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C Levinthal

Publications and source records attributed to C Levinthal.

At least 37 records · Page 2Linked to original sources
PubMed1983

Inhibitory mechanism in zebrafish optic tectum: visual response properties of tectal cells altered by picrotoxin and bicuculline.

In previous work we described 4 types of visual response among tectal cells of the zebrafish. Cells of one class, type I, have no spontaneous activity, but respond phasically at ON and OFF. Their responses to moving edges, to stimuli that grow in size, and to stimuli equal in size and shape to the whole receptive field (RF) suggest that these cells may receive inhibitory input from near neighbor cells of the same type in the tectum, as well as excitatory input from retinal fibers. In order to further investigate this hypothesis we have studied the effects of drugs on physiological properties of type I cells recorded in the stratum periventriculare layer of the zebrafish tectum. Small (10-50 nl) injections of drugs were made in the tectum while recording 100-500 microns away with extracellular microelectrodes. Both picrotoxin and bicuculline produce the following effects: (1) onset of spontaneous bursting multiunit activity. This noise can be recorded at all depths within the tectum; (2) abolition of the second postsynaptic wave of the optic nerve shock field potential and the current source responsible for it, which occurs in the upper tectal layers at 8 ms latency. This probably represents the secondary activation of inhibitory synapses in those layers; (3) alteration of visual response properties of individual type I tectal cells. The duration of response to small flashing spots and to stimuli that grow in size both increase significantly. Responses to moving edges, which normally occur mostly as the significantly. Responses to moving edges, which normally occur mostly as the edge is crossing the RF border, become extended to encompass the entire RF. Finally, the cells show reduced negative spatial summation following drug injection. All of these effects are fully reversible with time after injection as the drugs wash out. Control injections (of teleost Ringer's solution, 100 mM HCl, 165 mM NaCl, and strychnine 2 mM or 5 mM) do not elicit any of these effects. The results reported here are consistent with the hypothesis that tectal type I cells receive a delayed inhibitory input, probably via GABA synapses, which determines major properties of the visual response.

Animals↗
PubMed1983

Structure-function relationships for a voltage-dependent ion channel: properties of COOH-terminal fragments of colicin E1.

The effects on planar lipid bilayer membranes of carboxyl-terminal fragments derived from the bacteriocin colicin E1 by either proteolysis or CNBr cleavage are indistinguishable from those of the voltage-dependent parent colicin molecule. An upper limit to the length of the COOH-terminal peptide required for channel formation is 152 amino acid residues from the COOH-terminal end, as indicated by the CNBr fragment. In addition, use of carboxypeptidase shows that the COOH-terminal end of the molecule remains on the side of the membrane to which it was added. COOH-terminal peptides of colicin E1 spontaneously associate with oil or hexane droplets in an aqueous system and remain at the interface between the two phases to a significantly greater degree than other colicin E1 fragments or cytochrome c. These results, together with the amino acid sequence, suggest a model wherein the colicin E1 channel is formed first by spontaneous attachment to a membrane of an alpha-helical hairpin centered at a 35-residue hydrophobic region near the COOH-terminal end. Application of a potential of the correct polarity then facilitates a major conformational change in the protein, allowing insertion of the remainder of the COOH-terminal end to form the open channel.

Colicins↗
PubMed1982

Visual cells of zebrafish optic tectum: mapping with small spots.

The zebrafish optic tectum is anatomically similar to those of goldfish and other teleosts, both in its laminar structure and the morphology of intrinsic neurons as studied with Golgi stains. We have applied standard electrophysiological techniques to study the visual properties of tectal cells, utilizing a computer system for stimulus control and data recording. All tectal cells have very large receptive fields, averaging 25-39 degrees in linear dimensions. Retinal receptive fields are smaller, averaging 7-13 degrees. In many cases the receptive fields of tectal cells, but never of retinal cells, consist of two parts (main field and accessory field) separated by tens of degrees. The two parts are differentially adapted by background illumination, accessory fields becoming unresponsive under lit conditions while main fields do not. This may reflect separate retinal input channels. Four types of tectal cells are described, which differ in their spontaneous activity in the dark and response to stationary spots. Type I are not spontaneously active in the dark, but respond phasically at response to ON and OFF. Type T are tonically active and give more prolonged phasic responses to ON and OFF. They may also have pure-inhibitory receptive fields in which spot ON suppresses the spontaneous firing with no phasic excitation. Type S are also silent in the dark, but give sustained firing as long as a spot is ON in the receptive field. Cells of type B fire spontaneously in bursts; the burst rate may be raised or lowered by stationary spots, but there is no phasic response. Each of the four physiological types is found to occur among the cells of the periventricular layer, all of which share a stereotyped overall morphology. Tectal cells do not exhibit spatially separated ON and OFF areas or orientation specificity.

