Orexin supplementation in narcolepsy treatment: A review.

Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin/hypocretin neuronal loss. The orexin system regulates sleep/wake control via complex interactions with monoaminergic, cholinergic and GABA-ergic neuronal systems. Currently, no cure for narcolepsy exists, but some symptoms can be controlled with medication (eg, stimulants, antidepressants, etc). Orexin supplementation represents a more sophisticated way to treat narcolepsy because it addresses the underlying cause of the disease and not just the symptoms. Research on orexin supplementation in the treatment of sleep disorders has strongly increased over the past two decades. This review focuses on a brief description of narcolepsy, the mechanisms by which the orexin system regulates sleep/wake cycles, and finally, possible therapeutic options based on orexin supplementation in animal models and patients with narcolepsy.

Risk element accumulation in Coleoptera and Hymenoptera (Formicidae) living in an extremely contaminated area-a preliminary study.

The risk element accumulation ability of two groups of epigeic species, insects from families Coleoptera and Hymenoptera (namely Formicidae), was determined and related to soil risk element content and bioaccessibility. The study was conducted in the district of Príbram, Czech Republic, which was characterised by extremely high aged pollution in the soils, including risk elements, especially As, Pb, Zn and Cd, due to the former mining and smelting activity. Four sampling sites differing in their pseudo-total risk element contents were selected and composite samples of individuals representing either Coleoptera or Formicidae were sampled at the individual sampling points. The results indicate the ability of Coleoptera and Formicidae organisms to accumulate risk elements, especially at the location with extremely high soil risk element content. In soil containing up to 841 mg As kg-1, 84.6 mg Cd kg-1, 4250 mg Pb kg-1 and 8542 mg Zn kg-1, contents in insect bodies reached 239 mg As kg-1 As, 24.2 mg Cd kg-1, 70.4 mg Pb kg-1 and 335 mg Zn kg-1 in beetles and up to 20.9 mg As kg-1, 29.9 mg Cd kg-1, 111 mg Pb kg-1 and 657 mg Zn kg-1 in ants. Therefore, bioaccumulation factors (BAFs) varied between 0.02 and 0.55. Increasing Cd content in Coleoptera bodies with increasing soil pseudo-total element content was observed only among the investigated elements. However, the results indicate increasing BAF values with decreasing soil element levels, especially for Cd, Pb and Zn, indicating limited uptake of elements by the organisms living in contact with extremely contaminated soil.

Acute systemic MK-801 induced functional uncoupling between hippocampal areas CA3 and CA1 with distant effect in the retrosplenial cortex.

The hippocampus and retrosplenial cortex are integrated within a higher-order cognitive circuit supporting relational (spatial, contextual, episodic) forms of learning and memory. Hippocampal place cells can coordinate multiple parallel representations in the same physical environment. Novel environment exploration triggers expression of immediate-early genes (IEGs) Arc and Homer1a in spatial context-specific ensembles of CA1 and CA3 neurons. Less is know about ensemble coding in the retrosplenial cortex (RSC), a region directly connected and functionally coupled to CA1. Hippocampal and retrosplenial damage is found in patients with schizophrenia alongside cognitive deficits affecting relational memory. Systemic administration of non-competitive NMDAR antagonists such as MK-801 is used to model psychosis in animals and humans. Acute systemic MK-801 (0.15 mg/kg) impaired cognitive control in rats and ensemble code for spatial context in CA1. Here, we use expression of immediate-early genes Arc and Homer 1a to examine ensemble coding in rat CA3 and RSC to test if the effect of MK-801 extends upstream and downstream of CA1, respectively. Different rats explored the same context twice (A/A), explored two distinct contexts (A/B) or remained in their home cage (CC). In contrast to CA1, MK-801 did not affect ensemble coding in CA3. Unlike CA3 and CA1, similarity of RSC ensembles active during exploration did not reflect change in spatial context, but MK-801 (0.15 mg/kg) increased similarity in RSC ensembles active during spontaneous behavior in the home cage. The data provide support for MK-801-induced functional uncoupling between CA3 and CA1 and suggest that ensemble coding deficit may extend downstream of CA1. This deficit may reflect hyperassociative state in the cognitive circuit underlying cognitive disorganization in psychosis. © 2016 Wiley Periodicals, Inc.

