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Biomedical subjects

J T Schmidt

Publications and source records attributed to J T Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of conditioning lesions on regeneration of goldfish optic axons: time course of the cell body reaction to axotomy.

The time course of the cell body reaction to axotomy was determined in goldfish retinal ganglion cells by measuring cell body size and the amount of labelled protein conveyed by fast axonal transport to the optic tectum, both of which increase during regeneration of the optic axons. Following a single testing lesion of the optic nerve, the regenerating axons began to innervate the tectum at about 14 days after the lesion and the cell body reaction began to decline 2-3 weeks thereafter. If the testing lesion had been preceded by a conditioning lesion 2 weeks earlier, the time for the regenerating axons to arrive in the tectum was reduced by a week, because of the faster rate of axonal outgrowth, but the interval between their arrival and the beginning of the decline of the cell body reaction was unchanged. Electrophysiological measurements showed that synaptic transmission was initiated earlier when the axons reached the tectum faster. These results indicate that the mechanisms initiating the recovery of cell body metabolism are independent of those governing the rate of axonal outgrowth. The recovery of the cell body may begin shortly after synapses are established, regardless of whether they are correctly or incorrectly targetted. The correctness of the target may be a separate factor in determining how rapidly and completely the cell body recovers.

Action Potentials↗
PubMed1990

Activity-driven sharpening of the regenerating retinotectal projection: effects of blocking or synchronizing activity on the morphology of individual regenerating arbors.

Both blocking activity with intraocular tetrodotoxin (TTX) and synchronizing activity with a xenon strobe light (1 Hz) prevent retinotopic sharpening of regenerating optic projection in goldfish (Meyer, 1983; Schmidt, 1985; Cook and Rankin, 1986). In this study, we tested, in both normal and regenerating projections, the effects of these two treatments on individual optic arbors. Arbors were stained via anterograde transport of HRP, drawn in camera lucida from tectal whole mounts, and analyzed for spatial extent in the plane of the retinotopic map, order of branching, number of branch endings, depth of termination, and the caliber of the parent axon. In normal tectum, fine, medium, and coarse caliber axons gave rise to small, medium, and large arbors, which averaged 127 microns, 211 microns and 275 microns in horizontal extent, and terminated at characteristic depths. All three classes averaged roughly 21 branch endings. Optic arbors that regenerated with normal patterns of activity returned to a roughly normal appearance by 6-11 weeks postcrush: the same three calibers of axons gave rise to the same three sizes of arbors at the same depths, but they were much less stratified and well on average about 16% larger in horizontal extent. At this time point, arbors regenerated under TTX or strobe were on the average 71 and 119% larger, respectively, than the control-regenerated arbors (larger in all classes), although they had approximately the same number of branch endings and were equally poorly stratified. Synapses formed under strobe were also normal in appearance. Thus the only significant effect of both strobe and TTX treatment was to enlarge the spatial extent of arbor branches. Arbors that were not regenerating were very slightly (but significantly) enlarged by TTX block of activity or strobe illumination. As previous staining showed that regenerating axons initially make widespread branches and later retract many of those branches (Schmidt, Turcotte, Buzzard, and Tieman, 1988; Stuermer, 1988), the present findings support the idea that blocking activity or synchronizing activity prevents retinotopic sharpening by interfering with the elimination of some of the errant branches.

Animals↗
PubMed1990

Long-term potentiation and activity-dependent retinotopic sharpening in the regenerating retinotectal projection of goldfish: common sensitive period and sensitivity to NMDA blockers.

