Neuronal tracing

Kummer, W., Fischer, A., Kurkowski, R. etal. (1992). The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and doublelabelling immunohistochemistry. Neuroscience 49, 715-737. 

Neuronal Tracing Using Lipophilic Membrane Dyes, Fluorescent Dextrans, and Horseradish Peroxidase (HRP)... 

Neuronal tracing Fast Blue, Lucifer Yellow... 

Albanese, A. Bentivoglio, M. Retrograde fluorescent neuronal tracing combined with acetylcholinesterase histochemistry. J. Neurosci. Methods 1982, 6, 121-127. 

Lukas JR, Aigner M, Denk M et al (1998) Carbocyanine postmortem neuronal tracing. Influence of different parameters on tracing distance and combination with immunocytochemistry. J Histochem Cytochem 46 901-910... 

D multicolor super-resolution imaging offers improved accuracy in neuron tracing. PLoS One 7 e30826... 

The synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

Due to their physicochemical properties trace amines can pass the cell membrane to a limited extent by passive diffusion, with the more lipophilic PEA and TRP crossing membranes more readily than the more polar amines TYR. and OCT. In spite of these features, trace amines show a heterogeneous tissue distribution in the vertebrate brain, and for TYR. and OCT storage in synaptic vesicles as well as activity-dependent release have been demonstrated. So far, trace amines have always been found co-localized with monoamine neurotransmitters, and there is no evidence for neurons or synapses exclusively containing trace amines. 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Figure 2.12 From voltage-clamp to current-clamp micro-electrode recordings of synaptic current (/, lower trace) and synaptic potential with superimposed action potential (V, upper trace) from a neuron in an isolated rat superior cervical sympathetic ganglion following a single stimulus (S) applied to the preganglionic nerve trunk. The interval between the stimulus and the postsynaptic response includes the conduction time along the unmyelinated axons of the preganglionic nerve trunk. (SJ Marsh and DA Brown, unpublished)...

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The rate of melatonin synthesis is controlled primarily by the release of noradrenaline from sympathetic fibres originating in the superior cervical ganglion. The activity of these neurons and, consequently, the synthesis and release of melatonin, follows a circadian rhythm such that sympathetic input and melatonin synthesis are both increased in the dark. This coupling with the light cycle certainly involves the SCN since destruction of this nucleus greatly reduces the fluctuations in melatonin production. Moreover, retrograde transneural tracing has shown that there is a neuronal pathway... 

Kohler, C., and Steinbusch. H.W.M. Identification of serotonin and non-serotonin-containing neurons of the mid-brain raphe projecting to the entorhinal area and the hippocampal formation. A combined immunohistochemical and fluorescent retrograde tracing study in the rat brain. Neuroscience 7 951-975. 1982. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

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