On the significance of cross-bridges between microtubules and synaptic vesicles

Observations on the fine structure of synaptic and non-synaptic axoplasm in the spinal cord of the lamprey ammocoete ( Petromyzon marinus ) are described. Previous studies on this material revealed a close association between spherical vesicles and axoplasmic microtubules near central synapses, and observations were consistent with the suggestion that synaptic vesicles become detached from oriented microtubules in the focal clusters adjoining the presynaptic membrane across which transmitter release takes place. These observations have been extended to include axons containing non-spherical or ellipsoidal vesicles— possibly containing a transmitter chemically and functionally distinct from that in spherical synaptic vesicles. Structural cross-bridges between both microtubules and vesicle populations are now described; these are found not only in the vesicle concentrations bordering synaptic foci, but also in non-synaptic axoplasmic regions where sparsely distributed vesicles are found in association with microtubules. It is suggested that the bridging between vesicles and microtubules may reflect a mechanism for transport of the former—a possibility in accord with cumulative evidence of involvement of microtubules in rapid intracellular translocation in a variety of cells. It is proposed that arrival of excitation at a synaptic site is not only coupled with transmitter release across the axon plasma membrane, but that events at the cell membrane may in turn be coupled with a means of supplying vesicles to the synaptic locus. This hypothesis suggests that the synapse may rely on distant parts of the neuron, perhaps including the cell body, for materials involved in synaptic transmission.

1975 ◽  
Vol 190 (1100) ◽  
pp. 369-372 ◽  

When fragments of rat or frog brain are teased in albumin solution before fixation, the synapses show microtubules focused on the presynaptic membrane and in close association with synaptic vesicles.


Nature ◽  
1995 ◽  
Vol 377 (6544) ◽  
pp. 62-65 ◽  
Author(s):  
Dieter Bruns ◽  
Reinhard Jahn

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra Bunda ◽  
Brianna LaCarubba ◽  
Melanie Bertolino ◽  
Marie Akiki ◽  
Kevin Bath ◽  
...  

Abstract Presynaptic CaV2.2 channels control calcium entry that triggers neurotransmitter release at both central and peripheral synapses. The Cacna1b gene encodes the α1-pore forming subunit of CaV2.2 channels. Distinct subsets of splice variants of CaV2.2 derived from cell-specific alternative splicing of the Cacna1b pre-mRNA are expressed in specific subpopulations of neurons. Four cell-specific sites of alternative splicing in Cacna1b that alter CaV2.2 channel function have been described in detail: three cassette exons (e18a, e24a, and e31a) and a pair of mutually exclusive exons (e37a/e37b). Cacna1b mRNAs containing e37a are highly enriched in a subpopulation of nociceptors where they influence nociception and morphine analgesia. E37a-Cacna1b mRNAs are also expressed in brain, but their cell-specific expression in this part of the nervous system, their functional consequences in central synapses and their role on complex behavior have not been studied. In this report, we show that e37a-Cacna1b mRNAs are expressed in excitatory projection neurons where CaV2.2 channels are known to influence transmitter release at excitatory inputs from entorhinal cortex (EC) to dentate gyrus (DG). By comparing behaviors of WT mice to those that only express e37b-CaV2.2 channels, we found evidence that e37a-CaV2.2 enhances behavioral responses to aversive stimuli. Our results suggest that alternative splicing of Cacna1b e37a influences excitatory transmitter release and couples to complex behaviors.


1971 ◽  
Vol 178 (1053) ◽  
pp. 407-415 ◽  

When frog muscles are exposed for several hours to a solution of isotonic calcium chloride, the secretory response of the motor nerve terminals to imposed depolarization ultimately fails and the rate of spontaneous release of acetylcholine also declines towards zero. The failure of depolarization-evoked transmitter release is irreversible while spontaneous release reappears, though in highly abnormal fashion, when the muscle is returned to a normal ionic medium. Examination of motor end-plates, during various stages of calcium treatment, shows that there is gradual intra-axonal agglutination of synaptic vesicles which is only very incompletely reversible. This effect is presumably the consequence of gradual entry and intracellular accumulation of calcium ions. Analogous treatment with isotonic magnesium, while resulting in immediate loss of evoked transmitter release, does not lead to progressive agglutination of synaptic vesicles, nor to irreversible impairment of the secretory response of the nerve terminal. The possible relations between structural and functional changes during calcium and magnesium treatment are discussed.


1955 ◽  
Vol 1 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Eduardo D. P. De Robertis ◽  
H. Stanley Bennett

Electron micrographs are presented of synaptic regions encountered in sections of frog sympathetic ganglia and earthworm nerve cord neuropile. Pre- and postsynaptic neuronal elements each appear to have a membrane 70 to 100 A thick, separated from each other over the synaptic area by an intermembranal space 100 to 150 A across. A granular or vesicular component, here designated the synaptic vesicles, is encountered on the presynaptic side of the synapse and consists of numerous oval or spherical bodies 200 to 500 A in diameter, with dense circumferences and lighter centers. Synaptic vesicles are encountered in close relationship to the synaptic membrane. In the earthworm neuropile elongated vesicles are found extending through perforations or gaps in the presynaptic membrane, with portions of vesicles appearing in the intermembranal space. Mitochondria are encountered in the vicinity of the synapse, and in the frog, a submicroscopic filamentary component can be seen in the presynaptic member extending up to the region where the vesicles are found, but terminating short of the synapse itself.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Laurent Guillaud ◽  
Dimitar Dimitrov ◽  
Tomoyuki Takahashi

Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity. At the molecular level, SVs over-expressing vesicular glutamate transporter 1 (VGLUT1) showed higher mobility than VGLUT2-expressing SVs. Pharmacological disruption of the presynaptic microtubule network preferentially reduced long directional movements of SVs between release sites. Functionally, synaptic stimulation appeared to recruit SVs to active zones without significantly altering their mobility. Hence, the morphological features of nerve terminals and the molecular signature of vesicles are key elements determining vesicular dynamics and movements in central synapses.


2019 ◽  
Author(s):  
Justin S. Rosenthal ◽  
Jun Yin ◽  
Caixia Long ◽  
Emma Spillman ◽  
Chengyu Sheng ◽  
...  

AbstractConstruction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses in the insect central nervous system (CNS) is not known. To address this question, we investigated Drosophila ventral lateral neurons (LNvs) and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in these cells. With morphological and calcium imaging studies, we demonstrated their distinct roles in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our analyses revealed a transcriptional upregulation of Dα1 and downregulation of Dα6 during larval development, indicating a close association between the temporal regulation of nAchR subunits and synapse maturation. Together, our findings show transcriptional regulation of nAchR composition is a core element of developmental and activity-dependent regulation of central cholinergic synapses.


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