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Recent work on graph perception has focused on the nature of the processes that operate when people decode the information represented in graphs. We began our investigations by gathering evidence that people have generic expectations about what types of information will be the major messages in various types of graphs. These graph schemata suggested how graph type and judgment type would interact to determine the speed and accuracy of quantitative information extraction. These predictions were confirmed by the finding that a comparison judgment was most accurate when the judgment required assessing position along a common scale (simple bar chart), had intermediate accuracy on length judgments (divided bar chart), and was least accurate when assessing angles (pie chart). In contrast, when the judgment was an estimate of the proportion of the whole, angle assessments (pie chart) were as accurate as position (simple bar chart) and more accurate than length (divided bar chart). Proposals for elementary information processes involving anchoring, scanning, projection, superimposition, and detection operators were made to explain this interaction.

The cooperative emission process in KCl:O2 has been studied as a function of the dephasing rate of the transition dipole. As the temperature of the sample is increased from 10 to 30 K, the emission evolves continuously from that characteristic of superfluorescence to that of amplified spontaneous emission. These results are in qualitative agreement with the predictions of current theories, but quantitative agreement is obtained only when current theories are modified so that the noise source that initiates the emission process is allowed to act continuously during the superAuorescent buildup.It is well known that cooperative efIects involving many atoms can profoundly modify the nature of the spontaneous emission process. ' Two such eAects are superfluorescence, that is, cooperative spontaneous emission involving many atoms, and amplified spontaneous emission (ASE), ' ' ' in which the spontaneous emission from a single atom is amplified as it propagates through an inverted atomic medium. Extensive theoretical and experimental studies of these two processes have been performed. However, for the most part these processes have been studied independently, and relatively little work has been done in characterizing the nature of the emission process in the regime' ' intermediate between that of superfluorescence and that of ASE. In this Letter, we describe an experiment in which the nature of the cooperative emission process involving the super-oxide ion in potassium chloride (KC1:02 ) is studied as a function of temperature and, hence, as a function of the dephasing rate of the transition dipole. We selected KCl:02 for this experiment because it is the only solid-state system in which superfluorescence has been reported, ' and because the dephasing rate of a dipole imbedded in a solid increases rapidly with temperature. We find that the nature of the emission evolves gradually from that of superfluorescence to that of ASE as the dipole dephasing rate is increased.The simplest manifestation of superfluorescence occurs in the limiting case in which dephasing is negligible. All N excited atoms within the interaction volume participate, and the macroscopic dipole moment of the collection of atoms is approximately N times larger than the atomic dipole transition moment. As a result, the emission is highly directional and is emitted in the form of a pulse whose peak intensity scales as N and whose characteristic duration is rtt =8trr,~/ 3pk I, where r,~is the single-atom spontaneous decay time, k is the emission wavelength, p is the number density of atoms, and l is the length of the medium. The emitted pulse is delayed with respect to the exciting radiation by an interval'9 ro =rtt [ln(2trN) ' ] /4, which is typically 10 to 100 times longer than rR. This delay represents the time required for the individual atomic dipoles to come into phase lock due to the coupling between them.The presence of dephasing processes modifies this behavior by inhibiting the formation of the macroscopic dipole moment.If the dephasing rate is no...

Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29 -32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K ϩ channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K ϩ channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state.

Brain-derived neurotrophic factor (BDNF), a neurotrophin that binds specifically to the tyrosine kinase B (TrkB) receptor, has been shown to promote neuronal differentiation, maturation, and synaptic plasticity in the central nervous system (CNS) during development or after injury and onset of disease. Unfortunately, native BDNF protein-based therapies have had little clinical success due to their suboptimal pharmacological properties. In the past 20 years, BDNF mimetic peptides have been designed with the purpose of activating certain cell pathways that mimic the functional activity of native BDNF, but the interaction of mimetic peptides with cells can be limited due to the conformational specificity required for receptor activation. We report here on the incorporation of a BDNF mimetic sequence into a supramolecular peptide amphiphile filamentous nanostructure capable of activating the BDNF receptor TrkB and downstream signaling in primary cortical neurons in vitro. Interestingly, we found that this BDNF mimetic peptide is only active when displayed on a peptide amphiphile supramolecular nanostructure. We confirmed that increased neuronal maturation is linked to TrkB signaling pathways by analyzing the phosphorylation of downstream signaling effectors and tracking electrical activity over time. Furthermore, three-dimensional gels containing the BDNF peptide amphiphile (PA) nanostructures encourage cell infiltration while increasing functional maturation. Our findings suggest that the BDNF mimetic PA nanostructure creates a highly bioactive matrix that could serve as a biomaterial therapy in injured regions of the CNS. This new strategy has the potential to induce endogenous cell infiltration and promote functional neuronal maturation through the presentation of the BDNF mimetic signal.

