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The brain organizes experiences into memories that can be used to guide future behavior. Hippocampal CA1 population activity may reflect the retrieval of predictive models that contain information about future events, but little is known about how these kinds of memories develop with experience. We trained mice on a series of tone discrimination problems with or without a common statistical structure to observe how memories are formed and updated during learning. Mice that learned structured problems integrated their experiences into a predictive model that contained the solutions to upcoming novel problems. Retrieving the model during learning improved discrimination accuracy and facilitated learning by decreasing the amount of new information that needed to be acquired. Using calcium imaging to track the activity of thousands of CA1 neurons during learning on this task, we observed the emergence of a persistent hippocampal ensemble at the same time that mice formed a predictive model of their environment. This ensemble was reactivated during training and incorporated new neuronal activity patterns from each training problem. Interestingly, the degree to which mice reactivated the ensemble was related to how well their model predicted the content of the current problem, ensuring that the model was only updated with congruent information. In contrast, mice trained on unstructured problems did not form a predictive model or engage a persistent ensemble. These results show how hippocampal activity supports building predictive models by organizing newly learned information according to its congruence with existing memories.

The hippocampus, retrosplenial cortex and anterior thalamus are key components of a neural circuit known to be involved in a variety of memory functions, including spatial, contextual and episodic memory. In this review, we focus on the role of this circuit in contextual memory processes. The background environment, or context, is a powerful cue for memory retrieval, and neural representations of the context provide a mechanism for efficiently retrieving relevant memories while avoiding interference from memories that belong to other contexts. Data from experimental lesions and neural manipulation techniques indicate that each of these regions is critical for contextual memory. Neurophysiological evidence from the hippocampus and retrosplenial cortex suggest that contextual information is represented within this circuit by population-level neural firing patterns that reliably differentiate each context a subject encounters. These findings indicate that encoding contextual information to support context-dependent memory retrieval is a key function of this circuit.

The retrosplenial cortex (RSC) is thought to be involved in a variety of spatial and contextual memory processes. However, we do not know how contextual information might be encoded in the RSC or whether the RSC representations may be distinct from context representations seen in other brain regions such as the hippocampus. We recorded RSC neuronal responses while rats explored different environments and discovered 2 kinds of context representations: one involving a novel rate code in which neurons reliably fire at a higher rate in the preferred context regardless of spatial location, and a second involving context-dependent spatial firing patterns similar to those seen in the hippocampus. This suggests that the RSC employs a unique dual-factor representational mechanism to support contextual memory.

The retrosplenial cortex (RSC) has recently begun to gain widespread interest because of its anatomical connectivity with other well-known memory structures, such as the hippocampus and anterior thalamus, and its role in spatial, contextual, and episodic memory. Although much of the current work on the RSC is focused on spatial cognition, there is also an extensive literature that shows that the RSC plays a critical role in a variety of conditioning tasks that have no obvious spatial component. Many of these studies suggest that the RSC is involved in identifying and encoding behaviorally significant cues, particularly those cues that predict reinforcement or the need for a behavioral response. Consistent with this idea, recent studies have shown that RSC neurons also encode cues in spatial navigation tasks. In this article, we review these findings and suggest that the encoding of cues is an important component of the RSC contribution to many forms of learning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Summary Flexibly adapting to novel situations is critical for survival, which is impaired in neuropsychiatric disorders1. Thus, understanding whether and how novelty prepares, or primes, brain circuitry to facilitate cognitive flexibility has important translational relevance. Novelty recruits the hippocampus and medial prefrontal cortex (mPFC)2 and may prime hippocampal-prefrontal circuitry for subsequent learning-associated plasticity. We find that novelty resets ventral hippocampal-prefrontal (vHPC-mPFC) circuitry and facilitates overcoming an established strategy. Exposing mice to novelty disrupted a previously encoded strategy by reorganizing vHPC activity to local theta (4–12 Hz) oscillations and weakening existing vHPC-mPFC connectivity. As mice subsequently adapted to a new task, vHPC neurons developed new task-associated activity, vHPC-mPFC connectivity was strengthened, and mPFC neurons updated encoding with new rules. Without novelty, mice adhered to their established strategy. Blocking dopamine D1-receptors (D1Rs) or inhibiting novelty-tagged cells expressing D1Rs in the vHPC prevented these behavioral and physiological effects of novelty. Further, D1R activation mimicked the effects of novelty. These results suggest that novelty promotes adaptive learning by D1R-mediated resetting of vHPC-mPFC circuitry, thereby enabling learning-associated circuit plasticity.

