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A transient component of the developing corticospinal tract arises in visual cortex
N ~ Letters. 36 (1983) 243-248 Elsevier Scientific Publishers Ireland Ltd.
243
A TRANSIENT COMPONENT OF THE DEVELOPING CORTICOSPINAL V I S U ~ CORTEX
C.E. ADAMS', G.A. MIHAILOFF** and D.J. WOODWARD*"* Department of *Physiology and *'Cell Biology, University of Texas Health Science Center at Dallas, Dallas, TX 7523~ (U.S.A) (Received December 14th 1982; Revised version received February 4th 1983; Accepted February 14th 1983)
Key words: basilar pans - visual cortex - corticopontine system - corticospinal tract
Following injections of tritiated Icucine restricted to occipital (visual) regions of cerebral cortex during the first postnatal week (days 3-6), labeled corticofugal axons were followed caudally through the pans, medullary pyramicl, pyramidal decussation and into the cervical spinal cord. However, when similar injections were made into visual cortex durin8 the seeond postnatal week, labeled corticofupl axons could not he traced beyond mid.pontiac levels where abundam axon terminal lahelin8 was evident in the basilar pontine nuclei. Since axonal lahelin8 did not subsequently appear at levels caudal to the pans durins later stases of development or in the adult, it is suglgsted that the contribution to the corticospinal system made by visual cortical axons in the first postnatal week is a transient connection which is eventually lost either by a process of selective avon collateral elimination or cell death.
in the course of autoradiographic studies designed to describe the postnatal development of visual and sensorimotor corticopontine projections [I], it was found that following [JH]leucine injections restricted to occipital cortex on postnatal day 3, a contingent of labeled axons was present within cervical" portions of the corticospinal tract. By postnatal day 6, however, axonal labeling did not extend caudal to medullary levels, while on day 13, labeling did not extend beyond mid-pontine levels, a finding comparable to that reported for the visual corticopontine system in the adult [2]. This observation suuested that those occipital corticofugal axons which initially extend caudally4into the spinal cord are in some way eliminated during the course of development either by programmed cell death or selective degeneration of that part of the axon caudal to the pops. The present study was therefore undertaken to explore more fully this apparently transient connection linking the occipital cortex and spinal cord. A series of Long-Evans hooded rats (n = 24) received pressure injections of 0.15-0.20 ~! of tritiated leucine (65-70 tzCi/td; spec. act. 139 Ci/mmol) in sensorimotor (SM) or visual (VIS) cortex (Fig. 1) at various postnatal ages ranging from 0304-3940/83/~10 .--0000/5 03.00 © 198J Elsevier Scientific Publishers Ireland Ltd,
244
Oay 3
Day 13
Day6
~d
0
~D
°
..°
..
/ fS? ] 4 J
Spinal Co~d
l:i~. I. A `,eri~ of coronal brain¢,em ~e¢liou~, slimming the dislribution and extent of labeling of the tran,,lent x iStl,Zl cortical projection. ~Flle number of each section corre.,ponds to its approximate level within the brain~,zcm or spinal cord as illnslrated m the dra~ing of a dorsal ~-iew of the postnatal rat brain in the ]m~er right. The latlcr dra~'ing also delineates lh¢ s~Ies o l inj¢clion of triliated leucine in sensorinlotor I.~M~ and ~isual IVIS) cortices. Also represented oil a dorsal ~iew of the ral brain is the trajectory" of a z~'pical ocdpital corticofugal axon on dax" ] as il distributes to the basilar pous (BP) and spinal cord. A`, illustrated iu the Iransxer`,e brainslem ,,eclions ~,,'hich comprise the Day 3 ¢olum11, axonal labeling (solid arrox~') could be found x~ithin the cerebral peduncle (Ped) at lo~er pont!he levels (I), the medullary pyramid 12), p.vramidal decussation (P~'r. Dec.) (.~), and comralaleral coriicospinal (CST) tract (4). By po,,tuatal dax 6. the nlosl caudal extent of labeling was observed within the medullary p}'ramid, while on poslnazal da.~ 13, iabele~! corticofugal axons did not exlend beyond mid-pore!he levels.