The regenerating retinotectal projection in goldfish goes through an activity-driven refinement that appears to involve the elimination of inappropriate branches from early arbors. Retinotopically appropriate branches may be stabilized because the normally correlated firing of neighboring ganglion cells causes summation of their postsynaptic responses and increases their effectiveness by a Hebbian mechanism. In this study, I report that the regenerating projection has an increased capacity for long-term potentiation (LTP) that may be related to the activity-driven sharpening. In the normal projection, field potentials, reflecting currents from EPSPs elicited by optic nerve shock, are large (greater than 4 mV) and very stable. In newly regenerated projections, field potentials are initially small (less than 1 mV), but a train of 20 stimuli at 0.1 Hz results in a large (100-200%) increase in amplitude that is stable for at least 8 hr, and in 3 cases overnight. The capacity for potentiation is greatest from 20 to 40 d postcrush, the time just after arrival of the optic fibers, and during the period of retinotopic sharpening. A greater-than-normal capacity for potentiation persists for many months. Topical application of NMDA receptor blockers AP5 or AP7 at 25 microM prevents potentiation without decrementing ongoing responses. The closely related agent AP6, which is not an NMDA receptor blocker, does not prevent potentiation. In addition, infusion of the NMDA receptor blockers AP5 or AP7 into the tectal ventricle (4 microliters/d of 500 microM solution) for 2-3 weeks during regeneration prevented retinotopic sharpening, as assessed by electrophysiological mapping. At each tectal point, responsive areas in the visual field were enlarged to 28 degrees vs 11-12 degrees in control regenerates and normals. This was comparable to data from fish regenerating with activity blocked with intraocular tetrodotoxin or synchronized by stroboscopic illumination and indicates uncorrected errors in targeting of regenerated arbors (Schmidt, 1985). The results support the involvement of NMDA receptors in sharpening and suggest that the initial step in stabilizing appropriate branches may be a long-lasting increase in synaptic gain.

Animals↗
PubMed1988

Antibodies to ependymin block the sharpening of the regenerating retinotectal projection in goldfish.

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the tectum, then goes through an activity dependent refinement that appears to involve the elimination of inappropriate branches from early regenerated arbors. Retinotopically appropriate branches and synapses may be stabilized because the normally correlated firing of neighboring ganglion cells could cause summation of their postsynaptic responses, making them more effective. Thus, refinement of the map may be similar in several ways to associative learning. In this study, we therefore tested whether ependymin, a major protein component of the extracellular fluid that has been implicated in synaptic changes thought to be associated with learning a simple task in goldfish, may also be involved in refinement of the retinotopic map. Goldfish that had undergone unilateral optic nerve crush received intraventricular infusion of antiependymin IgG or of control IgG's beginning at 21 days postcrush. Tectal recordings from these fish at 39-56 days postcrush showed that the projection had failed to sharpen, much as in the fish with activity blocked or synchronized; the average size of the multiunit receptive fields was 31 degrees vs 11 degrees normally. The field potentials elicited from these tecta by optic nerve shock were not significantly smaller than in controls, suggesting normal levels of synaptogenesis. Control projections, identically treated but infused with either unrelated IgG or Ringer's alone regenerated normally, giving multiunit receptive fields of 12 degrees. Intact (non-regenerating) projections of the experimental fish were not rendered abnormal by the IgG treatment. Histology showed the retinas and tecta of the infused fish to be normal in appearance. The results show a specific block of sharpening by antiependymin IgG. The ependymal glia of the tectum stain positively for ependymin in normal fish, particularly the cell bodies in the ependymal layer. The tectum, particularly the ependymal layer, stains more intensely during regeneration, which appears to trigger increased synthesis of ependymins in the ependymal glia. This increase and the block of sharpening by specific antibodies to ependymin suggest a possible role for ependymin in activity dependent synaptic stabilization, possibly through its polymerization when calcium is focally depleted at active synapses.

Action Potentials↗
PubMed1988

Staining of regenerated optic arbors in goldfish tectum: progressive changes in immature arbors and a comparison of mature regenerated arbors with normal arbors.