It has long been hypothesized that a primary function of the hippocampus is to discover and exploit temporal relationships between events. Previously, it has been reported that sequences of “time cells” in the hippocampus extend for tens of seconds. Other studies have shown that neuronal firing in the hippocampus fluctuates over hours and days. Both of these mechanisms could enable temporal encoding of events over very different timescales. However, thus far, these two classes of phenomena have never been observed simultaneously, which is necessary to ascribe broad-range temporal coding to the hippocampus. Using in vivo calcium imaging in unrestrained mice, we observed sequences of hippocampal neurons that bridged a 10 s delay. Similar sequences were observed over multiple days, but the set of neurons participating in those sequences changed gradually. Thus, the same population of neurons that encodes temporal information over seconds can also be used to distinguish periods of time over much longer timescales. These results unify two previously separate paradigms of temporal processing in the hippocampus that support episodic memory.

Recent findings suggest that long-term spatial and contextual memories depend on the retrosplenial cortex (RSC) [1–5]. RSC damage impairs navigation in humans and rodents [6–8] and the RSC is closely interconnected with brain regions known to play a role in navigation, including the hippocampus and anterior thalamus [9, 10]. Navigation related neural activity is seen in humans [11] and rodents, including spatially localized firing [12, 13] and directional firing [12, 14, 15], and responses to navigational cues [16]. RSC neuronal activity is modulated by allocentric, egocentric, and route-centered spatial reference frames [17, 18], consistent with an RSC role in integrating different kinds of navigational information [19]. However, the relationship between RSC firing patterns and spatial memory remains largely unexplored, as previous physiology studies have not employed behavioral tasks with a clear memory demand. To address this, we trained rats on a continuous T-maze alternation task and examined RSC firing patterns throughout learning. We found that the RSC developed a distributed population-level representation of the rat’s spatial location and current trajectory to the goal as the rats learned. After the rats reached peak performance, RSC firing patterns began to represent the upcoming goal location as the rats approached the choice point. These neural simulations of the goal emerged at the same time that lesions impaired alternation performance, suggesting that the RSC gradually acquired task representations that contribute to navigational decision-making.

Memory retrieval requires coordinated intra- and inter-regional activity in networks of brain structures. Dysfunction of these networks and memory impairment are seen in many psychiatric disorders, but relatively little is known about how memory retrieval and memory failure are represented at the level of local and regional oscillatory activity. To address this question, we measured local field potentials (LFPs) from mice as they explored a novel context, retrieved memories for contextual fear conditioning, and after administration of two amnestic agents: the NMDA receptor antagonist MK-801 and muscarinic acetylcholine receptor antagonist scopolamine (SCOP). LFPs were simultaneously recorded from retrosplenial cortex (RSC), dorsal hippocampus (DH), and anterior cingulate cortex (ACC), which are involved in processing contextual memories, and analyzed for changes in intra-regional power and inter-regional peak coherence of oscillations across multiple frequency bands. Context encoding and memory retrieval sessions yielded similar patterns of changes across all three structures, including decreased delta power and increased theta peak coherence. Baseline effects of MK-801 and SCOP were primarily targeted to gamma oscillations, but in opposite directions. Both drugs also blocked memory retrieval, as indicated by reduced freezing when mice were returned to the conditioning context, but this common behavioral impairment was only associated with power and peak coherence disruptions after MK-801 treatment. These findings point to neural signatures for memory impairment, whose underlying mechanisms may serve as therapeutic targets for related psychiatric disorders.

