Are field potentials an appropriate method for demonstrating connections in the brain?

A common technique for demonstrating projections in the brain is to electrically stimulate one part of the brain and record mass or field potentials from another part. We showed in the visual system of the cat, where connections between retina, lateral geniculate nucleus, and superior colliculus are very well known, that the recording of field potentials is not at all sufficient to demonstrate connections. The most prominent potential after electrical stimulation of the optic tract is the field potential created by the Y-ganglion cell fibers of the optic nerve. We recorded this potential in the optic nerve head of the eye, in the lateral geniculate nucleus, and in the superior colliculus. To our surprise, we also could record this potential 7 mm in front of the retina, with the electrode in the vitreous, and 5 mm above the lateral geniculate nucleus and the superior colliculus, where there are no direct inputs from the optic tract. These results show quite clearly that field potentials can “stray” much farther than the underlying anatomical structure projects.     

Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system

The distribution of nicotinic acetylcholine receptors (AChR) in the rat and mouse central nervous system has been mapped in detail using monoclonal antibodies to receptors purified from chicken and rat brain. Initial studies in the chicken brain indicate that different neuronal AChRs are contained in axonal projections to the optic lobe in the midbrain from neurons in the lateral spiriform nucleus and from retinal ganglion cells. Monoclonal antibodies to the chicken and rat brain AChRs also label apparently identical regions in all major subdivisions of the central nervous system of rats and mice, and this pattern is very similar to previous reports of 3H-nicotine binding, but quite different from that of alpha-bungarotoxin binding. In several instances, the immunohistochemical evidence has strongly indicated that neuronal AChR undergoes axonal transport. The clearest example of this has been in the visual system, where labeling was observed in the retina, the optic nerve and tract, and in all of the major terminal fields of the optic nerve except the ventral suprachiasmatic nucleus. This was confirmed in unilateral enucleation experiments in the rat, where labeling was greatly reduced in the contralateral optic tract, ventral lateral geniculate nucleus, pretectal nuclei receiving direct visual input, superficial layers of the superior colliculus, and medical terminal nucleus, and was significantly reduced in the dorsal lateral geniculate nucleus. Clear neuronal labeling was also observed in dorsal root ganglion cells and in cranial nerve nuclei containing motoneurons that innervate branchial arch-derived muscles, although the possibility that neuronal AChR undergoes axonal transport in the latter cells was not tested experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)     

The visual pathways of the lorisid lemurs (Nycticebus coucang and Galago crassicaudatus)

The primary projections of the optic nerve were investigated in two species of lorisid lemurs (Nycticebus coucang and Galago crassicaudatus) following unilateral enucleation of an eye. In addition, the cytoarchitecture of the lateral geniculate body and of the pretectum is described. The lateral geniculate nucleus is composed of six cellular laminae – four magnocellular and two parvocellular. Optic nerve fibers from the retina of an eye terminate in laminae 1, 5 and 6 of the lateral geniculate body on the side opposite to the enucleated eye and laminae 2, 3 and 4 of the lateral geniculate body on the same side as the enucleated eye. Retinofugal fibers were also observed to project to the pregeniculate nucleus, nucleus of the optic tract, pretectal nucleus and superior colliculus on both the same side as and on the side opposite to the enucleated eye. A completely crossed accessory optic tract was noted. The lateral geniculate bodies of a Galago “borgne” (one blind atrophic eye) are also described.     

Is nerve growth factor required for the survival of retinal ganglion cells during development?

Staining for nerve growth factor receptor was observed in the ferret's retinal ganglion cell layer, optic nerve and tract, and in the lateral geniculate nucleus and superficial layers of the superior colliculus in the prenatal period, but had disappeared by birth. Thus the incidence of this transient staining does not correspond with the ganglion cell death that is known to occur in the ferret retina during the first postnatal week.     

