This paper surveys the use of Spreading Activation techniques onSemantic Networks in Associative Information Retrieval. The majorSpreading Activation models are presented and their applications toIR ...is surveyed. A number of works in this area are criticallyanalyzed in order to study the relevance of Spreading Activation forassociative IR.
The heterogeneity of γ-aminobutyric acid type A (GABA A ) receptors contributes to the diversity of neuronal inhibition in the regulation of information processing. Although most GABA A receptors are ...located synaptically, the small population of α 5 GABA A receptors is largely expressed extrasynaptically. To clarify the role of the α 5 GABA A receptors in the control of behavior, a histidine-to-arginine point mutation was introduced in position 105 of the murine α 5 subunit gene, which rendered the α 5 GABA A receptors diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither the sedative, anticonvulsant, nor anxiolytic-like activity of diazepam was impaired in α 5 (H105R) mice. However, in hippocampal pyramidal cells, the point mutation resulted in a selective reduction of α 5 GABA A receptors, which altered the drug-independent behavior. In line with the role of the hippocampus in certain forms of associative learning, trace fear conditioning, but not delay conditioning or contextual conditioning, was facilitated in the mutant mice. Trace fear conditioning differs from delay conditioning in that the conditioned and unconditioned stimulus are separated by a time interval. Thus, the largely extrasynaptic α 5 GABA A receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning.
Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and ...analyzed two mouse lines in which the α2 or α3 GABAA(γ-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABAAreceptors, which are largely expressed in the limbic system, but not by α3 GABAAreceptors, which predominate in the reticular activating system.
BACKGROUND AND PURPOSE The molecular substrates underlying the respiratory changes associated with benzodiazepine sedation are unknown. We examined the effects of different doses of diazepam and ...alprazolam on resting breathing in wild‐type (WT) mice and clarified the contribution of α1‐ and α2‐GABAA receptors, which mediate the sedative and muscle relaxant action of diazepam, respectively, to these drug effects using point‐mutated mice possessing either α1H101R‐ or α2H101R‐GABAA receptors insensitive to benzodiazepine.
EXPERIMENTAL APPROACH Room air breathing was monitored using whole‐body plethysmography. Different groups of WT mice were injected i.p. with diazepam (1–100 mg·kg−1), alprazolam (0.3, 1 or 3 mg·kg−1) or vehicle. α1H101R and α2H101R mice received 1 or 10 mg·kg−1 diazepam or 0.3 or 3 mg·kg−1 alprazolam. Respiratory frequency, tidal volume, time of expiration and time of inspiration before and 20 min after drug injection were analysed.
KEY RESULTS Diazepam (10 mg·kg−1) decreased the time of expiration, thereby increasing the resting respiratory frequency, in WT and α2H101R mice, but not in α1H101R mice. The time of inspiration was shortened in WT and α1H101R mice, but not in α2H101R mice. Alprazolam (1–3 mg·kg−1) stimulated the respiratory frequency by shortening expiration and inspiration duration in WT mice. This tachypnoeic effect was partially conserved in α1H101R mice while absent in α2H101R mice.
CONCLUSIONS AND IMPLICATIONS These results identify a specific role for α1‐GABAA receptors and α2‐GABAA receptors in mediating the shortening by benzodiazepines of the expiratory and inspiratory phase of resting breathing respectively.
•Sentiment lexicons can be augmented to create reputation polarity lexicons.•Learning PMI values from training data is very effective for reputation polarity.•Sentiment signals can be propagated to ...annotate reputation polarity.•Pairwise similarity performs better than clustering tweets thematically.•Weakly supervised annotation of reputation polarity is feasible.
The emergence of social media and the huge amount of opinions that are posted everyday have influenced online reputation management. Reputation experts need to filter and control what is posted online and, more importantly, determine if an online post is going to have positive or negative implications towards the entity of interest. This task is challenging, considering that there are posts that have implications on an entity's reputation but do not express any sentiment. In this paper, we propose two approaches for propagating sentiment signals to estimate reputation polarity of tweets. The first approach is based on sentiment lexicons augmentation, whereas the second is based on direct propagation of sentiment signals to tweets that discuss the same topic. In addition, we present a polar fact filter that is able to differentiate between reputation-bearing and reputation-neutral tweets. Our experiments indicate that weakly supervised annotation of reputation polarity is feasible and that sentiment signals can be propagated to effectively estimate the reputation polarity of tweets. Finally, we show that learning PMI values from the training data is the most effective approach for reputation polarity analysis.
