Physiological and Morphological Characterization of Organotypic Cocultures of the Chick Forebrain Area MNH and its Main Input Area DMA/DMP

Cocultures of the learning-relevant forebrain region mediorostrai neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were lightand electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intraceilular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain

Перспективы нефтегазоносности нижнеюрских резервуаров на основе комплексной интерпретации данных геотермии и бурения в Нюрольской мегавпадине (Томская область)

Объектом исследования является нефтематеринская тогурская свита и резервуары нижнеюрского нефтегазоносного комплекса. Цель работы – выполнение оценки перспектив нефтегазоносности нижнеюрских отложений Нюрольской мегавпадины на базе палеотектонических реконструкций и палеотемпературного моделирования, картирование плотности первично-аккумулированных тогурских нефтей, определение первоочередных объектов для постановки геолого-разведочных работ. Работа выполнена на основе геолого-геофизических данных, полученных при бурении глубоких скважин и лабораторных исследований керна с использованием публикаций по теме исследования и фондовым материалам.Object of research is the oil source togur suit and Lower Jurassic oil and gas oil and gas bearing complex. Work objective is to estimate lower Jurassic oil and gas potential of Nurolka mega depression using paleotectonic reconstructions and modeling, mapping of initially accumulated oil resources containing in togurskaya suit, determining premium objects for geological exploration. During research we analyzed publications and library materials. Geological and geophysical data obtained by well drilling and core analysis were also systematized and used in that work

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism

Imaging in Neurology Research III: Neurodegenerative Diseases

Positron emission tomography (PET) plays an outstanding role among imaging technologies since it enables visualization of physiological and pathophysiological processes at the molecular level in real time. Moreover, it combines low invasiveness with high sensitivity, and numerous biological processes can be measured repeatedly and quantitatively. Therefore, it is ideally suited for translational animal research to investigate different pathologies. Especially neurodegenerative diseases are of particular interest since a plethora of imaging agents exist (Table 30.1), which allow to investigate different molecular targets involved in neurodegenerative processes. Furthermore, various animal models with neurodegenerative diseases are available, facilitating to elucidate dysfunctions associated with the progression of neurodegeneration. Above all, small animal models of Alzheimer’s and Parkinson’s disease are mainly used in this field since they are the most common pathologies of neurodegenerative disease

Tau-imaging in neurodegeneration

Pathological cerebral aggregations of proteins are suggested to play a crucial role in the development of neurodegenerative disorders. For example, aggregation of the protein ss-amyloid in form of extracellular amyloid-plaques as well as intraneuronal depositions of the protein tau in form of neurofibrillary tangles represent hallmarks of Alzheimer's disease (AD). Recently, novel tracers for in vivo molecular imaging of tau-aggregates in the brain have been introduced, complementing existing tracers for imaging amyloid-plaques. Available data on these novel tracers indicate that the subject of Tau-PET may be of considerable complexity. On the one hand this refers to the various forms of appearance of tau-pathology in different types of neurodegenerative disorders. On the other hand, a number of hurdles regarding validation of these tracers still need to be overcome with regard to comparability and standardization of the different tracers, observed off-target/non-specific binding and quantitative interpretation of the signal. These issues will have to be clarified before systematic clinical application of this exciting new methodological approach may become possible. Potential applications refer to early detection of neurodegeneration, differential diagnosis between tauopathies and non-tauopathies and specific patient selection and follow-up in therapy trials. (C) 2017 Published by Elsevier Inc

Different pharmaceutical preparations of Delta(9)-tetrahydrocannabinol differentially affect its behavioral effects in rats

Based on the contribution of the endocannabinoid system to the pathophysiology of schizophrenia, the primary pro-psychotic ingredient of Cannabis sativa, Delta-9-tetrahydrocannabinol (Delta-9-THC), is used in preclinical as well as clinical research to mimic schizophrenia-like symptoms. While it is common to administer lipid-based formulations of Delta-9-THC in human studies orally, intraperitoneal injections of water-based solutions are used in animal models. Because of the poor water solubility of Delta-9-THC, solubilizers such as ethanol and/or emulsifiers are needed for these preparations. In order to test whether a lipid-based solvent would be superior over a water-based vehicle in rats, we compared the effects on locomotor activity and prepulse inhibition (PPI) of the acoustic startle reaction, as well as pharmacokinetic data obtained from rats' serum and brain tissue samples. Up to 50 mg/kg Delta-9-THC in the lipid-based formulation was not able to induce any behavioral alterations, while already 5 mg/kg of the water-based Delta-9-THC preparation significantly reduced locomotor activity. This also induced a small but significant PPI reduction, which was prepulse intensity dependent. Interestingly, the reflexive motor response to the startle stimulus was not affected by the water-based Delta-9-THC solution. Analysis of serum and brain Delta-9-THC levels by high-performance liquid chromatography/mass spectrometry revealed that although the final concentration reached in the brain was comparable for both pharmaceutical preparations, the water-based formulation achieved a faster kinetic. We, therefore, conclude that the slope of the Delta-9-THC concentration-time curve and the resulting cannabinoid receptor type 1 activation per time unit are responsible for the induction of behavioral alterations