Warren J. Scherer

Latency and temporal overlap of visually elicited contralateral and ipsilateral firing in Xenopus tectum during and after the critical period

The mechanisms underlying the development of proper topographic registration of binocular maps in the tectum of Xenopus laevis involve correlation of activity patterns of ipsilateral and contralateral inputs. Recent evidence implicates NMDA-type glutamate receptors in this process. In general, NMDA receptors are considered to function optimally when there are multiple, simultaneous excitatory inputs to a dendrite. In the binocular system of the frog, however, the ipsilateral eyes response to a visual stimulus reaches the tectum later than the contralateral eyes response. The reason for this delay is that the ipsilateral pathway to the tectum is indirect, involving a relay in the opposite tectum and nucleus isthmi. In this paper, we evaluate the duration of the delay between arrival of contralateral and ipsilateral input in response to cessation of light and we also gauge the extent of temporal overlap in responses of the two inputs. We find that the average delay is about 10 ms and that this delay is not significantly different during the critical period vs later in development. The temporal overlap is 40-60 ms in duration. We conclude that the intertectal delay does not prevent a substantial period of simultaneous firing of ipsilateral and contralateral inputs in response to sudden changes in illumination. Therefore, the firing patterns of these afferents are compatible with a mechanism of activity-dependent alignment of binocular maps in the tectum.

Physiological effects of chronic and acute application of N-methyl-d-aspartate and 5-amino-phosphonovaleric acid to the optic tectum of Rana pipiens frogs

Visually elicited activity contributes to the formation of orderly connections in the optic tectum of frogs. Glutamate receptors of the N-methyl-D-aspartate class participate in this process. Blocking those receptors interferes with activity-dependent refinement of maps in normal frogs and of ocular dominance bands in surgically produced animals with three eyes. Chronic application of N-methyl-D-aspartate sharpens the bands. The possibility that 5-amino-phosphonovaleric acid depresses tectal responsiveness was motivation for studying the effects of 5-amino-phosphonovaleric acid and N-methyl-D-aspartate applied both chronically and acutely. We evaluated tectal responsiveness to visual input by presenting flashes of light to one eye and recording responses in the ipsilateral tectal lobe. This method reveals the output of the tectal cells contralateral to the stimulated eye. These cells project via the nucleus isthmi to the opposite tectal lobe. We also mapped the receptive field dimensions of the crossed isthmotectal axons. Our results show that acute topical application of 500 microM or 1 mM N-methyl-D-aspartate dramatically increases spontaneous activity, while 100 microM N-methyl-D-aspartate causes little change. Chronic treatment with N-methyl-D-aspartate at a low dose (estimated to be in the micromolar range) shown to influence retinotectal mapping, reduces response latencies but produces no statistically significant changes in tectal cell firing rates or receptive field size. Acute application of 5-amino-phosphonovaleric acid produces complex results: 10 microM produces no changes in firing, 100 microM 5-amino-phosphonovaleric acid decreases firing, and doses of 500-100 microM increase the firing.(ABSTRACT TRUNCATED AT 250 WORDS)

Concanavalin A reduces habituation in the tectum of the frog

In the tectum of Rana pipiens, responses to repeated flashes of light to the ipsilateral eye display considerable habituation. We have employed the plant lectin concanavalin A (Con A), which can diminish desensitization of glutamate receptors in vitro, in order to examine whether desensitization of glutamate receptors contributes to this habituation. The ipsilateral eyes projection reaches each tectal lobe indirectly, being relayed from the opposite tectal lobe via the tecto-isthmo-tectal projection. One of the sites along this pathway at which habituation may take place is the retinotectal synapse, where glutamate is a putative transmitter. Pretreatment of one lobe of the tectum with Con A significantly diminished the habituation of responses recorded in the other tectal lobe to light offset, with less of an effect on responses to light onset. These data suggest that OFF habituation may reflect glutamate receptor desensitization at the retinotectal synapse. In contrast, recordings from retinotectal terminals indicate that a primary site of habituation of ON responses is within the retina.

