Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate posttranscriptional expression of protein-coding mRNAs, which may have important roles in the pathogenesis of neurologic disorders. In models of prolonged, injurious seizures (status epilepticus) and in experimental and human epilepsy, we found up-regulation of miR-134, a brainspecific, activity-regulated miRNA implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21%, and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus reduced the later occurrence of spontaneous seizures by over 90% and mitigated attendant pathologic features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure suppressant and Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Higher cognitive functions such as attention have been difficult to model in genetically tractable organisms. In humans, attentiondistracting stimuli interfere with trace but not delay conditioning, two forms of associative learning. Attention has also been correlated with activation of anterior cingulate cortex (ACC), but its functional significance is unclear. Here we show that a visual distractor interferes selectively with trace but not delay auditory fear conditioning in mice. Trace conditioning is associated with increased neuronal activity in ACC, as assayed by relative levels of c-fos expression, and is selectively impaired by lesions of this structure. The effects of the ACC lesions are unlikely to be caused by indirect impairment of the hippocampus, which is required for mnemonic aspects of trace conditioning. These data suggest that trace conditioning may be useful for studying neural substrates of attention in mice, and implicate the ACC as one such substrate. Selective attention is thought to contribute to conscious awareness, but its neural basis is poorly understood. The search for the neural substrates of attention has been concentrated in the primate visual system (1, 2). Although extremely useful for identifying neural correlates of attention, primates offer limited accessibility for functional perturbation experiments, prompting a search for alternative animal models more amenable to tests of causation. Although some attentional models have been established in rats (3), they depend on operant conditioning paradigms that have proven difficult to extend to mice, and require lengthy training periods.Studies in humans have suggested that attention is required for certain forms of associative learning (4). Associative learning paradigms, such as fear conditioning, have been successfully extended from rats to mice (5). Two commonly used variants of this procedure are delay and trace conditioning. In delay fear conditioning, a conditioned stimulus (CS), such as a tone, is immediately followed by an unconditioned stimulus (US), such as a foot shock. In trace conditioning, a time gap is introduced between the end of the CS and the start of the US. In human eye blink conditioning, another associative learning paradigm, distracting stimuli interfere with trace but not delay conditioning, suggesting that attention is necessary for the former type of learning (4, 6-10). More recent studies have suggested a similar requirement for attention in trace but not delay fear conditioning in humans (11).Potential neural substrates of attention have been identified by functional imaging in humans. For example, attention has been correlated with increased activity in the anterior cingulate cortex (ACC) (12-17). Furthermore, the ACC is preferentially activated during presentation of the conditional stimulus, compared with that of a meaningless stimulus, during aversive trace conditioning (18). The ACC has also been implicated in tasks requiring visual attention in rats (3,(19)(20)(21)(22)(23). Lesion studies have show...

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Internationally, evidence-based practice (EBP) is recognised as a foundational element of healthcare professional education. Achieving competency in this area is a complex undertaking that is reflected in disparities between ‘best EBP’ and actual clinical care. The effective development and implementation of professional education to facilitate EBP remains a major and immediate challenge. To ascertain nuanced perspectives on the provision of EBP education internationally, interviews were conducted with five EBP education experts from the UK, Canada, Australia and New Zealand. Definitive advice was provided in relation to (1) EBP curriculum considerations, (2) teaching EBP and (3) stakeholder engagement in EBP education. While a considerable amount of EBP activity throughout health profession education is apparent, effectively embedding EBP throughout curricula requires further development, with a ‘real-world’ pragmatic approach that engenders dialogue and engagement with all stakeholders required.

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The neuregulin-1 gene is widely expressed in the central nervous system and is associated with increased risk for schizophrenia. Using an ethologically based approach, the phenotype of neuregulin-1 heterozygous knockout mice was examined by revealing the individual elements of behaviour in the murine repertoire over the prolonged course of interaction with the environment. During initial exploration, neuregulin-1 mutants displayed a phenotype characterized by increases in locomotion and rearing free, with sex-specific alterations in sifting and grooming. Over subsequent habituation, certain initial effects endured while new phenotypic effects emerged, some of which were again sex-specific. These studies elaborate a pleiotropic role of neuregulin-1 in development, plasticity and function, including sexual dimorphism, by defining the elemental, temporal and sex-specific characteristics of the neuregulin-1 mutant ethogram.

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Cannabis use confers a two-fold increase in the risk for psychosis, with adolescent use conferring even greater risk. A high-low activity catechol-O-methyltransferase (COMT ) polymorphism may modulate the effects of adolescent D-9-tetrahydrocannabinol (THC) exposure on the risk for adult psychosis. Mice with knockout of the COMT gene were treated chronically with THC (4.0 and 8.0 mg/kg over 20 days) during either adolescence (postnatal days (PDs) 32-52) or adulthood (PDs 70-90). The effects of THC exposure were then assessed in adulthood across behavioral phenotypes relevant for psychosis: exploratory activity, spatial working memory (spontaneous and delayed alternation), object recognition memory, social interaction (sociability and social novelty preference), and anxiety (elevated plus maze). Adolescent THC administration induced a larger increase in exploratory activity, greater impairment in spatial working memory, and a stronger anti-anxiety effect in COMT knockouts than in wild types, primarily among males. No such effects of selective adolescent THC administration were evident for other behaviors. Both object recognition memory and social novelty preference were disrupted by either adolescent or adult THC administration, independent of genotype. The COMT genotype exerts specific modulation of responsivity to chronic THC administration during adolescence in terms of exploratory activity, spatial working memory, and anxiety. These findings illuminate the interaction between genes and adverse environmental exposures over a particular stage of development in the expression of the psychosis phenotype.