Changes in the size and shape of the synaptic vesicles in the sensorimotor cortex of the rat brain in the initial phases of kindling

The sensorimotor area of rat cerebral cortex was subjected to repeated electrical stimulation at 10-min intervals, with resultant formation and progressive lengthening of self-sustained after-discharges (SSAD). One and 60 min after the third SSAD ended, we carried out an electron microscopy morphometric analysis of the agranular synaptic vesicles in type I synapses (after Gray) in the second cortical layer of the homotopic area of the unstimulated hemisphere. One minute after the seizure ended, 5.8% enlargement of the synaptic vesicles compared with the control was demonstrated in zone II of the synapse (0.1-0.2 micron from the active zone of the synapse). Neither the size nor the shape of the synaptic vesicles in the other parts of the synaptic apparatus altered. Sixty min after the seizure ended, a 5.5% enlargement of the synaptic vesicles in zone I (0.0-0.1 micron) and a 5.4% enlargement of those in zone II was found. The synaptic vesicles in zone I in the experimental animals were more oval than in the controls. Our findings support the vesicular theory and testify that hyperfunction, up to temporary exhaustion of the synaptic apparatuses, produces a change in the transmitter content of the synaptic vesicles. A raised amount of transmitter in the synaptic vesicles near the active zone could be one of the factors responsible for continued hyperexcitability of the tissue one hour after the seizure had ended. The results likewise support the concept of two mechanisms of synaptic vesicle formation, and hence of the existence of two different vesicle populations.     

Diurnal variations in the photoreceptor synaptic terminals of the newt retina

Newt photoreceptor synaptic terminals undergo a variety of morphological changes over a 24-hr (LD 12:12) cycle. During the day, dense-cored synaptic vesicles were found to increase in number and accumulate near the synaptic lamellae; during the dark phase, the dense-cored vesicles decreased in number, while large clear vesicles and profiles of smooth endoplasmic reticulum increased in frequency. The most marked change in photoreceptor synaptic terminal morphology occurred after 10 hr of darkness, at 0730 hr. At this time, photoreceptor synaptic terminal cross-sectional area was found to increase dramatically. Morphometric analysis showed that the number of synaptic vesicles in these terminals remained constant throughout the day, as did the perimeter of photoreceptor terminal profiles. The observed increase in area of synaptic terminals at 0730 hr was found to be due to a decrease in the folding of the terminal plasma membrane. Qualitative observations showed endocytosis to be occurring at a rapid rate at this time as well; and since the number of synaptic vesicles and terminal perimeter did not change, exocytosis of synaptic vesicles was assumed to be occurring at an equally rapid rate. These findings support an extension to the hypothesis of Monaghan and Osborne (1975), suggesting that photoreceptor synaptic vesicles become "supercharged" with transmitter substance in the light.     

Identification and Characterization of the Major Proteins of Mammalian Brain Synaptic Vesicles

Highly purified rat and cow brain synaptic vesicles contain major proteins with molecular weights of approximately 74,000, 60,000, 57,000, 40,000, 38,000, and 34,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of the major proteins on synaptic vesicles was confirmed by immunoprecipitation of intact rat brain synaptic vesicles with a synaptic vesicle-specific monoclonal antibody. The 40,000-Mr protein appeared to be identical to the 38,000-Mr integral membrane glycoprotein, p38 or synaptophysin, previously identified as a major component of mammalian synaptic vesicles. The isoelectric point of the 75,000-Mr proteins from either rat or cow brain synaptic vesicles is 5.0, and the pI of the 57,000-Mr protein is approximately 5.1 in both species. The similarity in size and charge of several major proteins in rat and cow synaptic vesicles suggests a high degree of structure conservation of these proteins in diverse mammalian species and raises the possibility that a set of functions common to most or all mammalian synaptic vesicles is mediated by these proteins.     

Morphometry of the vesicular apparatus of the neuromuscular junction with different modes of transmitter release

Neuromuscular junctions in the diaphragm muscle of rats were studied, using a usual chemical fixation technique and quick prefreezing of the muscle. The number of synaptic vesicles in the vicinity of presynaptic membrane decreased significantly during synaptic function activation. Quantitative investigation of axon terminal vesicle apparatus revealed heterogeneity in the size of synaptic vesicle pool. The pattern of synaptic vesicle size distribution in different functional states of the synapse suggests that size heterogeneity reflects their functional peculiarities.     