245
day I to day 21 (birth = day 0). After a 24-72 h survival period, each animal was sacrificed and the brain processed for autoradiography in a routine manner as previously described [I0]. In those cases with isotope placements restricted to SM cortex, axonal labeling was invariably observed in the cerebral peduncle at pomine levels and was found to extend caudally through the medullary pyramid, pyramidal decussation and into the spinal cord. This pattern was clearly established by postnatal day 3 and was not modified during the period up to and including day 21 by which time most corticofugal systems had attained an adult-like configuration. A different pattern was noted, however, when tritiated leucine injections were limited to VIS cortex. Although on postnatal day 3 labeled axons were clearly present in the cerebral peduncle at pontine levels and extended through the pyramidal decussation into the cervical spinal cord (Figs. 1 and 2), by day 6 no evidence of
Fig. 2. The appearance of the transient visual cortical projection to the spinal cord is seen here in a series of dark-field photomicrographs from a postnatal day 3 rat. The midline is indicated by thin arrow~ near the bottom of each frame. Axonal labeling within the cerebral peduncle (Ped) at lower pontine le~ ~ls ip~ilateral to an injection of 13Hlleucine within the right visual cortex is shown in A. The presence of axonai label at a more caudal level within the medullary pyramid (Pyr) is illustrated in B. Labeled axons can be sceen crossing the midline at the pyramidal decussation in C. ThL5 photomicrograph (C) corresponds to section 3, Day 3 in Fig. !. In D, a section through the ro~tral portion of the cervical spinal cord. Icorrespondin~ to section 4, Day 3, Fig. I) labeling of axons within the corticospinal tract (CST) is clearly visible.
246 labeled axons was evident caudal to the medullary pyramid. In addition, in some animals, there was evidence of sparse axonal labeling in the brachium pontis and the restiform body (ipsilateral to the labeled pyramid). Also it is important to note
caudal levels was not s ~ p l y due to technical p r o b l ~ or a failure of axonal transport. By postnatal day 13, axonal labeling could not be traced beyond the rostfal one-half of the basilar pons where the normal pattern characteristic of visual corticopontine terminal labeling was present (Fig. I). Recent studies have described the normal developmental patterns established by growing conicofugal axons which eventually comprise the corticospinal system in the rat [5, 141 and hamster [13]. in the rat, corticospinal axons are present at low cervical levels by postnatal day I, whereas in the hamster growth apparently is somewhat slower since corticospinal axons were not present at mid-cervical levels until day 4. Moreover, it was reported that, in the rat, although corticospinal axons were present at cervical levels on day 1, they did not penetrate into the gray matter of the spinal cord until day 4 or 5, a finding which was also reported in the hamster. The observations described above concerning the development of the corticospinal tract were derived from experiments which involved conical lesions or injections of orthogradely transported markers into sensorimotor cortex. Previously, axonal transport techniques had been applied to studies of developing occipital corticofugal systems in the rabbit which led to the demonstration of transient descending cortical axon bundles [4]. The latter studies reported that labeled axons observed early in development in the medullary pyramid following an injection of tritiated proline in visual cortex were no longer present at a later stage of development when axonal and terminal labeling could not be traced beyond pontine levels. In addition these authors described a second bundle of aberrant corticofugal axons which bypassed the pontine nuclei and instead coursed directly into the paraflocculus of the cerebellum via the brachium pontis. Such axons (like the aberrant pyramidal tract fibers) were also eliminated later in development and thus have been termed transient bundles. Other studies utilizing retrograde transport methods have also reported the existence of transient pyramidal tract projections in the rat [3, 151. Following HRP placement in the corticospinal tract at cervical levels in the third postnatal wee~, D'Amato and Hicks [3] noted that most labeled cortical neurons occupied either of two regions, a rostral band corresponding to area 10 and a larger caudal group comprising areas 3, 4 and 6. However, when injections were made within the first two postnatal weeks (days 4-10), many labeled cortical neurons were located in the 'gap' between the rostral and caudal groups as well as medially in cingulate cortex and laterally in the isocortex of the frontal pole. The disappearance of the 'gap neurons' and other so-called extraneous corticospinal neurons in the third postnatal week was not marked by overt cortical necrosis.
