bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal development of serotonin 1B, 2 A and 2C receptors in brainstem motoneurons
Authors: Volgin Denys V. , Fay Richard , Kubin Leszek
Published: December 2004

The effects of serotonin (5‐HT) on motoneurons are mediated via multiple receptor subtypes. In hypoglossal (XII) motoneurons, the prototypic brainstem motoneurons whose functions change during the postnatal period, 5‐HT effects evolve from inhibitory to excitatory, probably in association with changes in receptor expression. We studied 5‐HT1B, 5‐HT2A and 5‐HT2C receptor mRNA in 414 dissociated XII motoneurons and 5‐HT2A protein in the XII, facial and spinal cervical (C2‐3) motor nuclei. The percentage of motoneurons expressing distinct mRNAs varied with the postnatal age (P3‐33 days) and receptor subtype. Initially, 5‐HT1B mRNA was present in 50–85% of cells, but on P14 its expression transiently decreased below 35%. 5‐HT2A mRNA was present in nearly all cells after P6, but in less than 65% on P3‐5. Normal and/or short splice variants of the 5‐HT2C mRNA were expressed in less than 20% of motoneurons on P3‐9, and in ∼ 35% thereafter. 5‐HT1B and 5‐HT2A mRNAs often were expressed in different cells during early and intermediate postnatal periods, whereas 5‐HT2C mRNA never occurred alone. The 5‐HT2A receptor protein level gradually increased through P15 in the XII and facial nuclei, with dendritic labelling appearing in XII motoneurons only after P12. In spinal motoneurons, both somatic and dendritic labelling was strongest on P5 and then decreased. The development of 5‐HT receptors in XII motoneurons may be related to changes in feeding behaviour, whereas different cues regulate 5‐HT receptor expression in upper spinal motoneurons.
‘One‐trial sensitization’ to the anxiolytic‐like effects of cannabinoid receptor antagonist SR141716A in the mouse elevated plus‐maze
Authors: Rodgers R. J. , Haller J. , Halasz J. , Mikics E.
Published: December 2004

Significant variability in the effects of cannabinoid CB1 receptor ligands on emotional reactivity in animals and humans suggests that the endocannabinoid system may selectively modulate certain types of anxiety. In view of substantial evidence for qualitative differences in the nature of anxiety elicited on initial and subsequent exposures to the elevated plus‐maze, the present studies contrasted the behavioural effects of the selective CB1 receptor antagonist SR141716A (0.1–10.0 mg/kg) and the reference benzodiazepine chlordiazepoxide (CDP, 15 mg/kg) both in maze‐naive mice (trial 1) and in mice that had been given a single undrugged exposure to the maze 24 h prior to testing (trial 2). Results confirmed the anxioselective effect of CDP on trial 1 but a complete absence of such activity on trial 2 (i.e. one trial tolerance). In marked contrast, SR141716A had no behavioural effects in maze‐naive mice but, at doses of 1.0–3.0 mg/kg (effect maximal at 1.0 mg/kg), significantly reduced anxiety‐like responses in maze‐experienced animals. Like the effect of CDP on trial 1, the antianxiety profile of SR141716A on plus‐maze trial 2 was observed in the absence of any change in general activity levels. The apparent experientially induced ‘sensitization’ to the anxiolytic‐like effects of SR141716A in the plus‐maze contrasts markedly with the widely reported loss of benzodiazepine efficacy in test‐experienced animals. Data are discussed in relation to the recently described phenotypes of CB1 receptor knockout mice and, in particular, to mounting evidence for the existence of a novel SR141716A‐sensitive neuronal cannabinoid receptor.
Modulation of the ability of clozapine to facilitate NMDA‐ and electrically evoked responses in pyramidal cells of the rat medial prefrontal cortex by dopamine: pharmacological evidence
Authors: Ninan Ipe , Wang Rex Y.
Published: December 2004

Previous studies have shown that dopamine (DA) may play an important role in mediating or modulating the facilitating action of clozapine in glutamatergic transmission. This possibility was tested further in the present study by pharmacological manipulation of the DA system. When rats were pretreated with reserpine (which blocks storage of biogenic amines) and alpha‐methyl para‐tyrosine (AMPT, which inhibits tyrosine hydroxylase, the rate‐limiting enzyme for the DA synthesis), the ability of clozapine to augment glutamatergic transmission in pyramidal cells of the medial prefrontal cortex (mPFC) was totally abolished. Furthermore, the application of l‐dihydroxyphenylalanine (L‐DOPA, the immediate precursor of DA which bypasses the synthesis step inhibited by AMPT) reversed the effect produced by reserpine plus AMPT and re‐instated the facilitating action of clozapine, whereas administration of 5‐hydroxytryptophan (5‐HTP), the immediate precursor of 5‐HT, was ineffective. In addition, DA D1 receptor antagonist SCH 23390 also completely prevented clozapine‐induced facilitating action in the mPFC pyramidal cells. The present results demonstrate that newly synthesized DA and DA D1 receptors are required for clozapine to elicit its facilitating action on glutamatergic neurotransmission in the mPFC.
The large conductance Ca2+‐activated potassium channel (pSlo) of the cockroach Periplaneta americana: structure, localization in neurons and electrophysiology
Authors: Derst C. , Messutat S. , Walther C. , Eckert M. , Heinemann S. H. , Wicher D.
Published: December 2004

