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S B Kater

Publications and source records attributed to S B Kater.

At least 37 records · Page 2Linked to original sources
PubMed1996

Functional compartmentalization of the neuronal growth cone: determining calcium's place in signaling cascades.

The growth cone is generally regarded as the basic unit of neuronal organization concerned with development of connections within the nervous system. The discussion below illustrates that the growth cone itself can be subdivided into distinct units of organization. It is this functional compartmentalization which enables the growth cone to read the molecular terrain it traverses and to convert this information into precise motor events. Our discussion will focus on the flow of information from the environment to the growth cone. In particular, we will follow signaling events from their remote processing within filopodia to the biological equivalent of a central processing unit in the core of the growth cone.

Animals↗
PubMed1995

Developmental regulation of plasticity along neurite shafts.

Although it is becoming increasingly clear that structural dynamics on neurite shafts play important roles in establishing neuronal architecture, the underlying mechanisms are unknown. The present study investigates local induction of filopodia along the shafts of neurites, a process that, by analogy to the growth cone, can represent the first stage in the generation of a new neuronal process. We show that filopodia can be induced reliably along the neurite shaft in response to a localized electric field stimulus that evokes large local intracellular calcium increases. Neither induction of filopodia nor a local rise in intracellular calcium occurred in calcium-free medium. Although calcium induction of neurite filopodia is highly reliable, forming in response to more than 90% of attempts, it is developmental state-dependent, since neurite filopodia could not be induced in neurons previously defined as "stable state." We have found two distinct changes in stable state neurons that can decrease the ability to induce new neurites. The first is a reduced calcium response: Field stimulation produced large local rises (280 nM) in intracellular calcium in growing neurons, whereas the identical stimulus produced smaller changes (148 nM) in stable state neurons. Second, stable state neurons change so that even when the stimulus intensity was increased to elicit a calcium response that would have been sufficient to induce filopodia in growing neurites, neurite filopodia were still not induced. Thus, intracellular calcium plays a key role in structural changes along the shafts of neurites. Furthermore, developmental changes in both calcium homeostatic components and in calcium responsiveness (i.e., the sensitivity of cellular components that modulate neurite morphology) underlie shifts from plasticity to stability of neuronal architecture in this system.

Animals↗
PubMed1995

Evidence for glutamate-mediated activation of hippocampal neurons by glial calcium waves.

Communication from astrocytes to neurons has recently been reported by two laboratories, but different mechanisms were though to underlie glial calcium wave activation of associated neurons. Neuronal calcium elevation by glia observed in the present report is similar to that reported previously, where an increase in neuronal calcium was demonstrated in response to glial stimulation. In the present study hippocampal neurons plated on a confluent glial monolayer displayed a transient increase in intracellular calcium following a short delay after the passage of a wave of increased calcium in underlying glia. Activated cells displayed action potentials in response to glial waves and showed antineurofilament immunoreactivity. Finally, the N-methyl-D-aspartate glutamate receptor antagonist DL-2-amino-5-phosphonovaleric acid and the non-NMDA glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione significantly reduced the responsiveness of neurons to glial calcium waves. Our results indicate that hippocampal neurons growing on hippocampal or cortical astrocytes respond to glial calcium waves with elevations in calcium and increased electrical activity. Furthermore, we show that in most cases this communication appears to be mediated by ionotropic glutamate receptor channels.

Action Potentials↗
PubMed1995

Depolarization and laminin independently enable bFGF to promote neuronal survival through different second messenger pathways.

This study presents evidence that cellular responsiveness to the neurotrophic factor basic fibroblast growth factor (bFGF) can be achieved by at least two classes of agents using different initial second messenger pathways. Embryonic chick ciliary ganglion neurons plated on polyornithine normally undergo rapid cell death in culture and could not be rescued by addition of bFGF. Similarly, neither exposure to laminin alone nor low levels of depolarization alone was sufficient to promote neuronal survival. In contrast, if ciliary ganglion neurons were exposed to bFGF in the presence of either laminin or low levels of depolarization, nearly all neurons were rescued from cell death. The observed synergistic effect of bFGF and low levels of depolarization required influx of calcium since addition of the L-type calcium channel antagonists PN200-110 completely prevented neuronal survival. The synergistic effect observed between laminin and bFGF was independent of changes in intracellular calcium since PN200-110 failed to block the synergistic effect and because neither addition of bFGF to neurons plated on laminin nor direct addition of laminin caused any significant changes in intracellular calcium. The ability of laminin to enable bFGF to promote neuronal survival could completely be blocked by the addition of antibodies to beta 1-integrin, suggesting a calcium-independent integrin-mediated response. Taken together, these results suggest that both laminin and depolarization can enable bFGF responsiveness by acting through different second messenger pathways.

