Vasopressin analogues and spatial working memory in the 24-arm radial maze

The effect of vasopressin analogues dAVP, dDAVP, and desgly NH₂ dDAVP on working memory was tested in the 24-arm radial maze in twelve 6-month-old and twelve 19-month-old rats. No age dependent effects were found. All three peptides tested (3 μg/kg) tended to improve the performance but only the desgly NH₂ dDAVP significantly decreased the number of errors. A second application of desgly NH₂ dDAVP was ineffective. The specificity of activation of memory mechanisms by desgly NH₂ dDAVP can be questioned.     

Vasopressin analogues and spatial short-term memory in rats

The effect of vasopressin analogues on short-term memory was tested in the 12-arm radial maze. After the first 6 choices rats (n=6) were removed from the apparatus and allowed to complete the remaining 6 choices 20 min later. Whereas desgly-NH₂-VP, AVP, dAVP and DAVP (3.0 μ/kg) administered 40 min before or immediately after the first 6 choices did not change the incidence of errors in the second series of choices (2.0 errors under control conditions), similarly applied dDAVP deteriorated the rat's performance almost to the chance level of 3 errors. The significance of short-term memory tests for assessing the mnestic role of peptide hormones is stressed.     

The hippocampus and memory: a comparative and ethological perspective

During the past year, considerable progress has been made in our understanding of the wide-ranging functions of the hippocampus. Highlights include the development of new tasks with which to assess spatial/topographic memory in humans and monkeys, novel tests of relational memory in rats, and episodic-like memory tasks in birds. In addition, novel theories of hippocampal function have been developed that are notable for their applicability to both humans and animal models.     

Blockade of gamma-secretase activity within the hippocampus enhances long-term memory

The gamma-secretase complex, a membrane-bound aspartyl protease, hydrolyzes the transmembrane domains of several integral membrane proteins including the key signaling molecules amyloid precursor protein (APP), Notch, deleted in colorectal cancer (DCC), and N- and E-cadherins. The proteolysis processing of these proteins is critical for generation of signaling molecules that may participate in neuronal communication and plasticity. Using a potent gamma-secretase inhibitor, L-685,458, we examined if blockade of its activity in the hippocampus can influence contextual and spatial memory in rats. Surprisingly, we observed that post-training blockade of gamma-secretase activity leads to enhanced long-term memory in two hippocampus-dependent tasks. This suggests that a signaling molecule(s) generated by gamma-secretase activity may have a negative influence on long-term memory formation.     

Some characteristics of spatial associative memory in the pigeon, Columba livia

Willson and Wilkie (1993) developed a novel procedure to assess pigeons' memory for the spatial location of food. Only one of four locations provided food each daily session. Each location consisted of an illuminated pecking key and grain feeder. Over different days different locations, randomly selected, provided food during a 16-min session. The pigeons tended to revisit the location at which food was found on the previous day thereby demonstrating memory for food-spatial location associations over 24 h. Three experiments were conducted to further investigate this phenomenon. In Experiment 1 the session duration was varied between 4 and 32 min. Longer sessions had no detectable effect on their ability to remember the rewarded location 24 h later, a result that suggests that only brief encounters with food at a particular location are necessary for recall. In Experiment 2 the necessity of an active search for the day's rewarded location was removed; a 5-min period in which only the rewarded key was lit preceded the regular 16-min session. Pecks to the lit key in this 5-min period produced grain on the standard schedule. This manipulation facilitated the pigeons' discovery of food but did not affect their ability to remember the rewarded location, suggesting that the process of search and discovery is not essential to the associative memory process. In Experiment 3, food was available during the complete session (non-depleting condition) or was available only during the first half of the session (depleting condition). No detectable differences in the birds' memory of yesterday's profitable location were found. This suggests that non-depletion of food is not a necessary condition for day-to-day recall of food location. Taken together these findings enlarge our understanding of the spatial associative memory process.     

Role for brain-derived neurotrophic factor in learning and memory

In addition to its actions on neuronal survival and differentiation, brain-derived neurotrophic factor (BDNF) has a role in the regulation of synaptic strength. Long-term potentiation, a form of synaptic plasticity, is markedly impaired in BDNF mutant mice, but the changes were restored by the re-expression of BDNF. BDNF also influences the development of patterned connections and the growth and complexity of dendrites in the cerebral cortex. These results suggest a role for BDNF in learning and memory processes, since memory acquisition is considered to involve both short-term changes in electrical properties and long-term structural alterations in synapses. Memory acquisition is associated with an increase in BDNF mRNA and TrkB receptor activation in specific brain areas. Moreover, the pharmacologic and genetic deprivation of BDNF or its receptor TrkB results in severe impairment of learning and memory in mice, rats and chicks. The effect of BDNF on learning and memory may be linked to the modulation of NMDA and non-NMDA receptor functions as well as the expression of synaptic proteins required for exocytosis. Activation of the mitogen-associated protein kinase and/or phosphatidylinositol 3-kinase signaling pathways may be involved in BDNF-dependent learning and memory formation. It is concluded that BDNF/TrkB signaling plays an important role in learning and memory.     

