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1.
Summary In the cichlid teleost Tilapia leucosticta, the origin and linear development of synaptic ribbons in retinal receptor cells have been studied. First ribbons are invariably found close to their future synaptic sites between two dendritic invaginations. They are then clearly shorter than at later stages and appear bifurcate, or of bulb or drop shape. From these precursors typical ribbons rapidly develop, and these vary considerably in length. From a shift in length distribution, a main growth phase can be detected which takes place at the time when the retina first becomes functional. Similar observations were made in Xenopus. Placing Tilapia larvae in conditions of 24 h continuous light had no effect on ribbon growth, while 24 h of continuous darkness resulted in a prevalence of shorter ribbons. Thus the growth of synaptic ribbons in the course of retinal development appears to be subject to modification by environmental light conditions.  相似文献   

2.
Summary To study the effects of bilateral ophthalmectomy on the circadian rhythm of the pineal gland, the number of the synaptic ribbons and ribbon fields in the pineal gland of female rats were determined by electron microscopy. In a preliminary experiment, the pineal gland was taken from rats at 15 days, and 1, 2, 3, 4, and 6 months after bilateral ophthalmectomy. It was found that the numbers of both synaptic ribbons and ribbon fields decreased markedly and reached a minimum at 1 month postoperatively, but recovered completely after 4 months. In the main experiment, the number of these intracellular elements was counted in both control and enucleated animals killed at 4 h intervals between 02:00 h and 22:00 h at either 1 month or 6 months after operation. All animals were kept under a lighting regimen of 12 h of illumination (06:00 to 18:00) and 12h of darkness (18:00 to 06:00). After 1 month, a remarkable decrease in the number of both the synaptic ribbons and ribbon fields was again noted but the circadian rhythm still remained. Complete quantitative and qualitative recovery in the circadian rhythm was obtained 6 months later.Supported by a grant-in-aid from the Japanese Ministry of Education, Science and Culture The authors wish to thank Mrs. Kazuko Moriwaki for her technical assistance  相似文献   

3.
This review highlights important events during the morphological development of retinal ganglion cells (RGCs), focusing on mechanisms that control axon and dendritic arborization as a means to understand synaptic connectivity with special emphasis on the role of neurotrophins during structural and functional development of RGCs. Neurotrophins and their receptors participate in the development of visual connectivity at multiple levels. In the visual system, neurotrophins have been shown to exert various developmental influences, from guiding the morphological differentiation of neurons to controlling the functional plasticity of visual circuits. This review article examines the role of neurotrophins, and in particular of BDNF, during the morphological development of RGCs, and discusses potential interactions between activity and neurotrophins during development of neuronal connectivity.  相似文献   

4.
The synaptic ribbon is an electron-dense structure found in hair cells and photoreceptors. The ribbon is surrounded by neurotransmitter-filled vesicles and considered to play a role in vesicle release. We generated an objective, quantitative analysis of the protein composition of the ribbon complex using a mass spectrometry-based proteomics analysis. Our use of affinity-purified ribbons and control IgG immunoprecipitations ensure that the identified proteins are indeed associated with the ribbon complex. The use of mouse tissue, where the proteome is complete, generated a comprehensive analysis of the candidates. We identified 30 proteins (comprising 56 isoforms and subunits) associated with the ribbon complex. The ribbon complex primarily comprises proteins found in conventional synapses, which we categorized into 6 functional groups: vesicle handling (38.5%), scaffold (7.3%), cytoskeletal molecules (20.6%), phosphorylation enzymes (10.6%), molecular chaperones (8.2%), and transmembrane proteins from the presynaptic membrane firmly attached to the ribbon (11.3%). The 3 CtBP isoforms represent the major protein in the ribbon whether calculated by molar amount (30%) or by mass (20%). The relatively high quantity of phosphorylation enzymes suggests a very active and regulated structure. The ribbon appears to comprise a concentrated cluster of proteins dealing with vesicle creation, retention and distribution, and consequent exocytosis.  相似文献   

