Distinct roles for inhibition in spatial and temporal tuning of local edge detectors in the rabbit retina.

This paper examines the role of inhibition in generating the receptive-field properties of local edge detector (LED) ganglion cells in the rabbit retina. We confirm that the feed-forward inhibition is largely glycinergic but, contrary to a recent report, our data demonstrate that the glycinergic inhibition contributes to temporal tuning for the OFF and ON inputs to the LEDs by delaying the onset of spiking; this delay was more pronounced for the ON inputs (∼ 340 ms) than the OFF inputs (∼ 12 ms). Blocking glycinergic transmission reduced the delay to spike onset and increased the responses to flickering stimuli at high frequencies. Analysis of the synaptic conductances indicates that glycinergic amacrine cells affect temporal tuning through both postsynaptic inhibition of the LEDs and presynaptic modulation of the bipolar cells that drive the LEDs. The results also confirm that presynaptic GABAergic transmission contributes significantly to the concentric surround antagonism in LEDs; however, unlike presumed LEDs in the mouse retina, the surround is only partly generated by spiking amacrine cells

Diverse synaptic mechanisms generate direction selectivity in the rabbit retina

The synaptic conductance of the On-Off direction-selective ganglion cells was measured during visual stimulation to determine whether the direction selectivity is a property of the circuitry presynaptic to the ganglion cells or is generated by postsynaptic interaction of excitatory and inhibitory inputs. Three synaptic asymmetries were identified that contribute to the generation of direction-selective responses: (1) a presynaptic mechanism producing stronger excitation in the preferred direction, (2) a presynaptic mechanism producing stronger inhibition in the opposite direction, and (3) postsynaptic interaction of excitation with spatially offset inhibition. Although the on- and off-responses showed the same directional tuning, the off-response was generated by all three mechanisms, whereas the on- response was generated primarily by the two presynaptic mechanisms. The results indicate that, within a single neuron, different strategies are used within distinct dendritic arbors to accomplish the same neural computation

Performance and evaluation of the Viking lander camera performance prediction program

A computer program is described for predicting the performance of the Viking lander cameras. The predictions are primarily concerned with two objectives: (1) the picture quality of a reference test chart (of which there are three on each lander) to aid in diagnosing camera performance; and (2) the picture quality of cones with surface properties of a natural terrain to aid in predicting favorable illumination and viewing geometries and operational camera commands. Predictions made with this program are verified by experimental data obtained with a Viking-like laboratory facsimile camera

The urban and regional segregation of indigenous Australians: Out of sight, out of mind?

Contrary to popular belief, the majority of Indigenous Australians live in cities and towns rather than remote areas of the country, yet remain segregated and \u27invisible\u27 from the daily lives of non-Indigenous Australians. In 2006, the Australian Indigenous population surpassed half a million. Yet while public and political discourse invariably concentrate on remote Australia, geographically, more than 75% of the Indigenous population is regional or urban and some 31% of Indigenous Australians live in the major cities

Local edge detectors: A substrate for fine spatial vision at low temporal frequencies in rabbit retina

Visual acuity is limited by the size and density of the smallest retinal ganglion cells, which correspond to the midget ganglion cells in primate retina and the beta- ganglion cells in cat retina, both of which have concentric receptive fields that respond at either light- On or light- Off. In contrast, the smallest ganglion cells in the rabbit retina are the local edge detectors ( LEDs), which respond to spot illumination at both light- On and light- Off. However, the LEDs do not predominate in the rabbit retina and the question arises, what role do they play in fine spatial vision? We studied the morphology and physiology of LEDs in the isolated rabbit retina and examined how their response properties are shaped by the excitatory and inhibitory inputs. Although the LEDs comprise only similar to 15% of the ganglion cells, neighboring LEDs are separated by 30 - 40 mu m on the visual streak, which is sufficient to account for the grating acuity of the rabbit. The spatial and temporal receptive- field properties of LEDs are generated by distinct inhibitory mechanisms. The strong inhibitory surround acts presynaptically to suppress both the excitation and the inhibition elicited by center stimulation. The temporal properties, characterized by sluggish onset, sustained firing, and low bandwidth, are mediated by the temporal properties of the bipolar cells and by postsynaptic interactions between the excitatory and inhibitory inputs. We propose that the LEDs signal fine spatial detail during visual fixation, when high temporal frequencies are minimal

