In central nervous system only a limited number of vesicles exist in the presynaptic terminals. The size and fusion modes of the vesicles were particularly important because of their potential impact on neuronal communications. Efficient methods were needed to analyze the recycling kinetics of synaptic vesicle and the size of readily releasable pool (RRP). In this study, fluorescent dyes with different affinity for membranes (FM1-43 with high affinity and FM2-10 with low affinity) were used to stain the functional synaptic vesicles of cultured hippocampal neurons and the kinetics of vesicle recycling was measured. The results showed that the destaining proportion was larger for FM2-10 than that for FM1-43 during the first trial, while it was greater for FM1-43 than FM2-10 during the second and third trials (first round, 93.0%+/-5.9% versus 57.9%+/-3.5% for FM2-10 and FM1-43, respectively, P<0.0001; second round, 1.4%+/-3.8% versus 24.0%+/-2.3%, P<0.0001; third round, 2.3%+/-1.6% versus 8.6%+/-1.5%, P=0.005). The results indicated that rapid endocytosis existed not only in the first round but also occurred when the vesicles were reused. Moreover, Both high-frequency stimuli and hypertonic sucrose stimuli were used to estimate the RRP sizes in the mix cultured hippocampal inhibitory neurons at 13-14 days in vitro (DIV). We found that the RRP size estimated by hypertonic sucrose stimuli [(200+/-23.0) pC] was much larger than that estimated by high-frequency stimuli [(51.1+/-10.5) pC]. One possible reason for the discrepancies in RRP estimates is that in mix cultured conditions, one neuron may receive inputs from several neurons and hypertonic sucrose stimuli will cause RRP of all those neurons release, while using dual patch recording, only the connection between two neurons was analyzed. Thus, to exclude out the impacts of inputs numbers on RRP sizes, it is more reasonable to use high-frequency stimuli to estimate the RRP size in mix cultured neurons.
Cells, Cultured ; Endocytosis ; Hippocampus ; cytology ; Neurons ; physiology ; Synaptic Vesicles ; physiology

Neurotransmission begins with neurotransmitter being released from synaptic vesicles. To achieve this function, synaptic vesicles endure the dynamic "release-recycle" process to maintain the function and structure of presynaptic terminal. Synaptic transmission starts with a single action potential that depolarizes axonal bouton, followed by an increase in the cytosolic calcium concentration that triggers the synaptic vesicle membrane fusion with presynaptic membrane to release neurotransmitter; then the vesicle membrane can be endocytosed for reusing afterwards. This process requires delicate regulation, intermediate steps and dynamic balances. Accumulating evidence showed that the release ability and mobility of synapses varies under different stimulations. Synaptic vesicle heterogeneity has been studied at molecular and cellular levels, hopefully leading to the identification of the relationships between structure and function and understanding how vesicle regulation affects synaptic transmission and plasticity. People are beginning to realize that different types of synapses show diverse presynaptic activities. The steady advances of technology studying synaptic vesicle recycling promote people's understanding of this field. In this review, we discuss the following three aspects of the research progresses on synaptic vesicle recycling: 1) presynaptic vesicle pools and recycling; 2) research progresses on the differences of glutamatergic and GABAergic presynaptic vesicle recycling mechanism and 3) comparison of the technologies used in studying presyanptic vesicle recycling and the latest progress in the technology development in this field.
Action Potentials ; Axons ; physiology ; Calcium ; physiology ; Endocytosis ; Humans ; Presynaptic Terminals ; physiology ; Synapses ; physiology ; Synaptic Transmission ; Synaptic Vesicles ; physiology

