Retinogeniculate Terminals Research Articles

An Early Enriched Experience Drives an Activated Microglial Profile at Site of Corrective Neuroplasticity in Ten-m3 Knock-Out Mice.

Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knock-out (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for six weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behavior, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioral rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localized increase in microglial density and activation profile within the identified geniculate region where corrective pruning was observed. No comparable response to EE was found in age-matched wild-type (WT) mice. These findings identify microglia as a potential mechanistic link through which EE drives the elimination of miswired neural circuits during early postnatal development. Activity driven, atypical recruitment of microglia to prune aberrant connectivity and restore function may have important therapeutic implications for neurodevelopmental disorders such as autistic spectrum disorder.

The parabigeminal nucleus is a source of "retinogeniculate replacement terminals" in mice that lack retinofugal input.

In the dorsal lateral geniculate nucleus (LGN) of mice that lack retinal input, a population of large terminals supplants the synaptic arrangements normally made by the missing retinogeniculate terminals. To identify potential sources of these "retinogeniculate replacement terminals," we used mutant mice (math5-/- ) which lack retinofugal projections due to the failure of retinal ganglion cells to develop. In this line, we labeled LGN terminals that originate from the primary visual cortex (V1) or the parabigeminal nucleus (PBG), and compared their ultrastructure to retinogeniculate, V1 or PBG terminals in the dLGN of C57Blk6 (WT) mice (schematically depicted above graph). Corticogeniculate terminals labeled in WT and math5-/- mice were similar in size and both groups were significantly smaller than WT retinogeniculate terminals. In contrast, the PBG projection in math5-/- mice was extensive and there was considerable overlap in the sizes of retinogeniculate terminals in WT mice and PBG terminals in math5-/- mice (summarized in histogram). The data indicate that V1 is not a source of "retinogeniculate replacement terminals" and suggests that large PBG terminals expand their innervation territory to replace retinogeniculate terminals in their absence.

Environmental Enrichment Partially Repairs Subcortical Mapping Errors in Ten-m3 Knock-Out Mice during an Early Critical Period.

Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.

Retinal and Tectal "Driver-Like" Inputs Converge in the Shell of the Mouse Dorsal Lateral Geniculate Nucleus.

The dorsal lateral geniculate nucleus (dLGN) is a model system for understanding thalamic organization and the classification of inputs as "drivers" or "modulators." Retinogeniculate terminals provide the primary excitatory drive for the relay of information to visual cortex (V1), while nonretinal inputs act in concert to modulate the gain of retinogeniculate signal transmission. How do inputs from the superior colliculus, a visuomotor structure, fit into this schema? Using a variety of anatomical, optogenetic, and in vitro physiological techniques in mice, we show that dLGN inputs from the superior colliculus (tectogeniculate) possess many of the ultrastructural and synaptic properties that define drivers. Tectogeniculate and retinogeniculate terminals converge to innervate one class of dLGN neurons within the dorsolateral shell, the primary terminal domain of direction-selective retinal ganglion cells. These dLGN neurons project to layer I of V1 to form synaptic contacts with dendrites of deeper-layer neurons. We suggest that tectogeniculate inputs act as "backseat drivers," which may alert shell neurons to movement commands generated by the superior colliculus. Significance statement: The conventional view of the dorsal lateral geniculate nucleus (dLGN) is that of a simple relay of visual information between the retina and cortex. Here we show that the dLGN receives strong excitatory input from both the retina and the superior colliculus. Thus, the dLGN is part of a specialized visual channel that provides cortex with convergent information about stimulus motion and eye movement and positioning.

Impaired clustered protocadherin-α leads to aggregated retinogeniculate terminals and impaired visual acuity in mice.

Clustered protocadherins (cPcdhs) comprising cPcdh-α, -β, and -γ, encode a large family of cadherin-like cell-adhesion molecules specific to neurons. Impairment of cPcdh-α results in abnormal neuronal projection patterns in specific brain areas. To elucidate the role of cPcdh-α in retinogeniculate projections, we investigated the morphological patterns of retinogeniculate terminals in the lateral geniculate (LG) nucleus of mice with impaired cPcdh-α. We found huge aggregated retinogeniculate terminals in the dorsal LG nucleus, whereas no such aggregated terminals derived from the retina were observed in the olivary pretectal nucleus and the ventral LG nucleus. These aggregated terminals appeared between P10 and P14, just before eye opening and at the beginning of the refinement stage of the retinogeniculate projections. Reduced visual acuity was observed in adult mice with impaired cPcdh-α, whereas the orientation selectivity and direction selectivity of neurons in the primary visual cortex were apparently normal. These findings suggest that cPcdh-α is required for adequate spacing of retinogeniculate projections, which may be essential for normal development of visual acuity.

