The Fine Structure of Photoreceptor Terminals in the Compound Eye of Pandalus borealis (Crustacea)

Seven of the photoreceptor axons of each ommatidium in the compound eye of the prawn Pandalus borealis end in two layers in the optic lamina. They have expanded terminals in the optic cartridges; four distally and three proximally in each cartridge. All seven receptor terminals are presynaptic to one lamina monopolar neuron (M₂) of the cartridge. This monopolar neuron is situated centrally in the cartridge and has a thick axis fibre with radially arranged branches, and its axon has a terminal in medulla externa. At the synapses, an arrowlike presynaptic bar is found facing three postsynaptic profiles. The receptor terminals have several characteristics. Their cytoplasm is filled with empty and coated vesicles, and contains numeorus large mitochondria and clusters of tubular elements. There is a longitudinally arranged fascicle of filaments partly surrounded by electron-dense amorphous material in the terminals. Centrally towards M₂, numerous neural spines invaginate into the terminal. Along the entire terminal periphery, there are invaginations from the glial cells. The terminals also form small knoblike protrusions extending into the surrounding glial cells.     

Activity-independent prespecification of synaptic partners in the visual map of Drosophila

Specifying synaptic partners and regulating synaptic numbers are at least partly activity-dependent processes during visual map formation in all systems investigated to date . In Drosophila, six photoreceptors that view the same point in visual space have to be sorted into synaptic modules called cartridges in order to form a visuotopically correct map . Synapse numbers per photoreceptor terminal and cartridge are both precisely regulated . However, it is unknown whether an activity-dependent mechanism or a genetically encoded developmental program regulates synapse numbers. We performed a large-scale quantitative ultrastructural analysis of photoreceptor synapses in mutants affecting the generation of electrical potentials (norpA, trp;trpl), neurotransmitter release (hdc, syt), vesicle endocytosis (synj), the trafficking of specific guidance molecules during photoreceptor targeting (sec15), a specific guidance receptor required for visual map formation (Dlar), and 57 other novel synaptic mutants affecting 43 genes. Remarkably, in all these mutants, individual photoreceptors form the correct number of synapses per presynaptic terminal independently of cartridge composition. Hence, our data show that each photoreceptor forms a precise and constant number of afferent synapses independently of neuronal activity and partner accuracy. Our data suggest cell-autonomous control of synapse numbers as part of a developmental program of activity-independent steps that lead to a "hard-wired" visual map in the fly brain.     

Compensatory synaptic growth in the rod terminals as a sequel to partial photoreceptor cell loss in the retina of chimaeric mice.

In the retina of chimaeric mice of rd and wild-type genotypic combination, selective loss of rd/rd photoreceptor cells, after initial development, leads to a mosaic retina with variable amounts of normal photoreceptor cells present over the retinal surface. In some of the rod terminals of these retinas the synaptic complexes with the second order retinal neurons are seen to contain multiple synaptic ribbons and an increased number of profiles of the postsynaptic elements. These changes are observed only in the rod terminals and not in the cone pedicles. Computer aided three-dimensional reconstruction of the altered synapses shows that these changes result from an increase in the number of synaptic sites, characterized by multiplication of the synaptic ribbons and enlargement of the second order neuronal processes. A quantitative analysis of such synapses, based on serial electron micrographs, shows that these are most frequently located in the retinal regions of the chimaeric individuals that have suffered maximum photoreceptor cell loss. Thus synaptic growth appears to take place as a reaction to the reduction of afferent input to the postsynaptic components. These findings demonstrate persistent synaptic plasticity in the rod terminals of mammalian retina during the maturational phase of late postnatal development. Compensatory synaptic growth in the rod terminals, as recorded here, can have important implications for the maintenance of visual sensitivity in the diseased or ageing retina.     

Fly photoreceptor synapses: their development, evolution, and plasticity

Recent studies are reviewed on the synapses of photoreceptor terminals in the first optic neuropile of the flies, Musca and Drosophila. Afferent synaptic contacts are of uniform dimensions; they have a postsynaptic tetrad with a membrane organization of P-face particles, resembling other inhibitory synapses. A distributed population of such contact sites forms progressively during synaptogenesis by the selective, sequential accretion of identified postsynaptic elements at the receptor terminal. The comparative anatomy of this synapse indicates that elements have also been added during its phylogeny from an ancestral dyad. All cells are homologs of those in other species of Diptera. The number of synaptic sites is regulated by both pre- and postsynaptic cells, in proportion to their cell surfaces; an independent size increase in the receptor terminals (procured in the Drosophila mutant gigas) produces an increase in their synaptic population. The number of sites declines with age, however, accompanied by an increase in size of those synaptic sites remaining; this occurs for both afferent and feedback photoreceptor synapses. Lastly, the number of sites changes with visual experience; the frequency of feedback synapses is larger following dark rearing during early adult life than following visual experience.     