Region-selective decline of in vivo lipid synthesis in the aged rat visual system

[¹⁴C]palmitate and [³H]choline were injected intravitreally and, at the same time, intraventricularly in Wistar male rats at 4, 10, and 24 mo of age. The precursor incorporation into lipids of the retina, optic nerve tract, superior colliculus, and lateral geniculate body was followed for 2 h. The specific radioactivity of precursors pool (choline, phosphorylcholine, and free fatty acids) showed a marked decrease in optic nerve tract and lateral geniculate body of aged rats, whereas in retinal tissue and superior colliculus no changes were observed as a function of age. In rats of the three age groups, whole retina and superior colliculus showed neither changes of choline incorporation into phosphatidylcholine and sphingomyelin nor alteration of palmitate incorporation into diacylglycerols, triacylglycerols, and major phospholipid classes as a function of age. In sharp contrast, the optic nerve tract and, to a lesser extent, the lateral geniculate body exhibited a significant age-related decline of either the incorporation of both precursors into all lipid classes or the specific radioactivities of endogeneous precursor pools. We concluded that the visual pathway structures are metabolically affected in a different manner by aging. Particularly, the ability of the retina and superior colliculus to metabolize lipids appeared to be age invariant. The marked decline of lipid biosynthesis with age, for some visual structures, is consistent with the trend generally observed in metabolic turnover and function of other CNS regions.     

Retinal projections in the native cat, Dasyurus viverrinus.

Retinal projections were examined in the native cat, Dasyurus viverrinus using Fink-Heimer material and autoradiography. We found six regions in the brain which receive retinal projections. These are (1) the dorsal lateral geniculate nucleus (2) the ventral lateral geniculate nucleus (3) the lateral posterior nucleus (4) the pretectum (5) the superior colliculus, and (6) the accessory optic system. We did not examine the hypothalamus. The accessory optic system and the lateral posterior nucleus receive a contralateral retinal projection only and the other four regions receive a bilateral retinal projection. There is extensive binocular overlap in the dorsal lateral geniculate nucleus. On the side contralateral to an eye injection of 3H leucine our autoradiographs show four contralateral layers which fill most of the nucleus. Three of these layers, 3, 4 and 5, also receive input from the opsilateral eye. Layer 1 which lies adjacent to the optic tract receives only contralateral retinal input. Layer 2 receives a direct retinal input only from the ipsilateral eye. The ipsilateral projection to the dorsal lateral geniculate nucleus forms a fairly continuous patch which is not divided into separate layers. The ipsilateral retinal input is located in the dorsal part of the lateral geniculate nucleus. The ventral quarter of the nucleus only receives a contralateral retinal input and therefore represents the monocular part of the visual field.     

An autoradiographic study of the projections from the lateral geniculate body of the rat.

The projections from the lateral geniculate body of the rat were followed using the technique of autoradiography after injections of [3H] proline into the dorsal and/or ventral nuclei of this diencephalic structure. Autoradiographs were prepared from either frozen or paraffin coronal sections through the rat brain. The dorsal nucleus of the lateral geniculate projected via the optic radiation to area 17 of the cerebral cortex. There was also a slight extension of label into the zones of transition between areas 17, 18 and 18a. The distribution of silver grains in the various layers of the cerebral cortex was analyzed quantitatively and showed a major peak of labeling in layer IV with minor peaks in outer layer I and the upper half and lowest part of layer VI. The significance of these peaks is discussed in respect to the distribution of geniculocortical terminals in other mammalian species. The ventral nucleus of the lateral geniculate body had 5 major projections to brain stem structures both ipsilateral and contralateral to the injected nucleus. There were two dorsomedial projections: (1) a projection to the superior colliculus which terminated mainly in the medial third of the stratum opticum, and (2) a large projection via the superior thalamic radiation which terminated in the ipsilateral pretectal area; a continuation of this projection passed through the posterior commissure to attain the contralateral pretectal area. The three ventromedial projections involved: (1) a geniculopontine tract which coursed through the basis pedunculi and the lateral lemniscus to terminate in the dorsomedial and dorsolateral parts of the pons after giving terminals to the lateral terminal nucleus of the accessory optic tract, (2) a projection via Meynert's commissure to the suprachiasmatic nuclei of both sides of the brain stem as well as to the contralateral ventral lateral geniculate nucleus and lateral terminal nucleus of the accessory optic tract, and (3) a medial projection to the ipsilateral zona incerta. The results obtained in these experiments are contrasted with other data on the rat's central visual connections to illustrate the importance of these connections in many subcortical visual functions.     