Antisense regulation of the rice waxy gene expression using a PCR-amplified fragment of the rice genome reduces the amylose content in grain starch

The waxy gene encodes a granule-bound starch synthase. A 1.0-kb portion of the sequence of the rice waxy gene, which includes the region between exon 4 and exon 9, was inserted in an antisense orientation between the 35 S promoter and the GUS gene of pBI221. The resultant plasmid, pWXA23, was introduced into rice protoplasts by electroporation. GUS activity was clearly detected in derived callus lines, suggesting that the antisense component of the fusion gene was also expressed. Transgenic rice plants were regenerated from these callus lines and their GUS activity was confirmed. Some of the rice seeds from these transformants showed a significant reduction in the amylose content of grain starch, even though they had become polyploid. These results suggest that even when intron sequences are included, antisense constructs can bring about a reduced level of expression of a target gene. The utility of GUS, included as a reporter gene, for the simple detection of expression of an antisense gene, was apparent from these results.     

On the time course of short-term forgetting: a human experimental model for the sense of balance

The primary aim of this study was to establish whether the decline of the memory of an angular displacement, detected by the semicircular canals, is best characterized by an exponential function or by a power function. In 27 subjects a conflict was created between the semicircular canals and the graviceptive systems. Subjects were seated, facing forwards, in the gondola of a large centrifuge. The centrifuge was accelerated from stationary to 2.5G_z. While the swing out of the gondola (66°) during acceleration constitutes a frontal plane angular-displacement stimulus to the semicircular canals, the graviceptive systems persistently signal that the subject is upright. During 6 min at 2.5G_z the perceived head and body position was recorded; in darkness the subject repeatedly adjusted the orientation of a luminous line so that it appeared to be horizontal. Acceleration of the centrifuge induced a sensation of tilt which declined with time in a characteristic way. A three-parameter exponential function (Y = Ae^−bt + C) and a power function (Y = At^−b + C) were fitted to the data points. The inter-individual variability was considerable. In the vast majority of cases, however, the exponential function provided a better fit (in terms of RMS error) than the power function. The mean exponential function was: y = 27.8e^−0.018t + 0.5°, where t is time in seconds. Findings are discussed with connection to possible underlying neural mechanisms; in particular, the head-direction system and short-term potentiation and persistent action potential firing in the hippocampus are considered.     

The making of a memory mechanism

Long-Term Potentiation (LTP) is akind of synaptic plasticity that manycontemporary neuroscientists believe is acomponent in mechanisms of memory. This essaydescribes the discovery of LTP and thedevelopment of the LTP research program. Thestory begins in the 1950's with the discoveryof synaptic plasticity in the hippocampus (amedial temporal lobe structure now associatedwith memory), and it ends in 1973 with thepublication of three papers sketching thefuture course of the LTP research program. Themaking of LTP was a protracted affair.Hippocampal synaptic plasticity was initiallyencountered as an experimental tool, thenreported as a curiosity, and finally includedin the ontic store of the neurosciences. Earlyresearchers were not investigating thehippocampus in search of a memory mechanism;rather, they saw the hippocampus as a usefulexperimental model or as a structure implicatedin the etiology of epilepsy. The link betweenhippocampal synaptic plasticity and learning ormemory was a separate conceptual achievement.That link was formulated in at least threedifferent ways at different times: reductively(claiming that plasticity is identical tolearning), analogically (claiming thatplasticity is an example or model of learning),and mechanistically (claiming that plasticityis a component in learning or memorymechanisms). The hypothesized link withlearning or memory, coupled with developmentsin experimental techniques and preparations,shaped how researchers understood LTP itself.By 1973, the mechanistic formulation of thelink between LTP and memory provided anabstract framework around which findings frommultiple perspectives could be integrated intoa multifield research program.     