Anatomical plasticity of synapses in the lamina of the optic lobe of the fly

Insects are frequently assumed to have hard-wired nervous systems that fail to demonstrate functional plasticity. We have produced changes in synaptic frequency, and analysed their developmental time course, dynamics and reversibility, in the lamina underlying the compound eye of the fly, by exposing young adults to different visual stimuli. The class of synapse examined feeds back from L2, one of the monopolar cells found in each lamina cartridge, to photoreceptor terminals; each site is a synaptic dyad marked by the presence of a few, round vesicles surrounding a T-shaped presynaptic ribbon and, in the photoreceptor, by a subsynaptic vacuole. In control adult flies reared in normal room lighting, the frequency of synaptic profiles scored in micrographs of single sections initially increased until one day post-eclosion (E + 1), but declined thereafter. Frequencies measured in left and right eyes of the same control animals were closely matched. Experimental flies were put for one to two days into an integrating sphere illuminated continuously with square-wave, 25 Hz green light. They had one eye occluded, so providing control comparisons between flicker-reared (FR) and occluded (dark-reared, DR) eyes within the same animal. The DR eyes invariably (n greater than 22) had higher frequencies of synaptic profiles than those seeing light, regardless of age or the period of light exposure, although the detailed relative effects of FR and DR depend upon the age of the animal. The evidence suggests that exposure to light actively depresses synaptic frequency and increases its variability. The greatest difference (30%) achieved was at two to four days after eclosion and there was no difference beyond six days, so demarcating a prospective sensitive period. Rearing in DC light was equally effective as FR, so visual contrasts per se are apparently inessential. Frequency values can change rapidly. During the first 24 h post-eclosion, DR resulted in new synapses adding to L2's complement of 25-35 at a maximum rate of 4 per 6 h, whereas light exposure caused a frequency decrease after as little as 6 h. Alternating 24 h periods of light and dark during the first two days produced reversible synaptic frequency changes. Individual synaptic contacts enlarge with age but not significantly with different visual experiences. The decrease in frequency of synaptic profiles with age thus actually underestimates the true decrease in synaptic number, whereas the altered synaptic frequencies seen after differential exposure represent true differences in synaptic number.(ABSTRACT TRUNCATED AT 400 WORDS)     

A survey of the cytology and synaptic organization of the insular trigeminal-cuneatus lateralis nucleus in the rat, including an identification of spinal afferent inputs

The cytology and synaptic organization of the insular trigeminal-cuneatus lateralis (iV-Cul) nucleus was examined in the rat. In addition, the ultrastructural morphology and synaptic connectivity of anterogradely labeled spinal afferent axons terminating in iV-Cul were examined following injection of horseradish peroxidase (HRP) into the cervical spinal cord. The uniformity of the ultrastructural features of iV-Cul neurons supports the presence of a homogeneous neuronal population. The most prominent feature of the iV-Cul neuropil is the presence of numerous interdigitating astrocytic processes, which extensively isolate neuronal somata and processes. iV-Cul contains a heterogeneous population of axonal endings that can be separated into three categories, depending upon whether they contain predominantly spherical-shaped agranular synaptic vesicles (R endings), predominantly pleomorphic-shaped agranular synaptic vesicles (P endings), or a heterogeneous population of dense-core vesicles (DC endings). The R endings represent the majority of axonal endings in iV-Cul and establish asymmetrical axodendritic and axospinous synaptic contacts, primarily along the distal portions of the dendritic tree. P endings establish symmetrical axosomatic, axodendritic, and axospinous synaptic contacts and exhibit a more generalized distribution along the somadendritic tree. DC terminals establish asymmetrical axodendritic synaptic contacts with distal dendritic processes and are the least frequently observed endings in the iV-Cul neuropil. Numerous synaptic glomeruli, exhibiting a single large central R bouton that establishes multiple axodendritic or axospinous synapses, characterize the iV-Cul neuropil. Axoaxonic synapses are conspicuously absent from the iV-Cul neuropil and glomeruli. The anterograde HRP labeling of spinal afferent axons that terminate in iV-Cul indicates that the terminals along these fibers are of the R type and that they are engaged predominantly in synaptic glomeruli. The results of this study indicate that the synaptic organization of iV-Cul is distinctly different from that of neighboring somatosensory nuclei, and supports the recent suggestion that this nucleus should be considered a separate precerebellar spinal relay nucleus in the lateral medulla.     