The retrosplenial cortex (RSC) plays an important role in memory and spatial navigation. It shares functional similarities with the hippocampus, including the presence of place fields and lesion-induced impairments in spatial navigation, and the RSC is an important source of visual-spatial input to the hippocampus. Recently, the RSC has been the target of intense scrutiny among investigators of human memory and navigation. fMRI and lesion data suggest an RSC role in the ability to use landmarks to navigate to goal locations. However, no direct neurophysiological evidence of encoding navigational cues has been reported so the specific RSC contribution to spatial cognition has been uncertain. To examine this, we trained rats on a T-maze task in which the reward location was explicitly cued by a flashing light and we recorded RSC neurons as the rats learned. We found that RSC neurons rapidly encoded the light cue. Additionally, RSC neurons encoded the reward and its location, and they showed distinct firing patterns along the left and right trajectories to the goal. These responses may provide key information for goal-directed navigation, and the loss of these signals may underlie navigational impairments in subjects with RSC damage.

Measurement of tumour and normal tissue perfusion in vivo in cancer patients will aid the clinical development of antiangiogenic and antivascular agents. We investigated the potential antiangiogenic effects of the drug razoxane by measuring the changes in parameters estimated from H(2)(15)O and C(15)O positron emission tomography (PET) to indicate alterations in vascular physiology. The study comprised 12 patients with primary or metastatic renal tumours >3 cm in diameter enrolled in a Phase II clinical trial of oral razoxane. Perfusion, fractional volume of distribution of water (VD) and blood volume (BV) were measured in tumour and normal tissue before and 4-8 weeks after treatment with 125 mg twice-daily razoxane. Renal tumour perfusion was variable but lower than normal tissue: mean 0.87 ml min(-1) ml(-1) (range 0.33-1.67) compared to renal parenchyma: mean 1.65 ml min(-1) ml(-1) (range 1.16-2.88). In eight patients, where parallel measurements were made during the same scan session, renal tumour perfusion was significantly lower than in normal kidney (P=0.0027). There was no statistically significant relationship between pretreatment perfusion and tumour size (r=0.32, n=13). In six patients scanned before and after razoxane administration, there was no statistically significant change in tumour perfusion: mean perfusion pretreatment was 0.81 ml min(-1) ml(-1) (range 0.46-1.26) and perfusion post-treatment was 0.72 ml min(-1) ml(-1) (range 0.51-1.15, P=0.15). Tumour VD and BV did not change significantly following treatment: mean pretreatment VD=0.66 (range 0.50-0.87), post-treatment VD=0.71 (range 0.63-0.82, P=0.22); pretreatment BV=0.18 ml ml(-1) (range 0.10-0.25), post-treatment BV=0.167 ml ml(-1) (range 0.091-0.24, P=0.55). Tumour perfusion, VD and BV did not change significantly with tumour progression. This study has shown that H(2)(15)O and C(15)O PET provide useful in vivo physiological measurements, that even highly angiogenic renal cancers have poor perfusion compared to surrounding normal tissue, and that PET can provide valuable information on the in vivo biology of angiogenesis in man and can assess the effects of antiangiogenic therapy.

Spatial navigation requires representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the hippocampus. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the hippocampus and as a target of the hippocampal-dependent systems consolidation of long-term memory.