Animals↗
PubMed1995

Laminin and fibronectin guideposts signal sustained but opposite effects to passing growth cones.

Guidepost cells are known to alter the behavior of growth cones in vivo, yet the nature of communication and the type of signals employed are largely undefined. The present study demonstrates that model guideposts, composed of a single molecular species, are sufficient to change the navigation and the behavior of advancing growth cones well beyond the time of contact. Laminin on model guideposts caused a sustained increase in growth cone velocity, whereas fibronectin led to a sustained decrease. A spatially discrete array of multiple laminin-model guideposts maintained increased growth rates on fibronectin, as expected for homogeneous laminin, and also provided unambiguous directional guidance information. Laminin-evoked growth cone responses required activation of protein kinase C-dependent intracellular signalling mechanisms.

Animals↗
PubMed1995

The sensory-motor role of growth cone filopodia.

Neuronal growth cones, the motile tips of elongating axons and dendrites, respond very precisely to cues encountered during pathfinding. During the past year, our knowledge about their sensory function, their integrative properties, and their motor function has advanced significantly. In particular, growth cone filopodia are currently being recognized for their prominent roles as sensors, transducers, and autonomous motor structures important for growth cone steering.

Animals↗
PubMed1994

Calpain inhibitors block Ca(2+)-induced suppression of neurite outgrowth in isolated hippocampal pyramidal neurons.

Ca2+ is an important regulator of neurite elongation and growth cone movements but the mechanism(s) mediating these Ca(2+)-dependent effects is unclear. Since cytoskeletal proteins are rapidly degraded by Ca(2+)-dependent proteinases (calpains) in vitro and in vivo, we investigated whether Ca(2+)-induced pruning or regression of neuronal processes is mediated by calpains. Isolated hippocampal pyramidal-like neurons were cultured and the ability of the membrane-permeable calpain inhibitors ethyl(+)-(2S,3S)-3-[(S)-methyl-1-(3-methylbutylcarbamoyl)-butyl carbamoyl]-2 - oxiranecarboxylate (EST) and carbobenzoxyl-valyl-phenylalanyl-H (MDL 28170) to block the Ca2+ ionophore A23187-induced suppression in neurite outgrowth was investigated. Addition of 100 nM A23187 to the culture medium resulted in a retraction of dendrites without altering axonal elongation. The addition of 300 nM A23187 to the culture medium resulted in a significant decrease in the rate of axonal elongation as well as a retraction of dendritic processes. Administration of EST (5 or 20 microM) to the culture medium completely blocked the pruning effect of 100 nM A23187 on dendrites and of 300 nM A23187 on axons, while EST alone did not significantly affect neurite outgrowth rate. MDL 28170 (20 microM) showed the same effect as EST in preventing ionophore-induced pruning of dendrites and axons at 100 and 300 nM concentrations, respectively, of A23187. EST (20 microM) did not block the A23187-induced rise of [Ca2+]i as measured with fura-2. These results suggest that calpains play a role in Ca(2+)-induced pruning of neurites in isolated hippocampal pyramidal neurons.

Animals↗
PubMed1994

CNS white matter can be altered to support neuronal outgrowth.

Previous work has demonstrated that white matter in the adult mammalian CNS inhibits cell adhesion and neurite outgrowth. This phenomenon has been investigated most recently by culturing neurons on cryostat sections of the adult CNS. Employing this same technique, we have found, in accord with others, that neurons seldom adhere to or grow on central nervous system white matter but will attach and grow on gray matter. In the experiments presented here, embryonic rat hippocampal neurons were grown on cryostat sections from the adult rat CNS, in the presence of brain derived glial cocultures. It was found that the white matter in cryostat sections can be modified by interaction with medium conditioned by brain-derived glial cells. Neurons plated on sections pretreated by such media show significant increases in both attachment and neurite outgrowth. The activity contained in glial conditioned medium is likely complex in nature. While the majority of the activity can be eliminated by heat treatment and trypsinization, neural adhesion but not neurite initiation is affected by protease treatment. Therefore, cell attachment and neurite outgrowth may be regulated by different factors in the conditioned media.

Animals↗
PubMed1994

Chondroitin sulfate proteoglycan elevates cytoplasmic calcium in DRG neurons.

