[Electron microscopy analysis of the structural elements of the vestibular input to nodulus Purkinje's cells in rats exposed to a 9-day space flight].

Electron microscopy was used to study structural elements of the vestibular afferent input to the cerebellar nodulus Purkinje's cells--terminals of mossy fibers and granular cells in the granular layer and parallel fibers and Purkinje's cell dendrites in the molecular layer in rats decapitated in 2-3 hours and 9 days after the 9-day space flight aboard NASA shuttle Columbia (STS 40, SLS-1 mission). Analysis of the revealed ultrastructural changes on the base of morphofunctional correlations leads to the following conclusions: 1) space flight induced a prolonged reduction in vestibular input to most of the mossy fiber terminals and nodulus Purkinje's cells; 2) within the initial hours of recovery the vestibular input to a part of mossy fiber terminals and granular cells was increasing due to elevation of the sensitivity of vestibular receptors in microgravity; 3) regain of the vestibular input to Purkinje's cells after space flight is hampered by structural, as a result of microgravity effects, and also functional, developing shortly after space flight, impediments, and 4) in 9 d after landing the vestibular input to Purkinje's cells was almost normal. The observed reduction in the vestibular input to the nodulus Purkinje's cells during and after the spaceflight microgravity is presumably the key to the mechanism altering the velocity storage in mammals in microgravity and on return from space flight.

Distribution and Structure of Synapses on Medial Vestibular Nuclear Neurons Targeted by Cerebellar Flocculus Purkinje Cells and Vestibular Nerve in Mice: Light and Electron Microscopy Studies.

Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (< 1 µm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons.

Sex differences in morphometric aspects of the peripheral nerves and related diseases.

BACKGROUND: The elucidation of the relationship between the morphology of the peripheral nerves and the diseases would be valuable in developing new medical treatments on the assumption that characteristics of the peripheral nerves in females are different from those in males. METHODS: We used 13 kinds of the peripheral nerve. The materials were obtained from 10 Japanese female and male cadavers. We performed a morphometric analysis of nerve fibers. We estimated the total number of myelinated axons, and calculated the average transverse area and average circularity ratio of myelinated axons in the peripheral nerves. RESULTS: There was no statistically significant difference in the total number, average transverse area, or average circularity ratio of myelinated axons between the female and male specimens except for the total number of myelinated axons in the vestibular nerve and the average circularity ratio of myelinated axons in the vagus nerve. CONCLUSIONS: The lower number of myelinated axons in the female vestibular nerve may be one of the reasons why vestibular disorders have a female preponderance. Moreover, the higher average circularity ratio of myelinated axons in the male vagus nerve may be one reason why vagus nerve activity to modulate pain has a male preponderance.

Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.

Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.

Extrusion of corpora amylacea from the marginal gila at the vestibular root entry zone.

We have studied the vestibular nerve in patents suffering from Meniere' s disease and vascular cross-compression syndrome of the root entry zone due to close contact with the nerve of the antero-inferior cerebellar artery or one of its branches. All patients underwent vestibular neurectomy using the restrosigmoid approach which allows the resection of a relatively long nerve segment. In all the studied vestibular nerves a central and a peripheral zone could be distinguished. In the central zone, a massive accumulation of corpora amylacea (CA) was detected in the cytoplasm of astrocytes. Many CA were seen to protrude from the central nervous system into the pial connective tissue. These structures resembled sessile or predunculated polyps, with a complex system of scissurae at their bases. CA were also found in extracellular location in the pial connective tissue near capillaries, and not wrapped by membranes. Our findings suggest that after their production in astrocytes, CA are transferred into a pial connective tissue across the glial-limiting lamina. Thus, the present results indicate that CA do not merely represent an accumulation of abnormal material, but they could instead be part of a glio-pial system devoted to the clearance of substances from the nervous system.

A regional ultrastructural analysis of the cellular and synaptic architecture in the chinchilla cristae ampullares.