The genetic relationships and conidial tolerances to high and low temperatures were determined for isolates of several Metarhizium species and varieties.Molecular-based techniques [AFLP and rDNA (ITS1, ITS2 and 5.8S) gene sequencing] were used to characterize morphologically identified Metarhizium spp. isolates from a wide range of sources. Conidial suspensions of isolates were exposed to wet heat (45 + or - 0.2 degrees C) and plated on potato dextrose agar plus yeast extract (PDAY) medium. After 8-h exposure, the isolates divided clearly into two groups: (i) all isolates of Metarhizium anisopliae var. anisopliae (Ma-an) and Metarhizium from the flavoviride complex (Mf) had virtually zero conidial relative germination (RG), (ii) Metarhizium anisopliae var. acridum (Ma-ac) isolates demonstrated high heat tolerance (c. 70-100% RG). Conidial suspensions also were plated on PDAY and incubated at 5 degrees C for 15 days, during which time RGs for Ma-an and Ma-ac isolates were virtually zero, whereas the two Mf were highly cold active (100% RG).Heat and cold exposures can be used as rapid tools to tentatively identify some important Metarhizium species and varieties.Identification of Metarhizium spp. currently relies primarily on DNA-based methods; we suggest a simple temperature-based screen to quickly obtain tentative identification of isolates as to species or species complexes.

Populations of the freshwater mussel genus Anodonta appear to be in a state of rapid decline in western North America, following a trend that unfortunately seems to be prevalent among these animals (Mollusca: Unionoida). Here we describe the patterns of molecular divergence and diversity among Anodonta populations in the Bonneville Basin, a large sub-basin of the Great Basin in western North America. Using amplified fragment length polymorphism (AFLP) analysis, we found a striking lack of nuclear diversity within some of these populations, along with a high degree of structuring among populations (FST = 0.61), suggesting post-Pleistocene isolation, due either to a long-term loss of hydrologic connectivity among populations or to more recent fish introductions. We also found evidence of recent hybridization in one of these populations, possibly mediated by fish-stocking practices. Using mitochondrial sequence data, we compared the Bonneville Basin populations to Anodonta in several other drainages in western North America. We found a general lack of resolution in these phylogenetic reconstructions, although there was a tendency for the Bonneville Basin Anodonta (tentatively A. californiensis) to cluster with A. oregonensis from the adjacent Lahontan Basin in Nevada. We recommend further investigation of anthropogenic factors that may be contributing to the decline of western Anodonta and a broad-scale analysis and synthesis of genetic and morphological variation among Anodonta in western North America.

A methodology for incorporating a description of material structure into a finite element formulation is presented. This modeling framework was used to study the development of deformation induced surface roughening in thin sheets machined from AA 7050 thick plate. Predicting this roughening phenomenon necessitates the quantification and representation of processes that exist over several size scales. This work describes an experiment/simulation — based study focused on the deformation behavior of thick AA 7050 aluminum plate. EBSD (Electron Back Scatter Diffraction) experiments were used for the material structure characterization, which included crystallographic texture, distributions in grain sizes, and a distribution in internal grain misorientation. These distributions in structure were used to create digital microstructures which represented virtual specimens composed of finite element‐discretized crystals, whose size, orientation and intra‐grain misorientations were chosen to match experimentally m...

Hypotony maculopathy after glaucoma filtering surgery with adjunctive mitomycin C has been reported to occur in 3% to 14% of cases. The authors evaluated its incidence when using a corneal safety-valve incisior intended to reduce its occurrence. The authors also evaluated a technique for reversing hypotony maculopathy by reoperation using two sets of stitches in the scleral flap, with one set tied tightly to temporarily raise the intraocular pressure, stretch the sclera, and flatten chorioretinal folds.The authors reviewed the results of 699 procedures performed between April 1991 and October 1994. All were performed or supervised by one surgeon (PFP).Hypotony maculopathy developed in 9 (1.3%) of 699 eyes. There was a statistically significant higher incidence in primary filters (4%) as compared to secondary filters or combined procedures. After revision, eight (89%) of nine recovered visual acuity of greater than or equal to 20/30 and the mean intraocular pressure was 14.5 +/- 4 mmHg at a mean follow-up of 15 months.The incidence of hypotony maculopathy after glaucoma filtering surgery with mitomycin C using a corneal safety-valve incision is less than that reported in the literature without this incision. There is an increased risk in myopes, young patients, and primary filters. Early intervention with the described scleral flap revision technique usually allows restoration of prefiltration visual acuity without compromise of bleb function.