Individual optic arbors, normal and regenerated, were stained via anterograde transport of HRP and viewed in tectal whole mounts. Camera lucida drawings were made of 119 normal optic arbors and of 242 regenerated arbors from fish 2 weeks to 14 months postcrush. These arbors were analyzed for axonal trajectory, spatial extent in the horizontal plane, degree of branching, number of branch endings, average depth, and degree of stratification. Normal optic arbors ranged in size from roughly 100 to 400 microns across in a continuous distribution, had an average of 20 branch endings with average of fifth-order branching, and were highly stratified into one of three planes within the major optic lamina (SO-SFGS). Small arbors arising from fine-caliber axons terminated in the most superficial plane of SO-SFGS; large arbors from coarse axons terminated in the superficial and middle planes; and medium arbors from medium-caliber axons terminated in the middle and deep planes of SO-SFGS, as well as deeper in the central gray and deep white layers. Arbors from central tectum tended to be much more tightly stratified than those in the periphery. No other differences between central and peripheral arbors were noted. Mature regenerated arbors (five months or more postcrush) were normal in their number of branch endings, order of branching, and depth of termination. Their branches covered a wider area of tectum, partially because of their early branching and abnormal trajectories of branches. Axonal trajectories were often abnormal with U-turns and tortuos paths. Fine-, medium-, and coarse-caliber axons were again present and gave rise to small, medium, and large arbors at roughly the same depths as in the normals. There was frequently a lack of stratification in the medium and large arbors, which spanned much greater depths than normal. Overall, however, regenerates reestablished nearly normal morphology except for axonal trajectory and stratification. Early in regeneration, the arbors went through a series of changes. At 2 weeks postcrush, regenerated axons had grown branches over a wider-than-normal extent of tectum, though they were sparsely branched and often tipped with growth cones. At 3 weeks, the branches were more numerous and covered a still wider extent (average of five times normal), many covering more than half the tectal length or width. At 4-5 weeks smaller arbors predominated, although a few enlarged arbors were present for up to 8 weeks. Additional small changes occurred beyond 8 weeks as the arbors became progressively more normal in appearance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Activity sharpens the regenerating retinotectal projection in goldfish: sensitive period for strobe illumination and lack of effect on synaptogenesis and on ganglion cell receptive field properties.

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the contralateral tectum and then sharpens it. Disruption of visual activity, either by blocking activity with intraocular tetrodotoxin (TTX; Schmidt and Edwards, 1983) or by synchronizing activity with strobe illumination (Schmidt and Eisele, 1985), disrupts the sharpening process: the map is correctly oriented but the multiunit receptive fields at each point average 25-40 degrees in diameter. In order to test whether strobe and TTX interfere with the same mechanism, we have tested whether their sensitive periods are the same, and whether strobe, like TTX treatment, does not affect either ganglion cell receptive field properties or synaptogenesis. In parallel studies, we exposed fish to 2 weeks of either strobe illumination or intraocular TTX beginning at various times after crush and determined via electrophysiological recordings that the periods of sensitivity were nearly identical. There was no effect of either treatment during the first 2 weeks (before the fibers arrive at the tectum), maximal disruption of sharpening between 14 and 50 days (the period of rapid synaptogenesis), decreasing disruption between 50 and 125 days, and no effect beyond that point or in the normal projection. In addition, long strobe exposures of up to 142 days produced no greater disruptions than shorter 2-3-week exposures, indicating no cumulative effect. The reestablishment of synaptic transmission in tectum, assayed by recording field potentials elicited by optic nerve shock, was not affected by stroboscopic illumination. Finally, individual ganglion cells, recorded intraretinally following long-term strobe exposure, had receptive fields that were normal both in size and in their characteristic responses to light-on, to light-off, or to both on and off. These findings support the hypothesis that strobe-like TTX prevents retinotopic refinement by preventing the correction of errors initially made by the ingrowing optic axons (Schmidt et al., 1988).

Animals↗
PubMed1987

Activity-dependent sharpening of the regenerating retinotectal projection in goldfish: relationship to the expression of growth-associated proteins.