Retinal projections to the superior colliculus and dorsal lateral geniculate nucleus in the tammar wallaby (Macropus eugenii): II. Topography after rotation of an eye prior to retinal innervation of the brain

Retinal projections to visual centers in a marsupial mammal, the tammar wallaby (Macropus eugenii), have been investigated after an eye rotation prior to retinal innervation of the brain. Retinal topography to the superior colliculus and dorsal lateral geniculate nucleus was mapped by using laser lesions of the retina and horseradish peroxidase histochemistry. Despite the change in orientation of optic axon outgrowth from the developing eye after rotation, retinal ganglion cells made orderly connections in the colliculus and geniculate according to their original retinal position within the eye and not their rotated position. Axons must have corrected their pathways at some point between the back of the eye and their targets. The optic chiasm was one such site. Optic axons from the rotated eye took an abnormal course at the caudal end of the chiasm. Growth of optic axons through aberrant pathways in the brain did not preclude specific innervation of targets. When by chance optic axons entered through the oculomotor nerve root they specifically innervated their correct visual centers, albeit in reduced density, and did not innervate inappropriate targets. These results support the idea of specific interactions between growing axons, the pathways they grow along, and their targets.     

Metabolic response to optic centers to visual stimuli in the albino rat: anatomical and physiological considerations

The functional organization of the visual system was studied in the albino rat. Metabolic differences were measured using the 14-C-2-deoxyglucose (DG) autoradiographic technique during visual stimulation of one entire retina in unrestrained animals. All optic centers responded to changes in light intensity but to different degrees. The greatest change occurred in the superior colliculus, less in the lateral geniculate, and considerably less in second-order sites such as layer IV of visual cortex. These optic centers responded in particular to on/off stimuli, but showed no incremental change during pattern reversal or movement of orientation stimuli. Both the superior colliculus and lateral geniculate increased their metabolic rate as the frequency of stimulation increased, but the magnitude was twice as great in the colliculus. The histological pattern of metabolic change in the visual system was not homogenous. In the superior colliculus glucose utilization increased only in stratum griseum superficiale and was greatest in visuotopic regions representing the peripheral portions of the visual field. Similarly, in the lateral geniculate, only the dorsal nucleus showed an increased response to greater stimulus frequencies. Second-order regions of the visual system showed changes in metabolism in response to visual stimulation, but no incremental response specific for type or frequency of stimuli. To label proteins of axoplasmic transport to study the terminal fields of retinal projections 14C-amino acids were used. This was done to study how the differences in the magnitude of the metabolic response among optic centers were related to the relative quantity of retinofugal projections to these centers. Fast and slow axoplasmic transport were studied using three separate amino acids. In each case over 64% of the radioactivity projecting contralateral from the eye was found in superior colliculus. considerably less isotope was found in dorsal lateral geniculate (11-17%), ventral lateral geniculate (3, 7-6.2%), pretectal nuclei (5-12%), and the accessory optic system (3-7%). The greatest concentration of radioactivity within each optic center was found in the visuotopic aspect subserving the superior visual field; particularly the medial aspects of the superior colliculus, olivary pretectal nucleus, and posterior pretectal nucleus, and the anterior portion of the nucleus of the optic tract. The representation of central vision in the colliculus was relatively pale, as was a zone within the middle of the contralateral dorsal lateral geniculate. The anatomical and physiological results of this study suggest that differences in deoxyglucose metabolism among optic centers are primarily related to the number of retinofugal endings and the kind of visual stimulation. Changes within any one center primarily reflect the density of retinal endings subserving the visual field.     

Connections of the pretectum in the cat.

