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M Meister

Publications and source records attributed to M Meister.

At least 19 recordsLinked to original sources
PubMed1999

Anticipation of moving stimuli by the retina.

A flash of light evokes neural activity in the brain with a delay of 30-100 milliseconds, much of which is due to the slow process of visual transduction in photoreceptors. A moving object can cover a considerable distance in this time, and should therefore be seen noticeably behind its actual location. As this conflicts with everyday experience, it has been suggested that the visual cortex uses the delayed visual data from the eye to extrapolate the trajectory of a moving object, so that it is perceived at its actual location. Here we report that such anticipation of moving stimuli begins in the retina. A moving bar elicits a moving wave of spiking activity in the population of retinal ganglion cells. Rather than lagging behind the visual image, the population activity travels near the leading edge of the moving bar. This response is observed over a wide range of speeds and apparently compensates for the visual response latency. We show how this anticipation follows from known mechanisms of retinal processing.

Animals↗
PubMed1998

Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes.

We have analyzed the Drosophila immune response in domino mutant larvae, which are devoid of blood cells. The domino mutants have a good larval viability, but they die as prepupae. We show that, on immune challenge, induction of the genes encoding antimicrobial peptides in the fat body is not affected significantly in the mutant larvae, indicating that hemocytes are not essential in this process. The hemocoele of domino larvae contains numerous live microorganisms, the presence of which induces a weak antimicrobial response in the fat body. A full response is observed only after septic injury. We propose that the fat body cells are activated both by the presence of microorganisms and by injury and that injury potentiates the effect of microorganisms. Survival experiments after an immune challenge showed that domino mutants devoid of blood cells maintain a wild-type resistance to septic injury. This resistance was also observed in mutant larvae in which the synthesis of antibacterial peptides is impaired (immune deficiency larvae) and in mutants that are deficient for humoral melanization (Black cells larvae). However, if domino was combined with either the immune deficiency or the Black cell mutation, the resistance to septic injury was reduced severely. These results establish the relevance of the three immune reactions: phagocytosis, synthesis of antibacterial peptides, and melanization. By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection.

Adipose Tissue↗
PubMed1998

Refractoriness and neural precision.

The response of a spiking neuron to a stimulus is often characterized by its time-varying firing rate, estimated from a histogram of spike times. If the cell's firing probability in each small time interval depends only on this firing rate, one predicts a highly variable response to repeated trials, whereas many neurons show much greater fidelity. Furthermore, the neuronal membrane is refractory immediately after a spike, so that the firing probability depends not only on the stimulus but also on the preceding spike train. To connect these observations, we investigated the relationship between the refractory period of a neuron and its firing precision. The light response of retinal ganglion cells was modeled as probabilistic firing combined with a refractory period: the instantaneous firing rate is the product of a "free firing rate, " which depends only on the stimulus, and a "recovery function," which depends only on the time since the last spike. This recovery function vanishes for an absolute refractory period and then gradually increases to unity. In simulations, longer refractory periods were found to make the response more reproducible, eventually matching the precision of measured spike trains. Refractoriness, although often thought to limit the performance of neurons, may in fact benefit neuronal reliability. The underlying free firing rate derived by allowing for the refractory period often exceeded the observed firing rate by an order of magnitude and was found to convey information about the stimulus over a much wider dynamic range. Thus, the free firing rate may be the preferred variable for describing the response of a spiking neuron.

Action Potentials↗
PubMed1998

A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina.

Current understanding suggests that mammalian rod photoreceptors connect only to an ON-type bipolar cell. This rod-specific bipolar cell excites the All amacrine cell, which makes connections to cone-specific bipolar cells of both ON and OFF type; these, in turn, synapse with ganglion cells. Recent work on rabbit retina has shown that rod signals can also reach ganglion cells without passing through the rod bipolar cell. This route was thought to be provided by electrical gap junctions, through which rods signal directly to cones and thence to cone bipolar cells. Here, we show that the mouse retina also provides a rod pathway bypassing the rod bipolar cell, suggesting that this is a common feature in mammals. However, this alternative pathway does not require cone photoreceptors; it is perfectly intact in a transgenic mouse whose retina lacks cones. Instead, the results can be explained if rods connect directly to OFF bipolar cells.

Aminobutyrates↗
PubMed1998

Mechanisms of concerted firing among retinal ganglion cells.