Membrane phosphatidylinositol-4,5-bisphosphate (PIP2) is critical for the function of many transient receptor potential (TRP) ion channels. The role of PIP2 in TRPA1 function is not well known. The effect of PIP2 on TRPA1 was investigated by direct application of PIP2 and by using polylysine and PIP2 antibody that sequester PIP2. In inside-out patches from HeLa cells expressing mouse TRPA1, polytriphosphate (PPPi) was added to the bath solution to keep TRPA1 sensitive to allyl isothiocyanate (AITC; mustard oil). Direct application of PIP2 (10 M) to inside-out patches did not activate TRPA1, but AITC and ⌬ 9 -tetrahydrocannabinol (THC) produced strong activation. In inside-out patches in which TRPA1 was first activated with AITC (in the presence of PPPi), further addition of PIP2 produced a concentration-dependent inhibition of TRPA1 [agonist concentration producing half-maximal activity (K 1/2), 2.8 M]. Consistent with the inhibition of TRPA1 by PIP2, AITC activated a large whole cell current when polylysine or PIP2 antibody was added to the pipette but a markedly diminished current when PIP2 was added to the pipette. In inside-out patches with PPPi in the bath solution, application of PIP2 antibody or polylysine caused activation of TRPA1, and this was blocked by PIP2. However, TRPA1 was not activated by polylysine and PIP2 antibody under whole cell conditions, suggesting a more complex regulation of TRPA1 by PIP2 in intact cells. These results show that PIP2 inhibits TRPA1 and reduces the sensitivity of TRPA1 to AITC. allyl isothiocynanate; tetrahydrocannabinol; neomycin; magnesium TRANSIENT RECEPTOR POTENTIAL (TRP) A1 (TRPA1) is highly expressed in a subset of sensory neurons and is activated by pungent and reactive chemicals such as allylisothiocyanate (from mustard), allicin (from garlic), cinnamaldehyde (from cinnamon), formaldehyde, N-methylmaleimide, and ␣,␤-unsaturated aldehydes (2, 3, 14, 37). These chemicals are believed to act directly on the cytoplasmic regions of TRPA1 and cause local covalent modification of the protein, leading to a conformational change and opening of the channel (13,(25)(26)(27). TRPA1 may also serve as a sensor of cold temperature and mechanical deformation; however, these roles are currently controversial (17,18,28,30,35,37,39). In addition to pungent chemicals found in nature, endogenously generated molecules such as bradykinin, reactive oxygen species, and 4-hydroxynonenal that are produced during inflammation and oxidative stress, respectively, can activate TRPA1 (2, 4, 39). Thus TRPA1 detects and transduces signals produced by nociceptive chemicals, chemical-induced damage, and inflammation.Recent studies show that activation, desensitization, and recovery from desensitization of several TRP ion channels in the TRPM (melastatin)and TRPV (vanilloid) families are dependent or regulated by membrane phosphatidylinositol-4,5-bisphosphate (PIP2) (5,10,21,23,33,40). For example, activation of TRPM8 by menthol requires the presence of PIP2, and factors that reduce membrane PIP2 c...

No abstract

TREK-2 expressed in mammalian cells exhibits small (∼52 pS) and large (∼220 pS) unitary conductance levels. Here we tested the role of the N-terminus (69 amino acids long) in the control of the unitary conductance, and role of the alternative translation initiation as a mechanism that produces isoforms of TREK-2 that show different conductance levels. Deletion of the first half ( 1-36) of the N-terminus had no effect. However, deletion of most of the N-terminus ( 1-66) resulted in the appearance of only the large-conductance channel (∼220 pS). In support of the critical function of the distal half of the N-terminus, the deletion mutants 1-44 and 1-54 produced ∼90 pS and 188 pS channels, respectively. In Western blot analysis, TREK-2 antibody detected two immunoreactive bands at ∼54 kDa and ∼60 kDa from cells expressing wild-type TREK-2 that has three potential translation initiation sites (designated M 1 M 2 M 3 ) within the N-terminus. Mutation of the second and third initiation sites from Met to Leu (M 1 L 2 L 3 ) produced only the ∼60 kDa isoform and the small-conductance channel (∼52 pS). Mutants designed to produce translation from the second (M 2 L 3 ) or third (M 3 ) initiation site produced the ∼54 kDa isoform, and the large conductance channel (∼185-224 pS). M 1 L 2 L 3 , M 2 L 3 and M 3 were relatively selectively permeable to K + , as judged by the 51-55 mV shifts in reversal potential following a 10-fold change in [K + ] o . P Na /P K values were also similar for M 1 L 2 L 3 (∼0.02), M 2 L 3 (∼0.02) and M 3 (∼0.03). Arachidonic acid, proton and membrane stretch activated, whereas dibutyryl-cAMP inhibited all three isoforms of TREK-2, indicating that deletion of the N-terminus does not abolish modulation. These results show that the small and large conductance TREK-2 channels are produced as a result of alternative translation initiation, producing isoforms with long and short N-termini, and that the distal half of the N-terminus controls the unitary conductance.