As the basic physiological function of synapses, vesicle cycling involves in many aspects of process. Among them, vesicle recycling is the basis of synaptic vesicle cycling. Studies show that clathrin mediated endocytosis is a major pathway of vesicle recycling, in which Dynamin plays an important role. Dynamin is a GTPases with molecular weight of 100 kD, which acts as "scissors" in the endocytosis, separating the clathrin coated pits from membrane. It has been found that Dynamin is associated with epilepsy, Alzheimer's disease, centronuclear myopathy, and several other neurological diseases. In this paper, we discussed the structure, function and regulation of Dynamin, and reviewed recent advance in the studies on Dynamin related diseases.
Clathrin ; physiology ; Coated Pits, Cell-Membrane ; physiology ; Dynamins ; physiology ; Endocytosis ; Humans ; Synapses ; physiology ; Synaptic Transmission ; Synaptic Vesicles ; physiology

Early postnatal period is considered as the critical period for formation and maturation of the synapses. And cerebellum has the major role in the development of equilibrium and somatic motor function, especially in the early postnatal age. So, I performed this study to investigate the morphological changes of the synapses in the rat cerebellar cortex. Sprague-Dawley rats were used as experimental animals. The ultrastructure of Synapses was observed in six groups ; 3-day, 1-week, 2-week, 3-week, 4-week, 5-week. The results are as followes. 1. After birth, the synaptic density was increased gradually by the forth week. 2. The length of postsynaptic densities was increased significantly in the period between first and second week. 3. There was significant correlation between the length of postsynaptic densities and the area of synaptic vesicle clusters. 4. The frequency of asymmetric and/or frown synapses was increased dramatically with advancing ages. According to the above results, the synaptogenesis in the rat cerebellum is very active in their early postnatal periods. And asymmetric and/or active frown synapses were the major type of synapses with advancing ages.
Animals ; Cerebellar Cortex* ; Cerebellum ; Critical Period (Psychology) ; Parturition ; Post-Synaptic Density ; Rats* ; Rats, Sprague-Dawley ; Synapses* ; Synaptic Vesicles

Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer disease. The loss of specific brain area, the substantia nigra pars compacta is known as a major etiology, however it is not fully understood how this neurodegeneration is initiated and what precisely causes this disease. As one aspect of pathophysiology for PD, synaptic dysfunction (synaptopathy) is thought to be an earlier appearance for neurodegeneration. In addition, some of the familial factors cumulatively exhibit that these factors such as α-synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced kinase 1, and DJ-1 are involved in the regulation of synaptic function and missense mutants of familial factors found in PD-patient show dysregulation of synaptic functions. In this review, we have discussed the physiological function of these genetic factors in presynaptic terminal and how dysregulation of presynaptic function by genetic factors might be related to the pathogenesis of Parkinson disease.
Alzheimer Disease ; Brain ; Neurodegenerative Diseases ; Parkinson Disease* ; Pars Compacta ; Phosphotransferases ; Presynaptic Terminals ; Synapses ; Synaptic Transmission ; Synaptic Vesicles

The neuromuscular junction (NMJ) has been studied for over a century as a model system for synaptic anatomy, physiology and development. Much of our knowledge of the NMJ has been obtained through imaging techniques, some of which were developed particularly to visualize this synapse's structure and function. In this paper we review the historical development of research on some key aspects of the NMJ, including its structure, nicotinic acetylcholine receptor distribution, the process of synaptic vesicle release, and its development.
Diagnostic Imaging ; Humans ; Neuromuscular Junction ; anatomy & histology ; physiology ; Receptors, Nicotinic ; physiology ; Synaptic Vesicles ; physiology

Intersectin is an evolutionarily conserved multifunctional adaptor protein with multifunctional domains. These domains interact with components of the endocytic and exocytic pathways, such as the clathrin mediating synaptic vesicle recycling, the protein related to endocytosis via caveolae, the with-no-lysine kinases related to the regulation of renal outer medullar potassium, and the Cdc42 mediating exocytic pathway. Recently, the understanding of intersectin function in the pathogenesis of endocrine tumor and many neurodegenerative diseases such as Down syndrome, Alzheimer disease has been deepened. This article reviewed the structure and roles in endocytosis/exocytosis and diseases of intersectin.
Adaptor Proteins, Vesicular Transport ; physiology ; Endocytosis ; Exocytosis ; Humans ; Synaptic Vesicles ; physiology