Voltage‐activated, Ca2+‐sensitive K+ channels (BK or maxi K,Ca channels) play a major role in the control of neuronal excitability. We have cloned pSlo, the BK channel α subunit of the cockroach Periplaneta americana. The amino acid sequence of pSlo shows 88% identity to dSlo from Drosophila. There are five alternatively spliced positions in pSlo showing differential expression in various tissues. A pSlo‐specific antibody prominently stained the octopaminergic dorsal unpaired median (DUM) neurons and peptidergic midline neurons in Periplaneta abdominal ganglia. HEK293 cells expressing pSlo exhibit K+ channels of 170 pS conductance. They have a tendency for brief closures, exhibit subconductance states and show slight inward rectification. Activation kinetics and voltage dependence are controlled by cytoplasmic [Ca2+]. In contrast to dSlo, pSlo channels are sensitive to charybdotoxin and iberiotoxin. Mutagenesis at two positions (E254 and Q285) changed blocking efficacy of charybdotoxin. In contrast to pSlo expressed in HEK293 cells, native IbTx‐sensitive K,Ca currents in DUM and in peptidergic neurons, exhibited rapid, partial inactivation. The fast component of the K,Ca current partly accounts for the repolarization and the early after‐hyperpolarization of the action potential. By means of Ca2+‐induced repolarization, BK channels may reduce the risk of Ca2+ overload in cockroach neurons. Interestingly, the neurons expressing pSlo were also found to express taurine, a messenger that is likely to limit overexcitation by an autocrine mechanism in mammalian central neurons.
The pyramidal neuron in occipital, temporal and prefrontal cortex of the owl monkey (Aotus trivirgatus): regional specialization in cell structure
Authors: Elston Guy N.
Published: December 2004

Recent studies have revealed marked regional variation in pyramidal cell morphology in primate cortex. In particular, pyramidal cells in human and macaque prefrontal cortex (PFC) are considerably more spinous than those in other cortical regions. PFC pyramidal cells in the New World marmoset monkey, however, are less spinous than those in man and macaques. Taken together, these data suggest that the pyramidal cell has become more branched and more spinous during the evolution of PFC in only some primate lineages. This specialization may be of fundamental importance in determining the cognitive styles of the different species. However, these data are preliminary, with only one New World and two Old World species having been studied. Moreover, the marmoset data were obtained from different cases. In the present study we investigated PFC pyramidal cells in another New World monkey, the owl monkey, to extend the basis for comparison. As in the New World marmoset monkey, prefrontal pyramidal cells in owl monkeys have relatively few spines. These species differences appear to reflect variation in the extent to which PFC circuitry has become specialized during evolution. Highly complex pyramidal cells in PFC appear not to have been a feature of a common prosimian ancestor, but have evolved with the dramatic expansion of PFC in some anthropoid lineages.
Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectum
Authors: Yu Chuan‐Jiang , Butt Christopher M. , Debski Elizabeth A.
Published: December 2004

Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both α‐bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch‐clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine‐induced increases in sPSCs. Activation of α‐bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2‐like muscarinic receptor antagonists himbacine or AF‐DX 384 and mimicked by application of the M2‐like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1‐like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity‐dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either α‐bungarotoxin insensitive, α‐bungarotoxin sensitive or M1‐like receptor antagonists resulted in map disruption. However, treatment with the M2‐like receptor antagonist, AF‐DX 384, compressed the map. We conclude that nicotinic or M1‐like muscarinic receptors control input to tectal cells while α‐bungarotoxin insensitive nicotinic receptors and M2‐like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels.
Mirror neurons responding to the observation of ingestive and communicative mouth actions in the monkey ventral premotor cortex
Authors: Ferrari Pier Francesco , Gallese Vittorio , Rizzolatti Giacomo , Fogassi Leonardo
Published: December 2004