Effect of voltage drop within the synaptic cleft on the current and voltage generated at a single synapse

In a model of a single synapse with a circular contact zone and a single concentric zone containing receptor-gated channels, we studied the dependence of the synaptic current on the synaptic cleft width and on the relative size of the receptor zone. During synaptic excitation, the extracellular current entered the cleft and flowed into the postsynaptic cell through receptor channels distributed homogeneously over the receptor zone. The membrane potential and channel currents were smaller toward the cleft center if compared to the cleft edges. This radial gradient was due to the voltage drop produced by the synaptic current on the cleft resistance. The total synaptic current conducted by the same number of open channels was sensitive to changes in the receptor zone radius and the cleft width. We conclude that synaptic geometry may affect synaptic currents by defining the volume resistor of the cleft. The in-series connection of the resistances of the intracleft medium and the receptor channels plays the role of the synaptic voltage divider. This voltage dividing effect should be taken into account when the conductance of single channels or synaptic contacts is estimated from experimental measurements of voltage-current relationships.     

Submicroscopic changes of the synapse after nerve section in the acoustic ganglion of the guinea pig; an electron microscope study

The degenerative changes of the synaptic regions after nerve section have been studied with the electron microscope in the interneuronal synapse of the ventral ganglion of the acoustic nerve of the guinea pig. Fixation with buffered osmic tetroxide was carried out 22, 44, and 48 hours after destruction of the cochlea on one side; the contralateral ganglion being used as control. The submicroscopic organization of normal axosomatic and axodendritic synapses is described. In the synaptic ending four morphological components are recognized: the membrane, the mitochondria, the synaptic vesicles (19, 20), and the cytoplasmic matrix. The intimate contact of glial processes with the endings and with the surface of the nerve cell is described. At the level of the synaptic junction there is a direct contact of the limiting membranes of the ending and of the cell body or dendrite. Both contacting membranes constitute the synaptic one with a total thickness of about 250 A. This membrane has regions of higher electron density where the synaptic vesicles come into intimate contact and fuse with it. Definite degenerative submicroscopic changes in the nerve endings were observed after 22 hours of destruction of the cochlea and were much more conspicuous after 44 and 48 hours. After 22 hours there is swelling of the ending and decreased electron density of the matrix. Most synaptic vesicles have disappeared or seem to undergo a process of clumping and dissolution. Some mitochondria also show signs of degeneration. After 44 hours the synaptic vesicles have practically disappeared; mitochondria are in different stages of lysis; the membrane of the ending becomes irregular in shape, and there is shrinkage and in some cases detachment of the ending. No changes in the postsynaptic cytoplasm were observed. These observations and particularly the rapid lysis of the synaptic vesicles are discussed in correlation with data from the literature indicating the early alteration of synaptic function and the biochemical changes occurring after section of the afferent nerve. The hypothesis that the synaptic vesicles may be carriers of acetylcholine or other active substances (19, 20) and that they may act as biochemical units in synaptic transmission is also discussed.(2)     

Neurotransmitter release: the dark side of the vacuolar-H+ATPase

Vacuolar-H⁺ATPase (V-ATPase) is a complex enzyme with numerous subunits organized in two domains. The membrane domain V0 contains a proteolipid hexameric ring that translocates protons when ATP is hydrolysed by the catalytic cytoplasmic sector (V1). In nerve terminals, V-ATPase generates an electrochemical proton gradient that is acid and positive inside synaptic vesicles. It is used by specific neurotransmitter-proton antiporters to accumulate neurotransmitters inside their storage organelles. During synaptic activity, neurotransmitters are released from synaptic vesicles docked at specialized portions of the presynaptic plasma membrane, the active zones. A fusion pore opens that allows the neurotransmitter to be released from the synaptic vesicle lumen into the synaptic cleft. We briefly review experimental data suggesting that the membrane domain of V-ATPase could be such a fusion pore.We also discuss the functional implications for quantal neurotransmitter release of the sequential use of the same V-ATPase membrane domain in two different events, neurotransmitter accumulation in synaptic vesicles first, and then release from these organelles during synaptic activity.     