Functional inactivation of the rat hippocampus disrupts avoidance of a moving object.

The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 µL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8). No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.

New species of Rhamphomyia (Diptera: Empididae) from Turkey with a key to species of the Middle East and adjacent territories.

Rhamphomyia (s. str.) academica sp. nov. (Turkey) and R. (s. str.) soukupi sp. nov. (Turkey) are described and illustrated. Rhamphomyia (Lundstroemiella) cimrmani Barták, 2006, is re-described and the female is newly described. The first records of Rhamphomyia (s. str.) argentata von Röder, 1887 and R. (Pararhamphomyia) intersita Collin, 1960 are reported from Turkey. A key to species of Rhamphomyia from the Middle East is presented.

Species of Bicellaria Macquart (Diptera: Hybotidae) of Europe, with descriptions of four new species.

Species of the genus Bicellaria (Diptera: Hybotidae) of Europe are reviewed. Altogether four new species are describes, viz B. andorra sp. nov. (Andorra, France), B. italica sp. nov. (Europe), B. kocoureki sp. nov. (Bulgaria), and B. setipalpus sp. nov. (Italy). Bicellaria dispar Oldenberg, 1920 is redescribed and lectotype is designated. Bicellaria bisetosa Tuomikoski, 1936 is newly synonymized with B. uvens Melander, 1928. Illustrations of male terminalia and a key to all known European species are provided.

Species of Bicellaria (Diptera: Hybotidae) from Asia.

Bicellaria amankutanensis sp. nov. (Uzbekistan), B. chimganensis sp. nov. (Uzbekistan), B. farkaci sp. nov. (China), B. globulicauda sp. nov. (Uzbekistan), B. koreana sp. nov. (North Korea, Russia), B. kovalevi sp. nov. (Georgia), B. setitibia sp. nov. (Georgia), B. shatalkini sp. nov. (Russia), B. thailandica sp. nov. (Thailand), and B. woodi sp. nov. (Japan) are described and illustrated. Bicellaria montana Kato is newly synonymised with B. uvens Melander. Bicellaria spuria ingrata Collin is considered a distinct species. A key to all known Asian species of Bicellaria is provided.

Loss of activity-dependent Arc gene expression in the retrosplenial cortex after hippocampal inactivation: interaction in a higher-order memory circuit.

The rodent hippocampus is well known for its role in spatial navigation and memory, and recent evidence points to the retrosplenial cortex (RSC) as another element of a higher order spatial and mnemonic circuit. However, the functional interplay between hippocampus and RSC during spatial navigation remains poorly understood. To investigate this interaction, we examined cell activity in the RSC during spatial navigation in the water maze before and after acute hippocampal inactivation using expression of two immediate-early genes (IEGs), Arc and Homer 1a (H1a). Adult male rats were trained in a spatial water maze task for 4 days. On day 5, the rats received two testing/training sessions separated by 20 min. Eight minutes before the second session, different groups of rats received bilateral intrahippocampal infusion of tetrodotoxin (TTX), muscimol (MUS), or vehicle. Another group of rats (uni-TTX) received infusion of TTX in one hippocampus and vehicle in the other. Signals from Arc and H1a RNA probes correspond to the post- and pre-infusion sessions, respectively. Bilateral TTX and MUS impaired spatial memory, as expected, and decreased Arc expression in CA1 of hippocampus. Importantly, bilateral inactivation of hippocampus resulted in loss of behavior-induced Arc expression in RSC. Despite a lateralized effect in CA1, Arc expression was equivalently and bilaterally decreased in RSC of uni-TTX rats, consistent with a network level interaction between hippocampus and RSC. We conclude that the loss of hippocampal input alters activity of RSC neurons and compromises their ability to engage plastic processes dependent on IEG expression.

Unexpected Previously Unknown Diversity of the Genus Microphor Macquart (Diptera: Dolichopodidae: Microphorinae) in the West Palaearctic.

