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Dopaminergic pathways (dopamine pathways, dopaminergic projections) in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. [1] Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.
The substantia nigra is located in the ventral midbrain of each hemisphere. It has two distinct parts, the pars compacta (SNc) and the pars reticulata (SNr). The pars compacta contains dopaminergic neurons from the A9 cell group that forms the nigrostriatal pathway that, by supplying dopamine to the striatum, relays information to the basal ganglia.
The mesolimbic pathway and its positioning in relation to the other dopaminergic pathways. The mesolimbic pathway is a collection of dopaminergic (i.e., dopamine-releasing) neurons that project from the ventral tegmental area (VTA) to the ventral striatum, which includes the nucleus accumbens (NAcc) and olfactory tubercle. [9]
The direct pathway mostly consists of monosynaptic connections driven by dopamine receptor D1, adenosine A1 receptor, and muscarinic acetylcholine receptor M4, while the indirect pathway relies on connections driven by dopamine receptor D2, adenosine A2A receptor, and muscarinic acetylcholine receptor M1. [1] [8]
[59] [61] [66] For example, direct electrical stimulation of dopamine pathways, using electrodes implanted in the brain, is experienced as pleasurable, and many types of animals are willing to work to obtain it. [67] Antipsychotic drugs reduce dopamine levels and tend to cause anhedonia, a diminished ability to experience pleasure. [68]
The balance of direct/indirect activity in movement is supported by evidence from neurodegenerative disorders, including Parkinson's disease (PD), which is characterized by loss of dopamine neurons projecting to the striatum, hypoactivity in direct pathway and hyperactivity in indirect pathway neurons, along with motor dysfunction. [21]
In the direct pathway, the motor cortices send activating signals to the caudate and putamen (which together form the dorsal striatum). The cells of the direct pathway in the caudate and putamen that receive these signals are inhibitory and, once they become activated, send inhibitory signals to the GPi and SNpr and stop activity there.
A direct pathogenetic role of tyrosine hydroxylase has also been suggested, as the enzyme is a source of H 2 O 2 and other reactive oxygen species (ROS), and a target for radical-mediated injury. It has been demonstrated that L -DOPA is effectively oxidized by mammalian tyrosine hydroxylase, possibly contributing to the cytotoxic effects of L ...