Evidence that P2X purinoceptors mediate the excitatory effects of alphabetamethylene-ADP in rat locus coeruleus neurones

Extracellular and whole-cell patch clamp recordings were used to study the excitatory responses elicited by purine nucleotides in pontine slices of the rat brain containing the locus coeruleus (LC). The P2 purinoceptor agonists, alphabeta-methyleneadenosine 5'-triphosphate (alphabetameATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPalphabetaS), and a novel purinoceptor agonist, alphabeta-methyleneadenosine 5'-diphosphate (alphabetameADP), elicited concentration-dependent increases in the spontaneous firing rate over the concentration range (1-300 microM). On vagus nerve or dorsal root preparations alphabetameADP (100 microM) had no agonist activity. In the presence of both alphabetameATP (300 microM), ADPbetaS (300 microM) elicited a further and significant increase in the firing rate of the LC neurones, whilst neither alphabetameATP nor alphabetameADP (300 microM) elicited a further response. The P2 purinoceptor antagonists, suramin (100 microM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 30 microM), markedly attenuated responses to all three agonists. Whole-cell recording of membrane current showed that, at - 60 mV, alphabetameATP and alphabetameADP (both 100 microM) elicited inward currents of a similar magnitude, whilst the inward currents elicited by a lower concentration of ADPbetaS (30 microM) were larger and faded in the presence of this agonist. In the presence of tetrodotoxin and a combination of other neurotransmission blockers, both alphabetameATP and alphabetameADP still produced inward currents. Based on the known selectivity of the agonists used in this study, there appear to be two distinct P2 purinoceptor types present on neurones in the LC, which correspond to the P2X and P2Y types. The responses elicited by alphabetameADP appear to be mediated through a putative P2X purinoceptor, although further work is required to determine which P2X receptor subtype(s) are involved.     

Radiolabeling of the rat P2X4 purinoceptor: evidence for allosteric interactions of purinoceptor antagonists and monovalent cations with P2X purinoceptors

The rat recombinant P2X4 purinoceptor was expressed in CHO-K1 cells, and binding studies were performed using the radioligand [35S]adenosine-5'-O-(3-thio)triphosphate ([35S]ATPgammaS). In 50 mM Tris/1 mM EDTA assay buffer, pH 7.4 at 4 degrees, [35S]ATPgammaS bound with high affinity to the P2X4 purinoceptor (KD = 0.13 nM, Bmax = 151 pmol/mg of protein). The purinoceptor agonists ATP and 2-methylthioadenosine triphosphate possessed nanomolar affinity for the P2X4 purinoceptor, whereas the antagonist suramin possessed much lower affinity (IC50 = 0.5 mM). Cibacron blue was more potent than suramin but produced a biphasic competition curve, whereas d-tubocurarine potentiated binding at concentrations in excess of 10 microM. The complex effects of cibacron blue and d-tubocurarine seemed to be due to an allosteric interaction with the P2X4 purinoceptor because these compounds affected radioligand dissociation, measured after isotopic dilution with unlabeled ATPgammaS. Cibacron blue (1-100 microM) and d-tubocurarine (0.1-1 mM) produced rapid (10 sec to 5 min) decreases or increases, respectively, in the level of [35S]ATPgammaS binding measured immediately after initiation of the dissociation reaction. However, the subsequent rates of radioligand dissociation were not markedly different from those measured in their absence. Monovalent cations produced similar affects on the P2X4 purinoceptor and, like d-tubocurarine, increased [35S]ATPgammaS binding. The actions of d-tubocurarine and sodium were not additive. The findings from this study indicate that [35S]ATPgammaS can be used to label the P2X4 purinoceptor and suggest that this binding can be enhanced by monovalent cations and d-tubocurarine and may be subject to negative allosteric modulation to varying degrees by different purinoceptor antagonists.     