Neural Organization of the Median Ocellus of the Dragonfly : II. Synaptic structure

Two types of presumed synaptic contacts have been recognized by electron microscopy in the synaptic plexus of the median ocellus of the dragonfly. The first type is characterized by an electron-opaque, button-like organelle in the presynaptic cytoplasm, surrounded by a cluster of synaptic vesicles. Two postsynaptic elements are associated with these junctions, which we have termed button synapses. The second synaptic type is characterized by a dense cluster of synaptic vesicles adjacent to the presumed presynaptic membrane. One postsynaptic element is observed at these junctions. The overwhelming majority of synapses seen in the plexus are button synapses. They are found most commonly in the receptor cell axons where they synaptically contact ocellar nerve dendrites and adjacent receptor cell axons. Button synapses are also seen in the ocellar nerve dendrites where they appear to make synapses back onto receptor axon terminals as well as onto adjacent ocellar nerve dendrites. Reciprocal and serial synaptic arrangements between receptor cell axon terminals, and between receptor cell axon terminals and ocellar nerve dendrites are occasionally seen. It is suggested that the lateral and feedback synapses in the median ocellus of the dragonfly play a role in enhancing transients in the postsynaptic responses.     

Correlation of glutamate binding activity with glutamate-binding protein immunoreactivity in the brain of control and alcohol-treated rats

Specific antibodies raised against a glutamate binding protein purified from bovine brain were used to trace the immunoreactivity of this protein in rat brain subcellular fractions. In the subcellular fractions obtained from whole brain homogenates, the synaptic membranes had the highest immunochemical reactivity towards the anti-glutamate-binding protein antibodies. The combination of measurements of glutamate binding activity and glutamate-binding protein immunoreactivity indicated that in brain synaptic membranes from control animals the highest activity in these two measures was associated with a synaptic plasma membrane subfraction that was enriched with synaptic junctions. In animals treated with ethanol for 14 days, there was a significant increase in the density of synaptic membrane glutamate binding sites. This increase in glutamate binding capacity was correlated with a greater than two-fold increase in the glutamate binding activity and binding protein immunoreactivity of the light synaptic membrane subfraction, a subfraction which does not contain many recognizable synaptic junctions. Acute administration of ethanol to rats produced a moderate but non-significant decrease in glutamate binding capacity of synaptic membranes. The increase in the number of glutamate binding protein subunits in brain plasma membranes may be an adaptive response of central nervous system neurons to the acute effects of ethanol on glutamate synaptic transmission.     

The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1

We have examined the cytoskeletal architecture and its relationship with synaptic vesicles in synapses by quick-freeze deep-etch electron microscopy (QF.DE). The main cytoskeletal elements in the presynaptic terminals (neuromuscular junction, electric organ, and cerebellar cortex) were actin filaments and microtubules. The actin filaments formed a network and frequently were associated closely with the presynaptic plasma membranes and active zones. Short, linking strands approximately 30 nm long were found between actin and synaptic vesicles, between microtubules and synaptic vesicles. Fine strands (30-60 nm) were also found between synaptic vesicles. Frequently spherical structures existed in the middle of the strands between synaptic vesicles. Another kind of strand (approximately 100 nm long, thinner than the actin filaments) between synaptic vesicles and plasma membranes was also observed. We have examined the molecular structure of synapsin 1 and its relationship with actin filaments, microtubules, and synaptic vesicles in vitro using the low angle rotary shadowing technique and QF.DE. The synapsin 1, approximately 47 nm long, was composed of a head (approximately 14 nm diam) and a tail (approximately 33 nm long), having a tadpole-like appearance. The high resolution provided by QF.DE revealed that a single synapsin 1 cross-linked actin filaments and linked actin filaments with synaptic vesicles, forming approximately 30-nm short strands. The head was on the actin and the tail was attached to the synaptic vesicle or actin filament. Microtubules were also cross-linked by a single synapsin 1, which also connected a microtubule to synaptic vesicles, forming approximately 30 nm strands. The spherical head was on the microtubules and the tail was attached to the synaptic vesicles or to microtubules. Synaptic vesicles incubated with synapsin 1 were linked with each other via fine short fibrils and frequently we identified spherical structures from which two or three fibril radiated and cross-linked synaptic vesicles. We have examined the localization of synapsin 1 using ultracryomicrotomy and colloidal gold-immunocytochemistry of anti-synapsin 1 IgG. Synapsin 1 was exclusively localized in the regions occupied by synaptic vesicles. Statistical analyses indicated that synapsin 1 is located mostly at least approximately 30 nm away from the presynaptic membrane. These data derived via three different approaches suggest that synapsin 1 could be a main element of short linkages between actin filaments and synaptic vesicles, and between microtubules and synaptic vesicles, and between synaptic vesicles in the nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Age-related changes in the synapses of the rat's neostriatum