Assessing the Role of Cell-Surface Molecules in Central Synaptogenesis in the Drosophila Visual System

A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements.     

The superposition eye of Cloeon dipterum: The organization of the lamina ganglionaris

Summary The lamina ganglionaris of the superposition eye of Cloeon dipterum is composed of separate optic cartridges arranged in a hexagonal pattern. Each optic cartridge consists of one central, radially branched monopolar cell (Li) surrounded by a crown of seven retinula cell terminals and two more unilaterally branched monopolar cells (La1/La2) situated close together outside the cartridge. Projections to neighbouring cartridges have not been observed.In most cases, synaptic contacts could be seen between a presynaptic retinula cell and more than two other postsynaptic profiles, which belong to monopolar cells or sometimes to glial cells.Seven retinula cell fibers of one ommatidium pass in a bundle through the basement membrane, run into their respective cartridges without changing orientation and terminate at approximately equal levels in the lamina. Long visual fibers with endings in the medulla are not visible in the superposition eye lamina, but are present in the lateral apposition eye. The relationship between the behaviour of the animal, optic mechanisms of the superposition eye and the structure of the lamina is discussed.     

Modulation of sensory input to the spinal cord by presynaptic ionotropic glutamate receptors

Sensory input from peripheral nerves to the dorsal horn of the spinal cord is mediated by a variety of agents released by the central terminals of dorsal root ganglion (DRG) neurons. These include, but are not limited to, amino acids, especially glutamate, peptides and purines. The unraveling of the mechanisms of synaptic transmission by central terminals of DRG neurons has to take into account various ways in which the message from the periphery can be modulated at the level of the first central synapse. These include postsynaptic and presynaptic mechanisms. Homomeric and heteromeric complexes of receptor subunits for the different transmitters released by DRG neurons and interneurons, clustered at the postsynaptic site of central synapses, can be expressed in different combinations and their rate of insertion into the postsynaptic membrane is activity-regulated. Inhibitory mechanisms are an important part of central modulation, especially via presynaptic inhibition, currently believed to involve GABA released by inhibitory intrinsic neurons. Recent work has established the occurrence of another way by which sensory input can be modulated, i.e. the expression of presynaptic ionotropic and metabotropic receptors in central terminals of DRG neurons. Microscopic evidence for the expression, in these terminals, of various subunits of ionotropic glutamate receptors documents the selective expression of glutamate receptors in functionally different DRG afferents. Electrophysiological and pharmacological data suggest that activation of presynaptic ionotropic glutamate receptors in central terminals of DRG neurons may result in inhibition of release of glutamate by the same terminals. Glutamate activating presynaptic receptors may spill over from the same or adjacent synapses, or may be released by processes of astroglial cells surrounding synaptic terminals. The wide expression of presynaptic ionotropic glutamate receptors, especially in superficial laminae of the dorsal horn, where Adelta- and C fibers terminate, provides an additional or alternative mechanism, besides GABA-mediated presynaptic inhibition, for the modulation of glutamate release by these fibers. Since, however, presynaptic ionotropic glutamate receptors are also expressed in terminals of GABAergic intrinsic interneurons, a decrease of GABA release resulting from activation of these receptors in the same laminae, may also play a role in central sensitization and hyperalgesia.     

Diurnal changes in the fine structure of photoreceptors in an abalone,Nordotis discus

Summary The ultrastructure of the synapses in the brain of the monogenean Gastrocotyle trachuri (Platyhelminthes) is described. The synapses consist of one presynaptic terminal separated by a uniformly wide synaptic cleft, from one or more postsynaptic elements. The presynaptic terminals are characterized by the presence of paramembranous dense projections and associated synaptic vesicles. The postsynaptic elements while possessing membrane densities, are usually devoid of vesicles.The structure of the synapses in the brain of Gastrocotyle is compared to synapses from other platyhelminths.     