Prenatal testosterone improves the spatial learning and memory by protein synthesis in different lobes of the brain in the male and female rat

The high density of the steroid hormone receptors in the structures of temporal lobe involved in learning and memory, such as the hippocampus, perirhinal cortex, entorhinal cortex and amigdaloid complex, shows that there must be a direct relationship between gonadal hormones and organizational effects of steroid hormones in those structures during development of the nervous system. The present study was undertaken in order to investigate the effect of testosterone administration during the third week of gestation on the spatial memory formation of the offspring rats and the level of soluble proteins in the temporal lobe and frontal lobe of brain, as evidence of important organizational effects of androgens during prenatal development in brain sexual dimorphism. Animals have received testosterone undecanoate on days 14, 15, 16 and 19, 20, 21 of gestation. Learning and memory tests were started 100 days after the testosterone treatment. At the end of the experiments, the temporal and frontal lobes of brain were removed for assessing the level of soluble proteins. Testosterone treatment significantly improved spontaneous alternations percentage of male offspring in Y-maze task comparative with female offspring and reference memory in radial 8 arm-maze task (decreasing in number of reference memory errors in both male and female offspring groups), suggesting effects of both short and long-term memory. Also, testosterone significantly increased the brain soluble protein level of treated female rats in 14–16 prenatal days compared with the control group as well as the brain soluble protein level of treated male rats. These results suggest that steroid hormones play an important role in the spatial learning and memory formation by means of protein synthesis in different lobes of the brain.     

To signal a conjunction of many inputs negative regulation is likely

Cells make many transitions from an old to a new phase of activity - between inactive and active states of an enzyme, or between phases of the cell cycle. If a cell is to survive, molecular prerequisites for functioning in the new phase should be available before a transition occurs. The cell’s survival is more likely if a regulatory network gates the transition, preventing its occurrence until the prerequisites are available. Suppose a specific conjunction of inputs is required for a network, from which a single output governs the transition. Then we suggest that cells are likely to use negative regulation - a gating network based on a logical disjunction of signals for the absence of prerequisites - rather than positive regulation - a logical conjunction of signals for their presence. That is, if a logical conjunction of n prerequisites A1 ANDA2 AND … ANDAn is needed in the new phase, a negative regulatory network is likely to enforce the corresponding logical disjunction, NOT (NOTA1 ORNOTA2 OR … ORNOTAn). Five examples illustrate this conclusion. Arguments based on performance criteria support the hypothesis: negative regulation is more economical than positive regulation, because networks for computing OR can use fewer and simpler parts than those for computing AND. Negative regulation can increase reliability, because a mechanism that uses fewer, simpler parts is less likely to fail. And, a negative regulatory network can be more robust - less susceptible to errors resulting from noisy input.     

Identification of a villin-related tobacco protein as a novel cross-reactive plant allergen

In a paradigmatic approach we identified cross-reactive plant allergens for allergy diagnosis and treatment by screening of a tobacco leaf complementary DNA (cDNA) library with serum IgE from a polysensitized allergic patient. Two IgE-reactive cDNA clones were isolated which code for proteins with significant sequence similarity to the actin-binding protein, villin. Northern- and Western-blotting demonstrate expression of the villin-related allergens in pollen and somatic plant tissues. In addition, villin-related proteins were detected in several plant allergen sources (tree-, grass-, weed pollen, fruits, vegetables, nuts). A recombinant C-terminal fragment of the villin-related protein was expressed in Escherichia coli, purified and shown to react specifically with allergic patients IgE. After profilin, villin-related proteins represent another family of cytoskeletal proteins, which has been identified as cross-reactive plant allergens. They may be used for the diagnosis and treatment of patients suffering from multivalent plant allergies.     

A Role for Oligonucleotide-Based RNA-Knock Down Technologies in Functional Genomics

Abstract

Functional genomics is inundating the pharmaceutical industry with large numbers of potential gene targets from several sources such as gene expression profiling experiments (DNA microchips, proteomics) or database mining. Oligonucleotide-based RNA-knock down technologies such as antisense or RNA interference can aid in the filtering and prioritization of target candidates in the drug discovery process.     

Identification of a novel centrosomal protein CrpF46 involved in cell cycle progression and mitosis

A novel centrosome-related protein CrpF46 was detected using a serum F46 from a patient suffering from progressive systemic sclerosis. We identified the protein by immunoprecipitation and Western blotting followed by tandem mass spectrometry sequencing. The protein CrpF46 has an apparent molecular mass of ~60 kDa, is highly homologous to a 527 amino acid sequence of the C-terminal portion of the protein Golgin-245, and appears to be a splice variant of Golgin-245. Immunofluorescence microscopy of synchronized HeLa cells labeled with an anti-CrpF46 monoclonal antibody revealed that CrpF46 localized exclusively to the centrosome during interphase, although it dispersed throughout the cytoplasm at the onset of mitosis. Domain analysis using CrpF46 fragments in GFP-expression vectors transformed into HeLa cells revealed that centrosomal targeting is conferred by a C-terminal coiled-coil domain. Antisense CrpF46 knockdown inhibited cell growth and proliferation and the cell cycle typically stalled at S phase. The knockdown also resulted in the formation of poly-centrosomal and multinucleate cells, which finally became apoptotic. These results suggest that CrpF46 is a novel centrosome-related protein that associates with the centrosome in a cell cycle-dependent manner and is involved in the progression of the cell cycle and M phase mechanism.