247
In a more recent study, Stanfield et al. [15] utilized a similar approach and injected a fluorescent tracer, True Blue, into the pyramidal decussation on postnatal day 2 (sacrificed on day 6) and observed labeled neurons throughout the cerebral cortex including occipital regions. However, when the tracer was injected on day 20 ( s a c r i f i ~ on day 25), ~nsorimotor regions of the cerebral cortex were again heavi, ly I ~ l e d whereas ~ p i ~ regions were devoid of labeled neurons' Fu~bermore, when the tracer was injected on day 2 and the animals allowed to survive until day 25, many labeled cells were retained in occipital cortex. Like the findings of D'Amato and Hicks [3] the latter observations suggest that the disappearance of pyramidal tract neurons during the course of development is not due to cell death but rather a selective elimination of corticofugal axonal branches caudal to the puns. A similar conclusion was drawn in studies of the development of the callosal connections of sensorimotor [6, 8, 9, 12] and visual [6, 7] cortices. It was shown that early in development, callosal neurons are diffusely distributed within sensorimotor and visual cortices, while in the adult such neurons exhibit a more restricted or focal pattern, it appears that the patchy distribution seen in the adult is not the result of cell death but rather that some cortical neurons lose their callosal collaterals early in the postnatal period but maintain their intrahemispheral or associational connections. The observations reported in the present study from the perspective of orthograde tracing methods confirm that transient pyramidal tract axons emanating from occipital cortex do exist in the rat and, although the aberrant bundle of corticofugal axons observed in the rabbit which passed directly into the cerebellum via the brachium pontis was not clearly evident, sparse labeling in the brachium pontis and restiform body suggested the possible existence of some direct cortico-cerebellar projections. However, the possibility that such labeling might represent transsynaptic transport must also be considered. Moreover, the present study demonstrates that trartsient pyramidal tract axons continue beyond the pyramidal decussation as part of the corticospinal tract and reach at least to lower cervical levels. The orthograde tracing technique employed in the present study provides little conclusive evidence regarding the mechanism involved in the loss of the visual corticospinal axons. However, a related series of autoradiographic studies [I] which described the maturation of both the sensorimotor and visual corticopontine systems tend to support the concept [I 5] which suggests that axon collateral elimination rather than cell death is responsible for the loss of pyramidal tract axons. The former studies [I ] demonstrated that the projection fields of both sensorimotor and visual corticopontine systems are larger in area and nlore diffuse early in development than at later stages and exhibit a gradual narrowing or focusing as development proceeds, in addition, an electron microscopic study of synaptogenesis in the pontine nuclei [11] has revealed evidence of what appears to be spontaneous degeneration of axons and axon terminals and thus might represent the ultrastruc-
tural correlate of the terminal field constriction (pyramidal tract collateral elimination) observed autoradioffraphically. This process of constriction or focusing of terminal fields in the pontine nuclei occurs during the period from day 8 to 16, and thus lags slightly behind the time period during which visual pyramidal tract axons
elimination. This work supported in part by DA2338 (NIDA) and BNS77-OII74 (NSF) to D.J.W. and NS 12644 (NIH) and BNS804)4853 (NSF) to G.A.M. The support of the Biological Humanics Foundation is also greatly appreciated. I Adams, C.E.. Woodtvard, D.J. and Mihailoff, G.A.. Autoradiographic studies of the postanatal development of scn.,~imotor and xisual corticopontine systems, Soc. Neurosci. Abstr., 7 (1981) 180. 2 Burnt, R.A.. Mihailoff, G.A. and Woodward, D.J., Visual corticopontine input to the paraflocculus: a combined autoradiographic and horseradish peroxidase study, Brain Res.. 143 (1978) 139-146. 3 D'Amato, C.J. and Iticks, S.P., Normal development and po~l-traumatic plasticity of corticospinal neurons in rats, Exp. Ncurol., 60 (1978) 557-569. 4 Distel. H. and Ilollander, H., Autoradiographic tracing of developing subcortical projections of the occipital region in fetal rabbits. J. cutup. Neurol., (1980) 192:505-518. 