensory input (odor concentration) and modulates motor output (sniffing) accordingly. Here we used air-dilution olfactometry to probe the time course of this olfactomotor mechanism. A stainless-steel computer-controlled olfactometer, equipped with mass flow controllers, temperature and humidity control, and on-line photo-ionization detection, was coupled to a highly sensitive pneumatotachograph that measured nasal flow. The olfactometer was used to generate four ascending concentrations of the odorants propionic acid and phenethyl alcohol. Sniff volume was inversely related to odor concentration ( P > 0.0001). Sniffs were uniform and concentration independent for the initial 150 ms but acquired a concentration-dependent flowrate as early as 160 ms following sniff onset for propionic acid ( P > 0.05) and 260 ms for phenethyl alcohol ( P > 0.05). Considering that odorant transduction takes around 150 ms and odorant-induced cortical evoked potentials have latencies of around 300 ms, the rapid motor adjustments measured here suggest that olfactomotor sniff feedback control is subcortical and may rely on neural mechanisms similar to those that modulate eye movements to accommodate vision and ear movements to accommodate audition.
Adaptive Changes in Early and Late Blind: A fMRI Study of Verb Generation to Heard Nouns
Authors: Burton H. , Snyder A. Z. , Diamond J. B. , Raichle M. E.
Published: May 2006

Literacy for blind people requires learning Braille. Along with others, we have shown that reading Braille activates visual cortex. This includes striate cortex (V1), i.e., banks of calcarine sulcus, and several higher visual areas in lingual, fusiform, cuneus, lateral occipital, inferior temporal, and middle temporal gyri. The spatial extent and magnitude of magnetic resonance (MR) signals in visual cortex is greatest for those who became blind early in life. Individuals who lost sight as adults, and subsequently learned Braille, still exhibited activity in some of the same visual cortex regions, especially V1. These findings suggest these visual cortex regions become adapted to processing tactile information and that this cross-modal neural change might support Braille literacy. Here we tested the alternative hypothesis that these regions directly respond to linguistic aspects of a task. Accordingly, language task performance by blind persons should activate the same visual cortex regions regardless of input modality. Specifically, visual cortex activity in blind people ought to arise during a language task involving heard words. Eight early blind, six late blind, and eight sighted subjects were studied using functional magnetic resonance imaging (fMRI) during covert generation of verbs to heard nouns. The control task was passive listening to indecipherable sounds (reverse words) matched to the nouns in sound intensity, duration, and spectral content. Functional responses were analyzed at the level of individual subjects using methods based on the general linear model and at the group level, using voxel based ANOVA and t-test analyses. Blind and sighted subjects showed comparable activation of language areas in left inferior frontal, dorsolateral prefrontal, and left posterior superior temporal gyri. The main distinction was bilateral, left dominant activation of the same visual cortex regions previously noted with Braille reading in all blind subjects. The spatial extent and magnitude of responses was greatest on the left in early blind individuals. Responses in the late blind group mostly were confined to V1 and nearby portions of the lingual and fusiform gyri. These results confirm the presence of adaptations in visual cortex of blind people but argue against the notion that this activity during Braille reading represents somatosensory (haptic) processing. Rather, we suggest that these responses can be most parsimoniously explained in terms of linguistic operations. It remains possible that these responses represent adaptations which initially are for processing either sound or touch, but which are later generalized to the other modality during acquisition of Braille reading skills.
Modulation of Dorsal Spinocerebellar Responses to Limb Movement. I. Effect of Serotonin
Authors: Bosco G. , Rankin A. , Poppele R. E.
Published: May 2006