The neuronal circuits mediating the sedative action of diazepam are unknown. Although the motor-depressant action of diazepam is suppressed in alpha1(H101R) homozygous knockin mice expressing ...diazepam-insensitive alpha1-GABA(A) receptors, global alpha1-knockout mice show greater motor sedation with diazepam. To clarify this paradox, attributed to compensatory up-regulation of the alpha2 and alpha3 subunits, and to further identify the neuronal circuits supporting diazepam-induced sedation, we generated Emx1-cre-recombinase-mediated conditional mutant mice, selectively lacking the alpha1 subunit (forebrain-specific alpha1(-/-)) or expressing either a single wild-type (H) or a single point-mutated (R) alpha1 allele (forebrain-specific alpha1(-/H) and alpha1(-/R) mice, respectively) in forebrain glutamatergic neurons. In the rest of the brain, alpha1(-/R) mutants are heterozygous alpha1(H101R) mice. Forebrain-specific alpha1(-/-) mice showed enhanced diazepam-induced motor depression and increased expression of the alpha2 and alpha3 subunits in the neocortex and hippocampus, in comparison with their pseudo-wild-type littermates. Forebrain-specific alpha1(-/R) mice were less sensitive than alpha1(-/H) mice to the motor-depressing action of diazepam, but each of these conditional mutants had a similar behavioral response as their corresponding control littermates. Unexpectedly, expression of the alpha1 subunit was reduced in forebrain, notably in alpha1(-/R) mice, and the alpha3 subunit was up-regulated in neocortex, indicating that proper alpha1 subunit expression requires both alleles. In conclusion, conditional manipulation of GABA(A) receptor alpha1 subunit expression can induce compensatory changes in the affected areas. Specifically, alterations in GABA(A) receptor expression restricted to forebrain glutamatergic neurons reproduce the behavioral effects seen after a global alteration, thereby implicating these neurons in the motor-sedative effect of diazepam.
GABAergic interneurons are highly diverse and operate with a corresponding diversity of GABA
A receptor subtypes in controlling behaviour. In this article, we review the significance of GABA
A ...receptor heterogeneity for neural circuit development and central nervous system pharmacology. GABA
A receptor subtypes were identified as selective targets for behavioural actions of benzodiazepines and of selected intravenous anesthetic agents using point mutations which render a specific receptor subtype insensitive to the action of the respective drugs and also by novel subtype-selective ligands. The pharmacological separation of anxiolysis and sedation guides the development of novel anxiolytics, while inverse agonism at extrasynaptic GABA
A receptors involved in learning and memory is currently being evaluated as a novel therapeutic principle for symptomatic memory enhancement.
Sleep has been shown to play a facilitating role in memory consolidation, whereas sleep deprivation leads to performance impairment both in humans and rodents. The effects of 4-h sleep deprivation on ...recognition memory were investigated in the Djungarian hamster (
Phodopus sungorus). Because sleep during the first hours after daily torpor has many similarities to recovery from sleep deprivation, the effects of spontaneous torpor on object recognition were also assessed.
A 4-h sleep deprivation, starting immediately after an object learning task, diminished the ability of the hamsters to: (1) discriminate between an already encountered object (target) and a novel object presented in a novel context, (2) retrieve a target within a complex spatial scene, and (3) detect a spatial rearrangement of familiar objects in a familiar context. Plasma stress hormone levels were similar in sleep-deprived and control hamsters. The occurrence of a daily torpor episode during retention was associated with impaired old–new object discrimination performance in the more effortful complex spatial scene task only, and in a two-object choice situation in a novel context no torpor-induced deficit was found.
Our results show that post learning sleep deprivation and daily torpor induce a deficit in familiar object retrieval performance in a complex spatial scene, while sparing familiarity-based recognition and novelty processing. Sleep deprivation during the first 4 h of memory consolidation hampered also recency memory for discrete objects. Stress was not a factor contributing to the sleep deprivation-induced impairment.
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