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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. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons or dopamine neurons.


The four major dopaminergic pathways are the mesolimbic pathway, the mesocortical pathway, the nigrostriatal pathway, and the tuberoinfundibular pathway. Other dopaminergic pathways include the hypothalamospinal tract and the incertohypothalamic pathway.The mesolimbic pathway and the mesocortical pathway form the mesocorticolimbic system. Two other pathways to be considered are the hypothalamospinal and incertohypothalamic pathways.

The dopamine neurons of the dopaminergic pathways synthesize and release the neurotransmitter dopamine.[2][3] Enzymes tyrosine hydroxylase and dopa decarboxylase are required for dopamine synthesis.[4] These enzymes are both produced in the cell bodies of dopamine neurons. Dopamine is stored in the cytoplasm and vesicles in axon terminals. Dopamine release from vesicles is triggered by action potential propagation-induced membrane depolarization.[4] The axons of dopamine neurons extend the entire length of their designated pathway.

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Pathway name Description Associated processes Associated disorders
Mesocorticolimbic projection system
Mesolimbic pathway
The mesolimbic pathway transmits dopamine from the ventral tegmental area (VTA), which is located in the midbrain, to the ventral striatum, which includes both the nucleus accumbens and olfactory tubercle. The "meso" prefix in the word "mesolimbic" refers to the midbrain, or "middle brain", since "meso" means "middle" in Greek.
Mesocortical pathway
The mesocortical pathway transmits dopamine from the VTA to the prefrontal cortex. The "meso" prefix in "mesocortical" refers to the VTA, which is located in the midbrain, and "cortical" refers to the cortex.
Nigrostriatal pathway The nigrostriatal pathway transmits dopaminergic neurons from the zona compacta of the substantia nigra[1] to the caudate nucleus and putamen.

The substantia nigra is located in the midbrain, while both the caudate nucleus and putamen are located in the dorsal striatum.

Tuberoinfundibular pathway The tuberoinfundibular pathway transmits dopamine from the arcuate nucleus (aka "infundibular nucleus") of the hypothalamus to the pituitary gland via dopamine release into the median eminence and subsequent circulation through the hypophyseal portal system.

This pathway controls the secretion of certain hormones, including prolactin, from the pituitary gland[2].

"Infundibular" in the word "tuberoinfundibular" refers to the cup or infundibulum, out of which the pituitary gland develops.

  • activity of this pathway inhibits the release of prolactin.
  • regulation of prolactin secretion[3]
Hypothalamospinal tract This pathway influences locomotor networks in the brainstem and spinal cord.
  • motor function.
Incertohypothalamic pathway This pathway from the zona incerta influences the hypothalamus and locomotor centers in the brainstem.
  • visceral and sensorimotor activities.

Four Major pathways (same as above)

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Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular

Other pathways

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Hypothalamospinal

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Incertohypothalamic

Major Functions[edit]

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Mesocorticolimbic projection[edit]

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The mesocorticolimbic pathway originates through the VTA and passes through the amygdala, nucleus accumbens, and hippocampus. These functions are relative to memory, emotional regulation, motivation, and reward.

The mesocortical pathway mesocorticolimbic system (mesocorticolimbic circuit) refers to both the mesocortical and mesolimbic pathways. Both pathways originate at the ventral tegmental area (VTA). Through separate connections to the prefrontal cortex (mesocortical) and ventral striatum (mesolimbic), the mesocorticolimbic projection has a significant role in learning, motivation, reward, memory and movement. Dopamine receptor subtypes, D1 and D2 have been shown to have complementary functions in the mesocorticolimbic projection, facilitating learning in response to both positive and negative feedback. Both pathways of the mesocorticolimbic system are associated with ADHD, schizophrenia and addiction.

Mesocortical pathway[edit]

Mesolimbic pathway[edit]

  • Referred to as the reward pathway, mesolimbic pathway projects from the ventral tegmental area to the ventral striatum ( VTA → Ventral striatum (nucleus accumbens and olfactory tubercle). When a reward is anticipated, the firing rate of dopamine neurons in the mesolimbic pathway increases. The mesolimbic pathway is involved with incentive salience, motivation, reinforcement learning, fear and other cognitive processes. In animal studies, depletion of dopamine in this pathway, or lesions at its site of origin, decrease the extent to which an animal is willing to go to obtain a reward (e.g., the number of lever presses for nicotine or time searching for food). Research is ongoing to determine the role of the mesolimbic pathway in the perception of pleasure.
The nigrostriatal pathway is involved in behaviors relating to movement and motivation.