Spinocerebellar neurons (DSCT) receive converging sensory information from various sensory receptors in the hindlimbs and lower trunk. Previous studies have shown that sensory processing by DSCT neurons results in a representation of global hindlimb kinematic parameters such as the length and the orientation of the limb axis. In addition to the sensory input, the DSCT circuitry also receives a descending input from the raphe nuclei in the brain stem. Recent studies have demonstrated that the raphe serotonergic terminals synapse directly on DSCT neurons and exert a differential modulatory influence on their sensory inputs. We examined the role of serotonergic modulation on the DSCT representation of hindlimb kinematic parameters by recording DSCT activity during passive hindlimb movements before and after perturbing serotonergic transmission. We used two types of perturbation: electrical stimulation of the raphe areas in the brain stem to release serotonin in the spinal cord (42 neurons) and intravenous administration of serotonergic agonists or antagonists, mostly the 5HTP2 antagonist ketanserin (30 neurons). We found that movement responses were altered in ∼70% of the DSCT units studied with each protocol. Changes could include shifts in mean firing rate, increases or decreases in response amplitude, and changes in response waveform. We used a principal component analysis (PCA) to examine waveform components and to determine how they contributed to the response waveform changes caused by serotonin perturbation. Such changes could be explained by new or different response components that might indicate a modification in the data processing or by a different weighting of existing components that might indicate a modification of synaptic weighting. The results were consistent with the second alternative. We found that the same underlying response components could account for both control responses and those altered by serotonin perturbations. The observed changes in waveform could be entirely accounted for by a re-weighting of response components. In particular, the changes observed after raphe stimulation could be accounted for by selective changes in the weighting of the first principal component (PC) with only minor changes of the weighting of the second PC. Because these response components were shown previously to correlate with the limb axis orientation and length trajectories respectively, the finding is consistent with the idea that limb axis length and orientation information are processed separately within the spinal circuitry.
Modulation of Dorsal Spinocerebellar Responses to Limb Movement. II. Effect of Sensory Input
Authors: Bosco G. , Poppele R. E.
Published: May 2006

Dorsal spinocerebellar tract (DSCT) neurons receive converging sensory inputs from muscle, skin, and joint receptors and their cerebellar projection is a product of the spinal sensory processing of movement-related information. We concluded earlier that DSCT activity relates to global rather than to local parameters of hindlimb postures and movement, specifically to a kinematic representation of the limb endpoint. The waveforms of principal components (PCs) derived from an ensemble of DSCT movement responses were found to correlate with either the waveform of the limb axis length or orientation trajectories. It was not clear, however, whether these global representations resulted from neural processing or from biomechanical factors. In this study, we perturbed the limb biomechanical factors by decoupling limb geometry from endpoint position during passively applied limb trajectories patterned after a step cycle. We used two types of perturbations: mechanical constraints that limited joint rotations and electrical stimulation of hindlimb muscles. We found that about half of the 89 cells studied showed statistically different response patterns during the perturbations. We compared the PCs of the altered responses with the PCs of the control responses, and found two basic results. With the joint constraints, >85% of the total variance in both control and changed responses was accounted for by the same five PCs that were also observed in the earlier study. The differences between altered and control responses could be fully accounted for by changes in the PC weighting, suggesting a modulation of global response components rather than an explicit representation of local parameters. With the muscle stimulation, only the first and third PCs were the same for the control and altered responses. The second PC was modified, and additional PCs were also required to account for the altered responses. This suggests that the stimulus parameters were specifically represented in the responses. The changes induced by both types of perturbation affected primarily the weighting or waveform of the second PC, which relates to the limb axis length trajectory. The results are consistent with the suggestion that information about limb orientation and length may be separately modulated.
Dopamine D4 Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in the Rat Supraoptic Nucleus
Authors: Azdad Karima , Piet Richard , Poulain Dominique A. , Oliet Stéphane H. R.
Published: May 2006