5 Donalelle, J.M., Growth of the cortico~pinal tract and the d~'elopmcnt of placing reactions in the poslnatal rat. J. cutup. Neurol., 175 (1977) 207~232. 6 hmc•enli, (i.M. and Caminiti, R., I'ostnatal sharing of eallosal connections from sensory areas, E~p, Brain Rcs., 38 (19N1) 381 394, 7 Innocenti, (;.M., (;ro,'th and reshaping of a,,ms in the establishment of visual callosal connections, ~'ience, 212 (1981) 824-827 8 Ivy, G.O., Akers, R.M. and Killack~', H,P., I)ifferential distribution of°callo~al projection neurons in the neonatal and adult rat, Brain Res.. 173 (1979) 53Z 537. 9 I~y, (3,0. and Killackcy, II.P., Ontogenetic changes in the projections of neocortical ncuron~, J. Neurosci.. 2 (1982) 735-743. I0 Mihailoff, G.A., Burn¢, R.A. and Woodward, D.J., Projections of the sen~sorimotorcortex to the basilar pontine nuclei in the rat: An autoradiographic study, Brain Res., 145 (1978) 347-354. I I Mihailoff, G.A., Synaptogenesis in the rat basilar pontine nuclei, Soc. Neuro~i. Abstr., 8 (1982) 447. 12 O'Leary, D.D.M., Stanfield, B.B. and Ccm'an, W.M., Evidence that the early postnatal restrk.lion of the cells of origin of the callosal proj~lion is due to the elimination of axon collaterals rather than to the death of neurons. Develop. Brain Rcs., I (1981) 60"/-617. 13 Reh, T. and Kalil, K., Development of the pyramidal tract in the hamster. I. #. light microscopic study, J. cutup. Neurol., 200 (1981) 55--67. 14 Schreyer, D.J. and Jones, E.G., Growth and target finding by axons of the corticospinal tract in prenatal and postnatal rats, Neurosciem:e, 7 (1982) 1837-1853. 15 Stanfield, B.B., O'l.eary, D.D.M. and Fricks, C., Selective axon collateral elimination in early postnatal development restricts cortical distribution of rat pyramidal tract neurons, Nature (Lond.), 298 (1982) 371-373.
243
A TRANSIENT COMPONENT OF THE DEVELOPING CORTICOSPINAL V I S U ~ CORTEX
C.E. ADAMS', G.A. MIHAILOFF** and D.J. WOODWARD*"* Department of *Physiology and *'Cell Biology, University of Texas Health Science Center at Dallas, Dallas, TX 7523~ (U.S.A) (Received December 14th 1982; Revised version received February 4th 1983; Accepted February 14th 1983)
Key words: basilar pans - visual cortex - corticopontine system - corticospinal tract
Following injections of tritiated Icucine restricted to occipital (visual) regions of cerebral cortex during the first postnatal week (days 3-6), labeled corticofugal axons were followed caudally through the pans, medullary pyramicl, pyramidal decussation and into the cervical spinal cord. However, when similar injections were made into visual cortex durin8 the seeond postnatal week, labeled corticofupl axons could not he traced beyond mid.pontiac levels where abundam axon terminal lahelin8 was evident in the basilar pontine nuclei. Since axonal lahelin8 did not subsequently appear at levels caudal to the pans durins later stases of development or in the adult, it is suglgsted that the contribution to the corticospinal system made by visual cortical axons in the first postnatal week is a transient connection which is eventually lost either by a process of selective avon collateral elimination or cell death.
in the course of autoradiographic studies designed to describe the postnatal development of visual and sensorimotor corticopontine projections [I], it was found that following [JH]leucine injections restricted to occipital cortex on postnatal day 3, a contingent of labeled axons was present within cervical" portions of the corticospinal tract. By postnatal day 6, however, axonal labeling did not extend caudal to medullary levels, while on day 13, labeling did not extend beyond mid-pontine levels, a finding comparable to that reported for the visual corticopontine system in the adult [2]. This observation suuested that those occipital corticofugal axons which initially extend caudally4into the spinal cord are in some way eliminated during the course of development either by programmed cell death or selective degeneration of that part of the axon caudal to the pops. The present study was therefore undertaken to explore more fully this apparently transient connection linking the occipital cortex and spinal cord. A series of Long-Evans hooded rats (n = 24) received pressure injections of 0.15-0.20 ~! of tritiated leucine (65-70 tzCi/td; spec. act. 139 Ci/mmol) in sensorimotor (SM) or visual (VIS) cortex (Fig. 1) at various postnatal ages ranging from 0304-3940/83/~10 .--0000/5 03.00 © 198J Elsevier Scientific Publishers Ireland Ltd,
244
Oay 3
Day 13
Day6
~d
0
~D
°
..°
..