Activity-Dependent Regulation of Retinogeniculate Signaling by Metabotropic Glutamate Receptors

Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically convey visual information from retina to the neocortex. Activation of metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural integration in dLGN; however, their direct influence on the primary sensory input, namely retinogeniculate afferents, is unknown. In the present study, we found that pharmacological or synaptic activation of type 1 mGluRs (mGluR(1)s) significantly depresses glutamatergic retinogeniculate excitation in rat thalamocortical neurons. Pharmacological activation of mGluR(1)s attenuates excitatory synaptic responses in thalamocortical neurons at a magnitude sufficient to decrease suprathreshold output of these neurons. The reduction in both NMDA and AMPA receptor-dependent synaptic responses results from a presynaptic reduction in glutamate release from retinogeniculate terminals. The suppression of retinogeniculate synaptic transmission and dampening of thalamocortical output was mimicked by tetanic activation of retinogeniculate afferent in a frequency-dependent manner that activated mGluR(1)s. Retinogeniculate excitatory synaptic transmission was also suppressed by the glutamate transport blocker TBOA (dl-threo-β-benzyloxyaspartic acid), suggesting that mGluR(1)s were activated by glutamate spillover. The data indicate that presynaptic mGluR(1) contributes to an activity-dependent mechanism that regulates retinogeniculate excitation and therefore plays a significant role in the thalamic gating of visual information.

Diffuse and Specific Tectopulvinar Terminals in the Tree Shrew: Synapses, Synapsins, and Synaptic Potentials

The pulvinar nucleus of the tree shrew receives both topographic (specific) and nontopographic (diffuse) projections from superior colliculus (SC), which form distinct synaptic arrangements. We characterized the physiological properties of these synapses and describe two distinct types of excitatory postsynaptic potentials (EPSPs) that correlate with structural properties of the specific and diffuse terminals. Synapses formed by specific terminals were found to be significantly longer than those formed by diffuse terminals. Stimulation of these two terminal types elicited two types of EPSPs that differed in their latency and threshold amplitudes. In addition, in response to repetitive stimulation (0.5–20 Hz) one type of EPSP displayed frequency-dependent depression whereas the amplitudes of the second type of EPSP were not changed by repetitive stimulation of up to 20Hz. To relate these features to vesicle release, we compared the synapsin content of terminals in the pulvinar nucleus and the dorsal lateral geniculate (dLGN) by combining immunohistochemical staining for synapsin I or II with staining for the type 1 or type 2 vesicular glutamate transporters (markers for corticothalamic and tectothalamic/retinogeniculate terminals, respectively). We found that retinogeniculate terminals do not contain either synapsin I or synapsin II, corticothalamic terminals in the dLGN and pulvinar contain synapsin I, but not synapsin II, whereas tectopulvinar terminals contain both synapsin I and synapsin II. Finally, both types of EPSPs showed a graded increase in amplitude with increasing stimulation intensity, suggesting convergence; this was confirmed using a combination of anterograde tract tracing and immunocytochemisty. We suggest that the convergent synaptic arrangements, as well as the unique synapsin content of tectopulvinar terminals, allow them to relay a dynamic range of visual signals from the SC.