Proteoglycans have been implicated in neuronal path-finding during development, yet related second messenger and signaling systems are unknown. We have used the calcium indicator fura-2/AM to monitor cytoplasmic calcium ion concentration ([Ca2+]i) in chick dorsal root ganglion (DRG) neuronal growth cones elongating on laminin during contact with chondroitin sulfate proteoglycan (CSPG): (1) to determine whether there is a change in [Ca2+]i in neurons that contact CSPG, and (2) to determine whether changes in [Ca2+]i are necessary for inhibition of growth cone migration. The majority of DRG neurons responded to CSPG contact with a transient rise in [Ca2+]i (mean delta[Ca2+]i above resting level was 554 +/- 109 nM; P < 0.0001). The effect of CSPG contact was concentration dependent and required the carbohydrate moiety of CSPG. Addition of soluble CSPG did not elevate [Ca2+]i. Treatment with reagents that blocked plasma membrane calcium channels, or that perturbed intracellular Ca2+ stores, indicated that extracellular Ca2+ was the major source of the [Ca2+]i elevation, and that Ca2+ entry occurred through non-voltage-gated calcium channels. Although general Ca2+ channel blockers abolished the CSPG-induced [Ca2+]i rise, they did not abolish growth cone avoidance of surface-bound CSPG in these assays. We conclude: (1) that DRG neurons elevate [Ca2+]i in response to CSPG contact to levels that can modify cytoskeletal mechanisms of growth cone migration, and (2) that avoidance of substratum-bound CSPG may not be dependent upon elevated [Ca2+]i.

Animals↗
PubMed1994

The unique and shared properties of neuronal growth cones that enable navigation and specific pathfinding.

The neuronal growth cone has as one of its primary functions the role of guiding the elongating neurite to its appropriate target. The events during pathfinding require that the neuronal growth cone responds to particular molecules in the environment by making appropriate changes in the behavior of the growth cone. This paper discusses the role of intracellular calcium as a signalling system mediating these responses. The specific roles of the growth cone filopodia in acting as antennae in advance of the motile growth cone are discussed in the context of calcium mediated pathfinding events.

Animals↗
PubMed1994

Self-recognition: a constraint on the formation of electrical coupling in neurons.

Electrical coupling between specific neurons is important for proper function of many neuronal circuits. Identified cultured neurons from the snail Helisoma show a strong correlation between electrical coupling and presence of gap junction plaques in freeze-fracture replicas. Gap junction plaques, however, were never seen between overlapping neurites from a single neuron, even though those same neurites formed gap junctions with neurites from another essentially identical identified neuron. This observation suggests that a form of self-recognition inhibits reflexive gap junction formation between sibling neurites. When one or both of those growth cones had been physically isolated from the neuronal cell body, both electrical coupling and gap junction plaques, between growth cones from the same neuron, were observed to form rapidly (within 30 min). Thus, inhibition of electrical coupling between sibling neurites apparently depends on cytoplasmic continuity between neurites, and not the molecular composition of neurite membrane. The formation of gap junctions is not likely due to the isolation process; rather, the physical isolation appears to release an inhibition of reflexive gap junction formation. These data demonstrate the existence of a previously unknown constraint on the formation of electrical synapses.

Animals↗
PubMed1994

Calcium wave fronts that cross gap junctions may signal neuronal death during development.

Embryonic anterior pagoda (AP) neurons in the leech interact with their segmental homologs in adjacent ganglia through transient axons that overlap during a critical period of development and then retract. However, when an AP neuron is ablated mechanically or by irradiation during this period, an adjacent homolog responds by reinitiating growth of its overlapped axon and thereby taking over vacated territory (Gao and Macagno, 1987b; Gao, 1989). The death of an AP cell is therefore communicated to its homolog, but the mechanism underlying this signaling is presently unknown. Since it was recently found that AP homologs are electrically and dye coupled through their transient axons (Wolszon et al., 1994), we investigated the possibility that gap junctions may mediate the cell death signal that could occur between developing neurons. Among several candidate intercellular signals, we began by studying calcium dynamics in embryonic AP cells, in situ, since calcium is known to cross gap junctions and is implicated in cell death in many systems. We found that elements that usually increase [Ca2+]i in adult neurons, such as releasable internal stores or voltage-dependent calcium channels, were not present at the critical period. Instead, mechanisms that reduce free calcium, such as buffering and pumping, were the most robust. When a large, focal calcium rise was produced in an AP axon by making a lesion with a UV microbeam (leading to eventual death of these neurons), calcium did not rise quickly throughout the cell, but rather moved in a slow (0.05-0.25 micron/sec) wave front away from the lesion site, into other processes of the damaged cell. Furthermore, when a calcium wave front reached the growth cone of a transient axon, it crossed at the gap junctions into the coupled axon of the neighboring AP neuron, but went no further. Since it is known that an AP responds to a neighbor's death by reinitiating growth only in that axon that contacts the dying cell (Gao and Macagno, 1987b; Gao, 1989), these observations are consistent with calcium playing a role in the signaling of cell death to homologs that are coupled to a dying cell.