/ fS? ] 4 J
Spinal Co~d
l:i~. I. A `,eri~ of coronal brain¢,em ~e¢liou~, slimming the dislribution and extent of labeling of the tran,,lent x iStl,Zl cortical projection. ~Flle number of each section corre.,ponds to its approximate level within the brain~,zcm or spinal cord as illnslrated m the dra~ing of a dorsal ~-iew of the postnatal rat brain in the ]m~er right. The latlcr dra~'ing also delineates lh¢ s~Ies o l inj¢clion of triliated leucine in sensorinlotor I.~M~ and ~isual IVIS) cortices. Also represented oil a dorsal ~iew of the ral brain is the trajectory" of a z~'pical ocdpital corticofugal axon on dax" ] as il distributes to the basilar pous (BP) and spinal cord. A`, illustrated iu the Iransxer`,e brainslem ,,eclions ~,,'hich comprise the Day 3 ¢olum11, axonal labeling (solid arrox~') could be found x~ithin the cerebral peduncle (Ped) at lo~er pont!he levels (I), the medullary pyramid 12), p.vramidal decussation (P~'r. Dec.) (.~), and comralaleral coriicospinal (CST) tract (4). By po,,tuatal dax 6. the nlosl caudal extent of labeling was observed within the medullary p}'ramid, while on poslnazal da.~ 13, iabele~! corticofugal axons did not exlend beyond mid-pore!he levels.
245
day I to day 21 (birth = day 0). After a 24-72 h survival period, each animal was sacrificed and the brain processed for autoradiography in a routine manner as previously described [I0]. In those cases with isotope placements restricted to SM cortex, axonal labeling was invariably observed in the cerebral peduncle at pomine levels and was found to extend caudally through the medullary pyramid, pyramidal decussation and into the spinal cord. This pattern was clearly established by postnatal day 3 and was not modified during the period up to and including day 21 by which time most corticofugal systems had attained an adult-like configuration. A different pattern was noted, however, when tritiated leucine injections were limited to VIS cortex. Although on postnatal day 3 labeled axons were clearly present in the cerebral peduncle at pontine levels and extended through the pyramidal decussation into the cervical spinal cord (Figs. 1 and 2), by day 6 no evidence of
Fig. 2. The appearance of the transient visual cortical projection to the spinal cord is seen here in a series of dark-field photomicrographs from a postnatal day 3 rat. The midline is indicated by thin arrow~ near the bottom of each frame. Axonal labeling within the cerebral peduncle (Ped) at lower pontine le~ ~ls ip~ilateral to an injection of 13Hlleucine within the right visual cortex is shown in A. The presence of axonai label at a more caudal level within the medullary pyramid (Pyr) is illustrated in B. Labeled axons can be sceen crossing the midline at the pyramidal decussation in C. ThL5 photomicrograph (C) corresponds to section 3, Day 3 in Fig. !. In D, a section through the ro~tral portion of the cervical spinal cord. Icorrespondin~ to section 4, Day 3, Fig. I) labeling of axons within the corticospinal tract (CST) is clearly visible.