Chronic effects of NMDA and APV on tectal output in Xenopus laevis

In the South African clawed-toed frog Xenopus laevis, visual experience plays a crucial role in the formation of matching binocular maps in the tectum. The ipsilateral eyes projection, relayed through the crossed isthmotectal projection, displays marked plasticity in response to altered visual input during a critical period of development. This plasticity and the events responsible for the end of the critical period are mediated by N-methyl-D-aspartate (NMDA) receptor function. We have previously reported that chronic blockade of tectal NMDA receptors with the NMDA antagonist 5-amino-phosphonovaleric acid (APV) prevents plasticity of the crossed isthmotectal projection during the critical period, while chronic treatment with NMDA restores this plasticity after the end of the critical period. These results raise the question of whether the effects on plasticity are due to changes in electrical responsiveness of the treated tissue. In this study, we have quantitatively assessed the actions of APV and NMDA on certain aspects of tectal cell activity in Xenopus during and after the critical period by recording the output of the nucleus isthmi cells that are activated by the tectum after three weeks of treatment. We have found that chronic APV treatment does not alter tectal output, as indicated by the firing of isthmotectal axons, during the critical period and that chronic NMDA treatment increases tectal output in postcritical period Xenopus. Tectal output does not differ between normal Xenopus during and after the end of the critical period.(ABSTRACT TRUNCATED AT 250 WORDS)

Xenopus exhibits seasonal variation in retinotectal latency but not tecto-isthmo-tectal latency

Summary1.The tectum of Xenopus receives visuotopic input from both eyes. The contralateral eyes projection reaches the tectum directly, via the optic nerve. The ipsilateral eyes projection reaches the tectum indirectly, via the nucleus isthmi and isthmotectal projection.2.Because of the multi-synaptic nature of the ipsilateral pathway, there is an inherent delay between the time that information from the contralateral eye reaches the tectum and the time that information from the ipsilateral eye arrives at the tectum. The length of the intertectal delay is a function of the latencies of the contralateral and ipsilateral pathways.3.The length of this intertectal delay has functional, as well as developmental, implications with regard to the role of N-methyl-D-aspartate receptors in tectal cell activity and development of orderly synaptic connections.4.We have found that the latencies of the contralateral and ipsilateral pathways exhibit a seasonal variation, increasing during the winter months. The increases of both latencies during the winter were of similar magnitude, indicating that there were no significant changes in intertectal delay. The seasonal alteration in contralateral latency was not affected by dark-rearing and was affected to only a minor extent by a week-long alteration of ambient temperature.

Differential intertectal delay between Rana pipiens and Xenopus laevis : Implications for species-specific visual plasticity

In the frog Xenopus laevis, the isthmotectal projection, which relays input from the ipsilateral eye, exhibits anatomical reorganization following surgical eye rotation performed during tadpole stages while the isthmotectal projection in the frog Rana pipiens fails to show reorganization. This plasticity has been shown to be dependent upon activation of the N-methyl-D-aspartate (NMDA) receptor located on tectal cell dendrites. The reorganization process in Xenopus is hypothesized to employ a Hebbian mechanism requiring correlated firing of ipsilateral and contralateral inputs to a given tectal cell; when an ipsilateral axon synapses onto a tectal cell that receives input from a contralateral axon with a matching receptive-field location, the correlation in activity triggers stabilization of the ipsilateral synapse. However, in neither Xenopus nor Rana do ipsilateral and contralateral inputs begin to fire simultaneously in response to a given visual stimulus; the ipsilateral input is delayed because it reaches the tectum indirectly, through a polysynaptic relay via the opposite tectum and nucleus isthmi. The objective of this experiment was to test whether there is a significant difference in this intertectal delay between Xenopus laevis and Rana pipiens in order to determine whether intertectal delay could be a contributing factor in this species-specific ability to exhibit visual plasticity. We have found that intertectal delay is 26.16 ms longer in Rana pipiens (36.53 ms) than in Xenopus laevis (10.37 ms).