pinecone/core-2020-05-10-deduplication huggingface dataset:
The impact of experienced stress on aged spatial discrimination: Cortical overreliance as a result of hippocampal impairment

© 2015 Wiley Periodicals, Inc. A large body of neuroscientific work indicates that exposure to experienced stress causes damage to both cortical and hippocampal cells and results in impairments to cognitive abilities associated with these structures. Similarly, work within the domain of cognitive aging demonstrates that elderly participants who report experiencing greater amounts of stress show reduced levels of cognitive functioning. The present article attempted to combine both findings by collecting data from elderly and young participants who completed a spatial discrimination paradigm developed by Reagh and colleagues [Reagh et al. (2013) Hippocampus 24:303-314] to measure hippocampal-mediated cognitive processes. In order to investigate the effect of stress on the cortex and, indirectly, the hippocampus, it paired the paradigm with electroencephalographic recordings of the theta frequency band, which is thought to reflect cortical/hippocampal interactions. Findings revealed that elderly participants with high levels of experienced stress performed significantly worse on target recognition and lure discrimination and demonstrated heightened levels of cortical theta synchronization compared with young and elderly low stress counterparts. Results therefore provided further evidence for the adverse effect of stress on cognitive aging and indicate that impaired behavioral performance among high stress elderly may coincide with an overreliance on cortical cognitive processing strategies as a result of early damage to the hippocampus
The Effects of Hippocampal Lesions on MRI Measures of Structural and Functional Connectivity

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph-theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical “hub” in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey-matter volume that was consistent across patients, and the fornix was the only major white-matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default-mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default-mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbicdiencephalic structures and larger-scale networks.Medical Research Council (Grant ID: MC-A060-5PR10); Biotechnology and Biological Sciences Research Council (Grant ID: BB/L02263X/1); Netherlands Organization for Scientific ResearchThis is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/hipo.2262
Selforganization of modular activity of grid cells

A unique topographical representation of space is found in the concerted activity of grid cells in the rodent medial entorhinal cortex. Many among the principal cells in this region exhibit a hexagonal firing pattern, in which each cell expresses its own set of place fields (spatial phases) at the vertices of a triangular grid, the spacing and orientation of which are typically shared with neighboring cells. Grid spacing, in particular, has been found to increase along the dorso-ventral axis of the entorhinal cortex but in discrete steps, that is, with a modular structure. In this study, we show that such a modular activity may result from the self-organization of interacting units, which individually would not show discrete but rather continuously varying grid spacing. Within our "adaptation" network model, the effect of a continuously varying time constant, which determines grid spacing in the isolated cell model, is modulated by recurrent collateral connections, which tend to produce a few subnetworks, akin to magnetic domains, each with its own grid spacing. In agreement with experimental evidence, the modular structure is tightly defined by grid spacing, but also involves grid orientation and distortion, due to interactions across modules. Thus, our study sheds light onto a possible mechanism, other than simply assuming separate networks a priori, underlying the formation of modular grid representations
Hippocampal CA1 activity correlated with the distance to the goal and navigation performance.

Coding the distance to a future goal is an important function of a neural system supporting navigation. While some evidence indicates the hippocampus increases activity with proximity to the goal, others have found activity to decrease with proximity. To explore goal distance coding in the hippocampus we recorded from CA1 hippocampal place cells in rats as they navigated to learned goals in an event arena with a win-stay lose-shift rule. CA1 activity was positively correlated with the distance - decreasing with proximity to the goal. The stronger the correlation between distance to the goal and CA1 activity, the more successful navigation was in a given task session. Acceleration, but not speed, was also correlated with the distance to the goal. However, the relationship between CA1 activity and navigation performance was independent of variation in acceleration and variation in speed. These results help clarify the situations in which CA1 activity encodes navigationally relevant information and the extent to which it relates to behavior
The response strategy and the place strategy in a plus-maze have different sensitivities to devaluation of expected outcome.