246 labeled axons was evident caudal to the medullary pyramid. In addition, in some animals, there was evidence of sparse axonal labeling in the brachium pontis and the restiform body (ipsilateral to the labeled pyramid). Also it is important to note
caudal levels was not s ~ p l y due to technical p r o b l ~ or a failure of axonal transport. By postnatal day 13, axonal labeling could not be traced beyond the rostfal one-half of the basilar pons where the normal pattern characteristic of visual corticopontine terminal labeling was present (Fig. I). Recent studies have described the normal developmental patterns established by growing conicofugal axons which eventually comprise the corticospinal system in the rat [5, 141 and hamster [13]. in the rat, corticospinal axons are present at low cervical levels by postnatal day I, whereas in the hamster growth apparently is somewhat slower since corticospinal axons were not present at mid-cervical levels until day 4. Moreover, it was reported that, in the rat, although corticospinal axons were present at cervical levels on day 1, they did not penetrate into the gray matter of the spinal cord until day 4 or 5, a finding which was also reported in the hamster. The observations described above concerning the development of the corticospinal tract were derived from experiments which involved conical lesions or injections of orthogradely transported markers into sensorimotor cortex. Previously, axonal transport techniques had been applied to studies of developing occipital corticofugal systems in the rabbit which led to the demonstration of transient descending cortical axon bundles [4]. The latter studies reported that labeled axons observed early in development in the medullary pyramid following an injection of tritiated proline in visual cortex were no longer present at a later stage of development when axonal and terminal labeling could not be traced beyond pontine levels. In addition these authors described a second bundle of aberrant corticofugal axons which bypassed the pontine nuclei and instead coursed directly into the paraflocculus of the cerebellum via the brachium pontis. Such axons (like the aberrant pyramidal tract fibers) were also eliminated later in development and thus have been termed transient bundles. Other studies utilizing retrograde transport methods have also reported the existence of transient pyramidal tract projections in the rat [3, 151. Following HRP placement in the corticospinal tract at cervical levels in the third postnatal wee~, D'Amato and Hicks [3] noted that most labeled cortical neurons occupied either of two regions, a rostral band corresponding to area 10 and a larger caudal group comprising areas 3, 4 and 6. However, when injections were made within the first two postnatal weeks (days 4-10), many labeled cortical neurons were located in the 'gap' between the rostral and caudal groups as well as medially in cingulate cortex and laterally in the isocortex of the frontal pole. The disappearance of the 'gap neurons' and other so-called extraneous corticospinal neurons in the third postnatal week was not marked by overt cortical necrosis.
247
In a more recent study, Stanfield et al. [15] utilized a similar approach and injected a fluorescent tracer, True Blue, into the pyramidal decussation on postnatal day 2 (sacrificed on day 6) and observed labeled neurons throughout the cerebral cortex including occipital regions. However, when the tracer was injected on day 20 ( s a c r i f i ~ on day 25), ~nsorimotor regions of the cerebral cortex were again heavi, ly I ~ l e d whereas ~ p i ~ regions were devoid of labeled neurons' Fu~bermore, when the tracer was injected on day 2 and the animals allowed to survive until day 25, many labeled cells were retained in occipital cortex. Like the findings of D'Amato and Hicks [3] the latter observations suggest that the disappearance of pyramidal tract neurons during the course of development is not due to cell death but rather a selective elimination of corticofugal axonal branches caudal to the puns. A similar conclusion was drawn in studies of the development of the callosal connections of sensorimotor [6, 8, 9, 12] and visual [6, 7] cortices. It was shown that early in development, callosal neurons are diffusely distributed within sensorimotor and visual cortices, while in the adult such neurons exhibit a more restricted or focal pattern, it appears that the patchy distribution seen in the adult is not the result of cell death but rather that some cortical neurons lose their callosal collaterals early in the postnatal period but maintain their intrahemispheral or associational connections. The observations reported in the present study from the perspective of orthograde tracing methods