Altered Development of Visual Subcortical Projections Following Neonatal Thalamic Ablation in the Hamster MARCY A. KINGSBURY, ETHAN R. GRAF, AND BARBARA L. FINLAY* Department of Psychology, Cornell University, Ithaca, New York 14853 ABSTRACT Previous research has demonstrated that precise patterns of axonal connectivity often develop during a series of stages characterized by pathfinding, target recognition, and address selection. This last stage involves the focusing of projections to a precisely defined region within the target. Because thalamic projections begin to innervate cortex before the latter stages are reached, these projections may be important in the establishment of adult-like patterns of cortical connectivity. To address this issue, we examined the mature corticopontine and corticospinal projections of visual cortex deprived of early thalamic input by visual thalamic ablation. Although ablations on the day of birth in hamsters did not disrupt the targeting of appropriate subcortical structures by visual cortical axons, they did alter the organization of projections within the basilar pons and spinal cord. The density and spread of visual corticopontine connections in lesioned animals was greatly increased relative to unlesioned animals, suggesting that thalamic afferents are required during address selection, when the topographic specificity of projections is established. To determine whether early visual thalamic ablation increases connectivity by stabilizing an exuberant develop- mental projection, we examined the normal development of visual corticopontine connections in hamsters ages postnatal days 1–17 (P1–P17). From the earliest ages, visual cortical axons innervate the pontine nucleus in regions specific to their adult projection zones and show progressive growth within these zones. At no time during development do projections exist that are equivalent to the projections found after thalamic ablation, suggesting that removal of thalamic input does not simply stabilize a developmental projection. J. Comp. Neurol. 424: 165–178, 2000. © 2000 Wiley-Liss, Inc. Indexing terms: corticopontine, corticospinal, dorsal lateral geniculate nucleus, visual cortex Adult isocortex is divided into a number of functionally distinct regions, each characterized by a unique pattern of connections. Developmental factors that generate this precise connectivity are increasingly well-understood for intracortical projection systems (i.e., vertical and horizon- tal connections; Lowel and Singer, 1992; Callaway and Lieber, 1996; Ruthazer and Stryker, 1996; Castellani and Bolz, 1997; Castellani et al., 1998; Dantzker and Calla- way, 1998), whereas factors contributing to the develop- ment of subcortical projection systems remain to be eluci- dated. Several indirect lines of evidence suggest that thalamocortical projections play a role in the patterning of subcortical projections. Thus, the present experiments were conducted to examine directly the role of thalamic input in the formation of corticopontine and corticospinal projections. Specific connections between cortical cells and their subcortical targets emerge during a series of developmen- tal stages (O’Leary et al., 1990). These stages correspond well to the sequential stages of pathway selection, target selection, and address selection used to describe other axonal projection systems (Goodman and Shatz, 1993). During pathway and target selection, imprecise connec- tions between cells and their target structures are formed. Contract grant sponsor: NIH; Contract grant number: R01 NS 19245. *Correspondence to: Dr. Barbara L. Finlay, Department of Psychology, Uris Hall, Cornell University, Ithaca, NY 14853. E-mail: blf2@cornell.edu Received 8 December 1999; Revised 18 April 2000; Accepted 18 April 2000 THE JOURNAL OF COMPARATIVE NEUROLOGY 424:165–178 (2000) © 2000 WILEY-LISS, INC.