The chinchilla crista ampullaris was studied in 10 samples, each containing 32 consecutive ultrathin sections of the entire neuroepithelium. Dissector methods were used to estimate the incidence of various synaptic features, and results were confirmed in completely reconstructed hair cells. There are large regional variations in cellular and synaptic architecture. Type I and type II hair cells are shorter, broader, and less densely packed in the central zone than in the intermediate and peripheral zones. Complex calyx endings are most common centrally. On average, there are 15-20 ribbon synapses and 25-30 calyceal invaginations in each type I hair cell. Synapses and invaginations are most numerous centrally. Central type II hair cells receive considerably fewer afferent boutons than do peripheral type II hair cells, but have similar numbers of ribbon synapses. The numbers are similar because central type II hair cells make more synapses with the outer faces of calyx endings and with individual afferent boutons. Most afferent boutons get one ribbon synapse. Boutons without ribbon synapses were only found peripherally, and boutons getting multiple synapses were most frequent centrally. Throughout the neuroepithelium, there is an average of three to four efferent boutons on each type II hair cell and calyx ending. Reciprocal synapses are rare. Most synaptic ribbons in type I hair cells are spherules; those in type II hair cells can be spherical or elongated and are particularly heterogeneous centrally. Consistent with the proposal that the crista is concentrically organized, the intermediate and peripheral zones are each similar in their cellular and synaptic architecture near the base and near the planum. An especially differentiated subzone may exist in the middle of the central zone.

The structural maturation of the stato-acoustic nerve in the cat.

The maturation of the stato-acoustic nerve in the cat was studied by light and electron microscopy from the fetal stage to the adult. Measurement of the outer diameter of the fibers and the study of the myelination process revealed that myelination begins earlier for the vestibular nerve than for the cochlear nerve: by the fifty-third day of gestation 64% of the vestibular fibres have already passed the promyelin stage whereas for the cochlear nerve this promyelin stage begins for the majority of fibers on the fifty-seventh gestation day. Afterward, maturation proceeds more rapidly for the cochlear nerve. In the case of both nerves, maturation is still incomplete at two months of age. Concerning the relationship between the thickness of the myelin sheath and the axoplasmic diameter, there is already a good correlation by the fifty-seventh day of gestation in the vestibular nerve, whereas it appears several days after birth in the cochlear nerve.

Ultrastructural evidence that early synapse formation on central vestibular sensory neurons is independent of peripheral vestibular influences.

Migration and early differentiation of neurons of the tangential vestibular nucleus of the chick take place between embryonic days 5 and 8. In the absence of primary vestibular afferents (otocyst-ablation), a previous light microscope study documented that early developmental events still occurred, but the neurons failed to complete differentiation and to survive. In order to understand why these neurons undergo normal early development, we have repeated the vestibular deafferentation paradigm followed by ultrastructural observations on these neurons. We found that the ultrastructural events associated with migration and differentiation in the deafferented tangential nucleus were essentially normal from 5 to 8 days. Most important, longitudinal fibers, presumably of central, nonvestibular origins, formed the first synapses at the same time and sequence as observed in normal embryos. Thus vestibular sensory neurons receive their first input from central fibers, initiating events in the formation of a central vestibular circuitry without the influence of peripheral vestibular fibers or endorgan.

A light and electron microscopic study of the development of the Mauthner cell and vestibular nerve in the axolotl.

Vestibular axons form synapses on a restricted area of the lateral dendrite of the Mauthner cell, a large, identified brainstem neuron found in fish and amphibians. The differentiation of the vestibular nerve, medullary neuropil, and Mauthner cell of the axolotl (Ambystoma mexicanum) was studied to understand better the means by which this synaptic specificity arises. The Mauthner cell first extends a medial process and then a lateral dendrite. The latter initially elongates as a simple process and later sends out branches. As the lateral dendrite grows, vestibular axons enter the brainstem to form one of the earliest of several discrete axon fascicles that course longitudinally through the neuropil. The fascicles, many of which are identifiable on the basis of their location and axonal morphology, are the precursors of the longitudinal tracts of the mature salamander. The lateral dendrite grows dorsally over the orthogonally oriented fascicles, making contact with each at a characteristic time and place. The first afferents to form synapses do so on the soma and proximal lateral dendrite; subsequent afferent groups terminate more distally. Axons within a given fascicle form synapses with the Mauthner cell in a discrete and initially homogeneous domain. As dendritic branches form and the organization of the longitudinal fascicles becomes more complex, the homogeneity of axons terminating on a given region of the Mauthner cell surface is lost, but no major rearrangement or migration of terminals is apparent. These observations are consistent with both active recognition and passive spatiotemporal models of synaptic site specificity.

Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus.

Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into medial and lateral parts. Utricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrastriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. Most afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have previously been classified into four types based on hair bundle morphology (Lewis and Li: Brain Res. 83:35-50, 1975). Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely contacted Type B and Type C hair cells, particularly on the outer rows of the medial striola. Afferents supplying more central striolar regions innervated fewer Type B and large numbers of Type E and Type F hair cells. Striolar afferents with thin parent axons largely supplied Type E hair cells with bulbed kinocilia in the innermost striolar rows.

Microtubule organization and synaptogenesis in the vestibular sensory cells.

Microtubule organization in type I hair cells has been investigated during the synaptogenesis of vestibular receptors in mammals. The different steps in the maturation of the synapse between the hair cell and the nerve chalice were: a slight symmetrical membrane densification; the appearance of synaptic bodies alongside microtubules closely associated with densified presynaptic membranes; the disappearance of synaptic bodies and the persistence of microtubules. During this development, microvesicules were never seen to be associated with microtubules.

Pathological changes during the development of the vestibular sensory and ganglion cells of the Bronx waltzer mouse. Scanning and transmission electron microscopy.

Vestibular receptors and ganglia of homozygous Bronx waltzer (bv/bv) mice were investigated by scanning and transmission electron microscopy at various stages between 3 days and 90 days after birth. Scanning electron microscopy revealed that there was already a considerable lack of hair bundles in the maculae utriculi, as well as in the cristae ampullares by the 3rd day after birth. During development, the growth of the remaining hair bundles was observed but the most of them exhibited morphological abnormalities. Transmission electron microscopy revealed early degeneration of sensory cells followed by delayed maturation of the remaining sensory cells. The sensory cells which seem unaffected displayed immature features in adult animals. In type I hair cells, the calyces were incomplete, contacts between the cell and the afferent calyces were immature and synaptic bodies persisted. In some type II hair cells, there was an abnormal overabundance of afferent nerve endings, which implies that these type II cells could be immature type I cells. Immature features were also observed in the vestibular ganglia, particularly the absence of the myelin sheath around the perikarya. We discuss the relationship between these vestibular morphogenetic abnormalities and those described in the cochlear system.

Potassium-evoked release of endogenous primary amine-containing compounds from the trout saccular macula and saccular nerve in vitro.

An in vitro preparation of the trout saccular macula, containing a large number of hair cells, served as a potential source of neurotransmitter(s) released at the acousticolateralis hair cell-afferent nerve synapse. An in vitro preparation of the saccular nerve, maintained in parallel, served to indicate the potential neural contribution to overall release from the macula. Efflux of 27 primary amine-containing compounds from the macula and nerve fractions was monitored by cation-exchange HPLC with fluorescence detection, and release by 53.5 mM potassium was determined at 1.45 mM calcium, 0.35 mM magnesium or 0 mM calcium, 10.1 mM magnesium. Taurine was released from the saccular macula in the greatest amount, accounting for 72% of the total evoked release of primary amine-containing compounds. Its release was calcium dependent and its time course prolonged. The contribution by myelinated nerve and associated Schwann cells within the macula to overall release of taurine from the macula in the presence of calcium, as determined from the saccular nerve preparation, was only 2%. Other components specifically released from the macula included ethanolamine, phosphoserine, beta-alanine, and glycine. Glutamate and aspartate were released from both the macula and saccular nerve fractions by potassium in the presence of calcium and in a ratio of 6:1 (glutamate:aspartate) for the macula and 7.5:1 for the nerve. The release of aspartate, but not that of glutamate, was lowered in saline containing 0 mM calcium, 10.1 mM magnesium. The calculated contribution from neural elements to overall release from the macula was 10% for aspartate and 18% for glutamate. These studies demonstrate that both the macula and saccular nerve fractions release the 'excitatory neurotransmitter' candidates aspartate and glutamate. Calcium-dependent, potassium-evoked release of taurine appears to be specific to the hair cell-supporting cell population of the saccular macula, and taurine may, therefore, be involved directly or indirectly in hair cell neurotransmission in labyrinthine organs. This study represents the first detailed biochemical characterization of efflux and release for an in vitro hair cell system of relatively high purity with respect to hair cells.

