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Eric A Newman

Publications and source records attributed to Eric A Newman.

7 recordsLinked to original sources
PubMed2005

Calcium increases in retinal glial cells evoked by light-induced neuronal activity.

Electrical stimulation of neurons in brain slices evokes increases in cytoplasmic Ca(2+) in neighboring astrocytes. The present study tests whether similar neuron-to-glial signaling occurs in the isolated rat retina in response to light stimulation. Results demonstrate that Müller cells, the principal retinal glial cells, generate transient increases in Ca(2+) under constant illumination. A flickering light stimulus increases the occurrence of these Ca(2+) transients. Antidromic activation of ganglion cell axons also increases the generation of Müller cell Ca(2+) transients. The increases in Ca(2+) transients evoked by light and antidromic stimulation are blocked by the purinergic antagonist suramin and by TTX. The addition of adenosine greatly potentiates the response to light, with light ON evoking large Ca(2+) increases in Müller cells. Suramin, apyrase (an ATP-hydrolyzing enzyme), and TTX substantially reduce the adenosine-potentiated response. NMDA, metabotropic glutamate, GABA(B), and muscarinic receptor antagonists, in contrast, are mainly ineffective in blocking the response. Light-evoked Ca(2+) responses begin in Müller cell processes within the inner plexiform (synaptic) layer of the retina and then spread into cell endfeet at the inner retinal surface. These results represent the first demonstration that Ca(2+) increases in CNS glia can be evoked by a natural stimulus (light flashes). The results suggest that neuron-to-glia signaling in the retina is mediated by neuronal release of ATP, most likely from amacrine and/or ganglion cells, and that the response is augmented under pathological conditions when adenosine levels increase.

Action Potentials↗
PubMed2004

Glial modulation of synaptic transmission in the retina.

Glial modulation of synaptic transmission and neuronal excitability in the mammalian retina is mediated by several mechanisms. Stimulation of glial cells evokes Ca(2+) waves, which propagate through the network of retinal astrocytes and Müller cells and result in the modulation of the activity of neighboring ganglion cells. Light-evoked spiking is enhanced in some ganglion cells and depressed in others. A facilitation or depression of light-evoked excitatory postsynaptic currents is also seen in ganglion cells following glial stimulation. In addition, stimulation of glial cells evokes a sustained hyperpolarizing current in ganglion cells which is mediated by ATP release from Müller cells and activation of neuronal A(1) adenosine receptors. Recent studies reveal that light-evoked activity in retinal neurons results in an increase in the frequency of Ca(2+) transients in Müller cells. Thus, there is two-way communication between neurons and glial cells, suggesting that glia contribute to information processing in the retina.

Animals↗
PubMed2004

The Drosophila tctex-1 light chain is dispensable for essential cytoplasmic dynein functions but is required during spermatid differentiation.

Variations in subunit composition and modification have been proposed to regulate the multiple functions of cytoplasmic dynein. Here, we examine the role of the Drosophila ortholog of tctex-1, the 14-kDa dynein light chain. We show that the 14-kDa light chain is a bona fide component of Drosophila cytoplasmic dynein and use P element excision to generate flies that completely lack this dynein subunit. Remarkably, the null mutant is viable and the only observed defect is complete male sterility. During spermatid differentiation, the 14-kDa light chain is required for the localization of a nuclear "cap" of cytoplasmic dynein and for proper attachment between the sperm nucleus and flagellar basal body. Our results provide evidence that the function of the 14-kDa light chain in Drosophila is distinct from other dynein subunits and is not required for any essential functions in early development or in the adult organism.

Amino Acid Sequence↗
PubMed2003

D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors.

d-serine has been proposed as an endogenous modulator of N-methyl-d-aspartate (NMDA) receptors in many brain regions, but its presence and function in the vertebrate retina have not been characterized. We have detected d-serine and its synthesizing enzyme, serine racemase, in the retinas of several vertebrate species, including salamanders, rats, and mice and have localized both constituents to Müller cells and astrocytes, the two major glial cell types in the retina. Physiological studies in rats and salamanders demonstrated that, in retinal ganglion cells, d-serine can enhance excitatory currents elicited by the application of NMDA, as well as the NMDA receptor component of light-evoked synaptic responses. Application of d-amino acid oxidase, which degrades d-serine, reduced the magnitude of NMDA receptor-mediated currents, raising the possibility that endogenous d-serine serves as a ligand for setting the sensitivity of NMDA receptors under physiological conditions. These observations raise exciting new questions about the role of glial cells in regulating the excitability of neurons through release of d-serine.

Animals↗
PubMed2003

Glial cell inhibition of neurons by release of ATP.

ATP is released by neurons and functions as a neurotransmitter and modulator in the CNS. Here I show that ATP released from glial cells can also serve as a potent neuromodulator, inhibiting neurons in the retina of the rat. Activation of glial cells by focal ejection of ATP, ATPgammaS, dopamine, thrombin, or lysophosphatidic acid or by mechanical stimulation evoked hyperpolarizing responses and outward currents in a subset of retinal ganglion cells by increasing a Ba(2+)-sensitive K(+) conductance in the neurons. This glia-evoked inhibition reduced the firing rate of those neurons that displayed spontaneous spike activity. The inhibition was abolished by the A(1) adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (10 nm) and was reduced by the ecto-ATPase inhibitor ARL-67156 (6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP) (50 microm) and by the ectonucleotidase inhibitor AOPCP [adenosine-5'-O-(alpha,beta-methylene)-diphosphonate] (250 microm). Selective activation of retinal glial cells demonstrated that Müller cells, but not astrocytes, mediate the inhibition. ATP release from Müller cells into the inner plexiform layer of the retina was shown using the luciferin-luciferase chemiluminescence assay. These findings demonstrate that activated glial cells can inhibit neurons in the retina by the release of ATP, which is converted to adenosine by ectoenzymes and subsequently activates neuronal adenosine receptors. The results lend support to the hypothesis that glial cells play an active role in information processing in the CNS.

Action Potentials↗
PubMed2003

New roles for astrocytes: regulation of synaptic transmission.

Abstract Although glia often envelop synapses, they have traditionally been viewed as passive participants in synaptic function. Recent evidence has demonstrated, however, that there is a dynamic two-way communication between glia and neurons at the synapse. Neurotransmitters released from presynaptic neurons evoke Ca2+ concentration increases in adjacent glia. Activated glia, in turn, release transmitters, including glutamate and ATP. These gliotransmitters feed back onto the presynaptic terminal either to enhance or to depress further release of neurotransmitter. Transmitters released from glia can also directly stimulate postsynaptic neurons, producing either excitatory or inhibitory responses. Based on these new findings, glia should be considered an active partner at the synapse, dynamically regulating synaptic transmission.

Adenosine Triphosphate↗