THE JOURNAL OF COMPARATIVE NEUROLOGY 400:417–439 (1998) Brainstem Inputs to the Ferret Medial Geniculate Nucleus and the Effect of Early Deafferentation on Novel Retinal Projections to the Auditory Thalamus ALESSANDRA ANGELUCCI, FRANCISCO CLASCA´ , AND MRIGANKA SUR* Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 ABSTRACT Following specific neonatal brain lesions in rodents and ferrets, retinal axons have been induced to innervate the medial geniculate nucleus (MGN). Previous studies have suggested that reduction of normal retinal targets along with deafferentation of the MGN are two concurrent factors required for the induction of novel retino-MGN projections. We have examined, in ferrets, the relative influence of these two factors on the extent of the novel retinal projection. We first characterized the inputs to the normal MGN, and the most effective combination of neonatal lesions to deafferent this nucleus, by injecting retrograde tracers into the MGN of normal and neonatally operated adult ferrets, respectively. In a second group of experiments, newborn ferrets received different combinations of lesions of normal retinal targets and MGN afferents. The resulting extent of retino-MGN projections was estimated for each case at adulthood, by using intraocular injections of anterograde tracers. We found that the extent of retino-MGN projections correlates well with the extent of MGN deafferentation, but not with extent of removal of normal retinal targets. Indeed, the presence of at least some normal retinal targets seems necessary for the formation of retino-MGN connections. The diameters of retino-MGN axons suggest that more than one type of retinal ganglion cells innervate the MGN under a lesion paradigm that spares the visual cortex and lateral geniculate nucleus. We also found that, after extensive deafferenta- tion of MGN, other axonal systems in addition to retinal axons project ectopically to the MGN. These data are consistent with the idea that ectopic retino-MGN projections develop by sprouting of axon collaterals in response to signals arising from the deafferented nucleus, and that these axons compete with other sets of axons for terminal space in the MGN. J. Comp. Neurol. 400:417–439, 1998. ௠ 1998 Wiley-Liss, Inc. Indexing terms: retinal ganglion cells; plasticity; development; subcortical auditory pathways; inferior colliculus A central question in developmental neurobiology is how axons select appropriate targets. One possibility is that Grant sponsor: National Institutes of Health; Grant number: Ey 07719; axons are intrinsically determined to make specific sets of Grant sponsor: March of Dimes; Grant sponsor: Fogarty International Fellowship [LGO]; Grant number: IFO5TWO4881. connections. Alternatively, factors extrinsic to the axons Dr. Angelucci’s current address: Department of Visual Science, Institute themselves might play an important role in target selec- of Ophthalmology, University College London, 11-43 Bath St., London, tion. One way of understanding the mechanisms that EC1V 9EL United Kingdom. regulate target choice is to investigate whether the process Dr. Clasca´’s current address: Departamento de Morfologia, Facultad de of target selection can be experimentally modified. Previ- Medicina, Universidad Autonoma, Arzobispo Morcillo s/n, 28029 Madrid, ous studies in rodents (Schneider, 1973; Devor, 1975; Spain. *Correspondence to: Mriganka Sur, Department of Brain and Cognitive Graziadei et al., 1979; Frost, 1981, 1982, 1986; Asanuma Sciences, Massachusetts Institute of Technology, E25–235, 45 Carleton and Stanfield, 1990) and ferrets (Sur et al., 1988; Roe et al., Street, Cambridge, MA 02139. E-mail: [email protected] 1993) have shown that, after selective brain lesions early Received 14 August 1997; Revised 15 June 1998; Accepted 28 June 1998 ௠ 1998 WILEY-LISS, INC. 418 A. ANGELUCCI ET AL. or late in development, axons can be induced to form stable ability to form anomalous connections is limited. Only a terminal arbors in targets that they would not normally subset of the entire population of available retinal axons innervate. The occurrence of ectopic connections in vivo could be induced to innervate novel targets. Moreover, in suggests that the process of target selection is not entirely ferrets, novel retinal projections to the MGN were appar- predetermined, and might be the result of competition ently formed only by one subpopulation of retinal ganglion among different populations of axons endowed with differ- cells, namely the W-cells (Roe et al., 1993; Pallas et al., ent degrees of intrinsic ‘‘preference’’ for different targets. 