In the ventral premotor cortex (area F5) of the monkey there are neurons that discharge both when the monkey performs specific motor actions and when it observes another individual performing a similar action (mirror neurons). Previous studies on mirror neurons concerned hand actions. Here, we describe the mirror responses of F5 neurons that motorically code mouth actions. The results showed that about one‐third of mouth motor neurons also discharge when the monkey observes another individual performing mouth actions. The majority of these ‘mouth mirror neurons’ become active during the execution and observation of mouth actions related to ingestive functions such as grasping, sucking or breaking food. Another population of mouth mirror neurons also discharges during the execution of ingestive actions, but the most effective visual stimuli in triggering them are communicative mouth gestures (e.g. lip smacking). Some also fire when the monkey makes communicative gestures. These findings extend the notion of mirror system from hand to mouth action and suggest that area F5, the area considered to be the homologue of human Broca's area, is also involved in communicative functions.
Effects of neonatal amygdala lesions on [125I] neurotensin binding in specific brain areas of adult rat
Authors: Bouwmeester Hans , Snapper Jolanda , Ronken Eric , Kruse Chris G. , Van Ree Jan M.
Published: December 2004

Neurotensin has been implicated in the pathophysiology of schizophrenia. The neonatal amygdala lesion in rat has been proposed to be a neurodevelopmental model for some aspects of schizophrenia. [125I] Neurotensin binding was assessed in adult rats using in vitro autoradiography following a lesion of the basolateral amygdala at postnatal day 7 (Pd 7) or postnatal day 21 (Pd 21). The Pd 7 and Pd 21 lesions differentially affected neurotensin receptor densities in the hippocampal complex and (less pronounced) in the dopaminergic cell regions, implying a neurodevelopmental cause. These results may be of relevance for the involvement of neurotensin in the pathogenesis of schizophrenia.
Blockade of cortical muscarinic but not NMDA receptors prevents a novel taste from becoming familiar
Authors: Gutiérrez Ranier , Téllez Luis A. , Bermúdez‐Rattoni Federico
Published: December 2004

Exposure to a novel taste solution in the rat is followed by a decrease in its intake known as neophobia. This effect gradually disappears, and consumption increases from the second presentation of the taste (attenuation of neophobia), reflecting that the animal learned that it is safe to drink it. Conversely, if gastric malaise is induced after first intake, the rat will develop a long‐lasting aversion (conditioned taste aversion). Previous attempts to elucidate the physiological nature of taste memory trace stems only from procedures that require malaise to measure taste memory. Here we assess the relevance of both muscarinic and N‐methyl‐d‐aspartate receptors, known to be involved in conditioned taste aversion, on taste memory using a nonaversive procedure (attenuation of neophobia learning). Attenuation of neophobia was impaired by the muscarinic receptor antagonist, scopolamine, microinjected 20 min before, immediately after or up to 2 h after the first taste experience, suggesting that muscarinic receptors are involved in the acquisition and consolidation of attenuation of neophobia learning. However, the N‐methyl‐d‐aspartate receptor antagonist, d,l‐2‐amino‐5‐phosphonovaleric acid, did not affect attenuation of neophobia even when the same dose of the drug was able to disrupt conditioned taste aversion learning, which suggests that attenuation of neophobia learning would be independent of N‐methyl‐d‐aspartate receptors activity in the insular cortex. The neophobic response induced by strong saccharin presentation was not affected by either of the treatments given, which rules out any impairment in taste perception. These results indicate that while cortical muscarinic receptors are important in the formation and consolidation of safe memory trace, N‐methyl‐d‐aspartate receptor activity appears to be noncritical.
Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons
Authors: Goldin Miri , Segal Menahem
Published: December 2004

The roles of protein kinase C and the MAP‐kinase extracellular receptor kinase in structural changes associated with long‐term potentiation of network activity were examined in cultured hippocampal neurons. A brief exposure to a conditioning medium that favours activation of the N‐methyl‐d‐aspartate receptor caused a rapid and specific increase in staining of neurons for the phosphorylated form of extracellular receptor kinase as well as of cyclic AMP response element binding protein. Exposure of the cultures to the conditioning medium was followed by a protein synthesis‐dependent formation of novel dendritic spines. An extracellular receptor kinase antagonist PD98059 blocked the phosphorylated form of extracellular receptor kinase response and the formation of novel spines. A selective protein kinase C agonist, phorbol 12‐myristate 13‐acetate, caused activation of extracellular receptor kinase and formation of novel spines. The protein kinase C antagonist GF109203x blocked the phosphorylated form of extracellular receptor kinase response and the subsequent spine formation by phorbol 12‐myristate 13‐acetate. Both the conditioning medium and phorbol 12‐myristate 13‐acetate caused a delayed increase in mean amplitude of miniature excitatory postsynaptic currents recorded in the hippocampal neurons. These results indicate that activation of extracellular receptor kinase mediates the effect of a conditioning protocol on the formation of dendritic spines. The formation of novel spines was associated with long‐term increase in network activity and functional synaptic connectivity among the cultured neurons.
High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus
Authors: Somogyi Peter , Dalezios Yannis , Luján Rafael , Roberts J. David B. , Watanabe Masahiko , Shigemoto Ryuichi
Published: December 2004