During regeneration of the optic nerve in goldfish, manipulations that disrupt the transmission of patterned visual information, if applied within the so-called 'sensitive period', lead to the formation of a diffuse retinotopic map (Schmidt, Cell. Mol. Neurobiol., 5 (1985) 65). The present study examined: (a) whether the sensitive period (14-50 days postcrush) coincides with the period in which specific 'growth-associated proteins' are present in the regenerating optic nerve terminals; and (b) whether manipulations that alter physiological activity during the sensitive period influence the expression of these proteins. Following bilateral optic nerve crush, goldfish regenerated their optic nerves either under normal illumination conditions (control), in total darkness, or with physiological activity suppressed in the nerve by intraocular injections of tetrodotoxin (TTX). At various times postcrush, proteins conveyed from the retina to the developing nerve endings were visualized by labeling the eye with [35S]methionine and then analyzing, by 2-dimensional gel electrophoresis and fluorography, radiolabeled proteins present in the optic tectum 15 h later. Rapidly-transported proteins that underwent large, specific increases during regeneration included the previously described 48 kDa growth-associated protein (GAP-48); labeling of GAP-48 was maximal during axonal outgrowth and then declined, but still remained well above background levels throughout the 'sensitive period'. Another group of rapidly-transported proteins, mol. wt. = 110-140 kDa (HMW), followed a similar time course, while levels of a 28 kDa protein peaked at 2 weeks and then declined rapidly. Thus, activity-dependent 'sharpening' processes occur during a period in which the levels of GAP-48 and HMW remain elevated in the nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A computer-assisted video technique for preparing high resolution pictures and stereograms from thick specimens.

A computer-assisted video technique is presented for rapidly and accurately gathering, storing and depicting three-dimensional anatomical structures in thick specimens. Several optical sections through the specimen are combined to produce high-resolution photographs with essentially infinite depth-of-field. Further, the depth information implicit in the series of optical sections makes the creation of stereoscopic pairs relatively simple. The technique employs a real-time digitizing frame store and a computer. A video camera is attached to a microscope and successive optical sections are stored digitally as the plane of focus is systematically changed. After storage, the image of each optical section is enhanced to emphasize elements that are sharply focussed. The final two-dimensional image is generated by selecting for each point in the final picture the darkest grey value occurring at the corresponding point in any of the pictures in the through-focus series. A picture with essentially infinite depth-of-field is produced when points of correspondence in the series are determined by a ray passing normal to the plane of optical section. Right and left pictures for a stereoscopic pair are produced when points of correspondence are determined by a ray slanting either left or right of normal. This technique is illustrated with cobalt chloride-filled neurons from whole-mounted cricket ganglia, with HRP-filled axons from whole-mounted goldfish tectum, with Golgi-Kopsch-impregnated neurons from cat visual cortex, and with sections of cobalt chloride-filled antennal afferents in cricket.

Algorithms↗
PubMed1985

Eye-specific segregation of optic afferents in mammals, fish, and frogs: the role of activity.

Eye-specific patches or stripes normally develop in the visual cortex and superior colliculus of many (but not all) mammals and are also formed, after surgically produced binocular innervation, in the optic tectum of fish and frogs. The segregation of ocular dominance patches or columns has been studied using a variety of anatomical pathway-tracing techniques, by electrophysiological recording of postsynaptic units or field potentials, and by the 2-deoxyglucose method following visual stimulation of only one eye. In the tectum of both fish and frogs and in the cortex and colliculus of mammals, eye-specific patches develop from initially diffuse, overlapping projections. Of the various mechanisms that might cause such segregation, the evidence favors an activity-dependent process that stabilizes synapses from the same eye because of their correlated activity. First, several environmental manipulations affect the segregation of afferents in visual cortex: strabismus and alternate monocular exposure apparently enhance segregation, whereas dark rearing slows the segregation process, and monocular deprivation causes the experienced eye to form larger patches at the expense of those of the deprived eye. Second, blocking activity in both eyes is effective in preventing the segregation both in the tectum of fish and frog and in the visual cortex of cat. With the eyes blocked, alternate stimulation of the optic nerves permits the segregation of ocular dominance, at least onto single cells in the cat visual cortex. These findings are discussed in terms of an activity-dependent stabilization of those synapses having correlated activity (those from neighboring ganglion cells within one eye) but not of those lacking correlated activity (those from left and right eyes). We suggest that the eye-specific patches represent a compromise between total segregation of the projections from the two eyes and the formation of a single continuous retinotopic map across the surface of the cortex or tectum.

