Axons terminals

Neurons have three parts the cell body and dendrites, the axon, and axon terminals. The cell body contains the nucleus and the organelles needed for metabolism, growth, and repair. The dendrites are branched extensions of the cell body membrane. The axon is a long, thin structure which transfers electrical impulses down to the terminals. The axon divides into numerous axon terminals and it is in this specialized region that neurotransmitters are released to transmit information from one neuron to its neighbors. The synapse has been defined as the space between two subsequent interrelated neurons. ... 

Neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of motoneurons with the highly excitable region of the muscle fibre s plasma membrane. Neuronal signals pass through the NMJ via the neurotransmitter ACh. Consequent initiation of action potentials across the muscle s cell surface ultimately causes the muscle contraction. 

After exocytosis, the vesicle membrane with its lipids and proteins is recycled, either by immediate re-filling with transmitter or by passing through a vesicle resting pool deeper inside the axon terminal. 

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Neuroanatomists have taken advantage of the phenomenon of fast retrograde transport to locate remote nerve cell bodies in the CNS of an experimental animal that are connected to an identified axonal fiber tract whose origin is uncertain. The tracer material [purified horseradish peroxidase (HRP) enzyme] is injected in the region of the axon terminals, where it is taken up by endocytosis and then is carried by retrograde axonal transport over a period of several hours to days back to the nerve cell body. The animal is sacrificed, and the enzyme tracer is localized by staining thin sections of the brain for peroxidase activity. 

Synaptic transmission. Transmission through the junction across which a nerve impulse passes from an axon terminal to a neuron, muscle cell, or gland cell. 

The axon terminals of one neuron synapse with other neurons either on the dendrites (axo-dendritic synapse) or soma (axo-somatic synapse). Synapses on another axon... 

Figure 1.6 Presynaptic inhibition of the form seen in the dorsal horn of the spinal cord, (a) The axon terminal (i) of a local neuron is shown making an axo-axonal contact with a primary afferent excitatory input (ii). (b) A schematic enlargement of the synapse, (c) Depolarisation of the afferent terminal (ii) at its normal resting potential by an arriving action potential leads to the optimal release of neurotransmitter, (d) When the afferent terminal (ii) is already partially depolarised by the neurotransmitter released onto it by (i) the arriving acting potential releases less transmitter and so the input is less effective...

Anatomical evidence can also be presented to support the concept of presynaptic inhibition and examples of one axon terminal in contact with another are well documented. These do not show the characteristics of either type I or II synapses but... 

Dendro-dendritic synapses have also been deseribed whieh show eharaeteristie synaptie eonneetions and we need to abandon the belief that one neuron ean only influenee another through its axon terminals. Dendro-dendritie synapses ean also be reeiproeal, i.e. one dendrite ean make synaptie eontaet with another and apparently be both pre- and postsynaptie to it. 

These are basically neurons whose cell body and axon terminals are both found in the same part of the CNS (Fig. 1.2). They are not concerned with transmitting information from one part of the CNS to another but in controlling activity in their own area. They can be excitatory but are more often inhibitory. They may act postsynaptically through conventional IPSPs (or slower potential changes) or presynaptically by modifying NT... 

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

When an action potential arrives at the axon terminal, it induces the release of a chemical transmitter. Transmitter release is a Ca +-dependent process (see Chapter 4) and requires a charge of Ca +. This is provided through the action potential-induced... 

The reaction of choline with mitochondrial bound acetylcoenzyme A is catalysed by the cytoplasmic enzyme choline acetyltransferase (ChAT) (see Fig. 6.1). ChAT itelf is synthesised in the rough endoplasmic reticulum of the cell body and transported to the axon terminal. Although the precise location of the synthesis of ACh is uncertain most of that formed is stored in vesicles. It appears that while ChAT is not saturated with either acetyl-CoA or choline its synthesising activity is limited by the actual availability of choline, i.e. its uptake into the nerve terminal. No inhibitors of ChAT itself have been developed but the rate of synthesis of ACh can, however, be inhibited by drugs like hemicholinium or triethylcholine, which compete for choline uptake into the nerve. 

There is much evidence (e.g. Cheramy, Leviel and Glowinski 1981) from both in vitro and in vivo perfusion studies that DA is released from the dendrites of DA neurons in both A9 and AlO even though those dendrites do not contain many vesicles compared with axon terminals. The release and changes in it may also be slower and longer than that at axon terminals and the synaptic arrangement between the releasing dendrites and postsynaptic target is not clear. DA receptors also appear to be on neurons other than dopamine ones and on the terminals of afferent inputs to A9 (and AlO). It seems that the activation of the DA neurons may partly be controlled by the effects of the dendritically released DA on such inputs. 

Figure 15.9 Peptide modulation of striatal input to the globus pollidus. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. 15.2 for details) is thought to inhibit GABA release from the same terminals so that feedback (auto) inhibition is reduced. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. (See Henry and Brotchie 1996 and Maneuf et al. 1995)...

Of course, cholinergic neurons are not the only ones with axon terminals in the cortex and if their degeneration does originate in the cortex then other afferants and their neurons could also be affected. This contention is supported by reported reductions in the number of NA neurons in the locus coeruleus, and 5-HT neurons in dorsal raphe but these are less marked (approximately 50%) than the loss of cholinergic neurons. Accompanying reductions in cortical NA and 5-HT are also seen but are again lower than those for ChAT but 5-HT2 receptors are reduced (43%). 

Lamina IV is composed of heterogeneous sized cells and is less densely packed than lamina III due to the number of nerve axons passing in this layer. At least three types of neurons have been identified in lamina IV, based on different dendritic projection patterns and these include SCT and PSDC cells. Another cell type has been described which has a dendritic pattern similar to SCT and PSDC, but with local axon terminations. Somas of STT cells are also found in lamina IV. 

O Heam, E. Battaglia, G. DeSouza, E.B. Kuhar, J. and Molliver, ME. Methylenedioxyamphetamme (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonin axon terminals in forebrain Immunocytochemical evidence for neurotoxicity. J Neurosci 8(8) 2788-2803, 1988. 

FIGURE 2. A schematic representation showing the two classes of raphe-cortical axon terminals that were identified by anterograde axon transport... 

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