Monoamine Pathways

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Monoamine Pathways

• The monoamine transmitters are derived from amino acids.
• Norepinephrine and dopamine are derived from tyrosine.
• The 3^rd major monoamine transmitter, serotonin, is derived from tryptophan.

• Monoamine-containing neurons are found mainly in the brainstem (although there are a few dopaminergic neurons in the forebrain).
• Despite this restricted distribution, these neurons have far-flung connections.
• This suggests that they are involved in regulating or tuning the activity of large portions of the CNS.

• Nevertheless, there are characteristic differences between the termination patterns of fibres containing norepinephrine, dopamine, and serotonin.
• This, together with consistent associations between certain transmitter systems and neurological syndromes (e.g., dopamine and Parkinson’s disease), suggests strongly that each of these transmitters play a distinctive role in the CNS.

Nolte (1993) The Human Brain 3^rd Ed. Table 11 (excerpt). p. 418

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• Noradrenergic neurons are found only in the pons and medulla.
• Half or more are located in the locus ceruleus, and the remainder in lateral parts of the medullary reticular formation, in the solitary nucleus and the dorsal motor nucleus of the vagus, and in a few other sites.
• Collectively, these noradrenergic neurons project to most of the CNS.

• Ascending fibres reach the thalamus, hypothalamus, limbic forebrain structures, and the cerebral cortex.

• The somatosensory cortex has particularly dense innervation.

• Descending fibres project to other parts of the brainstem and to all spinal levels.
• They also travel through the superior cerebellar peduncle to reach the cerebellar cortex and deep nuclei.

• The possible functions of this system are provided by the response patterns of neurons in the locus ceruleus.
• These cells are nearly silent electrically during sleep.
• They become somewhat active during wakefulness.
• They are most active in situations that are startling or call for watchfulness.
• Hence the locus ceruleus and other noradrenergic neurons may play a role in maintaining attention and vigilance.

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• Most dopaminergic neurons are mesencephalic.
• They are located in the compact part of the substantia nigra and in the medially adjacent ventral tegmental area.
• They project rostrally in 3 partially overlapping streams.

• The nigrostriatal projection (or mesostriatal projection) is from the substantia nigra to the caudate nucleus and putamen.

• The mesolimbic and mesocortical fibres originate primarily in the ventral tegmental area.
• They travel to a variety of forebrain destinations including the nucleus accumbens, septal area, amygdala, and cerebral cortex.

• The nigrostriatal and mesocortical projections to motor cortex are both consistent with the idea that the dopaminergic system is involved in the initiation of movement.
• Its disruption is instrumental in the movement deficits seen in Parkinson’s disease.

• However, the extensive dopaminergic projections to limbic structures and other cortical areas suggest that this system is also involved in motivation and cognition.

• Additional dopaminergic neurons are found in the retina, the olfactory bulb, and the hypothalamus.

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• Serotonergic neurons are found at most levels of the brainstem.
• They are concentrated in the raphe nuclei.
• These innervate virtually all parts of the CNS.

• Projections from the rostral raphe nuclei reach the forebrain.
• The cortical innervation is most dense in sensory and limbic areas.
• The caudal raphe nuclei provide most of the projection to the brainstem and spinal cord.

• The firing rate of serotonergic neurons also fluctuate with sleep and wakefulness.
• It has been proposed that the serotonin system is more important for determining the overall level of arousal while the norepineprine system more important for phasic changes in level of attention.
• In addition, the serotonin system has at least one other important role, as part of the descending pain-control system.

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