Synapsin Utilization Differs among Functional Classes of Synapses on Thalamocortical Cells

Several proteins in nerve terminals participate in synaptic transmission between neurons. The synapsins, which are synaptic vesicle-associated proteins, have widespread distribution in the brain and are assumed essential for sustained recruitment of vesicles during high rates of synaptic transmission. We compared the role of synapsins in two types of glutamatergic synapses on thalamocortical cells in the dorsal lateral geniculate nucleus of mice: retinogeniculate synapses, which transmit primary afferent input at high frequencies and show synaptic depression, and corticogeniculate synapses, which provide modulatory feedback at lower frequencies and show synaptic facilitation. We used electrophysiological methods to determine effects of gene knock-out of synapsin I and II on short-term synaptic plasticity in paired-pulse, pulse-train, and posttetanic potentiation paradigms. The gene inactivation changed the plasticity properties in corticogeniculate, but not in retinogeniculate, synapses. Immunostaining with antibodies against synapsins in wild-type mice demonstrated that neither synapsin I nor II occurred in retinogeniculate terminals, whereas both occurred in corticogeniculate terminals. In GABAergic terminals, only synapsin I occurred. In corticogeniculate terminals of knock-out mice, the density of synaptic vesicles was reduced because of increased terminal size rather than reduced number of vesicles and the intervesicle distance was increased compared with wild-type mice. In the retinogeniculate terminals, no significant morphometric differences occurred between knock-out and wild-type mice. Together, this indicates that synapsin I and II are not present in the retinogeniculate terminals and therefore are not essential for sustained, high-rate synaptic transmission.

Activity-Dependent Patterning of Retinogeniculate Axons Proceeds with a Constant Contribution from AMPA and NMDA Receptors

Neural activity is critical for the refinement of neural circuitry during development, although the mechanisms involved in stabilizing appropriate connectivity remain unclear. It has been proposed that the insertion of AMPA receptors at synapses with only NMDA receptors ("silent synapses") mediates this stabilization, leading to an increasing contribution from AMPA receptors as development proceeds. Here we show in a mammalian system known to undergo activity-dependent development [the segregation of retinal afferents into ON/OFF sublaminae in the ferret lateral geniculate nucleus (LGN)] that the refinement of the neural circuitry occurs in the presence of a constant functional contribution from AMPA and NMDA receptors. Although we detected a small number of silent synapses on LGN cells, their proportion did not decrease with age. The size and kinetics of NMDA-mediated spontaneous EPSCs (sEPSCs) were also stable over this period. Together with previous results reporting the stability of unitary AMPA-mediated EPSCs, the constancy of NMDA-mediated sEPSCs indicates an unchanging AMPA/NMDA contribution. Additionally, the CNQX-sensitivity did not increase for either sEPSCs or optic tract-evoked EPSCs. Likewise, the anatomical AMPA/NMDA ratio, as assayed by quantifying the colocalized expression of AMPA and NMDA receptor subunits, was fixed throughout ON/OFF sublamination. In particular, the colocalization of AMPA receptor subunits (GluR1 or GluR4) and NMDA receptor subunit NR1 opposite identified retinogeniculate terminals was stable during this period. These results add to the view of the population of retinogeniculate synapses as robustly stable or normalized during a period when retinogeniculate axons are undergoing dramatic activity-dependent refinement.

Retinal Projections to the Dorsal and Ventral Lateral Geniculate Nuclei in the Domestic Pig (Sus scrofa domesticus Brisson)

Retinal projections and cytoarchitectonic organization of the lateral geniculate nucleus (LGN) in domestic pig (Sus scrofa domesticus Brisson) were studied using the Nissl stain and anterograde transport of horseradish peroxidase (HRP) methods. In Nissl preparation, both the dorsal LGN (LGNd) and the ventral LGN (LGNv) of the domestic pig were divided into four laminae according to cell organization, respectively. They were named lamina I-IV in both nuclei in lateromedial order and another cell group located in the dorsal part of LGNv was named intergeniculate leaflet. The rostral and caudal end of the LGNd were shown with only lamina I. Two-thirds of middle part was composed with all laminae. Injection of HRP into the unilateral vitreous body demonstrated that many labeled optic fibers crossed at the optic chiasm and a few of them were uncrossed, and they entered into the brain stem via the optic tract. HRP labeled terminals were seen bilaterally in the LGNd and the LGNv of the thalamus, with contralateral predominance. Lamina I and II of the LGNd received contralateral retinal projections. Laminar III and IV received ipsilateral and bilateral retinal projections, respectively. Many retino-geniculate terminals were found in laminae I and III of the contralateral LGNv and a few of them were seen as a small tiny spot in the upper part of lamina II of the ipsilateral LGNv.

Y retinal terminals contact interneurons in the cat dorsal lateral geniculate nucleus.