Dynamics of dendritic spines and their afferent terminals: spines are more motile than presynaptic boutons

Previous work has established that dendritic spines, sites of excitatory input in CNS neurons, can be highly dynamic, in later development as well as in mature brain. Although spine motility has been proposed to facilitate the formation of new synaptic contacts, we have reported that spines continue to be dynamic even if they bear synaptic contacts. An outstanding question related to this finding is whether the presynaptic terminals that contact dendritic spines are as dynamic as their postsynaptic targets. Using multiphoton time-lapse microscopy of GFP-labeled Purkinje cells and DiI-labeled granule cell parallel fiber afferents in cerebellar slices, we monitored the dynamic behavior of both presynaptic terminals and postsynaptic dendritic spines in the same preparation. We report that while spines are dynamic, the presynaptic terminals they contact are quite stable. We confirmed the relatively low levels of presynaptic terminal motility by imaging parallel fibers in vivo. Finally, spine motility can occur when a functional presynaptic terminal is apposed to it. These analyses further call into question the function of spine motility, and to what extent the synapse breaks or maintains its contact during the movement of the spine.     

Synaptic terminal parameters in unanaesthetized rat cerebral cortex

The ultrastructure of synapses from the molecular layer of parietal cortex was examined in two groups of unanesthetized rats. Rats of the first group were killed by stunning across the back of the neck, and those of the second group by the introduction of fixative through a preimplanted carotid artery cannula. Comparison of synapses from the two groups revealed that the distribution of synaptic types was the same. A larger percentage of synapses of the cannulated group has vesicle attachment sites than did those of the stunned group. The area and perimeter of the presynaptic terminals were significantly larger in synapses from the cannulated group, although the equivalent length of the postsynaptic thickening was less. The mean value for synaptic curvature was greater in the cannulated group, although over 80% of synapses in both groups had positive curvatures. No significant differences were found between the groups for the relationships between presynaptic terminal area and synaptic vesicle number, and between postsynaptic thickening length and synaptic curvature. Membrane recycling is suggested as a mechanism of accounting for the differences. The preponderance of postively-curved synapses in unanesthetized material may indicate a preponderance of functioning synapses.     

The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina

The photoreceptor ribbon synapse is a highly specialized glutamatergic synapse designed for the continuous flow of synaptic vesicles to the neurotransmitter release site. The molecular mechanisms underlying ribbon synapse formation are poorly understood. We have investigated the role of the presynaptic cytomatrix protein Bassoon, a major component of the photoreceptor ribbon, in a mouse retina deficient of functional Bassoon protein. Photoreceptor ribbons lacking Bassoon are not anchored to the presynaptic active zones. This results in an impaired photoreceptor synaptic transmission, an abnormal dendritic branching of neurons postsynaptic to photoreceptors, and the formation of ectopic synapses. These findings suggest a critical role of Bassoon in the formation and the function of photoreceptor ribbon synapses of the mammalian retina.     

Quantification of the synapses in the hippocampus of aged rats

The synapses in the stratum lacunosum-molecular (str. L-M) of CA1 hippocampal field in 3-month old and 24-month old rats were examined using quantitative ultrastructural methods. No significant difference in the density of synapses and postsynaptic dendritic spines was found between the two age groups. The area of presynaptic terminals and postsynaptic dendritic spines was decreased slightly but significantly in the group of aged as compared to that in the group of young-mature rats. The vesicle number per presynaptic terminal, per area of presynaptic terminals and per volume of neuropil was not changed while the vesicle number per area of synaptic contact zones (SCZ) was increased in the group of aged rats. The mean length, total length and total surface of SCZ were diminished in the group of aged as compared to those in the group of young-mature rats. The same width of the str.radiatum and str.L-M in the two age groups showed that there was no any shrinkage of the neuropil in aged rats. The quantitative alterations in the synapses were accompanied by an increased number of dense and lamellar bodies in presynaptic terminals as well as with a presence of hypertrophic astroglial processes.     