In this article, we will discuss how the theories of crisis intervention, self-care, and behavior direct our psychiatric home care practice. A brief discussion of the theories will be followed by a case example that illustrates their application to a psychiatric home care situation.

Deformation and thermal processing operations can produce structurally heterogeneous and anisotropic alloys. Thick, hot-rolled aluminum plate is an excellent example of such a material. Due to the plate size and thermomechanical conditions experienced by the plate during processing, significant gradients in material structure arise. These gradients are especially strong in the through-thickness or normal direction (ND) of the plate. In AA 7050, an aluminum alloy developed for thick plate applications, gradients in microporosity, grain morphology and crystallographic texture are known to exist. These features have been linked to material properties and performance measures in this alloy. Recent advances in high speed machining technology have made it possible to consider thick AA 7050 plate for an increasingly large number of airframe components. Because of its inherent heterogeneity, however, designing flight-critical components machined from AA 7050 plate will require one to quantify and mathematically represent the variation of the relevant microstructural gradients.

Chemical kinetics is the study of the rates and mechanisms of chemical reactions and the factors that influence those rates and mechanisms. Ideally, one would like to obtain quantitative concentration vs. time data from which rate constants can be calculated and mechanisms deduced. In the absence of quantitative data, however, the sequence of chemical events can still be deduced, provided a technique exists for observing intermediate species.

does not appear. First page follows. Introduction In the winter of 1958 several grapefruit orchards near Hemet, California, developed severe copper deficiency symptoms. Because this deficiency is rarely seen in the field in California, its appearance in severe form presented an excellent opportunity for study of the diagnostic symptoms, for laboratory verification through leaf and soil analysis, and for field correction of the deficiency. This paper is a report of copper-deficiency symptoms as they appeared in the grapefruit, and of the use of sprays to achieve full recovery. Materials and Methods Experimental Orchards The three grapefruit orchards studied are located on Hanford sandy loam soil. Orchard A comprised 27 acres of Ruby red grapefruit scion on rough lemon rootstock, while orchard B comprised about 10 acres of Marsh grapefruit scion on rough lemon rootstock. Adjacent to these 10 acres of grapefruit were about 5 acres of Valencia oranges (orchard C) on rough lemon rootstock. Orchard D was a poor-appearing young grapefruit orchard (rootstock unknown) located about a mile south of orchard C. Leaf Sampling and Analysis Spring cycle leaves 4 to 6 months old were taken from fruiting terminals. In each case 10 leaves from each of 10 trees comprised the sample. Leaves were individually washed in tap water and Ivory soap, rinsed in tap water, and dried with clean cloths; this method of leaf washing has been employed in laboratories of the department of Soils and Plant Nutrition at Riverside, California for many years and has been subjected to thorough testing (Wallihan, 1953).3 The samples were then oven dried at 55° C and crumbled by hand previous to weighing a 2-gram sample for spectrographic analysis. Micro-element determinations were made by the spectrochemical method of (Vanselow et al. (1948)). Soil Sampling and Analysis Virgin soil samples of the 6 to 8-inches depth were collected from areas surrounding the orchards showing severe copper deficiency symptoms. Samples were analyzed for total copper by the method of (Pratt and Bradford (1958)).

An interactive computer program for calculating treatment times for 60Co single beam, opposing beam, or rotational beam radiation therapy is described. The program allows the user to enter parameters specific to his machine. Analytic expressions are used to represent the depth dose, backscatter factor, tissue-air ratio, collimator factor, and beam attenuation of a block-carrying tray.