The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a‐positive) were analysed. The presynaptic active zones of most GAD‐(77%) or GABA‐positive (94%) synaptic boutons on interneurons innervated by mGluR7a‐enriched glutamatergic terminals (mGluR7a‐decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a‐immunonegative. The mGluR7a‐decorated cells were mostly somatostatin‐ and mGluR1α‐immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP‐positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin‐positive synaptic terminals were rare on mGluR7a‐decorated cells, but on these neurons 73% of them were mGluR7a‐immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP‐positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target‐cell‐specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7‐decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites.
Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic cultures
Authors: Israel Jean‐Marc , Le Masson Gwendal , Theodosis Dionysia T. , Poulain Dominique A.
Published: December 2004

During suckling, oxytocin (OT) neurons display a bursting electrical activity, consisting of a brief burst of action potentials which is synchronized throughout the OT neuron population and which periodically occurs just before each milk ejection in the lactating rat. To investigate the basis of such synchronization, we performed simultaneous intracellular recordings from pairs of OT neurons identified retrospectively by intracellular fluorescent labelling and immunocytochemistry in organotypic slice cultures derived from postnatal rat hypothalamus. A spontaneous bursting activity was recorded in 65% of OT neurons; the remaining showed only a slow, irregular activity. Application of OT triggered bursts in nonbursting neurons and accelerated bursting activity in spontaneously bursting cells. These cultures included rare vasopressinergic neurons showing no bursting activity and no reaction to OT. Bursts occurred simultaneously in all pairs of bursting OT neurons but, as in vivo, there were differences in burst onset, amplitude and duration. Coordination of firing was not due to electrotonic coupling because depolarizing one neuron in a pair had no effect on the membrane potential of its partner and halothane and proprionate did not desynchronize activity. On the other hand, bursting activity was superimposed on volleys of excitatory postsynaptic potentials (EPSPs) which occurred simultaneously in pairs of neurons. EPSPs, and consequently action potentials, were reversibly blocked by the non‐NMDA glutamatergic receptor antagonist CNQX. Taken together, these data, obtained from organotypic cultures, strongly suggest that a local hypothalamic network governs synchronization of bursting firing in OT neurons through synchronous afferent volleys of EPSPs originating from intrahypothalamic glutamatergic inputs.
Selective modifications in GAD67 mRNA levels in striatonigral and striatopallidal pathways correlate to dopamine agonist priming in 6‐hydroxydopamine‐lesioned rats
Authors: Carta A.R. , Fenu S. , Pala P. , Tronci E. , Morelli M.
Published: December 2004

The present study investigated long‐term alterations in striatal gene expression after single exposure of unilaterally 6‐hydroxydopamine‐lesioned rats to different dopamine agonists (priming). Rats were primed with the D1 agonist SKF38393 (10 mg/kg), the D2/D3 agonist quinpirole (0.2 mg/kg), the dopamine precursor L‐DOPA (50 mg/kg) or with vehicle (drug‐naive), and GAD67, dynorphin and enkephalin mRNAs were evaluated in the striatum by in situ hybridization, 3 days after priming. To evaluate GAD67 mRNA in striatonigral and striatopallidal neurons, identified as enkephalin (−) and (+) neurons, double‐labelling in situ hybridization was used. Drug‐naive lesioned rats showed an increase in GAD67 mRNA in enkephalin (−) and (+) neurons, an increase in enkephalin and a decrease in dynorphin mRNAs. Priming with either SKF38393 or quinpirole further increased GAD67 mRNA in enkephalin (−) and (+) neurons, however, while SKF38393 produced a high and unbalanced activation toward enkephalin (−) neurons, after quinpirole the increase was of low intensity and similar in the two pathways. Dynorphin mRNA was increased by SKF38393 but not by quinpirole, whereas enkephalin mRNA was not changed by either priming. L‐DOPA produced a high and similar increase in GAD67 mRNA in enkephalin (−) and (+) neurons. Priming differentially affected peptides and GAD67 mRNA in striatopallidal and striatonigral neurons depending on the dopamine agonist used. The degree of enduring overactivity of the striatopallidal and striatonigral pathways may be related to the ability of L‐DOPA and D1 or D2/D3 receptor agonists to prime motor behavioural responses and to produce dyskinetic side‐effects.
The opposite effects of stress on dendritic spines in male vs. female rats are NMDA receptor‐dependent
Authors: Shors T. J. , Falduto J. , Leuner B.
Published: December 2004