RGS9 Knockout Causes a Short Delay in Light Responses of ON-Bipolar Cells

RGS9 and R9AP are components of the photoreceptor-specific GTPase activating complex responsible for rapid inactivation of the G protein, transducin, in the course of photoresponse recovery from excitation. The amount of this complex in photoreceptors is strictly dependent on the expression level of R9AP; consequently, the knockouts of either RGS9 or R9AP cause comparable delays in photoresponse recovery. While RGS9 is believed to be present only in rods and cones, R9AP is also expressed in dendritic tips of ON-bipolar cells, which receive synaptic inputs from photoreceptors. Recent studies demonstrated that knockouts of R9AP and its binding partner in ON-bipolar cells, RGS11, cause a small delay in ON-bipolar cell light responses manifested as a delayed onset of electroretinography b-waves. This led the authors to suggest that R9AP and RGS11 participate in regulating the kinetics of light responses in these cells. Here we report the surprising finding that a nearly identical b-wave delay is observed in RGS9 knockout mice. Given the exclusive localization of RGS9 in photoreceptors, this result argues for a presynaptic origin of the b-wave delay in this case and perhaps in the case of the R9AP knockout as well, since R9AP is expressed in both photoreceptors and ON-bipolar cells. We also conducted a detailed analysis of the b-wave rising phase kinetics in both knockout animal types and found that, despite a delayed b-wave onset, the slope of the light response is unaffected or increased, dependent on the light stimulus intensity. This result is inconsistent with a slowdown of response propagation in ON-bipolar cells caused by the R9AP knockout, further arguing against the postsynaptic nature of the delayed b-wave phenotype in RGS9 and R9AP knockout mice

Pediatric Poisoning: Overview, Treatment, and Prevention

Pediatric poisoning remains a common and preventable occurrence in the United States. Every year, prescription and over-the-counter medications account for a significant portion of documented poison exposures. Frequent causes of overdose in children include improper medication storage and caregiver or physician dosing error. As easily accessible medication experts, pharmacists have an opportunity to counsel patients in an effort to decrease these preventable poisoning cases. Because children frequently ingest products prescribed for adult use, pharmacist should relay safety considerations to all patients, regardless of age. This article provides a general review of toxicity concerns, discusses clinical implications of common medications resulting in poisonings and of those that are lethal in one or two doses, and describes the role of the pharmacist in poisoning treatment recommendations and prevention

Synthesis and Characterization of Ketone and Ketal Coronands Containing 2,6-Pyridino And/Or 6,6\u27-(2,2\u27-Dipyridino) Subunits.

Pyridyllithium reagents were employed in the synthesis of 6-substituted bis(2-pyridyl) ketones and 6,6\u27-disubstituted 2,2\u27-dipyridines. The resulting compounds were used in the attempted preparation of pyridine analogues of simple corrins. Coronands were generated from 2,2-bis(6\u27-bromo-2\u27-pyridyl)-1,3-dioxolane. Hydrolysis of the protecting dioxolane gave the corresponding ketone coronands, which could be reduced to macrocyclic carbinols with sodium borohydride. Although these compounds would not complex transition metal ions, several were observed to sequester neutral molecules. In particular, the hexaethylene glycol ketone coronand was proven by X-ray diffraction methods to encircle a molecule of water. Electron-poor aromatic ketones were discovered to decarbonylate under mild, basic conditions. The mechanism of this reaction was proposed to be analogous to that of the benzilic acid rearrangement. Coronands of 2,2\u27-dipyridine could be formed by the decarbonylation of the corresponding ketone macrocycles. Attempts to prepare pyridyl ketone and ketal coronands that possess a methylene unit between the heteroaromatic ring and the glycol bridge were thwarted by the photosensitivity of the parent bis(6-methyl-2-pyridyl) ketone. Efforts to functionalize the methyl groups of the dioxolane-protected ketone by free radical halogenation produced a plethora of virtually inseparable haloketones and ketals. 2,2-Bis(2\u27-pyridyl)- and 2,2-bis(6\u27-methyl-2-pyridyl)-1,3-dioxolane were observed to be excellent ligands for transition metal ions. X-ray analysis showed the chelation of the metal to occur primarily through the pyridine nitrogens, with a moderate interaction to one of the dioxolane oxygens. In the octahedral Ni(II) complex of the methylpyridyl ketal, the ligand was bound to the metal in a tridentate fashion. Coronands were formed from 6,6\u27-bis{2\u27\u27-6\u27\u27-bromo-2\u27\u27-pyridyl)-1\u27\u27,3\u27\u27-dioxolan-2\u27\u27-yl}-2,2\u27-dipyridine and subsequently hydrolyzed to the diketone coronands. The diketal coronand of bis(2-mercaptoethyl) ether formed complexes with transition metals