The connections of the pretectal complex in the cat have been examined by anatomical methods which utilize the anterograde axonal transport of tritiated proteins or the retrograde axonal transport of the enzyme horseradish peroxidase. Following injections of tritiated amino acids into the eye, label can be seen in the contralateral and ipsilateral nucleus of the optic tract and olivary nucleus where it appears as two or three finger-like strips. Following large injections of tritiated amino acids into the pretectal complex transported label accumulates ipsilaterally in a region dorsolateral to the red nucleus, the central and pericentral divisions of the tegmental reticular nucleus, the intermediate layers of the superior colliculus, the nucleus of Darkschewitch, the thalamic reticular nucleus, zona incerta and fields of Forel, the central lateral nucleus, the pulvinar nucleus and the ventral lateral geniculate nucleus. Contralaterally label accumulates in the nucleus of the posterior commissure, the interstitial nucleus of Cajal, the anterior, posterior and medial pretectal nuclei, and the ventral lateral geniculate nucleus From smaller injections, more or less well confined to single nuclei, the following patterns of connections are demonstrated. The nucleus of the optic tract projects to the ipsilateral ventral lateral geniculate nucleus and pulvinar nucleus and to the contralateral nucleus of the posterior commissure. The anterior pretectal nucleus projects to the ipsilateral central lateral nucleus, the reticular nucleus, zona incerta, fields of Forel, the region dorsolateral to the red nucleus and to the contralateral anterior pretectal nucleus. The posterior pretectal nucleus seems to project only to the ipsilateral reticular nucleus and zona incerta. The central tegmental fields deep to the pretectum project to the tegmental reticular nucleus of the brainstem. When the injection involves the nucleus of the posterior commissure label is seen in the ipsilateral nucleus of Darkschewitch, and in the contralateral nucleus of the posterior commissure and interstitial nucleus of Cajal but no nucleus of the pretectum could be positively identified as projecting to any of the motor nuclei of cranial nerves III, IV, and VI. Following large injections of horseradish peroxidase into the pretectal complex, labeled cells are seen in the superficial layers of the ipsilateral superior colliculus, in the ipsilateral ventral lateral geniculate nucleus, reticular nucleus and zona incerta and in the contralateral anterior, medial and posterior pretectal nuclei, nucleus of the optic tract and ventral lateral geniculate nucleus.     

Orderly anomalous retinal projections to the medial geniculate,ventrobasal, and lateral posterior nuclei of the hamster

Experiments were performed to determine (1) under what conditions early brain surgery can cause sensory afferents to the thalamus to form connections at abnormal thalamic sites and (2) the extent to which such ectopic projections are receptotopically organized. In newborn Syrian hamsters, two of the retina's principal synaptic targets, the superior colliculus and dorsal lateral geniculate nucleus, were destroyed, respectively, by a direct lesion and by retrograde degeneration following a lesion of the occipital cortex. In the same brains, alternative terminal space for the retinofugal axons was made available in auditory (medial geniculate) or somatosensory (ventrobasal) thalamic nuclei by lesions of ascending auditory or somatosensory pathways, respectively; additional terminal space was made in the lateral posterior nucleus by degeneration of afferents from the superior colliculus. The projections of the contralateral retina were traced in neonatally operated adults by making one or two small peripheral retinal lesions and intraocular injections of ³H-proline 5 days and 1 day, respectively, prior to sacrifice. The neonatal surgery reliably produced anomalous crossed retinal projections to the partially deafferented structures. These projections terminate preferentially at the nuclear surfaces. Computer reconstructions from serial sections demonstrated several signs of spatial order suggestive of receptotopic organization in the anomalous retinothalamic projections. In order of increasing stringency, these signs (which are not mutually exclusive) are: (1) In each nucleus, a restricted retinal sector gives rise to a limited part of the abnormal projection. (2) In each nucleus, different parts of the retina give rise to different parts of the anomalous projection. (3) In each nucleus, there is a more or less consistent polarity of the anomalous connection. Each small retinal sector appears to be represented along a “line of projection” in each of its abnormal thalamic targets, as it normally is in the dorsal and ventral lateral geniculate nuclei and in the superior colliculus. In some brains, some of the abnormal projections produce only a partial representation of the retina. However, in a single animal, a retinal sector not represented in the anomalous projections to one nucleus can contribute to the abnormal connections with another nucleus. In additional experiments, an attempt was made to direct developing auditory and somatosensory fibers normally terminating in the medial geniculate and ventrobasal nuclei, respectively, to anomalous thalamic targets. The axons were deprived of some of their normal thalamic sites of termination and alternative terminal space was made available in another thalamic sensory nucleus. These experiments failed to produce reliable evidence of ectopic auditory or somatosensory thalamic projections. The anomalous retinal projections to nuclei that normally recieve little (lateral posterior) or no (medial geniculate, ventrobasal) optic tract input, show that the preference of retinal axons for their normal targets is relative, not absolute. The orderliness of the ectopic projections opposes the hypothesis that the formation of retinotopic connections depends upon the matching of a set of signals distributed among the retinofugal fibers and a corresponding set of cues unique to the normal terminal fields of optic axons. The results are consistent with the formation of receptotopic connections by interactions among developing axons and suggest the action of additional factors that determine the terminal sites and organization of central neuronal connections.     