Previous studies have suggested that spatial navigation can be achieved with at least two distinct learning processes, involving either cognitive map‐like representations of the local environment, referred to as the “place strategy”, or simple stimulus‐response (S‐R) associations, the “response strategy”. A similar distinction between cognitive/behavioural processes has been made in the context of non‐spatial, instrumental conditioning, with the definition of two processes concerning the sensitivity of a given behaviour to the expected value of its outcome as well as to the response‐outcome contingency (“goal‐directed action” and “S‐R habit”). Here we investigated whether these two versions of dichotomist definitions of learned behaviour, one spatial and the other non‐spatial, correspond to each other in a formal way. Specifically, we assessed the goal‐directed nature of two navigational strategies, using a combination of an outcome devaluation procedure and a spatial probe trial frequently used to dissociate the two navigational strategies. In Experiment 1, rats trained in a dual‐solution T‐maze task were subjected to an extinction probe trial from the opposite start arm, with or without prefeeding‐induced devaluation of the expected outcome. We found that a non‐significant preference for the place strategy in the non‐devalued condition was completely reversed after devaluation, such that significantly more animals displayed the use of the response strategy. The result suggests that the place strategy is sensitive to the expected value of the outcome, while the response strategy is not. In Experiment 2, rats with hippocampal lesions showed significant reliance on the response strategy, regardless of whether the expected outcome was devalued or not. The result thus offers further evidence that the response strategy conforms to the definition of an outcome‐insensitive, habitual form of instrumental behaviour. These results together attest a formal correspondence between two types of dual‐process accounts of animal learning and behaviour
Salicylate induces anxiety-like behaviour and slow theta oscillation and abolishes the relationship between running speed and fast theta oscillation frequency

Salicylate intoxication is a cause of tinnitus in humans and it is often used to produce tinnitus?like perception in animal models. Here we assess whether salicylate induces anxiety?like electrophysiological and behavioural signs. Using microwire electrode arrays, we recorded local field potential in the ventral and, in some experiments dorsal hippocampus, in an open field arena 1 hour after salicylate (300mg/kg) injection. We found that animals treated with salicylate moved dramatically less than saline treated animals. Salicylate?treated animals showed a strong 4?6Hz (type 2) oscillation in the ventral hippocampus (with smaller peaks in dorsal hippocampus electrodes). Coherence in the 4?6Hz?theta band was low in the ventral and dorsal hippocampus when compared to movement?related theta coherence (7?10Hz). Moreover, movement related theta oscillation frequency decreased and its dependency on running speed was abolished. Our results suggest that salicylate?induced theta is mostly restricted to the ventral hippocampus. Slow theta has been classically associated to anxiety?like behaviours. Here we show that salicylate application can consistently generate low frequency theta in the ventral hippocampus. Tinnitus and anxiety show strong comorbidity and the increase in ventral hippocampus low frequency theta could be part of this association
Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Benzoyl-, Äthoxycarbonyl- und Vinylphosphonaten

The irradiation of the 3-phenyl-2H-azirines 1a-c in the presence of diethyl benzoylphosphonate (8) in cyclohexane solution, using a mercury high pressure lamp (pyrex filter), yields the diethyl (4,5-diphenyl-3-oxazolin-5-yl)-phosponates 9a-c (Scheme 3). In the case of 1b a mixture of two diastereomeric 3-oxazolines, resulting from a regiospecific but non-stereospecific cycloaddition of the benzonitrile-benzylide dipole 2b to the carbonyl group of the phosphonate 8, was isolated. Benzonitrile-isopropyIide (2a), generated from 2,2-dimethyl-3-phenyl-2H-azirine (1a), undergoes a cycloaddition reaction to the ester-carbonyl group of diethyl ethoxycarbonyl-phosphonate (15) with the same regiospecificity to give the 3-oxazoline derivative 16 (Scheme 5). The azirines 1a-c, on irradiation in benzene in the presence of diethyl vinylphosphonate (17) give non-regiospecifically the delta1-pyrrolines 13a-c and 14a-c (Scheme 6)
Diels-Alder Reactions of [2.2]Paracyclophane-1-ene and [2.2]Paracyclophane-1,9-diene with 3,6-Disubstituted 1,2,4,5-Tetrazines