Microphor baechlii sp. nov. (Switzerland, Turkey), M. chvalai sp. nov. (France), M. nevadensis sp. nov. (Spain), M. pallipes sp. nov. (Italy), and M. turcicus sp. nov. (Turkey) are described and illustrated. The neotype of M. anomalus (Meigen, 1824) is designated. Males of all known Palaearctic species of Microphor are keyed, genitalia are illustrated for new species and species previously inadequately illustrated, and main diagnostic characters are discussed. Microphorstrobli Chvála, 1986 is newly recorded from Bulgaria, M. anomalus (Meigen, 1824) is newly recorded from Turkey, and M. holosericeus (Meigen, 1804) is newly recorded from Turkey and Portugal.

Attention-like modulation of hippocampus place cell discharge.

Hippocampus place cell discharge is an important model system for understanding cognition, but evidence is missing that the place code is under the kind of dynamic attentional control characterized in primates as selective activation of one neural representation and suppression of another, competing representation. We investigated the apparent noise ("overdispersion") in the CA1 place code, hypothesizing that overdispersion results from discharge fluctuations as spatial attention alternates between distal cues and local/self-motion cues. The hypothesis predicts that: (1) preferential use of distal cues will decrease overdispersion; (2) global, attention-like states can be decoded from ensemble discharge such that both the discharge rates and the spatial firing patterns of individual cells will be distinct in the two states; (3) identifying attention-like states improves reconstructions of the rat's path from ensemble discharge. These predictions were confirmed, implying that a covert, dynamic attention-like process modulates discharge on a approximately 1 s time scale. We conclude the hippocampus place code is a dynamic representation of the spatial information in the immediate focus of attention.

Fanniidae (Diptera): new species, new records and first description of the male of Fannia latifrontalis Hennig.

Fannia bohemica sp. nov. (Czech Republic, Slovakia) is described and illustrated. Male of F. latifrontalis Hennig, 1955 is described and illustrated for the first time. Fannia jezoensis Nishida, 1976 is first reported from West Palaearctic, Fannia morrisoni Malloch, 1913 is first recorded from Palaearctic Region. Fannia umbrosa (Stein, 1895) and F. armata (Meigen, 1826; first record based on morphologically identified specimens) are new records from Nearctic Region. Six species (Fannia fuscitibia Stein, 1920, F. latifrontalis, F. limbata (Tiensuu, 1938), F. verrallii (Meade, 1891), F. gotlandica Ringdahl, 1926 and F. spathiophora, Malloch, 1918) are recorded for the first time from Slovakia.

Four new West Palaearctic species and new distributional records of Hybotidae (Diptera).

Megagrapha starki Barták & Grootaert, sp. nov. (Poland, Russia, Slovakia), Oedalea portugalica Barták & Grootaert, sp. nov. (Portugal), Hybos conicus Grootaert & Barták, sp. nov. (Greece, Turkey), and Platypalpus obscuroides Barták & Grootaert, sp. nov. (Slovakia) are described and illustrated. Diagnostic characters are discussed. The female of Syndyas merzi Shamshev & Grootaert, 2012 is described for the first time. New distributional records are presented: Megagrapha europaea Papp & Földvári, 2001 is first reported from Slovakia and Syndyas merzi Shamshev & Grootaert, 2012 is first reported from Turkey.

Plasticity-Related Activity in the Hippocampus, Anterior Cingulate, Orbitofrontal, and Prefrontal Cortex Following a Repeated Treatment with D2/D3 Agonist Quinpirole.