Animals↗
PubMed1985

Formation of retinotopic connections: selective stabilization by an activity-dependent mechanism.

During regeneration of the optic nerve in goldfish, the ingrowing retinal fibers successfully seek out their correct places in the overall retinotopic projection on the tectum. Chemospecific cell-surface interactions appear to be sufficient to organize only a crude retinotopic map on the tectum during regeneration. Precise retinotopic ordering appears to be achieved via an activity-dependent stabilization of appropriate synapses and is based upon the correlated activity of neighboring ganglion cells of the same receptive-field type in the retina. Four treatments have been found to block the sharpening process: (a) blocking the activity of the ganglion cells with intraocular tetrodotoxin (TTX), (b) rearing in total darkness, (c) correlating the activation of all ganglion cells via stroboscopic illumination and (d) blocking retinotectal synaptic transmission with alpha-bungarotoxin (alphaBTX). These experiments support a role for correlated visually driven activity in sharpening the diffuse projection and suggest that this correlated activity interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials (EPSPs). Other experiments support the concept that effective synapses are stabilized: a local postsynaptic block of transmission causes a local disruption in the retinotectal map. The changes that occur during this disruption suggest that each arbor can move to maximize its synaptic efficacy. In development, initial retinotectal projections are often diffuse and may undergo a similar activity-dependent sharpening. Indirect retinotectal maps, as well as auditory maps, appear to be brought into register with the direct retinotopic projections by promoting the convergence of contacts with correlated activity. A similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive-field types in the lateral geniculate nucleus. Activity-dependent synaptic stabilization may therefore be a general mechanism whereby the diffuse projections of early development are brought to the precise, mature level of organization.

Animals↗
PubMed1985

Stroboscopic illumination and dark rearing block the sharpening of the regenerated retinotectal map in goldfish.

Blocking activity with intraocular tetrodotoxin prevents the sharpening of the retinotectal map formed during regeneration of the optic nerve. If (under normal conditions) the initially diffuse map sharpens because of correlated activity in neighboring but not distant ganglion cells, then sharpening should also be prevented merely by disrupting the spatiotemporal correlation in the pattern of activity. To test this idea, fish were exposed during regeneration to stroboscopic illumination in a featureless environment, or were maintained in complete darkness. The regenerating cells remained visually responsive after axotomy, and the xenon strobe effectively drove each ganglion cell at a constant latency. The maps formed in the strobe-reared fish were normally oriented, but the multiunit receptive fields were greatly enlarged, averaging 32 degrees. In control regenerates, multiunit receptive fields averaged only 11-12 degrees, nearly the same as for single units. Dark rearing, which allows only spontaneous activity, also resulted in enlarged multiunit receptive fields, averaging more than 28 degrees. Both effects parallel those reported previously with tetrodotoxin block. The mature projection did not become diffuse as a result of the strobe rearing, and the sensitive period corresponded to the early stage of synaptogenesis (20-34 days). Periods of normal visual exposure after 35 days produced very little sharpening of the diffuse maps produced during either strobe or dark rearing. The results are attributed to an activity-dependent stabilization of developing synapses. The correlated firing of neighboring ganglion cells could allow postsynaptic summation of their responses, and the retention of those more effective, retinotopically placed synapses might then occur via a Hebbian mechanism.

Animals↗
PubMed1985

Apparent movement of optic terminals out of a local postsynaptically blocked region in goldfish optic tectum.

In goldfish tectum, alpha-bungarotoxin (alpha BTX) blocks postsynaptically generated field potentials elicited by either photic or electrical stimulation, but leaves presynaptic activity unaffected. To assess the chronic effects of blocking transmission on synaptic stability, small restricted areas of synaptic block were created by slow, low-pressure microinjection of toxin-Ringer's solution from a micropipette. Local transmission was blocked, but field potentials outside the injected region were unchanged. Radioautography of 125I-alpha BTX demonstrated that 6 days postinjection it was still highly localized and concentrated in discrete synaptic laminae of the tectal neuropil, in agreement with its known tight binding in goldfish brain (18). Electrophysiological maps made 6-8 days postinjection showed that few if any optic terminals could be recorded in the toxin-blocked zone, but there was no scotoma in the visual field. Terminals with receptive fields that would normally have corresponded to the region of injection were instead recorded from surrounding tectal areas. Since the normal units were also recorded there, this produced very large multiunit receptive fields. Apparently the optic terminals within the toxin-blocked area moved outward and innervated neighboring areas. In a minority of cases, no silent areas were noted and only the enlarged multiunit receptive fields were seen in the injection zone. All tecta injected with alpha BTX, but none injected with Ringer's, showed these disturbances in the map at the treated area at 6-8 days postinjection. By 2-3 wk, the maps in the alpha BTX-injected tecta had returned to normal. There were no silent areas and no enlarged receptive fields. The movement of the optic arbors was shown to be dependent on activity in the optic fibers. In fish receiving intraocular injections of tetrodotoxin (TTX) for the first 4-6 days, no changes were seen in the retinotectal maps recorded after the effects of the TTX wore off. When the entire surface of the tectum was blocked with multiple injections of alpha BTX, normal maps were recorded at 6-8 days postinjection. Thus in order to produce movements in optic terminals, the fibers require activity and an opportunity to make effective synapses in a nearby zone.

Animals↗
PubMed1985

Selective stabilization of retinotectal synapses by an activity-dependent mechanism.

How does each ingrowing retinal fiber select the right spot in the overall retinotopic projection? Chemospecific surface interactions appear to be sufficient only to organize a crude retinotopic map on the tectum during regeneration of the optic nerve of goldfish. Precise retinotopic ordering is achieved via an activity-dependent stabilization of appropriate synapses, based on the correlated activity of neighboring ganglion cells of the same receptive field type in the retina. Four treatments have been found to block the sharpening process: 1) blocking activity of the ganglion cells with intraocular tetrodotoxin (TTX); 2) rearing in total darkness; 3) correlated activation of all ganglion cells via stroboscopic illumination in a featureless environment; 4) block of retinotectal synaptic transmission with alpha-bungarotoxin. These experiments support a role for normal visually driven activity in sharpening the diffuse projection, and demonstrate that the correlated activity of the optic fibers interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials. Intraocular TTX experiments suggest that a similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive field types in the lateral geniculate nucleus. Thus, it may be a general mechanism whereby the diffuse projections of early development are brought to a mature level of organization.

Bungarotoxins↗
PubMed1984

Activity and the formation of ocular dominance patches in dually innervated tectum of goldfish.

This study tested (1) whether blocking impulse activity in both eyes of fish with one tectum prevents the formation of ocular dominance patches, (2) whether areas receiving a high density of innervation from one eye receive a low density from the other, and (3) whether there is an electrophysiological correlate to the anatomical patches. One tectum was removed in goldfish so that the optic nerve fibers from both eyes would compete for synaptic space in the remaining tectum. The terminal arbors from the two projections initially overlapped but by 50 to 60 days segregated into ocular dominance patches, demonstrated by labeling both projections, the normal one with horseradish peroxidase and the regenerating one with tritiated proline radioautography. Alternate sections were processed for radioautography and histochemistry. All projections were drawn by "blind" observers using a camera lucida and were fully reconstructed. Both the level of patchiness within each projection and the correspondence of patches and holes between the two projections were quantified from these reconstructions. Binocular tetrodotoxin (TTX) injections from 18 to 75 days after surgery significantly reduced patchiness, as compared to controls injected with citrate-Ringers solution. When the binocular block was continued until 95 days, segregation was still significantly reduced relative to controls. These results support a hypothesis for an activity-dependent mechanism of segregation of ocular dominance patches. In controls but not TTX-blocked fish, there was a significant tendency for high density areas in one projection to receive a lower density projection from the other eye, and vice versa. However, the two projections were not entirely complementary. Survival of control fish for an additional 5 months resulted in more sharply defined patches but no increase in complementarity. Recordings of field potentials evoked by shocking either optic nerve demonstrated an electrophysiological correlate to the anatomical patches in single tectal fish. Large field potentials from one eye were generally associated with small potentials from the other eye, and vice versa. When the recording sites were marked with electrolytic lesions, there was a direct and significant correlation between the magnitude of the field potentials and the density of the anatomical ocular dominance patches.

Animals↗
PubMed1983

The re-establishment of synaptic transmission by regenerating optic axons in goldfish: time course and effects of blocking activity by intraocular injection of tetrodotoxin.

Intraocular injections of tetrodotoxin were used to block activity for 27 days in normal fish and for the first 27 or 31 days of regeneration in fish with one optic nerve crushed. Synaptic activity was then assessed by a current source-density analysis of field potentials evoked by optic nerve shock at different times following the TTX treatment. In normal fish, the lack of activity for 4 weeks had no significant effect on the maintenance of synaptic strength. Likewise, in fish with nerve crush, lack of activity did not prevent the regenerating optic fibers from forming synapses that were nearly as effective as those formed in controls injected with the citrate buffer vehicle. The earliest synapses were formed at the rostromedial corner of the tectum (where the tract enters) at 20 days after nerve crush, when fibers had not yet reached the caudal areas. By 28 days synaptic potentials could be recorded everywhere on the surface of the tectum in both controls and TTX injected fish. However, the latency of the responses with TTX were longer, suggesting a smaller caliber of fiber, which is consistent with an earlier finding of decreased axonal transport in TTX fish. Maturation of the regenerating fibers proceeded slowly in both TTX and control fish. After more than 5 months, the projections were nearly normal but still not completely normal.

Animals↗
PubMed1983

Activity sharpens the map during the regeneration of the retinotectal projection in goldfish.

In the regenerating retinotectal projection of goldfish, we have used intraocular injections of tetrodotoxin (TTX) to determine whether activity plays a role in organizing or refining the retinotopic map. Repeated injections produced a continuous 27-day block without producing extraocular effects or causing deleterious effects in the retinal ganglion cells. The retinotectal maps regenerated in the TTX fish were normally organized but the multiunit receptive fields were grossly enlarged. In control regenerates, 1-3 units (arbors of retinal ganglion cell axons) were simultaneously recorded at each penetration and their combined receptive field averaged 11-12 degrees, nearly the same as for single units. In TTX fish each penetration yielded at least 5-10 units whose receptive fields were clustered over a wider area averaging 27 degrees across. Individual ganglion cell receptive fields were assessed both by tectal and by intraretinal recording and were not enlarged. Many fish were recorded up to 4 months after the release from TTX block, but no further refinement of the maps occurred. If the nerve was recrushed and regenerated a second time without TTX, a normal map was formed, ruling out any permanent changes in the retinal ganglion cells or in the tectum. Blocks during various portions of the regeneration process showed that lack of activity during the process of axonal elongation (first 2 weeks) does not cause enlargement of the multiunit receptive fields, but lack of activity during the period of synapse formation and maturation (14-34 days) does. The results are discussed in terms of an activity-dependent stabilization of synapses. Neighboring retinal ganglion cells are known to fire in a statistically correlated fashion and this could help in their elimination of incorrect branches following an early period of diffuse connections.

Animals↗
PubMed1983

Regeneration of the retinotectal projection following compression onto a half tectum in goldfish.

This study tested whether regeneration of the optic nerve following half-tectal compression in goldfish leads to the immediate reestablishment of the compressed projection or to an initial half map followed by the gradual compression. Half of the tectum was removed and the optic nerve crushed in large 12-18 cm goldfish which were kept at 20 degrees C and later mapped either in air or in water. At 35 to 41 days, the maps showed the presence of the nasal field projection and only the first 27 degrees of the temporal field. Most of the temporal field was represented after 200 days or more. After 253 to 343 days when the compression was largely complete, the optic nerve was recrushed. The projections mapped 35 to 41 days later were always compressed with up to 99% of the temporal field represented, as were projections regenerated at 28 degrees C and mapped at 23-25 days. Regeneration after compression restores the compressed projection, consistent with the concept of altered tectal markers.

Animals↗