Animals↗
PubMed1982

Visual response properties of zebrafish tectal cells.

The visual properties of zebrafish tectal cells have been studied with a variety of stimulation routines. These include illumination of the whole receptive field and of the surround, use of moving edges, very small spots, bars of varying orientations, moving spots with varying direction and speeds, growing discs, and pairs of spots whose presentation varies in position and sequence. A number of properties correlate with the classification scheme set forth in the preceding paper. Type B cells, unlike other types, are insensitive to moving stimuli. Experiments involving surround stimulation show that type S cells have inhibitory surrounds while those of type I do not. Type I cells, however, exhibit several properties which are consistent with an intratectal delayed inhibitory mechanism operating within the receptive field. These properties include the response to moving edges and growing stimuli, and the dependence of response duration on the size of a flashed stimulus. Various explanations of these properties are considered, and a specific model is proposed which states that cells of type I receive inhibitory input from neighbouring tectal cells of the same physiological type. The properties involved may be of direct importance in the visual behavior of the fish.

Animals↗
PubMed1982

Anomalous anatomy of identified neurons in the larval prawn: spontaneous and induced by microlesions.

The abdominal ganglia of the prawn Macrobrachium rosenbergii undergo developmental changes of fundamental interest between the time of hatching and metamorphosis. These changes include an increase in cell numbers and changes in the connectivity between identified neurons. The giant motoneurons involved in the escape response, which form a syncytium in the adult, are observed as separate neurons with crossed axons in early larvae. Anomalous growth and connections of identified neurons were studied in order to gain some understanding of the rules and mechanisms governing normal development. Spontaneous anomalies included: supernumerary axons and abnormal axonal trajectories. The plasticity and specificity of identified neurons were studied by following the anatomical effects of deletions of giant neurons. Microlesions were inflicted reproducibly by means of a focused beam of visible and ultraviolet light. Within a day, irradiated cell bodies are eliminated; complete disappearance of the axon takes about 10 days, indicating that the remarkable ability of some invertebrate neurons to survive without a soma is not present in the larval prawn. As a result of the removal of an axon, the most common effect found in central connections was the absence of the collaterals or axons deprived of their targets. No collateral sprouting was detected in the central nervous system. In about a third of the ganglia where a giant motoneuron was killed and structure was analyzed 2 or more weeks after irradiation, anomalous connections were found. They usually involved contacts between an interneuron deprived of its normal target and the contralateral motoneuron which remained intact. The restricted types of anomalies observed support the notion of a hierarchical order in the rules governing formation of central synapses, in which neuron type ranks higher than laterality.

Animals↗
PubMed1980

Growing optic nerve fibers follow neighbors during embryogenesis.

The embryonic development of the optic nerve of the zebrafish, Brachydanio rerio, was studied by three-dimensional computer reconstruction from serial section electron micrographs. Growing fibers from retinal ganglion cells had growth cones in contact with more mature fibers from adjacent cell bodies. In the observed growth pattern, the optic fibers immediately behind the eye were ordered in such a way that the rectangular coordinates of the fiber positions were approximately proportional to the polar coordinates of their cell body positions. We suggest that this transformation is achieved by a simple following mechanism that translates the time and position of ganglion cell differentiation into a well-defined spatial organization within the optic nerve.

Animals↗
PubMed1976

Conformational flexibility and protein folding: rigid structural fragments connected by flexible joints in subtilisin BPN.