By means of transmission electron microscopy, the age-related changes in axospinous (ASS) and axodendritic (ADS) synapses in the dorsal part of the rostral neostriatum in two groups of Wistar rats: young (3-month-old), and senescent (25-month-old) were examined. The changes in different parameters, characterizing the ASS and ADS: synaptic density (SD), number of synaptic vesicles (SV), number of synaptic contact zone (SCZ), and number of dendritic spines, bearing synapses (DS) were investigated morphometrically. The SD of the ASS decreased significantly during aging, but the SD of the ADS did not changed significantly. The mean area of the synaptic boutons increased significantly during aging in two types of synapses. The mean number of vesicles per synaptic bouton increased, but the number of vesicles per microm2 of synaptic bouton, and per microm3 of the neuropil decreased. The mean SCZ length increased in both types of synapses. The total SCZ length per 1000 microm2 of the neuropil, and the total area of the SCZ per 1000 microm3 of the neuropil decreased in ASS, but the same parameters of the ADS did not changed significantly. The mean number of synaptic DS per 1000 microm2 of the neropil decreased during aging, but the mean area of the synaptic DS increased. The present results support the hypothesis that the synaptic contacts change significantly during aging, and the ASS are more vulnerable during aging than the ADS.     

The effect of ethanol on the distribution of synaptic vesicles in cortical synaptosomes of the rat

Ethanol was shown to cause a redistribution of synaptic vesicles in incubated synaptosomes. While the number of synaptosomes containing synaptic vesicles attached to the presynaptic membrane decreased markedly, an increase in the number of synaptosomes lacking membrane-vesicle associations was observed. The findings support the possibility of a presynaptic action of ethanol and point to the role of membrane-attached vesicles in synaptic transmission.     

Studies of synaptic vesicle endocytosis in the nematode C. elegans

After synaptic vesicle exocytosis, synaptic vesicle proteins must be retrieved from the plasma membrane, sorted away from other membrane proteins, and reconstituted into a functional synaptic vesicle. The nematode Caenorhabditis elegans is an organism well suited for a genetic analysis of this process. In particular, three types of genetic studies have contributed to our understanding of synaptic vesicle endocytosis. First, screens for mutants defective in synaptic vesicle recycling have identified new proteins that function specifically in neurons. Second, RNA interference has been used to quickly confirm the roles of known proteins in endocytosis. Third, gene targeting techniques have elucidated the roles of genes thought to play modulatory or subtle roles in synaptic vesicle recycling. We describe a molecular model for synaptic vesicle recycling and discuss how protein disruption experiments in C. elegans have contributed to this model.     

Network Self-Organization Explains the Statistics and Dynamics of Synaptic Connection Strengths in Cortex

The information processing abilities of neural circuits arise from their synaptic connection patterns. Understanding the laws governing these connectivity patterns is essential for understanding brain function. The overall distribution of synaptic strengths of local excitatory connections in cortex and hippocampus is long-tailed, exhibiting a small number of synaptic connections of very large efficacy. At the same time, new synaptic connections are constantly being created and individual synaptic connection strengths show substantial fluctuations across time. It remains unclear through what mechanisms these properties of neural circuits arise and how they contribute to learning and memory. In this study we show that fundamental characteristics of excitatory synaptic connections in cortex and hippocampus can be explained as a consequence of self-organization in a recurrent network combining spike-timing-dependent plasticity (STDP), structural plasticity and different forms of homeostatic plasticity. In the network, associative synaptic plasticity in the form of STDP induces a rich-get-richer dynamics among synapses, while homeostatic mechanisms induce competition. Under distinctly different initial conditions, the ensuing self-organization produces long-tailed synaptic strength distributions matching experimental findings. We show that this self-organization can take place with a purely additive STDP mechanism and that multiplicative weight dynamics emerge as a consequence of network interactions. The observed patterns of fluctuation of synaptic strengths, including elimination and generation of synaptic connections and long-term persistence of strong connections, are consistent with the dynamics of dendritic spines found in rat hippocampus. Beyond this, the model predicts an approximately power-law scaling of the lifetimes of newly established synaptic connection strengths during development. Our results suggest that the combined action of multiple forms of neuronal plasticity plays an essential role in the formation and maintenance of cortical circuits.     

