In this first part of a review on recent insights into the structure and function of the γ-aminobuty rie acid type A - benzodiazepine receptor system, the γ-aminobutyric acid type A (GABAA) receptor and the different types of benzodiazepine (BDZ) receptors known at this moment are dicussed. GABAA- and BDZ receptors are coupled in a supramolecular GABAA-BDZ-ionophore receptor complex, each consisting of five acidic glycoprotein molecules called subunits. These subunits can be classified into five groups: α, β, γ, σ and ρ. Present evidence indicates the existence of multiple subtypes of these subunits. Multiple GABAA-BDZ receptors exist in the brain that show differential distribution and developmental patterns. These receptors differ from their subunit composition. The final functional properties of the receptor are determined by the different subunits constituting this receptor. Heterogeneity among α- subunits may determine the diversity of BDZ pharmacology in different regions of the nervous system.

Pavlov's first report on conditioning emphasized its role in allowing the animal to adjust to its environment. Contemporary theories have seen this adjustment in terms of developing accurate knowledge of the environment. Three aspects of that thinking are explored: how the animal acquires initial knowledge, how it changes its knowledge when conditions of the world change, and how it makes use of multiple knowledge representations.

This paper reports on digital transmitter architecture for the 450 MHz band using an envelope delta-sigma modulator realized in CMOS and a voltage-mode class-S (VMCS) power amplifier (PA) based on GaN monolithic microwave integrated circuits (MMICs). The class-S PA is characterized for narrowband single-tone signals and a single- as well as a four-carrier downlink wideband code division multiple access (WCDMA) signal with a peak-to-average power ratio of 7.5 dB. Using single-tone excitation the PA shows a maximum drain efficiency of 86% and a peak output power of 4.4 W. At 6 and 10 dB back-off, 59 and 36% efficiency are achieved, respectively. With the single- and four-carrier WCDMA input signals maximum drain efficiencies of 64 and 53% are reached, respectively, and peak output power is 0.7 W. The adjacent channel leakage ratio shows values of about −34 dBc (5 MHz) and −38 dBc (10 MHz) for single-carrier WCDMA excitation. This is the first complete VMCS PA chain characterized with standard communication signals.

Australian research into variations of the cosmic ray flux arriving at the Earth has played a pivotal role for more than 50 years. The work has been largely led by the groups from the University of Tasmania and the Australian Antarctic Division, and has involved the operation of neutron monitors and muon telescopes from many sites. In this paper, the achievements of the Australian researchers are reviewed and future experiments are described. Particular highlights include: the determination of cosmic ray modulation parameters; the development of techniques for modelling ground-level enhancements; the confirmation of the Tail-In and Loss-Cone sidereal anisotropies; the Spaceship Earth collaboration; and the Solar Cycle latitude survey.

Amacrine cells receive glutamatergic input from bipolar cells and GABAergic, glycinergic, cholinergic, and dopaminergic input from other amacrine cells. Glutamate, GABA, glycine, and acetylcholine (ACh) interact with ionotropic receptors and it is these interactions that form much of the functional circuitry in the inner retina. However, glutamate, GABA, ACh, and dopamine also activate metabotropic receptors linked to second messenger pathways that have the potential to modify the function of individual cells as well as retinal circuitry. Here, the physiological effects of activating dopamine receptors, metabotropic glutamate receptors, GABAB receptors, and muscarinic ACh receptors on amacrine cells will be discussed. The retina also expresses metabotropic receptors and the biochemical machinery associated with the synthesis and degradation of endocannabinoids and sphingosine-1-phosphate (S1P). The effects of activating cannabinoid receptors and S1P receptors on amacrine cell function will also be addressed.

Using rhodamine-labelled latex beads as a retrograde tracer, we have shown that a subset of the neurons projecting from the lateral thalamic nucleus to the optic tectum of the leopard frog are neuropeptide Y-like immunoreactive (NPY-IR). In juvenile frogs, approximately twice as many lateral thalamic nucleus cells from this area project to the ipsilateral tectum as project to the contralateral tectum. NPY-IR cells make up 25% of the projection to the ipsilateral tectum and 13% of the projection to the contralateral tectum. The ipsilateral NPY-IR projection from the lateral nucleus was present in tadpoles and was similar in its characteristics to that found in the juvenile frog. However, the contralateral tectal projection was virtually nonexistent in these animals. The results of these experiments suggest that NPY from the lateral nucleus is released into the ipsilateral tectal neuropil in both the developing and adult frog.

In recent months the US and the EU have agreed to change the modulation scheme for the new civil GPS and Galileo signals in the L1 band from Binary Offset Carrier (1,1) (BOC(1,1)) to a scheme having the so-called Multiplexed Binary Offset Carrier (MBOC) spectrum, although each system will implement this differently. This paper compares the performance of the new system in a number of areas against the original baseline. It is shown that the MBOC signal offers significant advantages in multipath and tracking performance, while retaining compatibility with BOC(1,1) receivers at the cost of a small correlation loss.