Conformational energy calculations are used to analyze the interactions of structural substructures in subtilisin BPN. These substructures are kept fixed or "rigid" so that the only variables in the calculations are the backbone segments that separate them. The flexible segments are assumed to be free turns. Using this representation of the protein it is possible to predict both a likely order of events along a folding pathway and preferred modes of conformational changes of the native protein. Moreover, when the native structure has been perturbed by moving the substructures apart, it is possible to assess the range of interactions that return the protein, upon energy minimization, to its original conformation. These results suggest an approach to the folding problem based on the piecemeal formation of tertiary structure from smaller prefolded fragments.

Computers↗
PubMed1975

Hemoglobin interaction in sickle cell fibers. I: Theoretical approaches to the molecular contacts.

Computerized molecular model building has been used to deduce the arrangement of sickle cell hemoglobin molecules (Hb-S) in the tubular fibers which form within sickling cells and in concentrated cell-free solutions of deoxygenated Hb-S. A "best" solution has been found which satisfies all of the reported properties of these fibers. In the proposed arrangement the contact between adjacent Hb-S molecules in the direction parallel to the fiber axis is primarily hydrophobic and in addition contains two salt bridges between the molecules. This contact would be disrupted with the Glu of Hb-A at the beta6 position instead of the Val of Hb-S, and it would not make a long fiber with oxygenated Hb-S. Residues in the A helix and the GH corner of the beta2 chain of one molecule are in contact with residues of the A, B, and E helices and the GH corner of the alpha1 chain of its neighbor. The intermolecular contact in the direction perpendicular to the fiber axis is mainly between the end of the E helix and the EF corner of the beta1 chain on the first molecule and the F helix and FG corner of the alpha2 chain of its neighbor. Some of the implications of these contacts are reported here, and others will be presented in subsequent papers.

Binding Sites↗
PubMed1974

Structure and development of neuronal connections in isogenic organisms: transient gap junctions between growing optic axons and lamina neuroblasts.

We previously showed that the growth of each bundle of eight optic fibers from one ommatidium into the optic lamina of Daphnia occurs in such a way that one of the eight fibers precedes the others into the lamina. The growth cone of this lead fiber makes surface contact with undifferentiated neuroblasts near the midplane. This is followed by a glial-like wrapping of each neuroblast around the fiber. In this report, gap junctions are shown to form for a short period of time between the growing lead fiber and the neuroblast that is wrapping around it. It is proposed that these junctions may represent a morphological correlate of informational exchange between axon and neuroblast. This signaling would then reflect the fact that the sequence of axon proliferation by the lamina neuroblasts within an optic cartrdige, ultimately composed of five lamina neurons and eight optic fibers, parallels the order in which the neuroblasts undergo the wrapping reaction with the lead fiber.

Animals↗
PubMed1973

Structure and development of neuronal connections in isogenic organisms: variations and similarities in the optic system of Daphnia magna.

It is readily apparent upon examination and comparison of organisms of the same and related species that to a large extent genes control morphological features. One means to ascertain the role and degree of genetic control is to study in detail the anatomy and development of a particular structure, say an identifiable neuron, in a population with a fixed genome, and at different stages of morphogenesis. The small crustacean, Daphnia, is well suited for this type of study, since it reproduces parthenogenically, its development is easily staged, and its nervous system is reasonably simple. In this paper comparisons of detailed morphology of neurons in the visual system of adult Daphnia magna are considered. Results indicate that gross features of the system are reproduced within the clone, but some of the finer details are not reproduced.

Animals↗
PubMed1973

Structure and development of neuronal connections in isogenic organisms: cellular interactions in the development of the optic lamina of Daphnia.

Some details of the growth and initial cellular interactions of optic nerve axons were examined in a parthenogenetic clone of Daphnia magna. Results are summarized as follows: (i) the final structure of the optic lamina is dependent upon interactions between growing optic nerve fibers and optic lamina neuroblasts closest to the midplane of the animal, which trigger the morphological differentiation of the neuroblasts; the specificity of connections is achieved by well-defined sequences of cell migration in the ganglion; (ii) only one of the eight optic nerve axons growing back from each ommatidium in the eye possesses a structure similar to the growth cones seen on termini of nerve fibers growing in vitro; and (iii) undifferentiated neuroblasts in the ganglion react to surface contact by this "lead axon" by enveloping the axon in a glial-like relationship.

Axons↗