Increased attention to spatial context increases both place field stability and spatial memory

The hippocampal formation is critical for the acquisition and consolidation of memories. When recorded in freely moving animals, hippocampal pyramidal neurons fire in a location-specific manner: they are "place" cells, comprising a hippocampal representation of the animal's environment. To explore the relationship between place cells and spatial memory, we recorded from mice in several behavioral contexts. We found that long-term stability of place cell firing fields correlates with the degree of attentional demands and that successful spatial task performance was associated with stable place fields. Furthermore, conditions that maximize place field stability greatly increase orientation to novel cues. This suggests that storage and retrieval of place cells is modulated by a top-down cognitive process resembling attention and that place cells are neural correlates of spatial memory. We propose a model whereby attention provides the requisite neuromodulatation to switch short-term homosynaptic plasticity to long-term heterosynaptic plasticity, and we implicate dopamine in this process.     

New synaptic bouton formation is disrupted by misregulation of microtubule stability in aPKC mutants

The Baz/Par-3-Par-6-aPKC complex is an evolutionarily conserved cassette critical for the development of polarity in epithelial cells, neuroblasts, and oocytes. aPKC is also implicated in long-term synaptic plasticity in mammals and the persistence of memory in flies, suggesting a synaptic function for this cassette. Here we show that at Drosophila glutamatergic synapses, aPKC controls the formation and structure of synapses by regulating microtubule (MT) dynamics. At the presynapse, aPKC regulates the stability of MTs by promoting the association of the MAP1Brelated protein Futsch to MTs. At the postsynapse, aPKC regulates the synaptic cytoskeleton by controlling the extent of Actin-rich and MT-rich areas. In addition, we show that Baz and Par-6 are also expressed at synapses and that their synaptic localization depends on aPKC activity. Our findings establish a novel role for this complex during synapse development and provide a cellular context for understanding the role of aPKC in synaptic plasticity and memory.     

Uniform and Residue-specific 15N-labeling of Proteins on a Highly Deuterated Background

A general method for stable-isotope labeling of large proteins is introduced and applied for studies of the E. coli GroE chaperone proteins by solution NMR. In addition to enabling the residue-specific (15)N-labeling of proteins on a highly deuterated background, it is also an efficient approach for uniform labeling. The method meets the requirements of high-level deuteration, minimal cross-labeling and high protein yield, which are crucial for NMR studies of structures with sizes above 150 kDa. The results obtained with the new protocol are compared to other strategies for protein labeling, and evaluated with regard to the influence of external factors on the resulting isotope labeling patterns. Applications with the GroE system show that these strategies are efficient tools for studies of structure, dynamics and intermolecular interactions in large supramolecular complexes, when combined with TROSY- and CRINEPT-based experimental NMR schemes.     

The Influence of Spike Rate and Stimulus Duration on Noradrenergic Neurons

We model spiking neurons in locus coeruleus (LC), a brain nucleus involved in modulating cognitive performance, and compare with recent experimental data. Extracellular recordings from LC of monkeys performing target detection and selective attention tasks show varying responses dependent on stimuli and performance accuracy. From membrane voltage and ion channel equations, we derive a phase oscillator model for LC neurons. Average spiking probabilities of a pool of cells over many trials are then computed via a probability density formulation. These show that: (1) Post-stimulus response is elevated in populations with lower spike rates; (2) Responses decay exponentially due to noise and variable pre-stimulus spike rates; and (3) Shorter stimuli preferentially cause depressed post-activation spiking. These results allow us to propose mechanisms for the different LC responses observed across behavioral and task conditions, and to make explicit the role of baseline firing rates and the duration of task-related inputs in determining LC response.     

Xylem embolism and stomatal regulation in two rubber clones (<Emphasis Type="Italic">Hevea brasiliensis</Emphasis> Muell. Arg.)

Vulnerability to water-stress-induced embolism of stems, petioles, and leaf midribs was evaluated for two rubber clones (RRIM600 and RRIT251). The xylem conduits were relatively vulnerable to cavitation with 50% of embolism measured for xylem pressures between –1 and –2 MPa. This feature can be related to the tropical-humid origin of the species. A distinct basipetal gradient of vulnerability was found, leaf midribs being the least vulnerable. Substantial variation in vulnerability to cavitation was found between the two clones only at the petiole level. A correlation was found between the stomatal behavior and the development of cavitation. Stomata were nearly closed when the xylem pressure reached the point of xylem dysfunction. Stomata may thus contribute to controlling the risk of cavitation. However, for one clone a poor correlation was found between stomatal regulation and petiole vulnerability. This was consistent with a high degree of embolism measured in the petioles after a soil drought event. Therefore, xylem cavitation might represent a promising criterion to evaluate the performance of rubber clones under drought conditions.     

Notch signaling: control of cell communication and cell fate

Notch is a transmembrane receptor that mediates local cell-cell communication and coordinates a signaling cascade present in all animal species studied to date. Notch signaling is used widely to determine cell fates and to regulate pattern formation; its dysfunction results in a tremendous variety of developmental defects and adult pathologies. This primer describes the mechanism of Notch signal transduction and how it is used to control the formation of biological patterns.     

The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria

The increasing rate of multidrug-resistant tuberculosis has led to more use of second-line antibiotics such as para-aminosalicylic acid (PAS). The mode of action of PAS remains unclear, and mechanisms of resistance to this drug are undefined. We have isolated PAS-resistant transposon mutants of Mycobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant of intracellular folate levels. BCG thyA mutants have reduced thymidylate synthase activity and are resistant to known inhibitors of the folate pathway. We also find that mutations in thyA are associated with clinical PAS resistance. We have identified PAS-resistant Mycobacterium tuberculosis isolates from infected patients, which harbour mutations in thyA and show reduced activity of the encoded enzyme. Thus, PAS acts in the folate pathway, and thyA mutations probably represent a mechanism of developing resistance not only to PAS but also to other drugs that target folate metabolism.     

Structural and functional diversity of lectin repertoires in invertebrates, protochordates and ectothermic vertebrates

During the past few years, substantial progress has been accomplished in the elucidation of the structural diversity of the lectin repertoires of invertebrates, protochordates and ectothermic vertebrates, providing particularly valuable information on those groups that constitute the invertebrate/vertebrate 'boundary'. Although representatives of lectin families typical of mammals, such as C-type lectins, galectins and pentraxins, have been described in these taxa, the detailed study of selected model species has yielded either novel variants of the structures described for the mammalian lectin representatives or novel lectin families with unique sequence motifs, multidomain arrangements and a new structural fold. Along with the high structural diversity of the lectin repertoires in these taxa, a wide spectrum of biological roles is starting to emerge, underscoring the value of invertebrate and lower vertebrate models for gaining insight into structural, functional and evolutionary aspects of lectins.