The mechanism by which dopamine induces or facilitates neurohypophysial hormone release is not completely understood. Because oxytocin- and vasopressin-secreting supraoptic neurons are under the control of a prominent GABAergic inhibition, we investigated the possibility that dopamine exerts its action by modulating GABA-mediated transmission. Whole cell voltage-clamp recordings of supraoptic neurons were carried out in acute hypothalamic slices to determine the action of dopamine on inhibitory postsynaptic currents. Application of dopamine caused a consistent and reversible reduction in the frequency, but not the amplitude, of miniature synaptic events, indicating that dopamine was acting presynaptically to reduce GABAergic transmission. The subtype of dopamine receptor involved in this response was characterized pharmacologically. Dopamine inhibitory action was greatly reduced by two highly selective D4 receptor antagonists L745,870 and L750,667 and to a lower extent by the antipsychotic drug clozapine but was unaffected by SCH 23390 and sulpiride, D1/D5 and D2/D3 receptor antagonists, respectively. In agreement with these results, the action of dopamine was mimicked by the potent D4 receptor agonist PD168077 but not by SKF81297 and bromocriptine, D1/D5 and D2/D3 receptor agonists, respectively. Dopamine and PD168077 also reduced the amplitude of evoked inhibitory postsynaptic currents, an effect that was accompanied by an increase in paired-pulse facilitation. These data clearly indicate that D4 receptors are located on GABA terminals in the supraoptic nucleus and that their activation reduces GABA release in the supraoptic nucleus. Therefore dopaminergic facilitation of neurohypophysial hormone release appears to result, at least in part, from disinhibition of magnocellular neurons caused by the depression of GABAergic transmission.
Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns
Authors: Ene F. Aura , Kullmann Paul H. M. , Gillespie Deda C. , Kandler Karl
Published: May 2006

The lateral superior olive (LSO) is a binaural auditory brain stem nucleus that plays a central role in sound localization. Survival and maturation of developing LSO neurons critically depend on intracellular calcium signaling. Here we investigated the mechanisms by which glutamatergic afferents from the cochlear nucleus increase intracellular calcium concentration in LSO neurons. Using fura-2 calcium imaging in slices prepared from neonatal mice, we found that cochlear nucleus afferents can activate all major classes of ionotropic and metabotropic glutamate receptors, each of which contributes to an increase in intracellular calcium. The specific activation of different glutamate receptor classes was dependent on response amplitudes and afferent stimulus patterns. Low-amplitude responses elicited by single stimuli were entirely mediated by calcium-impermeable AMPA/kainate receptors that activated voltage-gated calcium channels. Larger-amplitude responses elicited by either single stimuli or stimulus trains resulted in additional calcium influx through N-methyl-d-aspartate receptors. Finally, high-frequency stimulation also recruited group I and group II metabotropic glutamate receptors, both of which mobilized intracellular calcium. This calcium release in turn activated a strong influx of extracellular calcium through a membrane calcium channel that is distinct from voltage-gated calcium channels. Together, these results indicate that before hearing onset, distinct patterns of afferent activity generate qualitatively distinct types of calcium responses, which likely serve in guiding different aspects of LSO development.
Neurons in the Primate Orbitofrontal Cortex Respond to Fat Texture Independently of Viscosity
Authors: Verhagen Justus V. , Rolls Edmund T. , Kadohisa Mikiko
Published: May 2006

The primate orbitofrontal cortex (OFC) is a site of convergence from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the OFC that respond to orally applied fat (e.g., safflower oil) and to substances with a similar texture but different chemical composition, such as mineral oil (hydrocarbon) and silicone oil [(Si(CH3)2O)n]. These findings provide evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Use of an oral viscosity stimulus consisting of carboxymethyl-cellulose in the range 1–10,000 centipoise (cP) showed that the responses of these fat-sensitive neurons are not related to stimulus viscosity. Thus a textural component independent of viscosity and related to the slick or oily property is being used to activate these oral fat-sensitive neurons. Moreover, a separate population of neurons responds to viscosity (produced, e.g., by the carboxymethyl-cellulose series), but not to fat with the same viscosity. Thus there is a dissociation between texture channels used to sense fat viscosity and non–fat-produced viscosity. Further, free fatty acids such as linoleic acid do not activate these neurons, providing further evidence that the oral fat-sensing mechanism through which these OFC neurons are activated is not gustatory but textural. Most of this population of fat-sensitive neurons receive convergent taste inputs. These results provide evidence about how oral fat is sensed and are relevant to understanding the physiological and pathophysiological processes related to fat intake.
Reduction of Spontaneous Inhibitory Synaptic Activity in Experimental Heterotopic Gray Matter
Authors: Chen Huan-Xin , Roper Steven N.
Published: May 2006