Dendritic spines in the hippocampus are sources of synaptic contact that may be involved in processes of learning and memory [Moser (1999) Cell. Mol. Life Sci., 55, 593–600]. These structures are sensitive to sex differences as females in proestrus possess a greater density than males and females in other stages of the estrous cycle [Woolley et al.. (1990) J. Neurosci., 10, 4035–4039]. Moreover, exposure to an acute stressful event increases spine density in the male hippocampus but decreases spine density in the female hippocampus [Shors et al.. (2001) J. Neurosci., 21, 6292–6297]. Here we demonstrate that antagonism of N‐methyl‐d‐aspartate (NMDA) receptors prevents the increase in spine density as females transition from diestrus 2 to proestrus, when estrogen levels are rising. Antagonism of NMDA receptors during exposure to the stressful event also prevented the changes in spine density in males and females, despite differences in the direction of these effects. Thus, the stress‐induced increase in spine density was prevented in the male hippocampus as was the stress‐induced decrease in spine density in the female hippocampus. NMDA receptor antagonism during exposure to the stressful event did not alter corticosterone levels or the corticosterone response to stress. These data suggest that both increases and decreases in spine density can be dependent on NMDA receptor activation.
Pre‐ and postsynaptic contributions of voltage‐dependent Ca2+ channels to nociceptive transmission in rat spinal lamina I neurons
Authors: Heinke B. , Balzer E. , Sandkühler J.
Published: December 2004

Activation of voltage‐dependent Ca2+ channels (VDCCs) is critical for neurotransmitter release, neuronal excitability and postsynaptic Ca2+ signalling. Antagonists of VDCCs can be antinociceptive in different animal pain models. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the processing of pain‐related information, but the role of VDCCs to the activity‐dependent Ca2+ increase in lamina I neurons and to the synaptic transmission between nociceptive afferents and second order neurons in lamina I is not known. This has now been investigated in a lumbar spinal cord slice preparation from young Sprague–Dawley rats. Microfluorometric Ca2+ measurements with fura‐2 have been used to analyse the Ca2+ increase in lamina I neurons after depolarization of the cells, resulting in a distinct and transient increase of the cytosolic Ca2+ concentration. This Ca2+ peak was reduced by the T‐type channel blocker, Ni2+, by the L‐type channel blockers, nifedipine and verapamil, and by the N‐type channel blocker, ω‐conotoxin GVIA. The P/Q‐type channel antagonist, ω‐agatoxin TK, had no effect on postsynaptic [Ca2+]i. The NMDA receptor channel blocker D‐AP5 reduced the Ca2+ peak, whereas the AMPA receptor channel blocker CNQX had no effect. Postsynaptic currents, monosynaptically evoked by electrical stimulation of the attached dorsal roots with C‐fibre and Aδ‐fibre intensity, respectively, were reduced by N‐type channel blocker ω‐conotoxin GVIA and to a much lesser extent, by P/Q‐type channel antagonist ω‐agatoxin TK, and the L‐type channel blockers verapamil, respectively. No difference was found between unidentified neurons and neurons projecting to the periaqueductal grey matter. This is the first quantitative description of the relative contribution of voltage‐dependent Ca2+ channels to the synaptic transmission in lamina I of the spinal dorsal horn, which is essential in the processing of pain‐related information in the central nervous system.
Diversity beyond variance: modulation of firing rates and network coherence by GABAergic subpopulations
Authors: Földy Csaba , Aradi Ildiko , Howard Allyson , Soltesz Ivan
Published: December 2004

Computational modelling studies have revealed that heterogeneity in interneuronal networks can powerfully modulate firing rates, responses to excitatory inputs, theta‐gamma oscillations and network synchrony. In these previous studies, heterogeneity was represented by the degree of variance in various interneuronal synaptic and cellular parameters. However, a major characteristic of gamma‐amino‐butyric‐acid‐ergic (GABAergic) synaptic and interneuronal populations is the presence of distinct subgroups, which variance‐based approaches cannot fully address. Here we apply an information theory‐based measure of diversity, the Shannon–Wiener diversity index (equivalent to entropy), which takes into account both the number and relative abundance of categories within a population. Computational modelling data and experimental dynamic clamp results show that increasing the diversity index in the somatically injected inhibitory post synaptic currents (IPSC) peak conductances modulates the firing rates of CA1 pyramidal cells in a predictable manner that depends on both the mean and variance of the IPSC conductance. Furthermore, increases in the diversity index in interneuronal populations strongly decreased network coherence, even when population variance, the previously applied measure of heterogeneity, remained unchanged. These modelling and experimental results reveal a new approach to the study of interneuronal heterogeneity, and demonstrate the modulation of principal cell firing rates and interneuronal network coherence by parameter clustering at both the synaptic and cellular levels.
Host mortality, predation and the evolution of parasite virulence
Authors: Choo Karen , Williams Paul D. , Day Troy
Published: December 2004