Nigrostriatal pathway

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  • The nigrostriatal pathway is involved in behaviors relating to movement and motivation. The transmission of dopaminergic neurons to the dorsal striatum particularly plays a role in reward and motivation while movement is influenced by the transmission of dopaminergic neurons to the substantia nigra.[4][5] The nigrostriatal pathway is associated with conditions such as Huntington's disease, Parkinson's disease, ADHD, Schizophrenia, and Tourette's Syndrome. Huntington's disease, Parkinson's disease, and Tourette's Syndrome are conditions affected by motor functioning[6] while schizophrenia and ADHD are affected by reward and motivation functioning. This pathway also regulates associated learning such as classical conditioning and operant conditioning[7].
The tuberoinfundibular pathway transmits dopamine the hypothalamus to the pituitary gland.

Tuberoinfundibular pathway

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  • The tuberoinfundibular pathway transmits dopamine the hypothalamus to the pituitary gland. This pathway also regulates the secretion of prolactin from the pituitary gland, which is responsible for breast milk production in females. Hyperprolactinemia is an associated condition caused by an excessive amount of prolactin production that is common in pregnant women.[8]





References

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  1. ^ Hull, Elaine M.; Rodríguez-Manzo, Gabriela (2017), "Male Sexual Behavior", Hormones, Brain and Behavior, Elsevier, pp. 1–57, retrieved 2022-09-10
  2. ^ Habibi, Mitra (2017), "Acetylcholine ☆", Reference Module in Neuroscience and Biobehavioral Psychology, Elsevier, retrieved 2022-09-18
  3. ^ a b Hudepohl, Neha S.; Nasrallah, Henry A. (2012), "Antipsychotic drugs", Neurobiology of Psychiatric Disorders, Elsevier, pp. 657–667, retrieved 2022-09-18
  4. ^ Balleine, B. W.; Delgado, M. R.; Hikosaka, O. (2007-08-01). "The Role of the Dorsal Striatum in Reward and Decision-Making". Journal of Neuroscience. 27 (31): 8161–8165. doi:10.1523/JNEUROSCI.1554-07.2007. ISSN 0270-6474. PMC 6673072. PMID 17670959.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ Mishra, Akanksha; Singh, Sonu; Shukla, Shubha (2018). "Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson's disease". Journal of Experimental Neuroscience. 12: 117906951877982. doi:10.1177/1179069518779829. ISSN 1179-0695. PMC 5985548. PMID 29899667.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ Mariani, Elisa; Frabetti, Flavia; Tarozzi, Andrea; Pelleri, Maria Chiara; Pizzetti, Fabrizio; Casadei, Raffaella (2016-09-09). "Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression". PLOS ONE. 11 (9): e0161567. doi:10.1371/journal.pone.0161567. ISSN 1932-6203. PMC 5017670. PMID 27611585.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ Carmack, Stephanie A.; Koob, George F; Anagnostaras, Stephan G. (2017), "Learning and Memory in Addiction", Learning and Memory: A Comprehensive Reference, Elsevier, pp. 523–538
  8. ^ Attaar, PharmD, BCPS, Aamer; Curran, PharmD, BCPS, BCCCP, Molly; Meyenburg, PharmD, BCPS, Lyndsi; Bottner, DHA, PA-C, Richard; Johnston, MD, Clarissa; Mason, PharmD, BCPS, Kirsten Roberts (2021-08-01). "Perioperative pain management and outcomes in patients who discontinued or continued pre-existing buprenorphine therapy". Journal of Opioid Management. 17 (7): 33–41. doi:10.5055/jom.2021.0640. ISSN 1551-7489.{{cite journal}}: CS1 maint: multiple names: authors list (link)


Instructor Feedback (delete once addressed): Nice work on this article thus far! Why did you opt to delete information about two pathways?

-Response: After the peer review process I got more insight on what I should do with the table. I deleted the last two because on other sources it only mentioned the 4 major ones so I was not sure if those two were relevant. I expanded the information from the table to be more detailed in the "major functions" section but I am not sure what to do with the table anymore. It was suggested that I still touch on the "other" pathways but not in much detail which I think is a good idea, so I added them back.


Peer Review Response Summary:

- One of the suggestions I took into consideration was from use Birmaniahern about adding the two "other" pathways back to the table and article, which allowed me to touch on those briefly without distracting from the major ones. I also received helpful feedback from user Hkhan11 and added images of the pathways along with more detailed functions and why they contribute to the listed conditions/dysfunctions. It was suggested that I get rid of the table as a whole since I have the paragraphs below, but since I did not create it I am hesitant to go forward with that. I also took the suggestions from user Eresha8 to not edit or get rid of too much. During this round of editing I focused on what I can added (such as pictures, grammar corrections, and citations) rather than what I can delete. I also reviewed my bibliography and too the suggestion of Eresha8 to use meta analyses in which I was able to find one that was helpful toward the nigrostriatal pathway.