The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.
Animals ; Mice ; Mice, Knockout ; Motor Endplate ; Muscle, Skeletal* ; Muscles ; Myelin Sheath ; Neuregulin-1 ; Neuromuscular Junction ; Peripheral Nerves ; Presynaptic Terminals ; Protein-Tyrosine Kinases ; Schwann Cells* ; Synapses* ; Vertebrates

The purpose of this study was to investigate the distribution of neuropeptide Y (NPY) in the cat spinal trigeminal subnucleus caudalis following pulpectomy of mandibular premolars and molar by means of an immunohistochemical and immunoelectron microscopic study. The animals were divided into normal and experimental group which were sacrificed at 14 days after pulpectomy. The results were as follows; 1. On the light microscopic observation of the spinal trigeminal subnucleus caudalis in normal group, NPY-immunoreactivity (IR) was weak within lamina I and lamina II outer. In pulpectomy group, NPY-IR was strong and appeared to extend into lamina I and lamina II inner at 14 days. 2. On the immunoelectron microscopic observation of the spinal trigeminal subnucleus caudalis in normal group, NPY-IR was revealed in axon terminals, dendrites, myelinated axons and unmyelinated axons. NPY-IR was associated with membrane structures within microtubules, synaptic vesicles, outer membrane of mitochondria and inner surface of the axolemma. In NPY-immunoreactive structure, there was a small amount of DAB precipita-tions. 3. On the immunoelectron microscopic observation of the spinal trigeminal subnucleus caudalis at 14 days in pulpectomy group, the number of NPY-immunoreactive axon terminals, dendrites, myelinated axons and unmyelinated axons was increased than normal group. DAB precipitations in NPY-immunoreactive structure was increased than normal group. Some NPY-immunoreactive axon terminal formed synaptic glomerulus and axoaxonic synapse. 4. The results indicate that NPY-IR was increased in the spinal trigeminal subnucleus caudalis after pulpectomy, and it is speculated that the increased NPY by injury of peripheral nerve may participate in the processing of nociception.
Animals ; Axons ; Bicuspid ; Cats* ; Dendrites ; Immunohistochemistry ; Membranes ; Microtubules ; Mitochondria ; Molar ; Myelin Sheath ; Neuropeptide Y* ; Neuropeptides* ; Nociception ; Peripheral Nerves ; Presynaptic Terminals ; Pulpectomy* ; Synapses ; Synaptic Vesicles

The role of glycine as an inhibitory neurotransmitter is well established, and glycinergic neurons appear to play an important role in the mammalian retinae[Ikeda & Sheardown, 1983 ; Bolz et al., 1985]. Though it has been reported that certain conventional and displaced amacrine cells and a few of bipolar cells are consistently labeled with anti-glycine antiserum in the mammalian retinae so far[W ssle et al., 1986 ; Pourcho & Goebel, 1987 ; Davanger et al., 1991 ; Yoo & Chung, 1992], little has been studied on the synaptic circuitry of glycinergic neurons to clarify mechanism of its action in the visual processing of the mammalian retinae. This study was conducted to localize glycinergic neurons and to define their synaptic circuitry in the rat retina by immunocytochemical method using anti -glycine antiserum. The results were as follows : 1. Glycinergic neurons of the rat retina were conventional and displaced amacrine cells, interstitial cells and bipolar cells. 2. Glycinergic amacrine cells could be subdivided into two types, that is, A II amacrine cells and other amacrine cells, according to their ultrastructures. Glycinergic A II amacrine and other amacrine cell processes comprised postsynaptic dyad at the ribbon synapse of rod bipolar axon terminals in the sublamina b of the inner plexiform layer of the retina. Glycinprgic A II amacrine cell processes made gap junctions with axon terminals of unlabeled invaginating cone bipolar cells in the sublamina b, and made chemical synapses onto axon terminals of unlabeled flat cone bipolar cells and onto dendrites of ganglion cells in the sublamina a of the inner plexiform layer. In the sublamina b of the inner plexiform layer, g1ycinergic amacrine cell processes were postsynaptic to axon terminals of unlabeled invaginating cone bipolar cells, and made chemical output synapses onto axon terminals of unlabeled invaginating cone bipolar and rod bipolar cells and onto the dendrites of ganglion cells. Such cases that pre- and post-synaptic processes of glycinergic amacrine cell processes were non- glycinergic amacrine cell processes were frequently observed throughout the inner plexiform layer. In some cases, glycinergic amacrine cell processes receiving synaptic inputs from other glycinergic amacrine cell process made synaptic outputs onto the non-glycinergic or glycinergic amacrine cell processes. 3. Glycinergic bipolar cells could be subdivided into invaginating and flat cone bipolar cells. Postsynaptic dyads of cone bipolar cells at the ribbon synapses were non-glycinergic amacrine and amacrine cell processes, glycinergic amacrine and amacrine cell processes, glycinergic amacrine and non-glycinergic amacrine cell processes, and dendrite and dendrite of ganglion cells. These results demonstrate that [1] glycinergic A II amacrine cell receiving synaptic input from rod bipolar cells inhibit flat cone bipolar cells and OFF ganglion cells via chemical synapse, and excite ON cone bipolar cells via electrical synapse ; thereby visual information in the darkness can be transmitted to ON ganglion cells via ON cone bipolar cells, and [2] glycine released from glycinergic neurons inhibits directly ON and OFF ganglion cells or indirectly ON and OFF ganglion cells via non-glycinergic amacrine or bipolar cells.
Amacrine Cells ; Animals ; Darkness ; Dendrites ; Electrical Synapses ; Ganglion Cysts ; Gap Junctions ; Glycine ; Neurons* ; Neurotransmitter Agents ; Presynaptic Terminals ; Rats* ; Retina* ; Synapses