Neuronal heterotopia has a strong association with epilepsy, but the mechanisms that underlie this relationship are largely unknown. We have utilized the in utero irradiated rat model to study circuit abnormalities in experimentally induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from visualized heterotopic pyramidal neurons in in vitro hemispheric slices and compared with control neocortical pyramidal neurons using the whole cell patch-clamp technique. The frequency of spontaneous and miniature IPSCs was significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and kinetics of IPSCs were not different between the two groups. Spontaneous and miniature EPSCs were not different between the two groups. Short-term synaptic plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and facilitation in control pyramidal neurons. This study shows a selective impairment of the GABAergic circuitry in experimental heterotopic gray matter. We have reported similar findings in normotopic dysplastic cortex from this model. Taken together, these studies demonstrate a pervasive defect in inhibition throughout the cortex of irradiated rats with cortical dysplasia and neuronal heterotopia. This may have important implications regarding cortical development and function following in utero injuries.
Characterization and Developmental Changes of Na+Currents of Petrosal Neurons With Projections to the Carotid Body
Authors: Cummins Theodore R. , Dib-Hajj Sulayman D. , Waxman Stephen G. , Donnelly David F.
Published: May 2006

Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into an increase in spiking activity on the sinus nerve, and this response increases with postnatal age over the first week or two of life. Previous work from our laboratory has suggested a major role of axonal Na+ channels in the initiation of afferent spiking activity. Using RT–PCR of the petrosal ganglia we identified Na+ channel TTX-S isoforms Nav1.1, Nav1.6, and Nav1.7 and the TTX-resistant (TTX-R) isoforms Nav1.8 and Nav1.9 at high levels. Electrophysiologic recordings (at 3 ages: 3 days, 9 days, 18–20 days) of neurons that project to the carotid body exhibited predominantly fast-inactivating sodium currents, with a bimodal recovery from inactivation at −80 mV (fast component ∼ 8 ms; slow component ∼90 ms). Developmental age had little effect with no change in peak current density (approximately 1.4 nA/pF) and was associated with a slight, but significant increase in the speed of recovery from inactivation at −140 and −120 mV but not at other potentials. Assuming that the same Na+ channel complement is present at the nerve terminal as at the soma, the association of a sensory modality (chemoreception) with a relatively uniform Na+ channel profile suggests that the rapid kinetics of TTX-S channels may be essential for some aspects of chemoreceptor function beyond mediating simple axonal conduction.
Contrasting Neuronal Activity in the Supplementary and Frontal Eye Fields During Temporal Organization of Multiple Saccades
Authors: Isoda Masaki , Tanji Jun
Published: May 2006

The organization of a series of actions into an appropriate temporal order is of particular importance in the voluntary control of motor behavior. Previous reports have emphasized the importance of medial motor areas for the temporal organization of movements. The aim of this study was to compare the neuronal activity in the supplementary and frontal eye fields (SEF and FEF) during sequential performance of multiple saccades to clarify the role of the two cortical oculomotor areas in the temporal organization of saccades based on memorized information. We analyzed neuronal activity while monkeys performed three saccades to peripheral targets in orders that were instructed and memorized. We found that activity that reflected saccade sequence or the numerical position of a saccade within a sequence (rank) was more prevalent in the SEF, whereas activity reflecting saccade direction was more dominant in the FEF. Furthermore, a sizeable number of SEF neurons exhibited an increase in activity when the animals were required to discard a current sequence and compose a novel sequence. We propose that the SEF is primarily involved in the process of planning, decoding, and updating saccade sequences, whereas the FEF plays a major role in determining the direction of forthcoming saccades.
GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat
Authors: Matsumoto Noriaki , Kumamoto Eiichi , Furue Hidemasa , Yoshimura Megumu
Published: May 2006