confirm that transient pyramidal tract axons emanating from occipital cortex do exist in the rat and, although the aberrant bundle of corticofugal axons observed in the rabbit which passed directly into the cerebellum via the brachium pontis was not clearly evident, sparse labeling in the brachium pontis and restiform body suggested the possible existence of some direct cortico-cerebellar projections. However, the possibility that such labeling might represent transsynaptic transport must also be considered. Moreover, the present study demonstrates that trartsient pyramidal tract axons continue beyond the pyramidal decussation as part of the corticospinal tract and reach at least to lower cervical levels. The orthograde tracing technique employed in the present study provides little conclusive evidence regarding the mechanism involved in the loss of the visual corticospinal axons. However, a related series of autoradiographic studies [I] which described the maturation of both the sensorimotor and visual corticopontine systems tend to support the concept [I 5] which suggests that axon collateral elimination rather than cell death is responsible for the loss of pyramidal tract axons. The former studies [I ] demonstrated that the projection fields of both sensorimotor and visual corticopontine systems are larger in area and nlore diffuse early in development than at later stages and exhibit a gradual narrowing or focusing as development proceeds, in addition, an electron microscopic study of synaptogenesis in the pontine nuclei [11] has revealed evidence of what appears to be spontaneous degeneration of axons and axon terminals and thus might represent the ultrastruc-
tural correlate of the terminal field constriction (pyramidal tract collateral elimination) observed autoradioffraphically. This process of constriction or focusing of terminal fields in the pontine nuclei occurs during the period from day 8 to 16, and thus lags slightly behind the time period during which visual pyramidal tract axons
elimination. This work supported in part by DA2338 (NIDA) and BNS77-OII74 (NSF) to D.J.W. and NS 12644 (NIH) and BNS804)4853 (NSF) to G.A.M. The support of the Biological Humanics Foundation is also greatly appreciated. I Adams, C.E.. Woodtvard, D.J. and Mihailoff, G.A.. Autoradiographic studies of the postanatal development of scn.,~imotor and xisual corticopontine systems, Soc. Neurosci. Abstr., 7 (1981) 180. 2 Burnt, R.A.. Mihailoff, G.A. and Woodward, D.J., Visual corticopontine input to the paraflocculus: a combined autoradiographic and horseradish peroxidase study, Brain Res.. 143 (1978) 139-146. 3 D'Amato, C.J. and Iticks, S.P., Normal development and po~l-traumatic plasticity of corticospinal neurons in rats, Exp. Ncurol., 60 (1978) 557-569. 4 Distel. H. and Ilollander, H., Autoradiographic tracing of developing subcortical projections of the occipital region in fetal rabbits. J. cutup. Neurol., (1980) 192:505-518. 5 Donalelle, J.M., Growth of the cortico~pinal tract and the d~'elopmcnt of placing reactions in the poslnatal rat. J. cutup. Neurol., 175 (1977) 207~232. 6 hmc•enli, (i.M. and Caminiti, R., I'ostnatal sharing of eallosal connections from sensory areas, E~p, Brain Rcs., 38 (19N1) 381 394, 7 Innocenti, (;.M., (;ro,'th and reshaping of a,,ms in the establishment of visual callosal connections, ~'ience, 212 (1981) 824-827 8 Ivy, G.O., Akers, R.M. and Killack~', H,P., I)ifferential distribution of°callo~al projection neurons in the neonatal and adult rat, Brain Res.. 173 (1979) 53Z 537. 9 I~y, (3,0. and Killackcy, II.P., Ontogenetic changes in the projections of neocortical ncuron~, J. Neurosci.. 2 (1982) 735-743. I0 Mihailoff, G.A., Burn¢, R.A. and Woodward, D.J., Projections of the sen~sorimotorcortex to the basilar pontine nuclei in the rat: An autoradiographic study, Brain Res., 145 (1978) 347-354. I I Mihailoff, G.A., Synaptogenesis in the rat basilar pontine nuclei, Soc. Neuro~i. Abstr., 8 (1982) 447. 12 O'Leary, D.D.M., Stanfield, B.B. and Ccm'an, W.M., Evidence that the early postnatal restrk.lion of the cells of origin of the callosal proj~lion is due to the elimination of axon collaterals rather than to the death of neurons. Develop. Brain Rcs., I (1981) 60"/-617. 13 Reh, T. and Kalil, K., Development of the pyramidal tract in the hamster. I. #. light microscopic study, J. cutup. Neurol., 200 (1981) 55--67. 14 Schreyer, D.J. and Jones, E.G., Growth and target finding by axons of the corticospinal tract in prenatal and postnatal rats, Neurosciem:e, 7 (1982) 1837-1853. 15 Stanfield, B.B., O'l.eary, D.D.M. and Fricks, C., Selective axon collateral elimination in early postnatal development restricts cortical distribution of rat pyramidal tract neurons, Nature (Lond.), 298 (1982) 371-373.