Although the distribution of locus ceruleus terminals has been demonstrated in the fundus striati[nucleus accumbens septi] by light microscopy[Jones & Moore, 1977 ; Mason & Fibiger, 1979 ; Streit or et al., 1979 ; Groenewegen et al., 1980], the synaptic organization of its terminals was not clarified. The purpose of the present investigation was to demonstrate the direct monosynaptic connection of the locus ceruleus terminals to the neuronal elements of the fundus stirati, and to clarify the synaptic structures of its terminals by electron microscopy two days after unilateral electric coagulation of the locus ceruleus. In the ipsilateral fundus striati, many axon terminals undergone dark degeneration were observed. These degenerating terminals containing small clear vesicles have asymmetric synaptic contacts with dendritic spines. Already two days after locus ceruleus lesion, distinct features of terminal degenerations appeared in the fundus striati ; enlarged axon terminals with altered synaptic vesicles, decrease of synaptic vesicles detached from the synaptic site, multiplication of dense bodies and infiltration of floccular material. At the same time, a regressive change occurred in which astrocytic processes encircled totally degenerated synapses spiraled around the synaptic remnants. These observations indicate that monosynaptic noradrenertic afferent connections to the fungus striati are confirmed, and the locus ceruleus terminals characterized by small round vesicles might be formed asymmetrical axo-spinous synapses with spiny neurons in the fundus striati.
Animals ; Cats* ; Dendritic Spines ; Fungi ; Locus Coeruleus* ; Microscopy, Electron ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

An attempt has been made to discriminate synaptic diversity in the neostriatum of the cat with emphasis on the characteristic structures of axon terminals and postsynaptic profiles. The differentiation of the axon terminals was based on the size and shape of synaptic vesicles in the axoplasm. Three types of axon terminals could be differentiated: Type I, the terminals contained small round (45 nm in diameter) vesicles; type II, the terminals with large pleomorphic (50 nm) vesicles; and type III, the terminals contained flattened (45 x 25 nm) vesicles. The type I terminals were making asymmetrical or symmetrical synapses in contact with the somata, dendrites and dendritic spines of neurons in the neostriatum, and a few type I terminals making asymmetrical or symmetrical contact with axons were also observed. The type II and III terminals were making symmetrical contact with the somata and dendrites of neostriatal neurons. A few type II terminals formed at the node of Ranvier of myelinated nerve fibers were making symmetrical contact with large dendrites. Additionally, dendro-dendritic and serial syanpses were rarely found in the neostriatum. In the serial synapses composed of axo-dendritic and dendro-dendritic synapses, the type I terminals making asymmetrical contact and the type II making symmetrical contact were identified.
Animals ; Axons ; Cats* ; Dendrites ; Dendritic Spines ; Neostriatum* ; Nerve Fibers, Myelinated ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

The kinesin proteins (KIFs) make up a large superfamily of molecular motors that transport cargo such as vesicles, protein complexes, and organelles. KIF1A is a monomeric motor that conveys synaptic vesicle precursors and plays an important role in neuronal function. Here, we used the yeast two-hybrid system to identify the neuronal protein (s) that interacts with the tail region of KIF1A and found a specific interaction with synaptotagmin XI. The amino acid residues between 830 and 1300 of KIF1A are required for the interaction with synaptotagmin XI. KIF1A also bound to the tail region of synaptotagmin IV but not to other synaptotagmin in the yeast two-hybrid assay. KIF1A interacted with GST-synaptotagim XI fusion proteins, but not with GST alone. An antibody to synaptotagmin XI specifically co-mmunoprecipitated KIF1A associated with synaptotagimin from mouse brain extracts. These results suggest that KIF1A motor protein transports of synaptotagmin XI-containing synaptic vesicle precursors along microtubule.
Animals ; Brain ; Kinesin* ; Mice ; Microtubules ; Neurons ; Organelles ; Protein Transport ; Synaptic Vesicles ; Synaptotagmins* ; Two-Hybrid System Techniques