Nearby retinal ganglion cells often fire action potentials in near synchrony. We have investigated the circuit mechanisms that underlie these correlations by recording simultaneously from many ganglion cells in the salamander retina. During spontaneous activity in darkness, three types of correlations were distinguished: broad (firing synchrony within 40-100 ms), medium (10-50 ms), and narrow (<1 ms). When chemical synaptic transmission was blocked, the broad correlations disappeared, but the medium and narrow correlations persisted. Further analysis of the strength and time course of synchronous firing suggests that nearby ganglion cells share inputs from photoreceptors conveyed through interneurons via chemical synapses (broad correlations), share excitation from amacrine cells via electrical junctions (medium), and excite each other via electrical junctions (narrow). It appears that the firing patterns in the optic nerve are strongly shaped by electrical coupling in the inner retina.

Action Potentials↗
PubMed1998

Synchronous period-doubling in flicker vision of salamander and man.

Periodic flashes of light have long served to probe the temporal properties of the visual system. Here we show that during rapid flicker of high contrast and intensity the eye reports to the brain only every other flash of light. In this regime, retinal ganglion cells of the salamander fire spikes on alternating flashes. Neurons across the entire retina are locked to the same flashes. The effect depends sharply on contrast and flash frequency. It results from a period-doubling bifurcation in retinal processing, and a simple model of nonlinear feedback reproduces the phenomenon. Pharmacological studies indicate that the critical feedback interactions require only cone photoreceptors and bipolar cells. Analogous period-doubling is observed in the human visual system. Under bright full-field flicker, the electroretinogram (ERG) shows a regime of period-doubling between 30 and 70 Hz. In visual evoked potentials from the occiput, the subharmonic component is even stronger. By analyzing the accompanying perceptual effects, we find that retinal period-doubling begins in the periphery of the visual field, and that it is the cause of a long mysterious illusory flicker pattern.

Animals↗
PubMed1997

The structure and precision of retinal spike trains.

Assessing the reliability of neuronal spike trains is fundamental to an understanding of the neural code. We measured the reproducibility of retinal responses to repeated visual stimuli. In both tiger salamander and rabbit, the retinal ganglion cells responded to random flicker with discrete, brief periods of firing. For any given cell, these firing events covered only a small fraction of the total stimulus time, often less than 5%. Firing events were very reproducible from trial to trial: the timing jitter of individual spikes was as low as 1 msec, and the standard deviation in spike count was often less than 0.5 spikes. Comparing the precision of spike timing to that of the spike count showed that the timing of a firing event conveyed several times more visual information than its spike count. This sparseness and precision were general characteristics of ganglion cell responses, maintained over the broad ensemble of stimulus waveforms produced by random flicker, and over a range of contrasts. Thus, the responses of retinal ganglion cells are not properly described by a firing probability that varies continuously with the stimulus. Instead, these neurons elicit discrete firing events that may be the fundamental coding symbols in retinal spike trains.

Action Potentials↗
PubMed1997

Adaptation of retinal processing to image contrast and spatial scale.

Owing to the limited dynamic range of a neuron's output, neural circuits are faced with a trade-off between encoding the full range of their inputs and resolving gradations among those inputs. For example, the ambient light level varies daily over more than nine orders of magnitude, whereas the firing rate of optic nerve fibres spans less than two. This discrepancy is alleviated by light adaptation: as the mean intensity increases, the retina becomes proportionately less sensitive. However, image statistics other than the mean intensity also vary drastically during routine visual processing. Theory predicts that an efficient visual encoder should adapt its strategy not only to the mean, but to the full shape of the intensity distribution. Here we report that retinal ganglion cells, the output neurons of the retina, adapt to both image contrast-the range of light intensities-and to spatial correlations within the scene, even at constant mean intensity. The adaptation occurs on a scale of seconds, one hundred times more slowly than the immediate light response, and involves 2-5-fold changes in the firing rate. It is mediated within the retinal network: two independent sites of modulation after the photoreceptor cells appear to be involved. Our results demonstrate a remarkable plasticity in retinal processing that may contribute to the contrast adaptation of human vision.

Action Potentials↗
PubMed1997

Antimicrobial peptide defense in Drosophila.

Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 microM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine-induced activation of NF-kappa B in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune-deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review.

Amino Acid Sequence↗
PubMed1997

The light response of retinal ganglion cells is truncated by a displaced amacrine circuit.

The vertebrate retina contains ganglion cells that appear to be specialized for detecting temporal changes. The characteristic response of these cells is a transient burst of action potentials when a stationary image is presented or removed, and often a strong discharge to moving images. These transient and motion-sensitive responses are thought to result from processing in the inner retina that involves amacrine cells, but the critical interactions have been difficult to reveal. Here, we used a cell-ablation technique to remove a subpopulation of amacrine cells from the mouse retina. Their ablation changed transient ganglion cell responses into prolonged discharges. This suggests that transient responses are generated, at least in part, by a truncation of sustained excitatory input to the ganglion cells and that the ablated amacrine cells are critical for this process.