One of the largest influences on dorsal lateral geniculate nucleus (dLGN) activity comes from interneurons, which use the neurotransmitter gamma-aminobutyric acid (GABA). It is well established that X retinogeniculate terminals contact interneurons and thalamocortical cells in complex synaptic arrangements known as glomeruli. However, there is little anatomical evidence for the involvement of dLGN interneurons in the Y pathway. To determine whether Y retinogeniculate axons contact interneurons, we injected the superior colliculus (SC) with biotinylated dextran amine (BDA) to backfill retinal axons, which also project to the SC. Within the A lamina of the dLGN, this BDA labeling allowed us to distinguish Y retinogeniculate axons from X retinogeniculate axons, which do not project to the SC. In BDA-labeled tissue prepared for electron microscopic analysis, we subsequently used postembedding immunocytochemical staining for GABA to distinguish interneurons from thalamocortical cells. We found that the majority of profiles postsynaptic to Y retinal axons were GABA-negative dendrites of thalamocortical cells (117/200 or 58.5%). The remainder (83/200 or 41.5%) were GABA-positive dendrites, many of which contained vesicles (59/200 or 29.5%). Thus, Y retinogeniculate axons do contact interneurons. However, these contacts differed from X retinogeniculate axons, in that triadic arrangements were rare. This indicates that the X and Y pathways participate in unique circuitries but that interneurons are involved in the modulation of both pathways.

The role of spontaneous retinal activity before eye opening in the maturation of form and function in the retinogeniculate pathway of the ferret.

During early mammalian development, inputs from the two retinas intermix within the lateral geniculate nucleus (LGN), then segregate during the first postnatal week into layers that receive input from a single retina. Functionally, the LGN also changes markedly during the first postnatal month; early geniculate responses to retinal input are mainly excitatory, then inhibitory circuits mature within the LGN. These remarkable changes in form and function of the retinogeniculate pathway occur at a time when patterned visual activity is not present, but retinal ganglion cells already manifest spontaneous action potential activity. To examine the role of early retinal activity in these critical developmental processes, we placed the slow release polymer Elvax embedded with tetrodotoxin (TTX) into the vitreous chamber of one or both eyes of neonatal ferrets. Animals receiving monocular injection of TTX had the other eye treated with Elvax containing control citrate buffer. Intraocular injection of horseradish peroxidase was made at the end of the period of TTX treatment to reveal the retinal terminals in the LGN. Chronic monocular or binocular blockade of retinal activity during the first postnatal week did not prevent eye-specific segregation, although it made the boundaries between layers less distinct. Retinal terminals ended preferentially in the appropriate layer, but a large number of terminals were also present in the inappropriate layer. Further segregation was achieved during the second postnatal week of activity blockade, when most retinal terminals ended preferentially in the appropriate geniculate layer and sharper layer boundaries were present. However, a small but significant number of terminals still extended into the inappropriate layer. Together, these findings indicate that monocular as well as binocular blockade of retinal activity resulted in some anomalous retinogeniculate projections and delayed eye-specific patterning, but segregation was largely intact at the end of the second postnatal week. We also report here that intraocular tetrodotoxin had a marked effect on the maturation of intrinsic geniculate circuits prior to eye opening. Whole-cell patch-clamp recordings in the LGN slice preparation revealed that activity blockade prevented the maturation of the slow, but not the fast, hyperpolarizing potential of LGN neurons during the first postnatal month and up to P38, the oldest age studied. In conclusion, these results indicate that spontaneous retinal activity modulates the time course of binocular segregation but does not alone account for the segregation of retinogeniculate terminals. However, early retinal activity plays an important role in developing the intrinsic circuitry of the LGN.