5.
Synaptic ribbons are large proteinaceous scaffolds at the active zone of ribbon synapses that are specialized for rapid sustained synaptic vesicles exocytosis. A single ribbon‐specific protein is known, RIBEYE, suggesting that ribbons may be constructed from RIBEYE protein. RIBEYE knockdown in zebrafish, however, only reduced but did not eliminate ribbons, indicating a more ancillary role. Here, we show in mice that full deletion of RIBEYE abolishes all presynaptic ribbons in retina synapses. Using paired recordings in acute retina slices, we demonstrate that deletion of RIBEYE severely impaired fast and sustained neurotransmitter release at bipolar neuron/AII amacrine cell synapses and rendered spontaneous miniature release sensitive to the slow Ca2+‐buffer EGTA, suggesting that synaptic ribbons mediate nano‐domain coupling of Ca2+ channels to synaptic vesicle exocytosis. Our results show that RIBEYE is essential for synaptic ribbons as such, and may organize presynaptic nano‐domains that position release‐ready synaptic vesicles adjacent to Ca2+ channels.  相似文献   

6.
Ectopic release of synaptic vesicles   总被引:3,自引:0,他引:3  
Matsui K  Jahr CE 《Neuron》2003,40(6):1173-1183
Exocytosis of synaptic vesicles is generally assumed to occur only at ultrastructurally defined presynaptic active zones. If release is restricted to these sites, receptors not located within the synaptic cleft must be activated by transmitter that diffuses out of the cleft or not be activated at all. Here we report that AMPA receptor-mediated quantal events resulting from climbing fiber release are observed in Bergmann glial cells in the cerebellar cortex. These quantal events are not coincident with quanta recorded in neighboring Purkinje cells which receive input from the same climbing fiber. As Bergmann glial membranes are excluded from the synaptic cleft, we propose that exocytosis can occur from climbing fiber release sites located directly across from Bergmann glial membranes. Such ectopic release may account for the majority of the Bergmann glial AMPA response evoked by climbing fiber stimulation.  相似文献   

7.
Synaptic vesicles can be retrieved rapidly or slowly, but the molecular basis of these kinetic differences has not been defined. We now show that substantially different sets of molecules mediate fast and slow endocytosis in the synaptic terminal of retinal bipolar cells. Capacitance measurements of membrane retrieval were made in terminals in which peptides and protein domains were introduced to disrupt known interactions of clathrin, the AP2 adaptor complex, and amphiphysin. All these manipulations caused a selective inhibition of the slow phase of membrane retrieval (time constant approximately 10 s), leaving the fast phase (approximately 1 s) intact. Slow endocytosis after strong stimulation was therefore dependent on the formation of clathrin-coated membrane. Fast endocytosis occurring after weaker stimuli retrieves vesicle membrane in a clathrin-independent manner. All compensatory endocytosis required GTP hydrolysis, but only a subset of released vesicles were primed for fast, clathrin-independent endocytosis.  相似文献   

8.
Summary The three-dimensional structure of synaptic ribbons in photoreceptor cells of the frog retina was studied with freeze-etching and freeze-substitution methods, combined with a rapid-freezing technique. Although the synaptic ribbon consisted of two electron-dense plaques bisected by an electron-lucent layer in conventional thin sections, such lamellar nature was not so evident in freeze-etched replicas. The cytoplasmic surfaces of the synaptic ribbon presented an extremely regular arrangements of small particles 4–6 nm in diameter. Fine filaments 8–10 nm in diameter and 30–50 nm in length connected synaptic vesicles and the ribbon surface. These connections were mediated by large particles on both ends of the filaments. Approximately 3–5 filaments attached to one synaptic vesicle. Synaptic ribbons were anchored to a characteristic meshwork underlying the presynaptic membrane via another group of similar fine filaments. The meshwork seemed to be an etched replicated image of the presynaptic archiform density observed in thin sections.  相似文献   

9.
Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.  相似文献   

10.
Summary In the present investigation experiments were carried out to determine whether the functionally obscure synaptic ribbons of mammalian pinealocytes can be affected by acute changes in environmental lighting and which chemical processes may be involved in their regulation. Experiments carried out in male guinea-pigs have shown that the amounts of synaptic ribbons are immediately affected by changes in the lighting pattern. Extension of the light period reduced the normally occurring increase, whereas extension of the dark period inhibited the normally occurring decrease in the amount of synaptic ribbons. Results following injections of a number of drugs known to influence pineal function (noradrenaline, L-DOPA, propranolol, reserpine and p-chlorophenylalanine, respectively) suggest that synaptic ribbons may be directly or indirectly regulated by -adrenergic mechanisms.Dedicated to Professor Wolfgang Bargmann on the occasion of his 70th birthday.  相似文献   