Immunoelectron microscopy of AMPA receptor subunits reveals three types of putative glutamatergic synapse in the rat vestibular end organs.

To characterize the synapses between hair cells and afferent nerve endings in the rat vestibular end organs, the ultrastructural localization of AMPA receptor subunits (GluR1-4) was examined by postembedding immunogold cytochemistry. Immunoreactivities for GluR2/3 and GluR4 were associated with the synapses between type I hair cells and the surrounding chaliceal nerve endings and with the bouton type nerve endings contacting type II hair cells. There was no detectable immunoreactivity for GluR1. A third type of immunoreactive synapse was found between the outer face of chalices and type II hair cells. While the linear densities of gold particles (particles per micrometer postsynaptic specialization) of bouton type endings and chaliceal nerve endings were the same, the former type of ending showed larger postsynaptic specializations and, hence, a higher number of receptor molecules. These data indicate that there are three types of putative glutamatergic synapse in the vestibular end organ.

Subcellular immunolocalization of NMDA receptor subunit NR1, 2A, 2B in the rat vestibular periphery.

The immunohistochemical localization of the NMDA glutamate receptor subunits NR1, NR2A, and NR2B was investigated in the rat vestibular periphery at the light and electron microscopy level using specific antipeptide antibodies. The afferent calyceal terminals and nerve fibers innervating type I vestibular hair cells were strongly NR1, NR2A, and NR2B immunoreactive. Under electron microscopy, the basolateral type I hair cell membrane was NR1 immunoreactive. The type II hair cell and its afferent boutons were NR1, NR2A, and NR2B non-immunoreactive. Nearly all of Scarpa's ganglion neurons were NR1 immunoreactive, but there was a subset of NR2A non-immunoreactive neurons. Additionally, the larger sized Scarpa's ganglia neurons were NR2B immunoreactive, while the smaller neurons were non-immunoreactive. These findings are strong evidence for functional NMDA receptor mediation or modulation of afferent excitatory neurotransmission from type I but not type II vestibular hair cells to the primary afferent nerve. The receptor subtype(s) may be a combination of NR1/NR2A, NR1/NR2B, and/or NR1/NR2A/NR2B.

Ultrastructural study of calycine synaptic endings of colossal vestibular fibers in the cristae ampullares of the developing chick.

Bipolar vestibular ganglion cells give rise to the colossal vestibular fibers in the chicken. These fibers form the largest calycine endings in the cristae ampullares and also the spoon endings in the tangential vestibular nucleus of the medulla oblongata. Because these synaptic endings are two of the largest and most distinctive in the vertebrate nervous system, they are especially suitable for comparisons of the development of synapses and synaptic endings of a specific cell type. An ultrastructural study of the spoon endings and quantitative data on their synapses were available from material of 15-day-old chick embryos, hatchlings, and 3-yr-old chickens. Here we provide similar data on the large calyces. Briefly, large calyces exhibited no ultrastructural changes corresponding to the changes in the spoon endings apparent when they retract from their target cell surfaces around hatching time. However, the concentration of the ribbon synapses at the large calyces decreased around hatching, when the concentration of the chemical synapses at the spoon endings declined. Moreover, the concentration of the ribbon synapses at the large calyces corresponded closely to the concentration of the chemical synapses at the spoon endings at the same age. Thus at the developmental ages studied, there were similar concentrations in the peripheral and central synapses formed at two different synaptic endings, both derived from one cell type and participating in the same neural pathway. These findings raise the issue of how synapses are regulated locally, but also suggest the possibility for central-peripheral interactions to produce correlative changes in parallel.

Neuronal organization of the utricular macula concerned with innervation of single vestibular neurons in the cat.

We investigated whether cross-striolar inhibition, which may increase sensitivity to linear acceleration, contributed to utricular (UT) afferent innervation of single vestibular neurons (VNs). Excitatory and inhibitory postsynaptic potentials (EPSPs, IPSPs, respectively) were recorded from VNs after focal stimulation of the UT macula (M). From a total of 83 VNs, 25 (30%) neurons received inputs from both sides of the UTM, and the response patterns were opposite, i.e. cross-striolar inhibition was observed. In roughly 2/3 of these neurons, stimulation of the medial side of the UTM evoked EPSPs, while stimulation of the lateral side evoked IPSPs. In the remaining 1/3 neurons, the response patterns were opposite. Thirty-two (39%) of the 83 neurons received the identical pattern of inputs from both sides of the UTM: EPSPs in 26 neurons and IPSPs in six neurons. Twenty-six (31%) of the 83 neurons received inputs from either the medial or the lateral side of the UTM. These findings suggest that cross-striolar inhibition existed in the UT system, although it was not a dominant circuit that increased the sensitivity as in the saccular system [15].