Direct and indirect retinal input into degenerated dorsal lateral geniculate nucleus after striate cortical removal in monkey: implications for residual vision

We removed the striate cortex of one cerebral hemisphere in a macaque monkey, causing almost total retrograde degeneration of the corresponding dorsal lateral geniculate nucleus (dLGN) and extensive transneuronal degeneration of ganglion cells in the corresponding hemi-retina of each eye. The rare surviving geniculate projection neurons were retrogradely labelled by horseradish peroxidase (HRP) from extra-striate cortex and retinogeniculate terminals were labelled by an intraocular injection of HRP. Retinal terminals in the degenerated dLGN made synaptic contact exclusively with the dendrites of interneurons immunopositive for gamma-aminobutyric acid (GABA) in both parvocellular and magnocellular regions of dLGN. As well as being post-synaptic to retinal terminals these vesicle-containing dendrites were pre- and postsynaptic to other similar dendrites, and presynaptic to relay cells. Surviving labelled projection neurons received retinal input indirectly, via both the GABA-immunopositive interneurons and GABA-immunonegative terminals characteristic of those from the superior colliculus. In the degenerated, as opposed to the normal dLGN, about 20% of retinal terminals were GABA-immunopositive and GABA-immunoreactivity was prominently elevated in the ganglion and amacrine cell layers of the degenerated half of the retina. The optic nerve also contained numerous GABA-immunopositive axons but very few such axons were found in a normal optic nerve processed in identical manner. The surviving pathways from the retina must underlie the visual abilities that survive striate cortical removal in monkeys and human patients and may involve the degenerated dLGN as well as the mid-brain.

Organization of retinogeniculate projections in turtles of the genera Pseudemys and Chrysemys.

Organization of retinal projections to the dorsal lateral geniculate complex in turtles has been studied by means of light and electron microscopic axon tracing techniques. Orthograde degeneration studies with Fink-Heimer methods following restricted retinal lesions show the entire retina has a topologically organized projection to the contralateral dorsal lateral geniculate complex. The nasotemporal axis of the retina projects along the rostrocaudal axis of the geniculate complex; the dorsoventral axis of the retina projects along the dorsoventral axis of the geniculate complex. The projection to the ipsilateral dorsal lateral geniculate complex originates from the ventral, temporal and nasal edges of the retina. The nasotemporal axis of the ipsilateral retina projects along the rostrocaudal axis of the geniculate complex. It was not possible to determine the orientation of the dorsoventral axis of the ipsilateral retina on the geniculate complex. Light microscopic autoradiographic tracing experiments and electron microscopic degeneration experiments show the retinogeniculate projection has a laminar organization. Retinogeniculate terminals are found in both the neuropile and cell plate throughout all three subnuclei of the dorsal lateral geniculate complex but have a distinctive distribution in each subnucleus. In the subnucleus ovalis, they are frequent in both the neuropile and cell plate which forms the rostral pole of the complex. In the dorsal subnucleus, they are most prevalent in the outer part of the neuropile layer, less frequent in the inner part of the neuropile, and rare in the cell plate. In the ventral subnucleus, they are frequent in the outer part of the neuropile but are also common in the inner part of the neuropile and cell plate. These observations point to several principles of geniculate organization in turtles. First, the complex receives projections from the entire contralateral retina and a segment of the ipsilateral retina. It thus has monocular and binocular segments that together receive a topologically organized representation of the binocular visual space and the contralateral monocular visual space. Second, the three geniculate subnuclei receive information from different, specialized regions of the retina and visual space. Subnucleus ovalis receives information from the frontal binocular visual field. The ventral subnucleus receives information from the caudal binocular field. The dorsal subnucleus receives input from the contralateral monocular field. Third, there is a lamination of retinal inputs in the geniculate complex which differs in character within the three subnuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphology of retinogeniculate terminals in the turtle, Pseudemys scripta elegans.

The dorsal lateral geniculate complex in turtles receives a bilateral, topographic projection from the retina and projects to the telencephalon. This study examined the morphology of individual retinogeniculate terminals that were filled with horseradish peroxidase by injections in the optic tract or optic tectum. A large number of retinogeniculate terminals were successfully filled and detailed drawings were prepared of 87 terminals. Terminals were classified into three types based on the size and number of varicosities in the terminal, and (if a terminal formed a spatially restricted arbor) the volume of the arbor. Type I retinogeniculate terminals form spatially restricted, large-volume arbors with a low density of large varicosities. Type II retinogeniculate terminals form small volume arbors with a high density of small varicosities. Type III retinogeniculate terminals, in contrast to types I and II, do not form spatially restricted arbors. Rather, they consist of sparsely branched axons that parallel the optic tract and contain scattered en passant varicosities. Plots of the distribution of different terminal types throughout the geniculate complex show that all three terminal types occur throughout the rostrocaudal and mediolateral extents of the complex. However, each terminal type has a preferential distribution with type II terminals being concentrated in the outer half of the neuropile, type I terminals in the inner half of the neuropile, and type III terminals in the cell plate. All three types can arise from axons that continue caudally to terminate in the tectum. These findings raise the possibility that various classes of retinal ganglion cells differ in their mode of termination within the geniculate complex, but the precise relation between the three types of retinogeniculate terminals and the classes of ganglion cells remains to be determined.