Animals↗
PubMed1993

A sensory role for neuronal growth cone filopodia.

The dynamic nature of neuronal growth cone filopodia led to the suggestion that the primary function of filopodia is to sample their immediate environment, responding to and transducing environmental signals that affect growth cone behaviour and shape. Filopodia seem well suited to serve as antenna-like sensors, their broad span allows sampling of information over a greatly enhanced radius, and forward-projecting filopodia encounter potential cues in the molecular terrain long before the advancing growth cone itself. Filopodia in culture can serve structural roles, exert mechanical tension and selectively adhere to their surrounding. Whether or not filopodia have a general sensory role has not been tested directly, largely because of their small size, which limits an electrophysiological approach, and their integral relationship with the parent growth cone, which prevents resolution of their different functions. Here we use surgical procedures to isolate individual filopodia from their parent growth cone and, by monitoring their morphology and calcium second messenger systems, we show that neuronal growth cone filopodia contain signal transduction mechanisms that allow autonomous responses and the transmission of distant environmental information to their parent growth cone.

Acetylcholine↗
PubMed1993

Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones.

A myelin-associated protein from the central nervous system, the neurite growth inhibitor NI-35, inhibits regeneration of lesioned neuronal fiber tracts in vivo and growth of neurites in vitro. Growth cones of cultured rat dorsal root ganglion neurons arrested their growth and collapsed when exposed to liposomes containing NI-35. Before morphological changes, the concentration of free intracellular calcium ([Ca2+]i) showed a rapid and large increase in growth cones exposed to liposomes containing NI-35. Neither an increase in [Ca2+]i nor collapse of growth cones was detected in the presence of antibodies to NI-35. Dantrolene, an inhibitor of calcium release from caffeine-sensitive intracellular calcium stores, protected growth cones from collapse evoked by NI-35. Depletion of these caffeine-sensitive intracellular calcium stores prevented the increase in [Ca2+]i evoked by NI-35. The NI-35-evoked cascade of intracellular messengers that mediates collapse of growth cones includes the crucial step of calcium release from intracellular stores.

Animals↗
PubMed1993

Accommodation of mouse DRG growth cones to electrically induced collapse: kinetic analysis of calcium transients and set-point theory.

Electrical stimulation causes growth cones of mouse dorsal root ganglion neurons to collapse. During chronic stimulation, however, growth cones resume motility. In addition, these growth cones are now resistant to the collapsing effects of subsequent stimulation, a process we term accommodation. We compared the kinetics of electrically induced Ca2+ transients in naive and accommodated growth cones in order to determine whether the accommodation process results from a change in the Ca2+ transient, or a change in the Ca2+ sensitivity of the growth cones. Three kinetics were determined: (1) the initial increase to peak Ca2+ levels produced by 10 Hz stimulation; (2) recovery from peak Ca2+ levels during stimulus trains lasting 15 min; and (3) clearing of Ca2+ from growth cones after terminating the stimulus. These kinetics were analyzed using single exponential fits to changes in fura-2 fluorescence ratios. The electrically evoked increase in Ca2+ was significantly slower in accommodated growth cones (tau = 6.0 s) compared to naive growth cones (tau = 1.4 s). Despite the slower increase of [Ca2+]i in accommodated growth cones, peak [Ca2+]i was similar to that reached in naive growth cones, and the steady-state Ca2+ level was significantly elevated after chronic stimulation. Thus, accommodated growth cones maintained outgrowth at [Ca2+]i that caused collapse initially. Time course experiments show that accommodation is a slow process (t 1/2 = about 3 h). Accommodation did not induce measurable changes in the rates of Ca2+ homeostasis during or after stimulus trains. The kinetics of Ca2+ recovery during (tau = 90 s) and after 15 min of stimulation (tau = 8.5 s) was not significantly different in accommodated versus naive growth cones. Rates of 45Ca2+ efflux were also similar in both types of growth cones. These results suggest two regulatory processes contributing to growth cone motility during chronic stimulation: (1) recovery of [Ca2+]i to levels permissive to neurite outgrowth, and (2) an increase in the range of optimal [Ca2+]i for growth cone motility. These adaptive responses of mammalian growth cones to chronic stimulation could be involved in the modulation of CNS development by electrical activity of neurons.

Adaptation, Physiological↗