Strobe rearing prevents the convergence of inputs with different response timings onto area 17 simple cells

Strobe rearing prevents the convergence of inputs with different response timings onto area 17 simple cells. J. Neurophysiol. 80: 3005-3020, 1998. The preceding paper showed that the loss of direction selectivity in simple cells induced by strobe rearing reflects the elimination of spatially ordered response timing differences across the receptive field that underlie spatiotemporal (S-T) inseparability. Here we addressed whether these changes reflected an elimination of certain timings or an alteration in how timings were associated in single cells. Timing in receptive fields was measured using stationary bars undergoing sinusoidal luminance modulation at different temporal frequencies (0.5-6 Hz). For each bar position, response phase versus temporal frequency data were fit by a line to obtain two measures: absolute phase and latency. In normal cats, many individual simple cells display a wide range of timings; in layer 4, the mean range for absolute phase and latency was 0.21 cycles and 39 ms, respectively. Strobe rearing compressed the mean timing ranges in single cells, to 0.08 cycles and 31 ms, respectively, and this compression accounted for the loss of inseparability. A similar compression was measured in layer 6 cells. In contrast, the range of timing values across the simple-cell population was relatively normal. Single cells merely sampled narrower than normal regions of the timing space. We sought to understand these cortical changes in terms of how inputs from the lateral geniculate nucleus (LGN) may have been affected by strobe rearing. In normal cats, a wide range of absolute phase and latency values exists among lagged and nonlagged LGN cells, and these thalamic timings account for most of the cortical timings. Also, S-T inseparability in many simple cells can be attributed to the convergence of lagged and/or nonlagged inputs. Strobe rearing did not change the sampling of lagged and nonlagged cells, and the geniculate timings continued to account for most of the cortical timings. However, strobe rearing virtually eliminated cortical receptive fields with mixed lagged and nonlagged timing, and it compressed the timing range in cells dominated by one or the other geniculate type. Thus strobe rearing did not eliminate certain timings in LGN or cortex, but prevented the convergence of different timings on single cells. To account for these results, we propose a developmental model in which strobe stimulation alters the correlational structure of inputs based on their response timing. Only inputs with similar timing become associated on single cortical cells, and this produces S-T separable receptive fields that lack the ability to confer a preferred direction of motion.     

The MOS inversion layer as a minority carrier injector

In this paper we report the first experimental demonstration of the concept of MOS inversion layer injection (ILI). The new physical concept is based on the use of a MOS inversion layer as a minority carrier injector as part of a dynamic junction. The carrier injection of such a junction is entirely controlled by the MOS gate. Moreover, when the gate potential is reduced under the MOS threshold voltage, the junction collapses ensuring a very efficient turn-off mechanism. Based on this concept we propose two novel lateral three-terminal structures termed inversion layer diode (ILD) and inversion layer bipolar transistor (ILBT). The concept of inversion layer injection can be applied in power devices where effective MOS gate control of the active junctions is important     

Auditory-visual integration of temporal relations in infants.

A total of 100 3–4 mo old infants in 2 experiments were assigned to 1 of 2 groups: one group was first presented with temporally synchronous auditory and visual signals during habituation trials and then nonsynchronous signals during recovery; the other groups received the opposite sequence. The auditory and visual signals were spatially congruous in Exp I, but were separated in Exp II. Since the pulse rate of the visual stimuli was changed for the nonsynchronous trials, a control group was tested that received only the light during habituation and recovery trials. The groups initially presented synchronous signals showed habituation and recovery. Neither group presented nonsynchronous stimuli showed recovery. The group with the spatially separated sources habituated, while the group with the spatially congruous signals did not. Results suggest that infants coordinate the temporal relations. (French abstract) (12 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aberrant left pulmonary artery presenting as a right paratracheal mass in an adult

Aberrant left pulmonary artery, or pulmonary sling, is a rare variation of the pulmonary vasculature, with only one previous report of the condition being recognized in an adult. In this report a second case recognized de novo in an adult is presented. Both of these adults were evaluated because of right paratracheal masses which required differentiation from pulmonary malignancies. The barium swallow shows a characteristic indentation of the anterior esophageal wall and the lateral tomogram demonstrates absence of the left pulmonary artery from its normal position in the left hilum. The pulmonary arteriogram is diagnostic and allows avoidance of more invasive diagnostic measures.     

Practical applications of adaptive mesh refinement (Rezoning)

A collection of finite element problems that have been examined with a posteriori convergence measures is presented. Results show these local convergence measures can be used to indicate the quality of a finite element solution and to suggest boundaries for mesh rezones.