2 Neuroscience2.6 Neuroanatomy
2.6.6 Anatomical course of major neurochemical pathways
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Written by Resident Doctor Committee · Published
Dopamine pathways
There are four classic dopamine pathways, each with its own origin and target.
Pathway | Origin | Target | Effect of D2 blockade |
|---|---|---|---|
Nigrostriatal | Substantia nigra pars compacta | Dorsal striatum (caudate and putamen) | Parkinsonism, dystonia, akathisia, later tardive dyskinesia |
Mesolimbic | Ventral tegmental area | Nucleus accumbens (ventral striatum) | Fewer positive psychotic symptoms |
Mesocortical | Ventral tegmental area | Prefrontal cortex | Possible secondary negative and cognitive effects |
Tuberoinfundibular | Arcuate nucleus of the hypothalamus | Median eminence | Hyperprolactinaemia |
The substantia nigra pars compacta holds the largest population of dopaminergic neurones in the brain, and its degeneration causes the motor deficit of Parkinson's disease.
The ventral tegmental area lies medial to the substantia nigra and feeds two pathways: mesolimbic and mesocortical.
The mesolimbic pathway is the principal reward and reinforcement pathway, and drugs of dependence act on it.
Dopamine hypothesis of schizophrenia
Mesolimbic hyperfunction underlies positive symptoms.
Mesocortical hypoactivity underlies negative symptoms.
Prolactin control
Arcuate neurones release dopamine at the median eminence into portal blood, where it acts on D2 receptors on lactotrophs to inhibit prolactin release tonically.
The paraventricular nucleus differs: it supplies stimulatory releasing hormones and posterior lobe peptides, not prolactin-inhibiting dopamine.
Noradrenaline
The locus coeruleus, in the dorsal pons beneath the fourth ventricle, is the principal source of the brain's noradrenaline.
Its widely branching projections reach the cortex, hippocampus, amygdala, thalamus, cerebellum and spinal cord.
Serotonin
Serotonin cell bodies lie in the raphe nuclei along the brainstem midline, and the dorsal raphe is the largest.
Ascending projections reach the cortex, hippocampus and striatum and influence mood, anxiety and sleep.
Descending projections from the caudal raphe reach the spinal cord and modulate pain.
Acetylcholine
The nucleus basalis of Meynert, in the substantia innominata of the basal forebrain, is the main cholinergic input to the neocortex.
Its early loss in Alzheimer's disease underlies the cholinergic hypothesis and treatment with cholinesterase inhibitors such as donepezil.
Medial septal neurones supply the hippocampus through the fornix, and the pedunculopontine and laterodorsal tegmental nuclei supply the thalamus.
Histamine
Brain histamine comes from the tuberomammillary nucleus in the posterior hypothalamus, which projects to almost the whole cortex and fires most in waking.
H1 blockade explains the sedation caused by mirtazapine and older antihistamines.
Diffuse and point-to-point systems
Diffuse modulatory systems, such as the locus coeruleus and nucleus basalis, arise from small nuclei and branch widely to set state and responsiveness.
Point-to-point projections, such as glutamatergic corticostriatal fibres, arise from many topographically arranged cells and carry specific signals to restricted targets.