It became possible to visualise neurons which contained catecholamines when it was discovered that these amines reacted with formaldehyde vapour (later replaced by glyoxylic acid) to produce isoquinoline condensation products which emitted a bright-green fluorescence when visualised under ultra-violet light. This was distinguishable from the yellow fluorescence of 5-HT and could be separated from that for NA by appropriate pharmacological manipulations or adjustments to the microscopic techniques. Using this procedure, which is known as the Falk-Hillarp technique, Dahlstrom and Fuxe (1964) located and numbered nuclei in the hindbrain (pons medulla) in which either DA (A8-A12) or NA (1-7) was concentrated. The pathways were then established by axotomy since lesion of the axon is followed by loss of the NT and fluorescence at the neuron's terminals (destination of pathway) but not from its cell bodies (origin).

Most of the DA cell bodies (about 400 000) in the human brain are found in the A9 nucleus which forms the zona compacta (dorsal part) of the substantia nigra (SN), although a few cell bodies are found in the more ventral zona reticulata and in the zona lateralis as well (Fig. 7.1). A8 is lateral, caudal and somewhat dorsal to A9 and A10 whereas A10 is ventral to A9. Axons from A9 form the major contribution, together with some from A8, to the principal DA nigrostriatal pathway running to the striatum (caudate nucleus and putamen) and amygdala. This pathway is lateral to, but runs with, a more medial DA pathway, predominantly from A10, which innervates the nucleus accumbens and olfactory tubercle (mesolimbic pathway) as well as parts of the cortex (mesocortical system) such as the prefrontal and perirhinal cortex. The DA innervation to the anterior cingulate cortex also comes from A10 but with some axons from A9. There is in fact no clear divide between A9 and A10 and some overlap of their pathways. The DA mesolimbic tract and the noradrenergic bundles come together in the medial forebrain bundle before entering the cortex.

Neurotransmitters, Drugs and Brain Function. Edited by R. A. Webster ©2001 John Wiley & Sons Ltd

Putamen Amyg
Figure 7.1 Dopamine neuronal pathways. AMYG, amygdala; CN, caudate nucleus; MFB, medial forebrain bundle; NcA, nucleus accumbers; OT, olfactory tubercle; PUT, putamen; SN, substantia nigra. For full details see text and Moore and Bloom (1978) and Lindvall and Bjorkland (1978)

A further totally separate DA pathway arises from A12 in the arcuate nucleus and forms the tuberoinfundibular tract in the median eminence to the pituitary gland for controlling prolactin release. This is partly achieved by DA being released into capillaries of the hypothalamic-hypophyseal portal system and then inhibiting the prolactin releasing cells (lactotrophs) of the anterior pituitary.

While the nigrostriatal pathways are ipsilateral some crossing occurs in fibres from the ventral tegmental A10 nucleus. These pathways are shown diagramatically in Fig. 7.1. Further details can be obtained from Moore and Bloom (1978) and Lindvall and Bjorkland (1978). The nuclei provide distinct loci for activating the dopamine systems for electrophysiological, release and behavioural studies and for their destruction by electrolytic lesion or injection of the toxin 6-hydroxydopamine (6-OHDA).

The concentration of DA in different brain areas of the rat is in keeping with the distribution of its pathways. It is concentrated in the striatum (10 ^/g), nucleus accumbens (5 ^/g) and olfactory tubercle (6 ^/g) but in the cortex there is much less (0.1 ^/g). Cells in the substantia nigra in humans and primates differ from those in other species in containing granules of the lipoprotein pigment called neuromelanin. The melanin granules are free in the cytoplasm and give the SN a distinctive dark colour. Cells in this nucleus can also have hyaline inclusion bodies, the Lewy bodies, which are not common normally but appear to increase dramatically in patients with Parkinsonism. In humans the SN neurons are very closely aligned to blood vessels which could make them readily influenced by blood-borne agents and might explain why they are vulnerable as in Parkinson's disease. Certainly they will require considerable biochemical back-up to maintain function in all their terminals.

Continue reading here: Neurochemistry

Was this article helpful?

0 0