Synaptic Contacts of Neurons of Fascia Dentata Transplants with Nonspecific Targets in Neocortex of Recipients

We carried out an electron microscopy study of possible synaptic contacts of the neurons of intracortical transplants of the rat brain fascia dentata with targets in the recipient somatosensory cortex. The axons of fascia dentata granular cell and their synaptic terminals could be easily identified in the neocortex due to their distinct morphological features (mossy fibers), although the fascia dentate cells normally do not interact with the neocortex. Thin nonmyelenized mossy fibers were found in both an intermediate zone between the transplant and brain and in the adjacent brain. Their presynaptic buds, like in situ, had large size and formed characteristic terminal, intraterminal, and en passant multiple synaptic contacts and desmosome-like junctions. The aberrant nerve fibers used perykaryons, dendrites of varying diameter, and dendrite spikes of the somatosensory cortex pyramidal neurons as postsynaptic targets in the neocortex. In addition to vacant spaces that appeared in the brain as a result of transplantation, the ingrowing axons induced the formation of additional contact sites: deep invaginations of the plasmalemma of perykaryons, somatic spikes, terminal branchings of dendrites, and dendritic outgrowths of complex branched shape. These aberrant contacts were characterized by the presence of polyribosomes, endoplasmic reticulum cisternae, and mitochondria in the postsynaptic loci. Osmiophility and extension of desmosome-like junctions were also enhanced in such synapses. Thus, it was shown that mossy fibers ingrowing in the recipient neocortex were capable of forming cell-to-cell contacts with signs of functional synapses to atypical cell targets.     

Synaptic contacts of neurons of fascia dentata transplants with nonspecific targets in neocortex of recipients

We carried out an electron microscopy study of possible synaptic contacts of the neurons of intracortical transplants of the rat brain fascia dentata with targets in the recipient somatosensory cortex. The axons of fascia dentata granular cell and their synaptic terminals could be easily identified in the neocortex due to their distinct morphological features (mossy fibers), although the fascia dentate cells normally do not interact with the neocortex. Thin nonmyelenized mossy fibers were found in both an intermediate zone between the transplant and brain and in the adjacent brain. Their presynaptic buds, like in situ, had large size and formed characteristic terminal, intraterminal, and en passant multiple synaptic contacts and desmosome-like junctions. The aberrant nerve fibers used perykaryons, dendrites of varying diameter, and dendrite spikes of the somatosensory cortex pyramidal neurons as postsynaptic targets in the neocortex. In addition to vacant spaces that appeared in the brain as a result of transplantation, the ingrowing axons induced the formation of additional contact sites: deep invaginations of the plasmalemma of perykaryons, somatic spikes, terminal branchings of dendrites, and dendritic outgrowths of complex branched shape. These aberrant contacts were characterized by the presence of polyribosomes, endoplasmic reticulum cisternae, and mitochondria in the postsynaptic loci. Osmiophility and extension of desmosome-like junctions were also enhanced in such synapses. Thus, it was shown that mossy fibers ingrowing in the recipient neocortex were capable of forming cell-to-cell contacts with signs of functional synapses to atypical cell targets.     

The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2⁺ glial cell and a postsynaptic neuron share presynaptic terminals.     

Synaptic plasticity and functionality at the cone terminal of the developing zebrafish retina

Previous studies have analyzed photoreceptor development, some inner retina cell types, and specific neurotransmitters in the zebrafish retina. However, only minor attention has been paid to the morphology of the synaptic connection between photoreceptors and second order neurons even though it represents the transition from the light sensitive receptor to the neuronal network of the visual system. Here, we describe the appearance and differentiation of pre- and postsynaptic elements at cone synapses in the developing zebrafish retina together with the maturation of the directly connecting second order neurons and a dopaminergic third order feedback-neuron from the inner retina. Zebrafish larvae were examined at developmental stages from 2 to 7dpf (days postfertilization) and in the adult. Synaptic maturation at the photoreceptor terminals was examined with antibodies against synapse associated proteins. The appearance of synaptic plasticity at the so-called spinule-type synapses between cones and horizontal cells was assessed by electron microscopy, and the maturation of photoreceptor downstream connection was identified by immunocytochemistry for GluR4 (AMPA-type glutamate receptor subunit), protein kinase beta(1) (mixed rod-cone bipolar cells), and tyrosine hydroxylase (dopaminergic interplexiform cells). We found that developing zebrafish retinas possess first synaptic structures at the cone terminal as early as 3.5dpf. Morphological maturation of these synapses at 3.5-4dpf, together with the presence of synapse associated proteins at 2.5dpf and the maturation of second order neurons by 5dpf, indicate functional synaptic connectivity and plasticity between the cones and their second order neurons already at 5dpf. However, the mere number of spinules and ribbons at 7dpf still remains below the adult values, indicating that synaptic functionality of the zebrafish retina is not entirely completed at this stage of development.     