The development of the retinogeniculate pathways in normal and albino ferrets.

The retinogeniculate pathways of normal and albino ferrets have been studied with horseradish peroxidase and tritiated proline used as axonal markers. The uncrossed retinogeniculate projection of adult albino ferrets is abnormally small and occupies only a fraction of the geniculate area normally occupied by uncrossed afferents. The crossed pathway is correspondingly expanded, occupying almost the entire nucleus. The geniculate laminae in the albino ferret are abnormal, showing abnormal fusions between layers receiving crossed input and abnormal discontinuities next to the small cell islands receiving uncrossed afferents. In early development, retinofugal fibres can be labelled within the optic tracts on the 28th intrauterine day and a few crossed fibres can be traced into the lateral geniculate nucleus. At this stage, the uncrossed component is extremely small in normal and albino animals and cannot be traced beyond the tract. By day 32 retinal fibres are invading the lateral geniculate nucleus bilaterally, the invasion by the crossed component being significantly more advanced than that by the uncrossed component. The uncrossed pathway of the albinos is already abnormal in terms of its size, in terms of the position it occupies in the optic tract, and in terms of its limited invasion of the lateral geniculate nucleus. The abnormally reduced size of the uncrossed component appears earlier than the abnormal segregation of the retinogeniculate terminals, suggesting that the primary action of the albino gene upon central visual pathways is prechiasmatic. At postnatal stages (41 days after conception and older) the normal, gradual withdrawal of the uncrossed fibres from the monocular segment, and the separation of crossed from uncrossed retinogeniculate terminal arbors is significantly delayed in the albinos. The uncrossed retinogeniculate terminals are abnormally sparse initially and become distributed in an abnormal, interrupted pattern as development proceeds. The abnormal pattern of geniculate lamination appears to be secondary to the abnormal distribution of retinogeniculate afferents.

The fine structure of the perigeniculate nucleus in the cat

The fine structure of the cat's perigeniculate nucleus has been analyzed and compared to that of dorsal thalamic relay nuclei. Golgi preparations and electron micrographs of perigeniculate cells commonly show somatic spines. The most common presynaptic elements for these spines and for the adjacent perikaryal surfaces are relatively large axon terminals containing round synaptic vesicles and making multiple asymmetric contacts. These "RLD" terminals (so termed for their round vesicles, large average size of the terminals, and dark mitochondria) are also presynaptic to dendritic spines and shafts of proximal and secondary dendrites. Comparisons with adjacent parts of the dorsal lateral geniculate nucleus show that these RLD terminals are cytologically distinct from retinogeniculate terminals and that small numbers of RLD terminals also occur in the geniculate A laminae. Three other major classes of perigeniculate synaptic terminals, resemble major classes of terminals in the dorsal lateral geniculate nucleus. These include two types of terminal with flat or ovoid synaptic vesicles and dark mitochondria, "FD1" and "FD2" terminals, and a class of small terminal with densely clustered round vesicles and dark mitochondria, "RSD" terminals. RSD terminals, which resemble corticogeniculate axon terminals, represent the only class of perigeniculate terminal that does not contact perikarya. FD2 terminals resemble lateral geniculate presynaptic dendrites and participate in serial and triadic synaptic contacts, being both pre- and postsynaptic; however, in contrast to the arrangement characteristic of thalamic relay nuclei, these contacts do not occur within synaptic glomeruli. A fifth major class of perigeniculate presynaptic terminal has large flat or polymorphic synaptic vesicles and pale mitochondria. These "FP" terminals are seen infrequently in the lateral geniculate A laminae. Similarities between perigeniculate and lateral geniculate fine structure may relate in part to common sources of afferent input to the two nuclei.