[2.2] Paracyclophan-1-ene (1) and [2.2] paracyclophane-1,9-diene (6) apparently act as dienophiles with inverse electron demand and smoothly react with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (2a) at room temperature forming dihydropyridazine adducts, which are dehydrogenated to the pyridazino-anellated [2.2] paracyclophanes 5a and 8a, respectively. The molecular structure of 5a is determined by X-ray crystal-structure analysis. Under more rigorous conditions, phenyl-substituted derivatives 5b and 8b are obtained from 1 and 6, respectively, with 3,6-diphenyl-1,2,4,5-tetrazine. Compounds 1 and 6 are less reactive dienophiles than other strained cyclic olefins as shown by kinetic measurements
Paramagnetic Redox Stages of a Bisphane: An ESR and ENDOR Study

Seven redox stages, the dication 12+, the radical cation , the neutral 1, the radical anion , the dianion 12-, the radical trianion , and the tetraanion 14-, are indicated by cyclic voltammetry for the bisphane 1, in which the benzene decks of two lateral paracyclophane moieties are orthogonal to the plane of anthracene framework. In  and , the unpaired electron is accommodated into the central anthracene subsystem, and the same statement holds for the two positive or negative charges in 12+ and 12-. Formation of  and 1- occurs through admission of additional electrons one-by-one into the two paracyclophane moieties flanking the doubly charged anthracene subsystem in 12-. The above-postulated, successive release or uptake of electrons by the individual parts of the bisphane is in perfect accord with the hyperfine data determined by ESR and ENDOR spectroscopy for , , , as well as for radical ions of suitable reference compounds
Reactions of stable alpha-chlorosulfanyl chlorides with C=S-functionalized compounds

The smooth reaction of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (3) with 3,4,5-trisubstituted 2,3-dihydro-1H-imidazole-2-thiones 8 and 2-thiouracil (10) in CH2Cl2/Et3N at room temperature yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of Cl- of the sulfanyl chloride by the S-atom of the heterocyclic thione. The analogous reaction of 3-cyclohexyl-2,3-dihydro-4,5-diphenyl-1H-imidazole-2-thione (8b) and 10 with the chlorodisulfanyl derivative 16 led to the corresponding trisulfanes 17 and 18 (Scheme 4), respectively. On the other hand, the reaction of 3 and 4,4- dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione (12) in CH2Cl2 gave only 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-one (13) and the trithioorthoester derivative 14, a bis-disulfane, in low yield (Scheme 3). At -78°, only bis(1-chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)polysulfanes 15 were formed. Even at -78°, a 1 : 2 mixture of 12 and 16 in CH2Cl2 reacted to give 13 and the symmetrical pentasulfane 19 in good yield (Scheme 5). The structures of 11, 14, 17, and 18 have been established by X-ray crystallography
An unexpected formation of a 14-membered Cyclodepsipeptide

The treatment of diluted solutions of the hydroxy diamides 6a and 6b in toluene with HCl gas at 100° gave the dimeric, 14-membered cyclodepsipeptide 10 in up to 72% yield (Scheme 3). The same product was formed from the linear dimer of 6b, the depsipeptide 11, under the same conditions (cf. Scheme 4). All attempts to prepare the cyclic seven-membered monomer 9, starting with different precursors and using different lactonization methods failed, and 10 was the only product which was isolated (cf. Scheme 6). For example, the reaction of the ester 20 with NaH in toluene at 80° led exclusively to the cyclodimer 10. On the other hand, the base-catalyzed cyclization of the hydroxy diester 22, which is the 'O-analogue' of 20, yielded neither the seven- membered dilactone, nor the 14-membered tetralactone, but only the known trimer 23 and tetramer 24 of 2,2- dimethylpropano-3-lactone (cf. Scheme 7)
Selenium-containing heterocycles from Isoselenocyanates: Synthesis of 1H-5-Selena-1,3,6-triazaaceanthrylene derivatives

The reaction of aryl isoselenocyanates 8 with methyl 3-amino-4-chloro-1-ethylpyrrolo[3,2-c]quinoline-2-carboxylate (6) in boiling pyridine leads to tetracyclic selenaheterocycles of type 9 in high yield (Scheme 3). A reaction mechanism via an intermediate selenoureido derivative A and cyclization via nucleophilic substitution of Cl by Se is proposed (Schemes 3 and 5). The reaction of 6 with 4-bromophenyl isothiocyanate yields the analogous thiaheterocycle 12 (Scheme 4). The molecular structures of 9c and 12 have been established by X-ray crystallography
Regio- and stereoselective 1,3-Oxathiolane formation in the reaction of Thiolactones with optically active oxiranes