Animals↗
PubMed1997

Drosophila immunity: analysis of larval hemocytes by P-element-mediated enhancer trap.

Our aim was to identify new genes involved in the cellular aspects of defense mechanism of Drosophila, as well as in melanotic tumor formation processes that are linked to blood cell disregulation. We have screened 1341 enhancer detector fly lines for expression of the lacZ reporter gene in larval hemocytes at the end of the third instar. We have selected 21 lines in which we observed a reproducible lacZ expression in blood cells. These lines were classified according to the subsets of hemocytes in which lacZ was expressed, and we identified five lines that can be used as lamellocyte markers. Three lines were selected for further analysis. The first exhibited strong lacZ expression in all lamellocytes. The second expressed lacZ in plasmatocytes and lamellocytes, and exhibited a melanotic tumor phenotype in larvae homozygous for the insertion. A third line showed a striking insertion-linked phenotype of melanized lymph glands (the hematopoietic organ), which resulted in the total absence of circulating hemocytes in the mutant larvae. We anticipate that this mutation, which we named domino, will prove a useful tool in the analysis of the role of hemocytes during the various aspects of immune response and melanotic tumor formation.

Animals↗
PubMed1997

Decoding visual information from a population of retinal ganglion cells.

Decoding visual information from a population of retinal ganglion cells. J. Neurophysiol. 78: 2336-2350, 1997. This work investigates how a time-dependent visual stimulus is encoded by the collective activity of many retinal ganglion cells. Multiple ganglion cell spike trains were recorded simultaneously from the isolated retina of the tiger salamander using a multielectrode array. The stimulus consisted of photopic, spatially uniform, temporally broadband flicker. From the recorded spike trains, an estimate was obtained of the stimulus intensity as a function of time. This was compared with the actual stimulus to assess the quality and quantity of visual information conveyed by the ganglion cell population. Two algorithms were used to decode the spike trains: an optimized linear filter in which each action potential made an additive contribution to the stimulus estimate and an artificial neural network trained by back-propagation to match spike trains with stimuli. The two methods performed indistinguishably, suggesting that most of the information about this stimulus can be extracted by linear operations on the spike trains. Individual ganglion cells conveyed information at a rate of 3.2 +/- 1.7 bits/s (mean +/- SD), with an average information content per spike of 1.6 bits. The maximal possible rate of information transmission compatible with the measured spiking statistics was 13.9 +/- 6.3 bits/s. On average, ganglion cells used 22% of this capacity to encode visual information. When a decoder received two spike trains of the same response type, the reconstruction improved only marginally over that obtained from a single cell. However, a decoder using an ON and an OFF cell extracted as much information as the sum of that obtained from each cell alone.Thus cells of opposite response type encode different and nonoverlapping features of the stimulus. As more spike trains were provided to the decoder, the total information rate rapidly saturated, with 79% of the maximal value obtained from a local cluster of just four neurons of different functional types. The decoding filter applied to a given neuron's spikes within such a multiunit decoder differed substantially from the filter applied to that same neuron in a single-unit decoder. This shows that the optimal interpretation of a ganglion cell's action potential depends strongly on the simultaneous activity of other nearby cells. The quality of the stimulus reconstruction varied greatly with frequency: flicker components below 1 Hz and above 10 Hz were reconstructed poorly, and the performance was optimal near 2.5 Hz. Further analysis suggests that temporal encoding by ganglion cell spike trains is limited by slow phototransduction in the cone photoreceptors and a corrupting noise source proximal to the cones.

Action Potentials↗
PubMed1996

Isoprenylation of the G protein gamma subunit is both necessary and sufficient for beta gamma dimer-mediated stimulation of phospholipase C.

