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Changes in neuronal structure can contribute to the plasticity of neuronal connections in the developing and mature nervous system. However, the expectation that they would occur slowly precluded many from considering structural changes as a mechanism underlying synaptic plasticity that occurs over a period of minutes to hours. We took time‐lapse confocal images of retinotectal axon arbors to determine the timecourse, magnitude, and distribution of changes in axon arbor structure within living Xenopus tadpoles. Images of axons were collected at intervals of 3 min, 30 min, and 2 h over total observation periods up to 8 h. Branch additions and retractions in arbors imaged at 3‐ or 30‐min intervals were confined to shorter branches. Sites of additions and retractions were distributed throughout the arbor. The average lifetime of branches was about 10 min. Branches of up to 10 μm could be added to the arbor within a single 3‐min observation interval. Observations of arbors at 3‐min intervals showed rapid changes in the structure of branchtips, including transitions from lamellar growth cones to more streamlined tips, growth cone collapse, and re‐extension. Simple branchtips were motile and appeared capable of exploratory behavior when viewed in time‐lapse movies. In arbors imaged at 2‐h intervals over a total of 8 h, morphological changes included longer branches, tens of microns in length. An average of 50% of the total branch length in the arbor was remodeled within 8 h. The data indicate that the elaboration of the arbor occurs by the random addition of branches throughout the arbor, followed by the selective stabilization of a small fraction of the new branches and the retraction of the majority of branches. Stabilized branches can then elongate and support the addition of more branches. These data show that structural changes in presynaptic axons can occur very rapidly even in complex arbors and can therefore play a role in forms of neuronal plasticity that operate on a timescale of minutes. © 1996 John Wiley & Sons, Inc.

The developing brain is particularly susceptible to lead toxicity; however, the cellular effects of lead on neuronal development are not well understood. The effect of exposure to nanomolar concentrations of lead on several parameters of the developing retinotectal system of frog tadpoles was tested. Lead severely reduced the area and branchtip number of retinal ganglion cell axon arborizations within the optic tectum at submicromolar concentrations. These effects of lead on neuronal growth are more dramatic and occur at lower exposure levels than previously reported.Lead exposure did not interfere with the development of retinotectal topography. The deficient neuronal growth does not appear to be secondary to impaired synaptic transmission, because concentrations of lead that stunted neuronal growth were lower than those required to block synaptic transmission. Subsequent treatment of lead-exposed animals with the chelating agent 2,3-dimercaptosuccinic acid completely reversed the effect of lead on neuronal growth. These studies indicate that impaired neuronal growth may be responsible in part for lead-induced cognitive deficits and that chelator treatment counteracts this effect.Children exposed to lead, even at concentrations that were once considered low, have learning disabilities and behavioral problems (1-3), including deficits in visual system function (4, 5). Two of the major questions regarding lead toxicity concern the limits of exposure that cause neurological damage in children and the reversibility of the damage following transient exposure to lead. The Centers for Disease Control (6) recently lowered the level of blood lead considered harmful to 10 ,ug per 100 ml of blood (0.48 MiM); however, the issue of a threshold level for lead neurotoxicity remains controversial (7,8).Calcium disodium-EDTA, a commonly used chelation agent, reportedly causes a redistribution of lead to the brain (9). This does not occur following treatment with 2,3-dimercaptosuccinic acid (DMSA; ref. 10), an orally active lead chelating agent, which recently received Food and Drug Administration approval. Although DMSA lowers body lead burden (11-13), its ability to ameliorate behavioral deficits in lead-exposed children has not been demonstrated. DMSA is currently the subject of a double blind clinical study to test its ability to reverse the effect of lead on cognitive function.We tested the effect of lead exposure in nanomolar concentrations on the following aspects of the development of the visual projection in frogs: neuronal growth, synaptic transmission, and the maintenance of topographic retinotectal projections. We also assessed the ability of the chelating agent DMSA to reverse the effect of lead exposure on neuronal growth and compared this to the effect of simply removing the lead source from the animal. MATERIALS AND METHODSElvax Preparation and Surgical Implantation. Elvax was prepared and implanted over the optic tectum of Rana pipiens tadpoles as described (14). Elvax40P (DuPont) was prepared with stock...

Serotonin (5HT) and the cholinergic analogue carbachol (CCh) act on neurons in the hippocampal CA1 area through pre- and post-synaptic receptors. Previously, it was shown that post-synaptic actions of 5HT and CCh are affected by corticosteroids: predominant activation of high affinity mineralocorticoid receptors resulted in small hyperpolarizing responses to 5HT and small depolarizing responses to CCh; additional activation of low affinity glucocorticoid receptors led to increased 5HT and CCh responses. In the present study, we examined the consequences of steroid modulation of these post-synaptic membrane effects and/or possible pre-synaptic effects by 5HT and CCh for the excitability in the CA1 area, using extracellular field potential or intracellular recordings from individual pyramidal neurons. Steroid treatment by itself did not affect the amplitude or paired pulse properties of synaptic responses. In slices from adrenally intact rats, both 5HT (3-30 microM) and CCh (1-10 microM) induced a dose-dependent suppression of the synaptic field responses evoked in the CA1 area by stimulation of the Schaffer collaterals. No changes in these transmitter effects were observed after adrenalectomy. The 5HT induced suppression of the population spike amplitude was, however, reduced after selective occupation of mineralocorticoid receptors. Intracellularly, no significant steroid dependent modulation of (pre-synaptic) 5HT evoked changes in synaptic responses was observed. These data suggest that the steroids modulate post-synaptic but not pre-synaptic 5HT effects and that this modulation is reflected in the excitability of the CA1 region. The CCh induced suppression of the population spike was not affected by corticosteroid receptor activation, indicating that the previously found steroid modulation of post-synaptic CCh effects has no clear consequences for the CA1 excitability.

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