Early postnatal expression of L1 by retinal fibers in the optic tract and synaptic targets of the Syrian hamster

Previous immunohistochemical studies in mouse, rat, and chick have reported that the expression of the glycoprotein and cell adhesion molecule L1, a member of the immunoglobulin superfamily, shows regulation during development of retina and optic nerve. To extend our understanding of the role of L1 in developing neural circuitry, we have examined L1 expression in the optic tract and thalamic and midbrain synaptic targets of retinal fibers in the early postnatal Syrian hamster, a well-characterized developmental model of the primary visual projection. Metabolic labeling studies reveal that a synaptically targeted, sulfated, and glycosylated form of L1 undergoes rapid axonal transport from the retina. Retinofugal transport of L1 decreases commensurate with the decline in immunoreactivity of retinal fibers in the visual pathway. Retinal ganglion cell axons show intense L1 immunoreactivity as they navigate in highly fasciculated bundles in the optic tract overlying the lateral geniculate body and in the superior colliculus. We found no evidence of L1 immunoreactivity on retinal axon collaterals as they defasciculate from the optic tract and branch into target neuropils. L1 immunoreactivity wanes in optic tract as axon terminal arbors are elaborated in the lateral geniculate body and superior colliculus and as myelination in the visual pathway commences. This pattern of L1 expression suggests that, in the early postnatal period, L1 may support fasciculation of retinal fibers, maintaining them within the optic tract, and that subsequent down-regulation of L1 may facilitate their terminal arborization and myelination.     

The pretectal complex in the opossum: projections from the striate cortex and correlation with retinal terminal fields

Two terminal fields were revealed in the pretectal complex of the opossum by the Fink-Heimer method after striate cortical lesions. A rostral field is located within a rostrolateral strip of the compact part of the anterior pretectal nucleus, where a partial topographic arrangement of this projection is present. A caudal field is located within the sub-brachial nucleus of the optic tract, located between the brachium of the superior colliculus and the posterior pretectal nucleus. The corticotopic projection to this field is mirror-symmetric to that found in the superior colliculus and overlaps a bilateral projection from the retina. Based on hodological evidence, it is concluded that the nucleus of the optic tract in the opossum can be subdivided in (a) an intrabrachial nucleus receiving a direct projection from the contralateral retina and (b) a sub-brachial nucleus receiving projections from both retinae and from the striate cortex. The pretectal complex, as the superior colliculus, can be anatomically subdivided in a superficial region receiving visual input (theoptic pretectum) and a deep region only remotely connected to the visual system. The optic pretectum, however, differs from the superior colliculus in displaying a multiple-map arrangement within its constituent nuclei, instead of a single continuous representation of the visual field.     

Prenatal development of central optic pathways in albino rats.