We have previously shown that isoprenylation and/or additional post-translational processing of the G protein gamma 1 subunit carboxyl terminus is required for beta 1 gamma 1 subunit stimulation of phospholipase C-beta 2 (PLC beta 2) [Dietrich, A., Meister, M., Brazil, D., Camps, M., & Gierschik, P. (1994) Eur. J. Biochem. 219, 171-178]. To examine whether isoprenylation of the gamma 1 subunit alone is sufficient for beta 1 gamma 1-mediated PLC beta 2 stimulation or whether any of the two subsequent modifications, proteolytic removal of the carboxyl-terminal tripeptide and/or carboxylmethylation, is required for this effect, nonisoprenylated recombinant beta 1 gamma 1 dimers were produced in baculovirus-infected insect cells, purified to near homogeneity, and then isoprenylated in vitro using purified recombinant protein farnesyltransferase. Analysis of the beta 1 gamma 1 dimer after in vitro farnesylation by reversed phase high-performance liquid chromatography followed by delayed extraction matrix-assisted laser desorption/ionization mass spectrometry confirmed that the gamma 1 subunit was carboxyl-terminally farnesylated but not proteolyzed and carboxylmethylated. Functional reconstitution of in vitro-farnesylated beta 1 gamma 1 dimers with a recombinant PLC beta 2 isozyme revealed that farnesylation rendered recombinant nonisoprenylated beta 1 gamma 1 dimers capable of stimulating PLC beta 2 and that the degree of this stimulation was only approximately 45% lower for in vitro-farnesylated beta 1 gamma 1 dimers than for fully modified native beta 1 gamma 1 purified from bovine retinal rod outer segments. Taken together, these results suggest that isoprenylation of the gamma subunit is both necessary and sufficient for beta gamma dimer-mediated stimulation of phospholipase C.

Alkyl and Aryl Transferases↗
PubMed1996

Cloning of the gene encoding the antibacterial peptide drosocin involved in Drosophila immunity. Expression studies during the immune response.

A potent inducible antibacterial peptide carrying an O-glycosylated substitution has recently been isolated from Drosophila [Bulet, P., Dimarcq, J. L., Hetru, C., Lagueux, M., Charlet, M., Hegy, G., Van Dorsselaer, A. and Hoffmann, J. A. (1993) J. Biol. Chem. 268, 14893-14897]. Here we report cloning studies that show that Drosophila contains a single, intronless gene, located at position 51C1-6, which encodes the precursor protein from which drosocin is processed. The upstream and the downstream sequences of the drosocin gene contain putative cis-regulatory elements similar to mammalian regulatory motifs, namely three kappa B-related decameric sequences. The drosocin gene is silent in naive animals, and is strongly induced with acute phase kinetics after immune challenge in larvae and in adults. We have established several transgenic fly lines in which reporter genes were placed under the control of various drosocin promoter sequences. Our results indicate that 2.5 kb of upstream sequences confer inducibility and tissue specificity to the transgene, but that the level of its expression in the fat body after immune challenge is low. Addition of genomic regions downstream of the drosocin transcribed sequences results in increased transcription levels, which are similar for the fusion and the resident drosocin genes upon infection. Analysis of transgenic fly lines showed that the drosocin reporter gene is constitutively expressed in the oviducts of egg-laying females.

Amino Acid Sequence↗
PubMed1996

Multineuronal codes in retinal signaling.

The visual world is presented to the brain through patterns of action potentials in the population of optic nerve fibers. Single-neuron recordings show that each retinal ganglion cell has a spatially restricted receptive field, a limited integration time, and a characteristic spectral sensitivity. Collectively, these response properties define the visual message conveyed by that neuron's action potentials. Since the size of the optic nerve is strictly constrained, one expects the retina to generate a highly efficient representation of the visual scene. By contrast, the receptive fields of nearby ganglion cells often overlap, suggesting great redundancy among the retinal output signals. Recent multineuron recordings may help resolve this paradox. They reveal concerted firing patterns among ganglion cells, in which small groups of nearby neurons fire synchronously with delays of only a few milliseconds. As there are many more such firing patterns than ganglion cells, such a distributed code might allow the retina to compress a large number of distinct visual messages into a small number of optic nerve fibers. This paper will review the evidence for a distributed coding scheme in the retinal output. The performance limits of such codes are analyzed with simple examples, illustrating that they allow a powerful trade-off between spatial and temporal resolution.

Action Potentials↗
PubMed1996

Ecdysone and insect immunity: the maturation of the inducibility of the diptericin gene in Drosophila larvae.

The developmental analysis of the inducibility of the Drosophila diptericin gene promoter as a response to septic injury shows an important increase in the response during the third larval instar leading to a maximum in late larvae and early prepupae. This increase, or maturation, is temporally correlated with known ecdysone induced events of the salivary gland and we now present evidence, using wild type and mutant larvae, that it does indeed depend upon ecdysone. The response remains minimal in larvae carrying either the temperature sensitive ecdysone deficient late larval lethal allele ecd1, or l(1)t187, a deep orange allele known to be deficient in the ecdysone response. However, experiments with the late larval lethal Broad-Complex mutant l(1)t435 show that the regulation of this response is distinct from the developmental ecdysone regulated hierarchies.

Animals↗