Neuronal degeneration of primary cochlear and vestibular innervations after local injection of sisomicin in the guinea pig.

This paper reports on a dynamic study of the morphological changes within the cochlear and vestibular ganglia of the guinea pig after local application of Sisomicin in the inner ear. The treatment leads to a rapid, complete and irreversible destruction of the sensory cells in the cochlear and vestibular neuroepithelia. A progressive degeneration of the type I and type II afferent neurons, presenting a decreasing gradient from the base towards the apex of the cochlea, is rapidly observed and becomes almost complete as early as 15 days after the peripheral injury. Five months after the treatment the spiral ganglion cells have almost completely disappeared. At this time the vestibular ganglion cell density appears normal but the neurons exhibit important signs of alteration. Such damage to the cochlear and vestibular afferent neurons may result from either retrograde neuronal degeneration and/or direct neurotoxic effect of the drug. Thus the combination of the two mechanisms could lead to neuronal losses in spiral and Scarpa's ganglia after the local aminoglycoside intoxication of the inner ear. The difference in the time course of degeneration for these two afferent ganglia could be due to their specific susceptibilities or to their different anatomical locations.

Brainstem projections of different branches of the vestibular nerve: an experimental study by transganglionic transport of horseradish peroxidase in the cat. II. The anterior and posterior ampullar nerves.

The brainstem projections of the ampullar nerves from the vertical semicircular canals, the anterior (AAN) and the posterior ampullar nerve (PAN), were studied in adult cats using the transganglionic horseradish peroxidase (HRP) method. Each nerve was exposed in three experiments. Two animals in each group had labeling which allowed detailed mapping. From the AAN, terminal-type labeling was found in two separate groups, one laterally and one medially, both in the lateral (LV) and in the superior (SV) vestibular nucleus. In addition, such labeling was found in all parts of the medial vestibular nucleus (MV). Labeled structures were found also in the descending vestibular nucleus, (DV) more densely over its lateral part, except for cell group f, where no labeling was found. From the PAN, terminal-type labeling was found medially and laterally in the LV and in the medial part of the SV. In the MV, such labeling was evenly distributed rostrally but concentrated laterally in caudal parts. In the DV, terminal-type labeling was present rostrally, whereas no labeling was seen caudally. In the interstitial nucleus of the vestibular nerve, terminal-type labeling was observed from the AAN but not from the PAN. No labeled fibers from either of the two ampullar nerves were seen outside the vestibular root and nuclei, except for small-caliber fibers from the SV heading towards the brachium conjunctivum. The findings clearly indicate a specific termination for each of the two ampullar nerves.

Early innervation and differentiation of hair cells in the vestibular epithelia of mouse embryos: SEM and TEM study.

Early afferent innervation and differentiation of sensory vestibular cells were studied in mouse embryos from gestation day (GD) 13 to 16. Afferent neurites were found as early as GD 13 in the epithelium when there were no clearly differentiated sensory cells. By GD 14 the earliest sensory cells which exhibited short hair bundles at their luminal pole were then contacted by afferent endings at their basal part. On GD 15 nerve endings establishing specialized synaptic contacts, characterized by asymmetrical membrane densities and synaptic bodies, were observed. At this stage, microtubules contacting the presynaptic membranes, as well as coated vesicles were found. On GD 16 the hair cells were multi-afferented and numerous synaptic bodies were found. These results showing a concomitance between the hair cell differentiation and the establishment of nerve contacts are discussed with particular respect to nerve-hair cell interactions during sensory differentiation. This study does not point to a primary induction of vestibular hair cell differentiation by nerve endings, but it is consistent with the possibility that the ingrowth of nerve fibers is one of many factors that influence the differentiation of receptor cells. With respect to synapse formation, it is assumed that the location of synaptic bodies at presynaptic densities is determined by the arrival of afferent nerve endings.