The development of the central optic projections in albino rat fetuses has been studied using light and electron microscopic degeneration techniques and the horseradish peroxidase method for demonstrating axonal projections of neurons. The first optic axons to reach the region of the optic chiasm arrive at day 15. By day 16, a substantial optic chiasm is seen and the optic tract can be traced into the epithalamus, having first passed through the ventral lateral geniculate nucleus and a thin lamina of cells which is thought to correspond to part of the future dorsal geniculate nucleus. A growth rate of 80-100 mum per hour is estimated for the fastest growing axons. By day 16-1/3 the first axons have entered the anterior border of the superior colliculus and in the next day have grown across the entire rostrocaudal extent with the exception of the medial and lateral edges. The optic axons are recognized at day 17 as bundles lying just below the surface, but in older animals they come to lie deeper, as the whole layer of optic innervation broadens. The first synapses to be formed in the superior colliculus (some of them of optic origin) appear on day 17. Subsequently, there is a gradual increase in the number of contacts, the great majority being formed by optic axons. Compared with previous studies on Xenopus and chick, one of the most striking features of the development of the central visual connections in the rat is the relatively long time before the first optic axons reach the brain and the speed with which they innervate the central structures once they have arrived.     

Efferent projections of the intergeniculate leaflet and the ventral lateral geniculate nucleus in the rat

The intergeniculate leaflet (IGL) and the ventral lateral geniculate nucleus (VLG) are ventral thalamic derivatives within the lateral geniculate complex. In this study, IGL and VLG efferent projections were compared by using anterograde transport of Phaseolus vulgaris-leucoagglutinin and retrograde transport of FluoroGold. Projections from the IGL and VLG leave the geniculate in four pathways. A dorsal pathway innervates the thalamic lateral dorsal nucleus (VLG), the reuniens and rhomboid nuclei (VLG and IGL), and the paraventricular nucleus (IGL). A ventral pathway runs through the geniculohypothalamic tract to the suprachiasmatic nucleus and the anterior hypothalamus (IGL). A medial pathway innervates the zona incerta and dorsal hypothalamus (VLG and IGL); the lateral hypothalamus and perifornical area (VLG); and the retrochiasmatic area (RCA), dorsomedial hypothalamic nucleus, and subparaventricular zone (IGL). A caudal pathway projects medially to the posterior hypothalamic area and periaqueductal gray and caudally along the brachium of the superior colliculus to the medial pretectal area and the nucleus of the optic tract (IGL and VLG). Caudal IGL axons also terminate in the olivary pretectal nucleus, the superficial gray of the superior colliculus, and the lateral and dorsal terminal nuclei of the accessory optic system. Caudal VLG projections innervate the lateral posterior nucleus, the anterior pretectal nucleus, the intermediate and deep gray of the superior colliculus, the dorsal terminal nucleus, the midbrain lateral tegmental field, the interpeduncular nucleus, the ventral pontine reticular formation, the medial and lateral pontine gray, the parabrachial region, and the accessory inferior olive. This pattern of IGL and VLG projections is consistent with our understanding of the distinct functions of each of these ventral thalamic derivatives.     

Autoradiographic study of the retinal projections in the Chinese pangolin, Manis pentadactyla

Autoradiography was used to investigate the optic system of the Chinese pangolin, Manis pentadactyla. The pattern of retinal projections in the Chinese pangolin is similar to that described in other mammals. Each retina projects bilaterally to the suprachiasmatic nucleus, dorsal and ventral lateral geniculate nuclei, pretectal area, and superior colliculus (SC). Only contralateral projections are found to the medial, lateral, and dorsal accessory optic nuclei. The large lateral nucleus receives a dense projection from the retina and forms a compact mass on the dorsolateral area of the cerebral peduncle. The lamination of the SC could not be clearly demonstrated in the brain of the Chinese pangolin.     

Functional organization of the ventral lateral geniculate complex of the tree shrew (Tupaia belangeri): II. Connections with the cortex,thalamus, and brainstem

Connections of the ventral lateral geniculate complex (GLv) in the tree shrew were traced by anterograde and retrograde transport of WGA-HRP. The results buttress earlier findings that GLv in this species is composed of two main divisions, lateral and medial, each of which differs in its connections with the brainstem and cerebral cortex. The connections of the lateral division (GLv) suggest that it participates in visuosensory functions: it receives input from the retina, striate cortex, pretectum, and retino-recipient layers of the superior colliculus. These connections help clarify the identification of the internal and external subdivisions of GLv inasmuch as projections from both the superior colliculus and pretectum terminate in the external subdivision and each, in turn, receives a projection from the internal subdivision. Connections of the medial division suggest that this part of the nucleus is involved with visuomotor functions. Thus, the medio-caudal subdivision projects to the pontine nuclei, the prerubral field and the central lateral nucleus. The medio-caudal subdivision also receives projections from the lateral cerebellar nucleus, so that the GLv-ponto-cerebello-GLv loop involves mainly one subdivision of GLv. The medio-rostral subdivision receives projections from the pretectum and parietal cortex. Its output is directed primarily at the intermediate and deep layers of the superior colliculus. All of these targets of GLv, the pons, prerubral field, and deep layers of the superior colliculus, are known to play a role in the coordination of head and eye movements. Additional connections of GLv with the vestibular nuclei, intralaminar nuclei, hypothalamus, and facial motor nucleus are also described. © 1993 Wiley-Liss, Inc.     

Effect of optic nerve transection onN-acetylaspartylglutamate immunoreactivity in the primary and accessory optic projection systems in the rat

Evidence has been presented in recent years that support the hypothesis thatN-acetylaspartylglutamate (NAAG) may be involved in synaptic transmission in the optic tract of mammals. Using a modified fixation protocol, we have determined the detailed distribution of NAAG immunoreactivity (NAAG-IR) in retinal ganglion cells and optic projections of the rat. Following optic nerve transection, dramatic losses of NAAG-IR were observed in the neuropil of all retinal target zones including the lateral geniculate nucleus, superior colliculus, nucleus of the optic tract, the dorsal and medial terminal nuclei and suprachiasmatic nucleus. Brain regions were microdissected and NAAG levels measured by a radioimmunoassay (RIA) (IC₅₀:NAAG= 2.5nM,NAA= 100 μM;smallest detectable amount= 1–2pg/assay). decreases (50–60%) in NAAG levels were detected in the lateral geniculate, superior colliculus and suprachiasmatic nucleus. Moderate losses (25–45%) were noted in the pretectal nucleus and the nucleus of the optic tract. Smaller changes (15–20%) were detected in the paraventricular nucleus and the pretectal area. These results are consistent with a synaptic communication role for NAAG in the visual system.     

Depletion of cortical target induced by prenatal ionizing irradiation: effects on the lateral geniculate nucleus and on the retinofugal pathways.

Studies using neonatal surgical lesions to reduce the target area of the retina have supported the idea that developing axons show only a limited specificity in their targeting. This investigation tested whether retinogeniculate axons adjust for partial target depletion by repositioning of axons. We used adult Swiss mice exposed to gamma rays at the time when layer IV cells are generated in the ventricular zone (16 days of gestation). Nissl-stained brain sections were used for histological analyses in thalamus and cortex. Retinal ganglion cells were backfilled from the optic tract with horseradish peroxidase. Intraocular injections of horseradish peroxidase were used to study the retinal projections. In the posterior cortex there was a nearly complete absence of layer IV. The irradiated animals showed a 75% reduction of the dorsal lateral geniculate nucleus. The ventral division, superior colliculus, and other visually related nuclei were not affected. The loss in the ganglion cells (15.7%) was significant but clearly smaller than that observed in the dorsal lateral geniculate nucleus (75%). Therefore, the shrinkage of the dorsal lateral geniculate nucleus led to a reduction in the area available for retinal projections. Despite partial target loss, pattern of retinal projections did not differ from that of the controls. The effect on the dorsal lateral geniculate nucleus is discussed in the light of differences between prenatal and neonatal damage of the presumptive visual cortex. The absence of aberrant retinal projections suggests that repositioning of axons is not the first mechanism employed by retinal axons to match connections in numerically disparate populations.