In the inner plexiform layer, amacrine cells receive glutamatergic input from bipolar cells. Glutamate can depolarize amacrine cells by activation of ionotropic glutamate receptors or mediate potentially more diverse changes via activation of G protein-coupled metabotropic glutamate receptors (mGluR5). Here, we asked whether selective activation of metabotropic glutamate receptor 5 is linked to modulation of the voltage-gated Ca2+ channels expressed by cultured GABAergic amacrine cells. To address this, we performed whole-cell voltage clamp experiments, primarily in the perforated-patch configuration. We found that agonists selective for mGluR5, including (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), enhanced the amplitude of the voltage-dependent Ca2+ current. The voltage-dependent Ca2+ current and CHPG-dependent current enhancement were blocked by nifedipine, indicating that L-type Ca2+ channels, specifically, were being modulated. We have previously shown that activation of mGluR5 produces Ca2+ elevations in cultured amacrine cells (Sosa et al., 2002). Loading the cells with 5 mM BAPTA inhibited the mGluR5-dependent enhancement, suggesting that the cytosolic Ca2+ elevations are required for modulation of the current. Although activation of mGluR5 is typically linked to activation of protein kinase C, we found that direct activation of this kinase leads to inhibition of the Ca2+ current, indicating that stimulation of this enzyme is not responsible for the mGluR5-dependent enhancement. Interestingly, direct stimulation of protein kinase A produced an enhancement of the Ca2+ current similar to that observed with activation of mGluR5. Thus, activation of mGluR5 may modulate the L-type voltage-gated Ca2+ current in these GABAergic amacrine cells via activation of protein kinase A, possibly via direct activation of a Ca2+-dependent adenylate cyclase.

Crayfish photoreceptors exhibit a voltage-dependent potassium conductance, GK, that is generally similar to the delayed rectifier channel described in neurons and other arthropod retinular cells. GK activation (i.e. the apparent threshold, Vth) occurs near the resting potential and GK is substantially reduced by 25 mM extracellular tetraethylammonium (TEA) and by intracellular Cs+ injections. Light exposure, sufficient to reduce visual sensitivity 100-fold, increases Vth (shifts it in the depolarizing direction) by about 20 mV. The light-dependent change in Vth does not depend upon the corresponding increase (depolarization) of the steady-state membrane potential nor does it depend upon inward calcium currents. Vth is slightly influenced by fluctuations in Ko associated with the light-elicited currents. During light exposure Ko (measured with K+-sensitive electrodes) increases by 2.1 mM (equivalent to an 8 mV increase in EK). This increase in EK makes only a modest contribution to the light-dependent change in Vth as determined by perfusion with high potassium salines. Intracellular calcium injections increase Vth by 10 to 20 mV and reduce visual sensitivity by 5- to 10-fold. The results imply that during exposure to high levels of illumination, K+ currents at the steady-state membrane potential are diminished by a calcium-dependent change in GK gating and, to a smaller degree, by a reduced K+ concentration gradient. It is notable that Ca2+ appears to inhibit both GK and the light-elicited conductance from both inside and outside the plasma membrane. As a consequence of the light-dependent change in Vth, GK makes only modest contributions to the changes in sensitivity and speed normally associated with light adaption. These functions are regulated by the transduction pathway and are revealed at the resting potential in the time course and magnitude of the light-elicited currents.

Centrifugal modulation of visual responsiveness of tectal cells by the isthmo-optic nucleus (ION) through the retina was studied in homing pigeons. Visual activity evoked by computer-generated stimuli was reduced by an average of 59% in tectal cells whose receptive fields (RFs) either overlapped with, or were close to, those of isthmo-optic cells whose activity was blocked by the injection of lidocaine through micropipettes. Activity usually recovered to 87% of pre-drug controls in 8–17 min (average 12.3 min) after stopping lidocaine injections. Those tectal cells whose RFs were far from those of ION cells did not show clear-cut changes in their visual responsiveness to isthmo-optic lidocaine application. The spatial relationship between receptive fields of tectal and isthmo-optic cells, saline controls, as well as the specificity, reproducibility and reversibility of effects of ION-injected lidocaine on tectal activity, show that this chemical action is pharmacological, not toxicological. Neuronal circuitry underlying centrifugal modulation of tectal activity by isthmo-optic cells is discussed.

This study was performed in order to define Schistosoma mansoni antigens that are able to function as modulator agents in the granulomatous hypersensitivity to parasite eggs in BALB/c and C57BL/6 mice. A fraction of S. mansoni, designated PIII, derived from adult worm antigen preparation (SWAP) was obtained using anion-exchange chromatography on an FPLC system. Immunization of mice with PIII in the presence of Corynebacterium parvum and Al(OH)3 as adjuvant induced an immune response in these animals as determined by ELISA and spleen cell proliferation assays against S. mansoni antigens SEA, SWAP and PIII. In addition, PIII caused a significant degree of protection against a challenge infection in immunized mice as observed by the decrease on worm burden recovered from the portal system. We also showed that PIII profoundly inhibited the vigorous anamnestic granulomatous response to eggs in the liver and lungs. This suppression correlated with a significant decrease in granuloma size. From these results we conclude that the PIII preparation contains antigens that can mediate protective anti-parasite immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs.