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D K Simon

Publications and source records attributed to D K Simon.

22 records · Page 2Linked to original sources

Limited topographic specificity in the targeting and branching of mammalian retinal axons.

We have studied in rats the topographic targeting of retinocollicular axons anterogradely labeled by focal retinal injections of the axon tracer DiI. We find that developing retinal axons widely mistarget along both the medial-lateral and the rostral-caudal axes of the superior colliculus (SC). In neonatal rats, labeled axons originating from injection sites in the temporal periphery covering less than 1% of the retina grow over most of the contralateral SC, suggesting that the growth cones of many axons initially fail to recognize their appropriate target region at the rostral SC border. Some of these axons correct their targeting errors and are retained; most do not and are eliminated. In neonates, peripheral nasal axons transiently develop branches throughout the SC. Branches formed by nasal axons are later restricted to a discrete terminal zone at the topographically appropriate, caudal SC border. At the neonatal stage, injections in temporal or nasal retina do result in a zone of increased labeling in the topographically correct region of the SC, but this zone is considerably larger than that labeled by a similar injection at a later stage. Thus, although the early projection is very diffuse, there is some bias for the correct region of the SC. Our findings indicate that in rats, developing retinal axons show only a limited specificity in their topographic targeting and branching. We conclude that mechanisms in addition to directed axon growth are required to establish the order characteristic of mature mammalian retinal projections.

Aging↗

Intrahippocampal grafts of fetal basal forebrain tissue alter place fields in the hippocampus of rats with fimbria-fornix lesions.

Intrahippocampal grafts of fetal basal forebrain tissue have been shown to restore several aspects of neural function, including some degree of behavioral recovery in spatial memory tasks, in rats with fimbria-fornix lesions. Place fields, the behavioral correlates of complex-spike unit activity recorded in the hippocampus of rats, are altered by fimbria-fornix lesions, and provide an important measure of the functioning circuitry of the hippocampus after grafts. To investigate the effects of grafts on hippocampal circuitry, complex-spike units were recorded while the rats traversed a radial maze. Quantitative analyses of spatial activity showed that units in normal rats had spatially clustered, reliable place fields that were stable despite alterations of the maze. In contrast, units in rats with fimbria-fornix lesions had more dispersed, less reliable place fields that were disrupted when the maze was covered or rotated. Compared to rats with fimbria-fornix lesions, rats with grafts and units with more tightly clustered, more reliable, and more stable place fields when the maze was altered. The results suggest that: (1) fimbria-fornix lesions disrupt some aspects of complex-spike place field activity; (2) the functioning of hippocampal circuitry is influenced by fetal basal forebrain grafts; and (3) the grafts may ameliorate the effects of lesions on spatial behaviors by influencing critical aspects of place field activity in the hippocampus.

Action Potentials↗

Growth of embryonic retinal neurites elicited by contact with Schwann cell surfaces is blocked by antibodies to L1.

Explants from embryonic rat retina plated on Schwann cell monolayers were used to examine the mechanisms by which these central neurons interact with Schwann cell surfaces. Embryonic retinal explants extend neurites reliably on Schwann cell surfaces (Kleitman et al., 1988, J. Neurosci. 8: 653). Antibodies to molecules thought to be present on Schwann cell surfaces (laminin and the 217C antigen), on retinal neurite surfaces (Thy-1.1), or on both surfaces (L1) were tested for their ability to influence this neurite growth. Of these, only antibodies to L1 were effective in blocking retinal neurite extension on Schwann cells. Inhibition of neurite growth by anti-L1 was shown to be specific to growth on Schwann cell surfaces because neurite growth on air-dried collagen (a substratum known to support retinal neurite outgrowth) was not affected. This blockage was dose-dependent. At a low titer of anti-L1 Fab fragments defasciculation of neurites was prominent; at high titers 95% of neurite outgrowth was inhibited. This virtual elimination of the ability of Schwann cell surfaces to support embryonic retinal neurite growth in the presence of antibodies to L1 indicates that binding of the L1 molecule is a critical component of the mechanism by which Schwann cells foster the growth of these neurites. The present experiments concur with the growing body of evidence that L1 plays an important role in supporting neurite growth on cell surfaces and raise the possibility that L1 may also mediate the striking ability of adult retinal axons to regenerate in a peripheral nerve environment.

Animals↗