1994). Under normal circumstances, this competition among One possible explanation for the limited and selective axon populations is likely to be tightly constrained by induction of fibers to novel targets, is that only a subset of developmental temporal and spatial factors. Selective retinal ganglion cell axons are endowed with intrinsic lesions early in development constitute a powerful experi- plastic properties (Roe et al., 1993). An alternative expla- mental tool to modify these temporal and spatial con- nation is that the ability of axons to innervate novel straints. Thus, understanding the developmental rules targets is determined by factors extrinsic to the axons that govern the establishment of anomalous connections themselves. One such factor might be the developmental might shed some light on how normal connections are age at which the experimental manipulations are per- specified. formed, such that a larger proportion of axons would form Redirection of specific afferents to inappropriate loci has novel connections if the necessary manipulations were been shown to occur when normal targets are reduced in done at earlier ages (Roe et al., 1993). Another extrinsic size early in development, and alternative space is created factor that might influence the extent of anomalous retino- by partially deafferenting an ectopic target. Thus, for MGN projections, and the one that we have examined in example, in rodents (Schneider, 1973; Frost, 1981, 1982) the present study, is the extent of the specific lesions and ferrets (Sur et al., 1988; Roe et al., 1993), retinal axons performed at birth. In previous lesion paradigms, both were redirected to the auditory thalamus by partial neona- removal of normal retinal targets and deafferentation of tal ablation of the lateral geniculate nucleus (LGN) and/or the MGN were incomplete (Frost, 1981, 1982; Sur et al., the superior colliculus (SC), two main retinal targets, 1988; Roe et al., 1993). Specifically, ablation of the LGN along with transection of the brachium of the inferior was obtained indirectly by lesioning the visual cortex, thus colliculus (BIC) and/or ablation of the inferior colliculus inducing only partial degeneration of the LGN, whereas (IC) to partially deafferent the medial geniculate nucleus deafferentation of the MGN was performed mainly by (MGN). It was argued that both factors, i.e., normal retinal transecting the BIC, and estimated solely by direct exami- target removal and MGN deafferentation, are necessary to nation of the BIC lesion. However, over the past decade, induce sprouting of retinal axons into the MGN (Roe et al., anatomical studies on the connectivity of the cat MGN 1993). However, these studies seem to indicate that the have shown that a wide diversity of brainstem afferents Abbreviations BC brachium conjunctivum MSO medial nucleus of the superior olivary complex BCM marginal nucleus of the brachium conjunctivum OT optic tract BIC brachium of the inferior colliculus P pyramidal tract BIN nucleus of the brachium of the inferior colliculus PAG periaqueductal gray CAE locus coeruleus PBG parabigeminal nucleus cIC contralateral inferior colliculus Po lateral part of the posterior group of thalamic nuclei CP cerebral peduncle PoM medial division of the posterior nuclear thalamic complex Cu cuneiform nucleus PR paramedian reticular formation CUN cuneate nucleus PT pretectal nuclei DMV dorsal motor nucleus of the vagus RGCS retinal ganglion cells DR dorsal nucleus of the raphe RN Csred nucleus FTC central tegmental field RTN reticular thalamic nucleus FTG magnocellular tegmental field SAG nucleus sagulum FTL lateral tegmental field SC superior colliculus FTP paralemniscal tegmental field SCC commissure of the superior colliculus GR gracile nucleus SCd deep layers of the superior colliculus IC inferior colliculus SCs superficial layers of the superior colliculus iIC ipsilateral inferior colliculus Sg suprageniculate nucleus IOd dorsal nucleus of the inferior olive SN substantia nigra IOm medial nucleus of the inferior olive SO superior olivary complex LC linear central nucleus of the raphe ST nuclei of the solitary tract LGd dorsal lateral geniculate nucleus STT spinothalamic tract LGN lateral geniculate nucleus T nucleus of the trapezoid body LGv ventral lateral geniculate nucleus VB ventrobasal thalamic complex LLD dorsal nucleus of the lateral lemniscus vl pars lateralis of the ventral division of the medial genicu- LLV ventral nucleus of the lateral lemniscus late nucleus LP lateral posterior thalamic nucleus VN vestibular nuclei LRN lateral reticular formation V4 4th ventricle LSO lateral nucleus of the superior olivary complex 3 oculomotor nuclei MGN medial geniculate nucleus 5P principal sensory trigeminal nerve MGd dorsal division of the medial geniculate nucleus 5SP spinal nucleus of the trigeminal nerve MGm medial division of the medial