One of the most accepted views in the theoretical literature on virulence evolution is that a parasite's virulence will evolve to higher levels when its host's background mortality rate increases. Surprisingly, however, although many sources of background mortality involve predation, there has not yet been any theoretical research that explicitly considers how the dynamics of this important ecological interaction affects virulence evolution. Here, we consider how predation affects virulence evolution by explicitly introducing a predator into a classical susceptible–infected–susceptible epidemiological model. We find that, contrary to previous predictions, different sources of host mortality affect virulence evolution in different ways. Moreover, the way in which virulence evolution is affected depends on how tightly coupled the predator's dynamics are to the host population, and this can result in somewhat counterintuitive results. For example, indirect ecological effects can cause elevated host mortality to result in the evolution of lower parasite virulence, even if this elevated mortality arises from factors unrelated to predation.
Invasive aliens and sampling bias
Authors: Simons Andrew M.
Published: December 2004

Two hypotheses have been proposed to explain the observation of increased vigour of invasive alien plants in their nonindigenous ranges: phenotypic plasticity, and the post‐invasion evolution of increased competitive ability (EICA). Here I specify how a general pattern of increased vigour may result from sampling bias. Ignoring failed invasions can account for the illusion of increased vigour over a broad range of assumptions. Plasticity and EICA need not be viewed as explanations for a general pattern of increased vigour even if they are the mechanisms underlying every occurrence.
Spatial heterogeneity reduces temporal variability in stream insect communities
Authors: Brown Bryan L.
Published: December 2004

Although all natural systems are heterogeneous, the direct influence of spatial heterogeneity on most ecological variables is unknown. In many systems, spatial heterogeneity is positively correlated with both microhabitat refugia and species richness. Both an increased number of microhabitat refugia and the effects of statistical averaging via increased species richness should lead to an inverse relationship between spatial heterogeneity and variability in community composition. To test this prediction, I measured diversity and temporal variability of invertebrate communities in a northern New Hampshire stream along a natural gradient of spatial heterogeneity formed by variation in stream substrates. On average, there was a 42% decrease in community variability along a gradient of increasing heterogeneity. This pattern was robust to changes in metrics of both heterogeneity and community variability. There was also a significant positive relationship between taxon richness and spatial heterogeneity with predicted taxon richness increasing c. 1.5× along the heterogeneity gradient. By resampling community abundance data, I estimated that statistical averaging accounted for only 4% of the observed decrease in community variability in this study. I concluded that the remaining decrease was very likely explained by a greater number of refugia from predation and/or flooding in high‐heterogeneity habitats. The results of this study suggest that maximizing heterogeneity in ecological restoration programmes may promote temporally stable and diverse communities and may aid in responsible management of aquatic resources.
Mechanisms of coexistence of a bacteria and a bacteriophage in a spatially homogeneous environment
Authors: Lythgoe K. A. , Chao L.
Published: December 2004

When bacteriophage are added to laboratory bacteria populations, bacteria mutants that are resistant to the phage quickly dominate the population. The phage will only persist in the long‐term if there are sufficient bacteria in the population that show susceptibility to the phage. We investigated the mechanisms allowing for coexistence by adding the virulent bacteriophage φ6 to cultures of the bacterium Pseudomonas syringae pv. phaseolicola in a spatially homogeneous environment. We saw large differences between replicate cultures, in particular when one or both of the species persisted. These differences can be explained by variation in the timing of the appearance of various resistant phenotypes in the bacteria populations before the phage were added, which determines their relative frequencies within the populations. Although these resistant phenotypes have similar fitnesses in the presence and in the absence of the phage, they have a profound effect on the persistence of the phage. Our results give a clearer understanding of the ecological mechanisms that lead to the coexistence of bacteria and virulent phage in environments where there are no spatial refuges available to the bacteria population.
Local dispersal can facilitate coexistence in the presence of permanent spatial heterogeneity
Authors: Snyder Robin E. , Chesson Peter
Published: December 2004

Abstract In the presence of permanent spatial heterogeneity, local dispersal, especially short‐range dispersal, can facilitate coexistence by concentrating low‐density species in the areas where their rates of increase are higher. We present a framework for predicting the effects of local dispersal on coexistence for arbitrary forms of dispersal and arbitrary spatial patterns of environmental variation. Using the lottery model as an example, we find that local dispersal contributes to coexistence by enhancing the effects of environmental variation on scales longer than typical dispersal distances, which can be characterized solely by the variance of the dispersal kernel. Higher moments of the dispersal kernel are not important.
Community‐wide character displacement in barnacles: a new perspective for past observations
Authors: Marchinko Kerry B. , Nishizaki Michael T. , Burns K.C.
Published: December 2004