The reactions of 3H-isobenzofuran-1-thione (1) with (S)-2-methyloxirane (2) and (R)-2-phenyloxirane (6) in the presence of SiO2 in anhydrous CH2Cl2 led to two pairs of diastereoisomeric spirocyclic 1,3-oxathiolanes, i.e., 3 and 4 with a Me group at C(5'), and 7 and 8 with a Ph group at C(4'), respectively (Schemes 2 and 3). In both cases, 3H-isobenzofuran-1-one (5) was formed as a main product. The analogous reactions of 3,4-dihydro-2H-[1]benzopyran-2-thione (9) and 3,4,5,6-tetrahydro-2H-pyran-2-thione (14) with 2 and 6 yielded four pairs of the corresponding diastereoisomeric spirocyclic compounds 10 and 11, 12 and 13, 15 and 16, and 18 and 19, respectively (Schemes 4 - 7). In the reaction of 14 with 6, the 1,3-oxathiolane 20 with a Ph group at C(2) was also formed. The structures of 3, 7, 8, 10, 19, and 20 were established by X-ray crystallography (Figs.1-4). In contrast to the thiolactones 1, 9, and 14, the thioesters 21a-21d did not react with (R)-2-phenyloxirane (6) either in the presence of SiO2 or under more-drastic conditions with BF3 . Et2O or SnCl4 (Scheme 8). The results show that spirocyclic 1,3-oxathiolanes can be prepared from thiolactones with oxiranes. The nucleophilic attack of the thiocarbonyl S-atom at the SiO2-activated oxirane ring proceeds with high regio- and stereoselectivity via an SN2-type mechanism
Synthesis of Cyclohexapeptides containing Pro and Aib residues

Cyclization reactions on hexapeptides containing several alpha-aminoisobutyric acid (= 2-amino-2-methylpropanoic acid; Aib) residues and the turn-promoting glycine (Gly) and proline (Pro) residues were investigated. Eight linear hexapeptides were synthesized, and their cyclization was attempted with various coupling reagents. The macrolactamization step proved to be difficult since only three hexapeptides could be cyclized. Two of these latter peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Aib-Aib-Phe-Pro-Aib-Gly) (1). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site by using DEPBT as the coupling reagent, whereas the cyclization at the  Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively (DEPBT = 3-[(diethoxyphosphoryl)oxy]-1,2,3-benzotriazin-4(3H)-one, PyAOP = (1H-7-azabenzotriazol-1-yloxy)tripyrroli- din-1-ylphosphonium hexafluorophosphate, DEPC = diethyl phosphorocyanidate). Another cyclic hexapeptide, cyclo(Aib-Aib-Gly-Aib-Pro-Gly) (2) was prepared in 34% yield when DEPC was used in the cyclization step. The solid-state conformation of 1 was established by X-ray crystallography
H(5)dotasa (=(alpha RS)-alpha-(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), an asymmetrical derivative of H(4)dota (=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) substituted at one acetate pendant arm: H-1-NMR and potentiometric studies of the ligand and its lanthanide(III) complexes

