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Y Dudai

Publications and source records attributed to Y Dudai.

17 recordsLinked to original sources
PubMed1992

A quantitative study of the Ca2+/calmodulin sensitivity of adenylyl cyclase in Aplysia, Drosophila, and rat.

Studies in Aplysia and Drosophila have suggested that Ca2+/calmodulin-sensitive adenylyl cyclase may act as a site of convergence for the cellular representations of the conditioned stimulus (Ca2+ influx) and unconditioned stimulus (facilitatory transmitter) during elementary associative learning. This hypothesis predicts that the rise in intracellular free Ca2+ concentration produced by spike activity during the conditioned stimulus will cause an increase in the activity of adenylyl cyclase. However, published values for the Ca2+ sensitivity of Ca2+/calmodulin-sensitive adenylyl cyclase in mammals and in Drosophila vary widely. The difficulty in evaluating whether adenylyl cyclase would be activated by physiological elevations in intracellular Ca2+ levels is in part a consequence of the use of Ca2+/EGTA buffers, which are prone to several types of errors. Using a procedure that minimizes these errors, we have quantified the Ca2+ sensitivity of adenylyl cyclase in membranes from Aplysia, Drosophila, and rat brain with purified species-specific calmodulins. In all three species, adenylyl cyclase was activated by an increase in free Ca2+ concentration in the range caused by spike activity. Ca2+ sensitivity was dependent on both calmodulin concentration and Mg2+ concentration. Mg2+ raised the threshold for adenylyl cyclase activation by Ca2+ but also acted synergistically with Ca2+ to activate maximally adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1991

Morphology of a sensory neuron in Drosophila is abnormal in memory mutants and changes during aging.

Several mutations in Drosophila impair learning and the cAMP cascade. We report here that the fine morphology of an identified mechanosensory neuron is abnormal in two of these mutants, dunce (dnc) and rutabaga (rut). The neuron innervating the antero-notopleural bristle was filled with horseradish peroxidase and studied at the light- and electron-microscopy level. In the mutants dnc and rut, this neuron has an abnormally large number of side branches and varicosities in a defined segment of the axon. In wild-type flies, age tends to decrease the number of side branches and variacosities in the same axonal segment that is affected by the mutations. Ultrastructural studies are compatible with the interpretation that the varicosities are potential synaptic sites. The results suggest that the cAMP cascade plays a role in shaping neuronal connectivity.

Aging↗
PubMed1979

Cholinergic binding sites in rat hippocampal formation: properties and ontogenesis.

The hippocampal formation of the rat contains two types of membrane-bound cholinergic binding sites, as revealed by specific binding of [3H]quinuclidinyl benzilate (QNB) or of a-[125I]bungarotoxin (a-Btx). The sites differ in pharmacological profile, sensitivity to detergents and ontogenesis. The major binding site (about 17 pmol per adult hippocampus) is of a muscarinic nature, and binds [3H]QNB with an on-rate of 2 x 10(6) M-1 sec-1 and an apparent KD of 0.4 nM. This binding is displaced by low concentrations of muscarinic ligands but not of nicotinic ligands. The earliest increase in binding level is detected at about day 4 postnatal and a sharp increase in total binding takes place between days 10 and 15. Total binding continues to increase gradually about 3-fold until an age of about 7 weeks, at a rate resembling that of acetylcholinesterase. a-Btx-binding sites (about 0.6 pmol per adult hippocampus) display a nicotinic profile with an on-rate constant for a-[125I]Btx of 6 x 10(4) M-1 sec-1 and an apparent KD of 2 nM. Ontogenesis of these sites clearly differs from that of muscarinic sites and acetylcholinesterase. Absolute binding reaches mature levels at an age of 12--14 days postnatal, and binding per tissue protein is higher during the first postnatal days than at maturity. It appears that the level of toxin-binding sites attains mature values before the major synaptogenetic events in the area are completed.

Age Factors↗
PubMed1978

Distribution of an alpha-bungarotoxin-binding cholinergic nicotinic receptor in rat brain.

Cholinergic nicotinic receptors in rat brain were demonstrated by the use of the potent nicotinic antagonist [125I]alpha-bungarotoxin [125I]alpha-Btx). Biochemical studies on binding of [125I]alpha-Btx to rat hippocampal homogenates revealed saturable binding sites which are protected by nicotine, D-tuborcurarine and acetylcholine but not by atropine or oxotremorine. The hippocampus and hypothalamus displayed relatively high [125I]alpha-Btx specific binding whereas the cerebellum was devoid of specific binding. Other regions displayed intermediate binding levels. Analysis of the regional distribution of [125I]alpha-Btx binding by autoradiography of frontal brain sections revealed high labeling in the hippocampus, hypothalamic supraoptic, suprachiasmatic and periventricular nuclei, ventral lateral geniculate and the mesencephalic dorsal tegmental nucleus. It is suggested that the limbic forebrain and midbrain structures as well as sensory nuclei are the main nicotinic cholinoceptive structures in the brain.

Animals↗
PubMed1978

Properties of an alpha-bungarotoxin-binding cholinergic nicotinic receptor from Drosophila melanogaster.

alpha-[125I]Bungarotoxin specifically binds to homogenates of Drosophila melanogaster head at levels of 0.3-0.8 pmol/mg protein. The dissociation constant calculated from rates of association and dissociation of toxin.receptor complex, is 0.6.10(-9) M. Ca2+, and to a lesser extent Na+, inhibit the reaction. alpha-[125I]Bungarotoxin binding is inhibited by low concentrations of unlabelled toxin, nicotinic ligands and eserine, but not by low concentrations of muscarinic ligands, decamethonium or an organophosphate. The receptor is membrane bound and can be partially released into 100 000 X g supernatant by combination of 1 M NaCl and 1% Triton X-100. Most of the activity in the supernatant sediments after further centrifugation at 200 000 X g for 2 h. Toxin binding sites are distinct from acetylcholinesterase molecules as revealed by pharmacological, biochemical and genetic techniques. The gene for the toxin-binding nicotinic receptor in Drosophila is apparently not located adjacent to the gene for acetylcholinesterase.

Acetylcholinesterase↗
PubMed1976

dunce, a mutant of Drosophila deficient in learning.

Normal Drosophilia learn to avoid an odorant associated with electric shock. An X-linked mutant, dunce, has been isolated that fails to display this learning in spite of being able to sense the odorant and electric shock and showing essentially normal behavior in other respects.

Animals↗