Synaptic potential in the motor giant axon of the crayfish

Some electrical properties of the synapses between central giant axons (presynaptic) and the motor giant axon (postsynaptic) of the crayfish abdominal nerve cord have been investigated. Postsynaptic potential change in response to presynaptic volleys contains two components: a spike potential and a synaptic potential of very long time course. Amplitude of the synaptic potential is graded according to the number of active presynaptic axons. Conductance increase in the synaptic membrane endures over most of the period of potential change, and it is this rather than the "electrical time constant" of the membrane that in large measure determines the form of the synaptic potential. Temporal summation of synaptic potential occurs during repetitive presynaptic stimulation, and after such stimulation the rate of decay of synaptic potential is greatly slowed.     

Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber

Acetylcholinesterase (AChE) in skeletal muscle is concentrated at neuromuscular junctions, where it is found in the synaptic cleft between muscle and nerve, associated with the synaptic portion of the myofiber basal lamina. This raises the question of whether the synaptic enzyme is produced by muscle, nerve, or both. Studies on denervated and regenerating muscles have shown that myofibers can produce synaptic AChE, and that the motor nerve may play an indirect role, inducing myofibers to produce synaptic AChE. The aim of this study was to determine whether some of the AChE which is known to be made and transported by the motor nerve contributes directly to AChE in the synaptic cleft. Frog muscles were surgically damaged in a way that caused degeneration and permanent removal of all myofibers from their basal lamina sheaths. Concomitantly, AChE activity was irreversibly blocked. Motor axons remained intact, and their terminals persisted at almost all the synaptic sites on the basal lamina in the absence of myofibers. 1 mo after the operation, the innervated sheaths were stained for AChE activity. Despite the absence of myofibers, new AChE appeared in an arborized pattern, characteristic of neuromuscular junctions, and its reaction product was concentrated adjacent to the nerve terminals, obscuring synaptic basal lamina. AChE activity did not appear in the absence of nerve terminals. We concluded therefore, that the newly formed AChE at the synaptic sites had been produced by the persisting axon terminals, indicating that the motor nerve is capable of producing some of the synaptic AChE at neuromuscular junctions. The newly formed AChE remained adherent to basal lamina sheaths after degeneration of the terminals, and was solubilized by collagenase, indicating that the AChE provided by nerve had become incorporated into the basal lamina as at normal neuromuscular junctions.     

Development of the myoneural junction in the rat

Summary The structure of the myoneural junction in the striated muscle of rat embryos and postnatal rats was studied by electron microscopy in order to assess at ultrastructural level the roles of neuronal and muscular elements and the sequence of events resulting in the formation of a functionally mature synaptic organization.From the observations it is concluded that the axon terminals enveloped by Schwann cells contain vesicles prior to apposition of the prospective synaptic membranes. Subsequently, subsarcolemmal thickening of the postsynaptic membrane takes place after the synaptic gap has been formed by disappearance of the teloglial cell from between the synaptic membranes but before the primary synaptic cleft in the strict sense is formed. Secondary synaptic clefts are formed later, when the primary synaptic cleft is regular in width, by local finger-like invaginations of the postsynaptic membrane, which thereafter expand basally, in a plane transverse to the axis of the axon terminal, to resemble flattened flasks. The junction is formed between multinucleated muscle cells and multiple axons, which at first lie side by side and later, when formation of adult-type secondary synaptic clefts is in progress, become separated by folds of the sarcoplasm and the teloglia. In extraocular muscles of adult rats the sarcoplasmic reticulum is closely associated with the postjunctional sarcoplasm.In the light of earlier observations on the development of contractibility after nerve stimulation, cholinesterase histochemistry and muscle fibre physiology, these observations are interpreted to indicate that functional differentiation of the myoneural synapse results from induction by the motor axon and that the association of the sarcoplasmic reticulum with the postjunctional sarcoplasm in adult extraocular muscles is related to modified fibre physiology.The author wishes to thank Prof. Antti Telkkä, M.D., Head of the Electron Microscope Laboratory, University of Helsinki, for placing the electron microscopic facilities at his disposal.