The ligand H5dotasa (=(alphaRS)-alpha-(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is a H4dota-like macrocyclic ligand with a carboxymethyl CH2COOH substituent moiety at the C(alpha) atom of one of the four acetate pendant arms of H4dota (=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), present as a racemic mixture of (alphaR) and (alphaS) enantiomers. The protonation constants of the ligand were determined by potentiometry, giving values close to H4dota except for the extra pK3 value of 5.35 assigned to protonation of the extra carboxylate group in the alpha-substituted (=succinic acid) pendant arm. The 1H-NMR spectra of H5dotasa at different pH values are too complex to allow the determination of its microscopic protonation scheme, due to the presence of multiple isomeric structures in solution. The thermodynamic stability constant of its Gd3+ chelate was determined by a potentiometric method, and the value obtained, log KML = 27.2 (0.2), is higher than for the [Gd(dota)(OH2)]- complex. The solution structure of the asymmetrical Ln3+ chelates of dotasa was studied by 1H-NMR spectroscopy, indicating the presence of four isomers, corresponding to the combination of the antiprismatic (M) and twisted antiprismatic (m) helicities of the pendant arms and to the (alphaR) and (alphaS) configurations of the substituted pendant arm. The m/M isomer ratio decreases along the lanthanide series, with the m isomer decreasing from 90% at La to about 50% from Eu-Lu. This shows that  the expected m isomer population of the [Gd(dotasa)(OH2)]2- complex  is higher than for the unsubstituted [Gd(dota)(OH2)]- (circa 15%) but lower than for a Gd3+ chelate of a alpha-alpha’-alpha’’,alpha’’’-tetrasubstituted(RRRR)-configurated dota (circa 70%). Thus the stabilisation of the m isomer by C monosubstitution at the dota acetate pendant arms in [Gd(dotasa)(OH2)]2- is responsible for its increased H2O exchange rate and higher relaxivity
[2+3]-Cycloadditions of Phosphonodithioformate S-Methanides with C=S, N=N, and C=C Dipolarophiles

The reaction of the methyl (dialkoxyphosphinyl)-dithioformates (= methyl dialkoxyphosphinecarbodithioate 1-oxides) 10 with CH2N2 at − 65° in THF yielded cycloadducts which eliminated N2 between − 40 and − 35° to give the corresponding phosphonodithioformate S-methanides ( =methylenesulfonium (dialkoxyoxidophosphino)(methylthio)methylides) 11 (Scheme 3). These reactive 1,3-dipoles were intercepted by aromatic thioketones to yield 1,3-dithiolanes. Whereas the reaction with thiobenzophenone (12b) led to the sterically more congested isomers 15 regioselectively, a mixture of both regioisomers was obtained with 9H-fluorene-9-thione (12a). Trapping of 11 with phosphono- and sulfonodithioformates led exclusively to the sterically less hindered 1,3-dithiolanes 16 and 18, respectively (Scheme 4). In addition, reactive C[DOUBLE BOND]C dipolarophiles such as ethenetetracarbonitrile, maleic anhydride, and N-phenylmaleimide as well as the N[DOUBLE BOND]N dipolarophile dimethyl diazenedicarboxylate were shown to be efficient interceptors of 11 (Scheme 5)
Synthesis and reactions of a new cyclobutanethione derivative

The 3,3-dichloro-2,2,4,4-tetramethylcyclobutanethione (4b) was prepared from the parent diketone by successive reaction with PCl5 and Lawesson reagent in pyridine. This new thioketone 4b was transformed into 1-chlorocyclobutanesulfanyl chloride 5 and chloro 1-chlorocyclobutyl disulfide 9 by treatment with PCl5 and SCl2, respectively, in chlorinated solvents (Schemes 1 and 2). These products reacted with S- and P-nucleophiles by substitution of Cl− at the S-atom; e.g., the reaction with 4b yielded the di- and trisulfides 6b and 11, respectively. Surprisingly, only pentasulfide 12 was formed in the reaction of 9 with thiobenzophenone (Scheme 3). In contrast to 5 and 9, the corresponding chloro 1-chlorocyclobutyl trisulfide 13 could not be detected, but reacted immediately with the starting thioketone 4b to give the tetrasulfide 14 (Scheme 4). Oxidation of 4b with 3-chloroperbenzoic acid (mCPBA) yielded the corresponding thione oxides (= sulfine) 15, which underwent 1,3-dipolar cycloadditions with thioketones 3a and 4b (Scheme 5). Furthermore, 4b was shown to be a good dipolarophile in reactions with thiocarbonylium methanides (Scheme 6) and iminium ylides (= azomethine ylides; Scheme 7). In the case of phenyl azide, the reaction with 4b gave the symmetrical trithiolane 25 (Scheme 8)
A new 2H-Azirin-3-amine as a synthon for 2-Methylaspartate

The synthesis of a novel 2,2-disubstituted 2H-azirin-3-amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme 2). In 11, each of the protecting groups was removed selectively (Scheme 3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1-(naphthalen-1-yl)ethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme 2). However, the diastereoisomers of the synthons 3b and 3c could not be separated by chromatography