Distribution of actin in cone photoreceptor synapses

The invaginated photoreceptor terminal harbours a great number of postsynaptic dendrites that contact the photoreceptor terminal at morphologically distinct synapses. In this paper we studied the subcellular distribution of actin in cone photoreceptor synapses of light-adapted goldfish and guppy retinas and its relation to ribbon and spinule synapses. In the outer plexiform layer, fluorescent staining for actin by antibodies and also by fluorescently labelled phalloidin was discontinuous and showed large dot-like immunoreactive structures (3–5 m in diameter). Immunogold electron microscopy of light-adapted retinas isolated 3 h after the onset of light demonstrated that these dot-like structures corresponded to dendritic profiles of bipolar and horizontal cells within the synaptic cavity of cones. A much less intense staining was observed within the presynaptic cone photoreceptor terminal itself. Immunogold particles were also found overlying the tips of horizontal and bipolar dendrites that form the triadic postsynaptic complex of the ribbon synapse. In contrast to the triads light-induced terminal outgrowings of horizontal cells, also known as spinules, remained largely unlabelled. These observations suggest that actin plays a role in maintenance and/or certain steps of the formation of the postsynaptic dendritic complex.     

Dendritic position is a major determinant of presynaptic strength

Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.     

Capabilities of neurexins in the chick ciliary ganglion

Transcellular interactions between neuroligins (NL) and beta-neurexin have been widely documented to promote maturation and function of both glutamatergic and GABAergic synapses. Recently it has been shown that neuroligin-1 plays a similar role at nicotinic synapses on chick ciliary ganglion neurons in culture, acting from the postsynaptic side to enhance transmitter release from adjacent cholinergic terminals and boost nicotinic input to the cells. We show here that the ciliary ganglion expresses three forms of neuroligin as well as two beta-neurexins and an alpha-neurexin. Overexpression of the beta-neurexins, but not the alpha-neurexin, can induce clustering of endogenous PSD-95 in adjacent neurons, presumably engaging neuroligin in the postsynaptic cell. The trans effects of beta-neurexins are selective; though both alpha3- and alpha7-containing nicotinic receptors are available on opposing cells, beta-neurexins induce coclustering of alpha3- but not alpha7-containing nicotinic receptors. Overexpression of other putative synaptogenic molecules, including SynCAM and L1, are ineffective at trans-clustering of PSD-95 on adjacent neurons. The beta-neurexins also exert a cis effect, coclustering presynaptic markers along with beta-neurexin in neurites juxtaposed to postsynaptic proteins, consistent with organizing presynaptic components as well. Striated muscle, the synaptic target of ciliary neurons in vivo, also expresses neuroligin. The results demonstrate that NL and neurexins are present at multiple sites in nicotinic cholinergic pathways and suggest the possibility of both cis- and trans-interactions to influence nicotinic signaling.     

BDNF increases synapse density in dendrites of developing tectal neurons in vivo

Neuronal connections are established through a series of developmental events that involve close communication between pre- and postsynaptic neurons. In the visual system, BDNF modulates the development of neuronal connectivity by influencing presynaptic retinal ganglion cell (RGC) axons. Increasing BDNF levels in the optic tectum of Xenopus tadpoles significantly increases both axon arborization and synapse density per axon terminal within a few hours of treatment. Here, we have further explored the mechanisms by which BDNF shapes synaptic connectivity by imaging tectal neurons, the postsynaptic partners of RGCs. Individual neurons were co-labeled with DsRed2 and a GFP-tagged postsynaptic density protein (PSD95-GFP) to visualize dendritic morphology and postsynaptic specializations simultaneously in vivo. Immunoelectron microscopy confirmed that PSD95-GFP predominantly localized to ultrastructurally identified synapses. Time-lapse confocal microscopy of individual, double-labeled neurons revealed a coincident, activity-dependent mechanism of synaptogenesis and axon and dendritic arbor growth, which is differentially modulated by BDNF. Microinjection of BDNF into the optic tectum significantly increased synapse number in tectal neuron dendritic arbors within 24 hours, without significantly influencing arbor morphology. BDNF function-blocking antibodies had opposite effects. The BDNF-elicited increase in synapse number complements the previously observed increase in presynaptic sites on RGC axons. These results, together with the timescale of the response by tectal neurons, suggest that the effects of BDNF on dendritic synaptic connectivity are secondary to its effects on presynaptic RGCs. Thus, BDNF influences synaptic connectivity in multiple ways: it enhances axon arbor complexity expanding the synaptic territory of the axon, while simultaneously coordinating synapse formation and stabilization with individual postsynaptic cells.