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

The ultrastructure of the excitotoxic lesion similar to that occurring in the degenerative neuronal disease was produceby stereotaxic injections of 1 nmol and 10 mnol of kainic acid nto the corpus striatum of adult rat brain There were rnarked swellings in the neuronal dendrites at injected sites. Neurotubules and neurofilarnents were disrupted as and amorphous materials and scattered throughout the interior of distended dendrites. Internal cristae and membranes of mitochondria were destroyed with the loss of integrity of intracellular organelles. Disruption of cellular and nuclear membranes occurered in severe cases. But there was no apparent pathologic change in the other structure, ie, synapses, presynaptic and postsynaptic parts, axons and glial cells. The synapses between dendrites and axon terminals were not destroyed despite of marked distension of dendrites. The local administration of excitatory amino acid into the brain caused the destruction of dendrites and neuronal cell bodies, but axons and axon terminals were intact With the lapse of time, axons and axon terminals from the destroyed neuron degenerate Therelore stereotaxic injection of excitatory amino acid into the brain may provldes a method of investigating neuronal connectivity.
Adult ; Animals ; Axons* ; Brain ; Corpus Striatum* ; Dendrites ; Excitatory Amino Acids ; Humans ; Kainic Acid* ; Membranes ; Mitochondria ; Neuroglia ; Neurons* ; Nuclear Envelope ; Organelles ; Presynaptic Terminals ; Rats ; Synapses

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.
Animals ; Astrocytes ; Axons ; Chronic Pain ; Oligodendroglia ; Presynaptic Terminals ; Regeneration ; Spinal Cord ; Spinal Nerve Roots ; Synapses

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been reported to play important roles in the regulation of olfactory information in the mammarian olfactory bulb. Although the distribution of nitric oxide synthase (NOS)-immunoreactive neurons in the olfactory bulb in the rat and other animals have been investigated by light microscopy, ultrastructures of the synaptic organization between NOS-immunoreactive neurons have not been studied yet. This study was conducted in order to identify NOS- immunoreactive neurons in the rat olfactory bulb and to define their synaptic organizations under the electron microscope using the preembedding immunocytochemical method which utilizes anti-NOS antiserum. MATERIALS AND METHODS: The olfactory bulbs of the rats were cut into 50 micromiter thick vertical sections and immunostained using the ABS method. Stained sections were observed under the light microscope. Some of the stained sections, additionally stained with uranyl acetate and dehydrated, were embedded in Epon 812 and prepared into 80 nm thick sections to be observed under the electron microscope. RESULT: NOS-immunoreactive neurons of the rat olfactory bulb made up 25.0% of periglomerular cells and 18.9% of granule cells. NOS-immunoreactive periglomerular cells received synaptic input from unlabeled axon terminals of the olfactory nerve and unlabeled periglomerular cells within the glomeruli. The output targets of NOS immunoreactive periglomerular cells were unlabeled axon terminals of the olfactory nerve and unlabeled periglomerular cells. NOS-immunoreactive granule cells received synaptic input from unlabeled processes of granule cells and axon terminals of mitral cells, and made output synapses onto the unlabeled axon terminals of mitral cells. CONCLUSION: NOS-immunoreactive neurons are periglomerular cells and granule cells, and NO liberated from NOS cells may play important roles in the modulation of olfactory transmission.
Animals ; Microscopy ; Neurons* ; Nitric Oxide Synthase* ; Nitric Oxide* ; Olfactory Bulb ; Olfactory Nerve ; Presynaptic Terminals ; Rats* ; Synapses

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

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