Studies of kinetics of non -isothermal reactions in real timeusing Fourier transform infrared (FTIR) spectroscopyM. P. Miller, R. E. Miller and E. C. PenskiResearch Directorate, Chemical Research and Development CenterAberdeen'Proving Ground MD. 21010AbstractAn all- Teflon cell fitted with an ATR prism has been constructed and used to study ratesof rapid non -isothermal reactions of trivalent phosphorus compounds with sulfur. Both li-quid /liquid and liquid /solid reactions have been studied. In some cases rate constants andactivation energy can be calculated from data obtained during a single reaction.IntroductionWhen dealing with reactions of practical interest, one is not always free to select re-action conditions at will. This was the situation we faced in studying the kinetics of rapidexothermic reactions of (a) neat liquids, (b) a neat liquid and a solid and (c) fairly con-centrated solutions. This report deals with our approach to studying such reactions and someof the results achieved.A review of the literature1, along with some preliminary observations of our own sug-gested that the reactions of organophosphorus compounds of interest to us could possibly befollowed using infrared spectroscopy. Because the liquids of interest are highly absorbingwe chose to use attenuated total reflectance (ATR) spectroscopy2 to avoid difficulties asso-ciated with poor transmission. The use of ATR also permits the design of cells with adequatedimensions so that attempting to mix liquids and solids in confined space is avoided.We chose to pursue real -time studies rather than take a time -resolved approach becausethe reactions did not lend themselves to rapid repetition. Since we were interested in theeffect of temperature on reaction rates and products, we constructed the reaction cell ofTeflon, a material selected for its insulating ability as well as its chemical inertness.ExperimentalSystem design.The all- Teflon cell used in these studies was constructed with a common lower portion andinterchangeable upper portions. The lower portion contained a threaded thermocouple well, aport for introducing a liquid reactant, a venting port, a port for a ZnSe ATR prism, and amagnetic stirring bar, and was mounted atop a magnetic stirrer motor. This assembly was inturn mounted on a beam condenser designed to fit into the sample chamber of a Nicolet 7199DFTIR spectrometer. The upper cell portion for liquid /liquid reactions was a cover which wasthreaded into the lower portion. It contained two ports for introduction of the liquid re-actants from a syringe, and a venting port. The upper portion of the cell for liquid /solidreactions contained a friction -fitted Teflon disk intended to hold the solid in placeuntil a pulse of air dislodged the disk at a suitable time. Further details of the cell de-sign are given in another report3. Temperature changes were measured with a Chromel -Alumelthermocouple, amplified by an Omega model Omni II -B thermocouple amplifier and recorded on aNicolet model 206 digital oscilloscope. Absorbance changes were measured with a Nicolet7199D FTIR spectrometer system running on rapid -scan software. Up to 8 spectra /s at 4 cm -1resolution were collected. Temperature changes were precisely correlated with absorbancechanges by optically interfacing the spectrometer with the oscilloscope by positioning aphototransistor in front of the spectrometer sweep light. The output from the transistortriggered the oscilloscope and provided a time base for the temperature measurements whichwas common with that of the spectral scans.Procedures. Experiments were begun by first obtaining a background spectrum of the emptycell. Then a liquid reactant was introduced into the lower portion of the cell and its spec-trum obtained. The spectrometer was then started in rapid scan mode: collection of 8 inter -ferograms/s with co- adding of two interferograms in a file before incrementing to the nextfile. When the oscilloscope trace passed a pre -positioned cursor, the second reactant wasrapidly added. Spectra collection proceeded for several minutes, then was stopped. After aperiod ranging from 30 to 60 minutes a final spectrum of products was recorded. Starting ma-terials and products were analyzed by 31P NMR and their compositions reported as mole% phos-phorus- containing compounds. The results of these analyses were used with absorbance data(peak intensities) to calculate molar absorptivities. These were in turn used to calculate

The question of the number of radii which are necessary to accurately determine the average tissue–air ratio (TAR) to be used in 60Co rotational radiation therapytreatment planning was studied using actual patient contours. It was found that 12 radii adequately determine the average TAR for clinical purposes. Key words: TAR, 60Co, rotational therapy