We tested for community‐wide character displacement of feeding leg length and shell morphology in two barnacle communities on the west coast of North America (southern California, USA and Vancouver Island, Canada). Neither community exhibited even displacement in shell morphology. Both barnacle communities, however, exhibited remarkably evenly displaced feeding leg length, despite large differences in geography and species composition (between the orders Pedunculata and Sessilia). Previous experiments suggest that this pattern results from competition, although the competitive mechanism remains unknown. Displacement of leg length may reflect dietary specialization, spatial competition, or both. In some cases the results from two null models differed, illustrating the importance of employing a null model that considers mean and variance, rather than character means alone. Overall, the observed pattern of character displacement provides a new perspective for re‐examining the complex relationship between morphology and interspecific competition among intertidal barnacles.
Plant‐dependent active biological containment system for recombinant rhizobacteria
Authors: Van Dillewijn Pieter , Vílchez Susana , Paz José A. , Ramos Juan L.
Published: December 2004

This work describes the construction of the rhizobacterium Pseudomonas putida strain CS‐4, which contains an active biological containment (ABC) system that ensures bacterial suicide in the absence of proline. Maize plants exudate proline, which allows CS‐4 to colonize the rhizosphere at a similar level to that of the wild‐type strain. However, when the plants are removed, the CS‐4 population decreased in bulk soil at a higher rate than the wild‐type strain.
Host specificity in marine sponge‐associated bacteria, and potential implications for marine microbial diversity
Authors: Taylor Michael W. , Schupp Peter J. , Dahllöf Ingela , Kjelleberg Staffan , Steinberg Peter D.
Published: December 2004

Biodiversity is fundamental to both eukaryote and prokaryote ecology, yet investigations of diversity often differ markedly between the two disciplines. Host specificity – the association of organisms with only a few (specialism) or many (generalism) host species – is recognized within eukaryote ecology as a key determinant of diversity. In contrast, its implications for microbial diversity have received relatively little attention. Here we explore the relationship between microbial diversity and host specificity using marine sponge–bacteria associations. We used a replicated, hierarchical sampling design and both 16S rDNA‐ and rpoB‐based denaturing gradient gel electrophoresis (DGGE) to examine whether three co‐occurring sponges from temperate Australia –Cymbastela concentrica, Callyspongia sp. and Stylinos sp. – contained unique, specialized communities of microbes. Microbial communities varied little within each species of sponge, but variability among species was substantial. Over five seasons, the microbial community in C. concentrica differed significantly from other sponges, which were more similar to seawater. Overall, three types of sponge‐associated bacteria were identified via 16S rDNA sequencing of excised DGGE bands: ‘specialists’– found on only one host species, ‘sponge associates’– found on multiple hosts but not in seawater, and ‘generalists’ from multiple hosts and seawater. Analogous to other high diversity systems, the degree of specificity of prokaryotes to host eukaryotes could have a potentially significant effect on estimates of marine microbial diversity.
A retrospective clinical, laboratory and outcome analysis in 43 cases of acute aseptic meningitis
Authors: Nowak D. A. , Boehmer R. , Fuchs H‐H.
Published: December 2004

Forty‐three consecutive cases of acute aseptic meningitis (AAM) presenting within a 24‐months period were retrospectively analysed with respect to clinical symptomatology, cerebrospinal fluid (CSF) findings, clinical course, treatment and outcome. Nineteen of the 43 AAM cases (44%) were caused by enterovirus, one by HIV (2%), two by Varicella zoster virus (5%), three due to herpes simplex virus I (7%), two due to herpes simplex virus II (5%), one due to Central European encephalitis virus (2%), and in 15 patients (35%) the aetiology of AAM remained unknown. Headache (100%) and fever (93%) were the presenting symptoms in the majority of cases. Signs of preceding infection were predominantly gastrointestinal in the enterovirus subgroup, but were inconsistently observed in the other subgroups. CSF findings at the first lumbar tap on admission generally revealed lymphomonocytic pleocytosis of less than 500 cells per μl, mild to moderately elevated protein and normal lactate and glucose levels. Initial therapy consisted of an empirical antiviral and antibiotic regimen until a serological diagnosis was available. Acyclovir, effective only in herpes family viruses, was initially administered to all AAM cases. Effective therapy for other viral pathogens are not broadly available and treating AAM of unknown aetiology imposes a particular problem. The average hospitalization time ranged from 16 to 31 days. Patients were either discharged home (72%) or transferred to a rehabilitation centre (28%). The outcome was good (40%) to fair (51%) in the majority of cases.
Post‐operative progress of dystonia patients following globus pallidus internus deep brain stimulation
Authors: Yianni J. , Bain P. G. , Gregory R. P. , Nandi D. , Joint C. , Scott R. B. , Stein J. F. , Aziz T. Z.
Published: December 2004

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.
Early‐onset Alzheimer's disease with presenilin‐1 M139V mutation: clinical, neuropsychological and neuropathological study
Authors: Larner A. J. , Du Plessis D. G.
Published: December 2004