Quinpirole (QNP) sensitization is a well-established model of stereotypical checking relevant to obsessive-compulsive disorder. Previously, we found that QNP-treated rats display deficits in hippocampus-dependent tasks. The present study explores the expression of immediate early genes (IEG) during QNP-induced stereotypical checking in the hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC). Adult male rats were injected with QNP (0.5 mg/mL/kg; n = 15) or saline (n = 14) daily for 10 days and exposed to an arena enriched with two objects. Visits to the objects and the corners of the arena were recorded. QNP-treated rats developed an idiosyncratic pattern of visits that persisted across experimental days. On day 11, rats were exposed to the arena twice for 5 min and sacrificed. The expression of IEGs Arc and Homer1a was determined using cellular compartment analysis of temporal activity by fluorescence in situ hybridization. IEG-positive nuclei were counted in the CA1 area of the hippocampus, ACC, OFC, and mPFC. We found significantly fewer IEG-positive nuclei in the CA1 in QNP-treated rats compared to controls. The overlap between IEG expressing neurons was comparable between the groups. We did not observe significant differences in IEG expression between QNP treated and control rats in ACC, OFC, and mPFC. In conclusion, treatment of rats with quinpirole decreases plasticity-related activity in the hippocampus during stereotypical checking.

Electric field detection as floral cue in hoverfly pollination.

Pollinators can detect the color, shape, scent, and even temperature of the flowers they want to visit. Here, we present the previously unappreciated capacity of hoverflies (Eristalis tenax and Cheilosia albipila) to detect the electric field surrounding flowers. Using hoverflies as key dipteran pollinators, we explored the electrical interactions between flies and flowers-how a hoverfly acquired a charge and how their electrical sensing ability for target flowers contributed to nectar identification and pollination. This study revealed that rapid variations in a floral electric field were related to a nectar reward and increased the likelihood of the fly's return visits. We found that thoracic hairs played a role in the polarity of hoverfly charge, revealing their electro-mechanosensory capability, as in bumblebees (Bombus terrestris). Electrophysiological analysis of the hoverfly's antennae did not reveal neural sensitivity to the electric field, which favors the mechanosensory hairs as putative electroreceptive organs in both species of hoverflies.

Rapid activation of plasticity-associated gene transcription in hippocampal neurons provides a mechanism for encoding of one-trial experience.

The hippocampus is hypothesized to support rapid encoding of ongoing experience. A critical prerequisite for such function is the ability to readily recruit enduring synaptic plasticity in hippocampal neurons. Hippocampal long-term potentiation (LTP) and memory consolidation require expression of the immediate-early gene (IEG) Arc. To determine whether Arc transcription could be driven by limited and controlled behavioral experience, we used a rectangular track paradigm. In past electrophysiological studies, pyramidal neurons recorded from rats running in one direction on similar tracks typically exhibited a single firing field. Using fluorescence in situ hybridization, we show that the behavioral activity associated with a single lap around the track was sufficient to trigger Arc transcription in complete CA3 neuronal ensembles, as predicted given the role of CA3 in one-trial learning. In contrast, Arc transcription in CA1 ensembles was recruited incrementally, with maximal activation achieved after four laps a day for 4 consecutive days. To test whether Arc transcription is linked to learning and plasticity, or merely elicited by location-specific firing, we inactivated the medial septum, a treatment that compromises hippocampus-dependent learning and LTP but spares location-specific firing in CA1 neurons. Septal inactivation abolished track training-induced Arc transcription in CA1 and CA3 neurons, showing that Arc transcription requires plasticity-inducing stimuli. Accordingly, LTP induction activated Arc transcription in CA1 neurons in vivo. These findings demonstrate for the first time that a single brief experience, equivalent to a single crossing of a firing field, can trigger IEG expression required for long-term plasticity in the hippocampus.

Two new West Palaearctic species of Atelestus Walker (Diptera, Atelestidae) and new distributional records of the family.

Atelestus turcicus Barták, sp. nov. (Turkey) and Atelestus ibericus Barták, sp. nov. (Spain) are described and illustrated. A key to all known Palaearctic species of Atelestus is provided and the main diagnostic characters are discussed. The female of Nemedina acutiformis Carles-Tolrá, 2008 is described for the first time. New distributional records are presented: Atelestus dissonans Collin, 1961 - first records from Spain and Bulgaria, A. pulicarius (Fallén, 1816) - first record from Turkey, Nemedina alamirabilis Chandler, 1981 - first record from Bulgaria and N. acutiformis Carles-Tolrá, 2008 - first record from Turkey.

