Axons presynaptic terminals

Neurons constitute the most striking example of membrane polarization. A single neuron typically maintains thousands of discrete, functional microdomains, each with a distinctive protein complement, location and lifetime. Synaptic terminals are highly specialized for the vesicle cycling that underlies neurotransmitter release and neurotrophin uptake. The intracellular trafficking of a specialized type of transport vesicles in the presynaptic terminal, known as synaptic vesicles, underlies the ability of neurons to receive, process and transmit information. The axonal plasma membrane is specialized for transmission of the action potential, whereas the plasma... 

Vesicular proteins and lipids that are destined for the plasma membrane leave the TGN sorting station continuously. Incorporation into the plasma membrane is typically targeted to a particular membrane domain (dendrite, axon, presynaptic, postsynaptic membrane, etc.) but may or may not be triggered by extracellular stimuli. Exocytosis is the eukaryotic cellular process defined as the fusion of the vesicular membrane with the plasma membrane, leading to continuity between the intravesicular space and the extracellular space. Exocytosis carries out two main functions it provides membrane proteins and lipids from the vesicle membrane to the plasma membrane and releases the soluble contents of the lumen (proteins, peptides, etc.) to the extracellular milieu. Historically, exocytosis has been subdivided into constitutive and regulated (Fig. 9-6), where release of classical neurotransmitters at the synaptic terminal is a special case of regulated secretion [54]. 

Specific membrane components must be delivered to their sites of utilization and not left at inappropriate sites [3]. Synaptic vesicles and other materials needed for neurotransmitter release should go to presynaptic terminals because they serve no function in an axon or cell body. The problem is compounded because many presynaptic terminals are not at the end of an axon. Often, numerous terminals occur sequentially along a single axon, making en passant contacts with multiple targets. Thus, synaptic vesicles cannot merely move to the end of axonal MTs. Targeting of synaptic vesicles thus becomes a more complex problem. Similar complexities arise with membrane proteins destined for the axolemma or a nodal membrane. 

Dephosphorylated synapsin inhibits axonal transport of MBOs in isolated axoplasm, while phosphorylated synapsin at similar concentrations has no effect [21]. When a synaptic vesicle passes through a region rich in dephosphorylated synapsin, it may be cross-linked to the available MF matrix by synapsin. Such cross-linked vesicles would be removed from fast axonal transport and are effectively targeted to a synapsin- and MF-rich domain, the presynaptic terminal. 

At the ends of axons, the part farthest from the cell body, they branch into structures known as axon terminals or presynaptic terminals. The number of axon terminals varies from axon to axon. Some have thousands. The great majority of these axon terminals function to transmit signals to the dendrites, cell bodies, and, less commonly, to the axons of other neurons. A far smaller number transmit signals to muscle cells. We can begin to see the development of vast networks and circuits within theCNS. 

As indicated earlier, the relaxant effects of the toxin are likewise temporary, and these effects typically diminish within 2 to 3 months after injection.91 The effects apparently wear off because a new presynaptic terminal sprouts from the axon that contains the originally affected presynaptic terminal. This new terminal grows downward, reattaching to the skeletal muscle and creating a new motor end plate with a new source of acetylcholine. The effects of the previous injection are overcome when this new presynaptic terminal begins to function. Another injection will be needed to block the release from this new presynaptic terminal, thus allowing another 2 to 3 months of antispasticity effects. This fact raises the question of how... 

Hersch et al. (1995) found that D1 immunoreactive terminals presynaptic to symmetrical synapses were exceedingly rare whereas the D2 immunoreactive terminals were quite frequent. Synapses formed by D2 immunoreactive terminals were not easy to identify due to a lack of pronounced pre or postsynaptic densities, but many D2 positive presynaptic terminals made symmetrical synapses with dendritic shafts and spines. Consistent with this, many presynaptic D2 receptors were also seen in terminals which were not positive for TH, suggesting they may be heteroreceptors (Sesack et al., 1994). This is confirmed by the demonstration of the D2 positive GABA axon terminals presynaptic to symmetrical synapses (Delle Donne et al., 1997). 

As shown in Fig. 3 (Top Panel), dietary tyrosine is transported into axon terminals of DA neurons and converted in the cytoplasm to DOPA by the rate limiting enzyme TH. DOPA is then rapidly decarboxylated by DDC to DA which is taken up and stored in synaptic vesicles until release. Excess newly synthesized DA is metabolized by mitochondrial monoamine oxidase (MAO) to DOPAC which rapidly diffuses out of neurons and is taken up and converted to homovanillic acid (HVA) by catechol-O-methyltransferase (COMT)-containing glial cells in the neuropil (Hansson and Sellstrom, 1983 Kimelberg, 1986). Upon arrival of an action potential at the axon terminal, vesicular DA is released into the synapse via calcium-dependent exocytosis where it is free to interact with stimulatory Di and/or inhibitory D2 DA receptors on postsynaptic target cells and inhibitory D2 autoreceptors on presynaptic terminals. A major portion of DA is removed from the synapse by high affinity DA transporters located on presynaptic terminals, and recaptured DA is either metabolized to DOPAC by mitochondrial MAO or stored in synaptic vesicles for subsequent re-release. A small portion of DA can also be taken up from the synapse by glia and metabolized to 3-methoxytyramine (3MT) and HVA. 

The process of information flow between neurons is termed synaptic transmission, and in its most basic form it is characterized by unidirectional communication from the presynaptic to postsynaptic neuron. The process begins with the initiation of an electrical impulse in the axon of the presynaptic neuron. This electrical signal—the action potential—propagates to the axon terminal, which thereby stimulates the fusion of a transmitter-fllled synaptic vesicle with the presynaptic terminal membrane. The process of synaptic vesicle fusion is highly regulated and involves numerous biochemical reactions it culminates in the release of chemical neurotransmitter into the synaptic cleft. The released neurotransmitter diffuses across the cleft and binds to and activates receptors on the postsynaptic site, which thereby completes the process of synaptic transmission. 

Axon is a polarized extension from cell body, and its plus-end nerve terminal contains presynaptic terminal. The growing axons often contain grow th cones at the nerve terminal, mobility of which is critically important for the axonal plasticity. The axon is packed with cargo moving along a unipolar microtubule array either tov ard the nerve terminal (anterograde transport)... 

Synthesis from amino acid and common metabolic precursors usually occurs in the cytoplasm of the presynaptic nerve terminal. The synthetic enzymes are transported by fast axonal transport from the cell body, where they are synthesized, to the presynaptic terminal. 

When an action potential arrives at the nerve cell s axon, a depolarization-induced exocytosis of neurotransmitter from its storage sites in the presynaptic terminal occurs. Through this process, the action potential continues the flow of information to the target site, typically the postsynaptic cell. The neurotransmitter Is believed to diffuse across the extracellular fluid filled space known as the synapse and to interact with postsynaptic receptors. The released neurotransmitter, however, also may be capable of Interacting with presynaptic receptors located on the neurons that just released the neurotransmitter. The function of these receptors typically Involve the regulation of nerve transmission and are termed autoreceptors, because the neurotransmitters that activate them function to control their own release. 

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