The clinical, neuropsychological and neuropathological features of a patient with early‐onset Alzheimer's disease as a result of the M139V presenilin‐1 (PSEN‐1) mutation are presented, and compared with previous reports of patients with the same mutation. Similarities, such as the age at onset and the relative preservation of naming skills, and differences, such as the significant basal ganglia, thalamic and cerebellar pathology, are noted. This clinical and pathological heterogeneity in patients with the same PSEN‐1 mutation suggests phenotype modulation by genetic and/or epigenetic factors.
Spectrum of superficial posterior cerebral artery territory infarcts
Authors: Kumral E. , Bayulkem G. , Ataç C. , Alper Y.
Published: December 2004

Posterior cerebral artery (PCA) territory infarction is not uncommon. Published series were concentrated either on isolated deep PCA territory infarcts or on incomplete calcarine artery territory infarcts. Although, correlations between clinical symptoms, causes of stroke and outcome at 6‐months in patients with superficial PCA territory stroke are less well known. We sought prospectively stroke causes, infarct topography, and clinical findings of 137 patients with superficial PCA territory infarcts with or without mesencephalic/thalamic involvement, representing 11% of patients with posterior circulation ischemic stroke in our Stroke Registry. We analyzed patients by subdividing into three subgroups; (1) cortical infarct (CI) group; (2) cortical and deep infarcts (CDI) (thalamic and/or mesencephalic involvement) group; (3) bilateral infarcts (BI) group. We studied the outcomes of patients at 6‐month regarding clinical findings, risk factors and vascular mechanisms by means of comprehensive vascular and cardiac studies. Seventy‐one patients (52%) had cortical (CI) PCA infarct, 52 patients (38%) had CDI, and 14 patients (10%) had bilateral PCA infarct (BI). In the CDI group, unilateral thalamus was involved in 38 patients (73%) and unilateral mesencephalic involvement was present in 27% of patients. The presumed causes of infarction were intrinsic PCA disease in 33 patients (26%), proximal large‐artery disease (PLAD) in 33 (24%), cardioembolism in 23 (17%), co‐existence of PLAD and cardioembolism in 7 (5%), vertebral or basilar artery dissection in 8 (6%), and coagulopathy in 2. The death rate was 7% in our series and stroke recurrence was 16% during 6‐month follow‐up period. Features of the stroke that was associated with significant increased risk of poor outcome included, consciousness disturbances at stroke onset (RR, 66.6; 95% CI, 8.6–515.5), mesencephalic and/or thalamic involvement (RR, 3.79; 95% CI, 1.49–9.65), PLAD (RR, 2.71; 95% CI, 1.09–6.73), and basilar artery disease (RR, 5.94; 95% CI, 1.73–20.47). The infarct mechanisms in three different types of superficial PCA territory stroke were quite similar, but cardioembolism was found more frequent in those with cortical PCA territory infarction. Although, the cause of stroke could not reliably dictate the infarct topography and clinical features. Visual field defect was the main clinical symptom in all groups, but sensorial, motor and neuropsychological deficits occurred mostly in those with CDI. Outcome is good in general, although patients having PLAD and basilar artery disease had more risk of stroke recurrence and poor outcome rather than those with intrinsic PCA disease.
Health‐related Quality of Life in Children with Epilepsy: Development and Validation of Self‐report and Parent Proxy Measures
Authors: Ronen Gabriel M. , Streiner David L. , Rosenbaum Peter ,   Canadian Pediatric Epilepsy Network
Published: December 2004

Summary:  Purpose: To answer a need to include and measure accurately the impact and burden of epilepsy as outcomes of interventions with affected children, we developed and validated self‐report and parent‐proxy respondent health‐related quality of life (HRQL) instruments for preadolescent children with epilepsy.

Methods: We combined qualitative and quantitative research methods. Items were extracted from focus group discussions involving children with epilepsy and their parents. We created scales formatted with alternative paired options of forced responses and used factor analysis to generate relevant subscales and reduce the number of items. We checked internal consistency, assessed test–retest reliability 10–14 days apart, and documented construct validity.

Results: A sample of 381 children with epilepsy, age 6–15 years, and their parents independently completed a 67‐item questionnaire, from which we chose five items for each subscale. The measures share four subscales, but each measure has an additional distinct subscale. The children and parents could discern differences and report differentially between the various aspects of the HRQL. Internal consistency measured with Cronbach's α was acceptable for all subscales; construct validity has been demonstrated from the testing of several hypotheses. Test–retest reliability examined with the intraclass correlation coefficient was satisfactory for the parents and for children age 8 years and older. The correlations between the mothers' and children's responses was poor to moderate.

Conclusions: The data demonstrate sound psychometric properties for both related measures, which are easy to administer for children with epilepsy who are 8 years and older and their parents. The subscales encompass HRQL dimensions judged most important by children with epilepsy for the self‐report measure and by parents for the proxy response measure. The parent‐proxy measure should be useful as a complement to the child self‐report measure in evaluating the validity of parental assessment of the child's health status; in longitudinal outcome research; and in HRQL assessment of children who are unable to respond independently.