11.
The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons.  相似文献   

12.
Dendrites constitute over 80 per cent of the receptive surface area in cat motoneurons. Calculations based on matched electrical and gemoetrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on the dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties.  相似文献   

13.
A Gidon  I Segev 《Neuron》2012,75(2):330-341
Synaptic inhibition plays a key role in shaping the dynamics of neuronal networks and selecting cell assemblies. Typically, an inhibitory axon contacts a particular dendritic subdomain of its target neuron, where it often makes 10-20 synapses, sometimes on very distal branches. The functional implications of such a connectivity pattern are not well understood. Our experimentally based theoretical study highlights several new and counterintuitive principles for dendritic inhibition. We show that distal "off-path" rather than proximal "on-path" inhibition effectively dampens proximal excitable dendritic "hotspots," thus powerfully controlling the neuron's output. Additionally, with multiple synaptic contacts, inhibition operates globally, spreading centripetally hundreds of micrometers from the inhibitory synapses. Consequently, inhibition in regions lacking inhibitory synapses may exceed that at the synaptic sites themselves. These results offer new insights into the synergetic effect of dendritic inhibition in controlling dendritic excitability and plasticity and in dynamically molding functional dendritic subdomains and their output.  相似文献   

14.
15.
RS Jones  RC Carroll  S Nawy 《Neuron》2012,75(3):467-478
Light-evoked responses of all three major classes of?retinal ganglion cells (RGCs) are mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs). Although synaptic activity at RGC synapses is highly dynamic, synaptic plasticity has not been observed in adult RGCs. Here, using patch-clamp recordings in dark-adapted mouse retina, we report a retina-specific form of AMPAR plasticity. Both chemical and light activation of NMDARs caused the selective endocytosis of GluA2-containing, Ca(2+)-impermeable AMPARs on RGCs and replacement with GluA2-lacking, Ca(2+)-permeable AMPARs. The plasticity was expressed in ON but not OFF RGCs and was restricted solely to the ON responses in ON-OFF RGCs. Finally, the plasticity resulted in a shift in the light responsiveness of ON RGCs. Thus, physiologically relevant light stimuli can induce a change in synaptic receptor composition of ON RGCs, providing a mechanism by which the sensitivity of RGC responses may be modified under scotopic conditions.  相似文献   

16.
17.
Summary The synaptic complexes of the rat pinealocytes are neither cholinergic nor adrenergic. In the synaptic vesicles, a neurotransmitter carrier substance of lipid nature reacting with OsO4-Zn I2 mixture (similar to that present in both cholinergic and adrenergic vesicles) was not found.In addition, there were no indications of glucose-6-phosphatase or thiamine-pyrophosphatase activity in the synaptic vesicles. Thus, it appears that the synaptic vesicles do not originate from the rough or smooth endoplasmic reticulum.The synaptic ribbons do not contain carbohydrates, are of protein nature and possess some chemical resemblance to microtubules and microtubular bouquets.Appropriate ultracytochemical reactions have not shown detectable quantities of sodium and calcium ions in pinealocyte synaptic complexes.Grateful acknowledgment is made to Mr. P.-A. Milliquet for technical assistance and to Dr. T. Jalanti (C.M.E., Lausanne) for his help in the use of the X-ray microanalyser.Dedicated to Professor Dr. med. G. Töndury on the occasion of his 70th birthday.  相似文献   

18.
19.
In the vertebrate retina the presence of synaptic ribbons (SRs) is well documented in two sites only, viz., in photoreceptor axon terminals in the outer plexiform layer and in bipolar cell axons in the inner plexiform layer. The present paper reports the presence of non-photoreceptor SRs in the outer plexiform layer of cattle and mouse, where they were seen in small numbers in thin cell processes near cone pedicles of light-adapted animals. They were never seen near rod spherules. Quantitative data obtained in mice killed at different time-points revealed that the SRs under consideration increased in number during day time and were absent during the dark phase. Moreover, under high light intensity of 10000 lux they were more frequent in number compared to 100-lux-exposed animals. It is concluded that the cell processes revealing the temporary presence of SRs are processes of flat bipolar cells which may provide a feedback to cones during the light phase.  相似文献   

20.
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