Development of terminal arbors of retino-geniculate axons in the kitten—II. Electron microscopical observations

Individual retino-geniculate axon arbors from kittens of 1 to 8 postnatal weeks were densely filled with horseradish peroxidase. The light-microscopical appearance of various types of immature growing tips was correlated with their synaptic relations as seen in the electron-microscope. During the first 2 postnatal weeks, the broad irregular bases of spray-like terminal extensions as well as foliate growth-cone-like terminals contain the round synaptic vesicles and pale mitochondria characteristic of adult retinal terminals. They form elementary glomerular arrangements in which they are the central profile synapsing with dendritic profiles. Many postsynaptic profiles contain large electron-lucent vesicles characteristic of growing neurites, whereas the immature retinal terminations do not. The more numerous finger-like growing tips also contain round synaptic vesicles and make short en passage contacts onto dendrites and outgrowths of perikarya of geniculate cells. The latter type of contact is not seen in the adult. After 3 weeks, retinal terminals are larger and make contacts in distinctly glomerular arrangements. Glial sheaths are evident for the first time. By 6–8 weeks, the terminals which appear crenulated in the light-microscope are always the central profile in a mature glomerulus. Smaller rounder terminals make simple axo-dendritic contacts as in the adult. The few immature terminal structures seen at 8 weeks also contain synaptic vesicles, but their contacts are not adult-like, nor are their synaptic arrangements entirely surrounded by glia. These findings, along with those of the previous paper, 17 demonstrate that (a) many retino-geniculate terminals establish synaptic contacts long before attaining their adult form; (b) during the period optimal for induction of translaminar axon sprouting (1–2 weeks postnatal), only a few immature terminal forms participate in elementary glomeruli; (c) the decreasing malleability of these axons after 3 weeks is accompanied by an increase in crenulated terminals that enter glomeruli surrounded by glial sheaths. It is suggested that ensheathing of synaptic arrangements by astrocytic glia may be one factor which subsequently impedes axon sprouting in older animals.

Plasticity in the chick ventral lateral geniculate nucleus.

The chick ventral lateral geniculate nucleus (GLv) receives topographically corresponding projections from the retina and optic tectum. Tectal lesions produced on the day of hatching removed the tectogeniculate input to the GLv region corresponding to the tectal lesion and also severed some retinotectal axons. Following a survival period of 3 to 10 weeks, a patch of augmented retinogeniculate projection was noted in the GLv segment that corresponds topographically to the damaged area of the tectum. Changing the site of the tectal lesion led to changes in the locus of heavy retinal projection to the GLv predictable from topographic maps. Nuclei which received retinal but not tectal projections did not appear to have regions of augmented retinal termination nor did nuclei which received tectal but not retinal innervation. It is unlikely that the increased retinogeniculate termination is due to rerouting of growing retinotectal axons since the chick retinofugal pathway is well established by the time of hatching. Furthermore, there was no evidence of a projection from the ipsilateral eye to the affected GLv. On the basis of these light microscopic studies, it would appear that retinogeniculate terminals have sprouted in the GLv and that competition for terminal space, conservation of terminal space, proximity, and perhaps other factors are necessary for the augmented projection to occur.

The synaptic organization of terminals traced from individual labeled retino-geniculate axons in the cat

Individual retino-geniculate axons in the dorsal lateral geniculate nucleus of the cat were filled with horseradish peroxidase and studied with both the light and electron microscope. A procedure was followed which allowed us to identify the size, shape and arrangement of particular terminal swellings by light microscopy and then to study their patterns of synaptic contacts with the electron microscope. Many of the labeled terminals in laminae A and Al have the same fine structural features as retino-geniculate terminals that have been described previously. They are large, contain round synaptic vesicles and pale mitochondria, and are the central processes in glomeruli where they form asymmetric contacts with dendrites and terminals containing pleomorphic synaptic vesicles. Other terminals have the same cytological features but are quite small and are not the central processes in glomeruli. Some of these small terminals form simple axo-dendritec contacts while others participate in very large glomeruli containing several terminals from a single retino-geniculate axon. These different patterns of synaptic contacts made by different terminals can be found on branches of a single axon and correspond to the variations in terminal arbors described in the preceding paper ( MASON & ROBSON, 1978).