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms.

Despite the substantial knowledge accumulated by past research, the exact mechanisms of the pathogenesis of schizophrenia and causal treatments still remain unclear. Deficits of cognition and information processing in schizophrenia are today often viewed as the primary and core symptoms of this devastating disorder. These deficits likely result from disruptions in the coordination of neuronal and neural activity. The aim of this review is to bring together convergent evidence of discoordinated brain circuits in schizophrenia at multiple levels of resolution, ranging from principal cells and interneurons, neuronal ensembles and local circuits, to large-scale brain networks. We show how these aberrations could underlie deficits in cognitive control and other higher order cognitive-behavioural functions. Converging evidence from both animal models and patients with schizophrenia is presented in an effort to gain insight into common features of deficits in the brain information processing in this disorder, marked by disruption of several neurotransmitter and signalling systems and severe behavioural outcomes.

Networks of neurons, networks of genes: an integrated view of memory consolidation.

Investigations into the mechanisms of memory formation have abided by the central tenet of the consolidation theory-that memory formation occurs in stages which differ in their requirement for protein synthesis. The current most widely accepted hypothesis posits that new memories are encoded as neural activity-induced changes in synaptic efficacy, and stabilization of these changes requires de novo protein synthesis. However, the basic assumptions of this view have been challenged by concerns regarding the specificity of the effects of the protein synthesis inhibitors used to support the claim. Studies on immediate-early genes (IEGs), in particular Arc, provide a distinct and independent perspective on the issue of the requirement of new protein synthesis in synaptic plasticity and memory consolidation. The IEG Arc and its protein are dynamically induced in response to neuronal activity, and are directly involved in synaptic plasticity and memory consolidation. Although we provide extensive data on Arc's properties to address the requirement of genomic and proteomic responses in memory formation, Arc is merely one element in a network of genes that interact in a coordinated fashion to serve memory consolidation. From gene expression and other studies, we propose the view that the stabilization of a memory trace is a continuous and ongoing process, which does not have a discrete endpoint and cannot be reduced to a single deterministic "molecular cascade". Rather, memory traces are maintained within metastable networks, which must integrate and update past traces with new ones. Such an updating process may well recruit and use many of the plasticity mechanisms necessary for the initial encoding of memory.

Using immediate-early genes to map hippocampal subregional functions.

Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal functional dissociations with a particular focus on the CA3 subregion. We first discuss the cellular functions of IEGs and the brain system interactions that govern their dynamic expression in hippocampal neurons to provide a more solid framework for interpreting the findings from IEG studies. We show the pitfalls and shortcomings of conventional IEG imaging studies and describe advanced methods using IEGs for imaging of neuronal activity or functional intervention. We review the current IEG evidence of hippocampal function, subregional-specific contribution to different stages of memory formation, systems consolidation, functional dissociation between memory and anxiety/behavioral inhibition along the septotemporal axis, and different neural network properties of hippocampal subregions. In total, IEG studies provide support for (1) the role of the hippocampus in spatial and contextual learning and memory, (2) its role in continuous encoding of ongoing experience, (3) septotemporal dissociations between memory and anxiety, and (4) a dynamic relationship between pattern separation and pattern completion in the CA3 subregion. In closing, we provide a framework for how cutting-edge IEG imaging and intervention techniques will likely contribute to better understanding of the specific functions of CA3 and other hippocampal subregions.

Hybotidae (Diptera) from Turkey, with descriptions of seven new species.

The family Hybotidae is systematically studied from Turkey for the first time. Altogether 51 species are reported from Turkey, of which 36 species are first recorded from this country and seven species are described as new for science: Platypalpus academicus sp. nov., P. anomalus sp. nov., P. bohousi sp. nov., P. diminuticornis sp. nov., P. dursuni sp. nov., P. moceki sp. nov., and P. seticauda sp. nov. Seven additional probably undescribed species remain unnamed due to insufficient material. Tachypeza subnubila Raffone, 2002 is proposed as new subjective junior synonym of Tachypeza nubila (Meigen, 1804).