An ischemia-induced change in glutamatergic transmission was investigated in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique; the ischemia was simulated by superfusing an oxygen- and glucose-free medium (ISM). Following ISM superfusion, 21 of 37 SG neurons tested produced an outward current (23 ± 4 pA at a holding potential of −70 mV), which was followed by a slow and subsequent rapid inward current; the remaining neurons had only inward currents. During such a change in holding currents, spontaneous excitatory postsynaptic currents (EPSCs) were remarkably decreased in a frequency with time (half-decay time of the frequency: about 65 s). The frequency of spontaneous EPSCs was reduced to 28 ± 13% ( n = 37) of the control level during the generation of the slow inward current (about 4 min after the beginning of ISM superfusion) without a change in the amplitude of spontaneous EPSCs. When ISM was superfused together with either bicuculline (10 μM) or CGP35348 (20 μM; GABAA and GABAB receptor antagonists, respectively), spontaneous EPSC frequency reduced by ISM recovered to the control level and then the frequency markedly increased [by 325 ± 120% ( n = 22) and 326 ± 91% ( n = 17), respectively, 4 min after ISM superfusion]; this alteration in the frequency was not accompanied by a change in spontaneous EPSC amplitude. Superfusing TTX (1 μM)-containing ISM resulted in a similar recovery of spontaneous EPSC frequency and following increase (by 328 ± 26%, n = 12) in the frequency; strychnine (1 μM) did not affect ISM-induced changes in spontaneous EPSC frequency ( n = 5). It is concluded that the ischemic simulation inhibits excitatory transmission to SG neurons, whose action is in part mediated by the activation of presynaptic GABAAand GABAB receptors, probably due to GABA released from interneurons as a result of an ischemia-induced increase in neuronal activities. This action might protect SG neurons from an excessive excitation mediated by l-glutamate during ischemia.
Somatostatin Depresses Long-Term Potentiation and Ca2+ Signaling in Mouse Dentate Gyrus
Authors: Baratta Michael V. , Lamp Tyra , Tallent Melanie K.
Published: May 2006

The selective loss of somatostatin (SST)-containing interneurons from the hilus of the dentate gyrus is a hallmark of epileptic hippocampus. The functional consequence of this loss, including its contribution to postseizure hyperexcitability, remains unclear. We address this issue by characterizing the actions of SST in mouse dentate gyrus using electrophysiological techniques. Although the majority of dentate SST receptors are located in the outer molecular layer adjacent to lateral perforant path (LPP) synapses, we found no consistent action of SST on standard synaptic responses generated at these synapses. However, when SST was present during application of high-frequency trains that normally generate long-term potentiation (LTP), the induction of LTP was impaired. SST did not alter the maintenance of LTP when applied after its induction. To examine the mechanism by which SST inhibits LTP, we recorded from dentate granule cells and examined the actions of this neuropeptide on synaptic transmission and postsynaptic currents. Unlike findings in the CA1 hippocampus, we observed no postsynaptic actions on K+ currents. Instead, SST inhibited Ca2+/Ba2+ spikes evoked by depolarization. This inhibition was dependent on N-type Ca2+currents. Blocking these currents also blocked LTP, suggesting a mechanism through which SST may inhibit LTP. Our results indicate that SST reduction of dendritic Ca2+ through N-type Ca2+ channels may contribute to modulation of synaptic plasticity at LPP synapses. Therefore the loss of SST function postseizure could result in abnormal synaptic potentiation that contributes to epileptogenesis.