Misplaced Pages

Revision as of 00:13, 10 January 2017

Dopaminergic pathways, sometimes called dopaminergic projections, are the sets of projection neurons in the brain that synthesize and release the neurotransmitter dopamine. Individual neurons in these pathways are referred to as dopamine neurons.

Dopamine neurons have axons that run the entire length of the pathway. The neurons' somata produce the enzymes that synthesize dopamine, and they are then transmitted via the projecting axons to their synaptic destinations, where most of the dopamine is produced. Dopaminergic nerve cell bodies in such areas as the substantia nigra tend to be pigmented due to the presence of the black pigment melanin.

Pathways

There are eight dopaminergic pathways. The four major ones are:

Named pathways (same as above)

Mesocorticolimbic

• VTA → Prefrontal cortices
• VTA → Nucleus accumbens

Nigrostriatal

• SNc → Caudate nucleus
• SNc → Putamen

Tuberoinfundibular

• Tuberal hypothalamus (Infundibular nucleus) → Median eminence (dopamine released at the median eminence reaches the pituitary gland via the hypophyseal portal system)

Minor pathways

• VTA → Amygdala
• VTA → Hippocampus
• VTA → Cingulate cortex
• VTA → Olfactory bulb

The mesocortical and mesolimbic pathways are sometimes referred to simultaneously as the mesocorticolimbic projection, system, or pathway.

Function

The nigrostriatal circuits that project from the substantia nigra pars compacta into the striatum are part of a loop relevant to various psychiatric diseases, called the cortico-basal ganglia-thalamo-cortical circuit. The SNc gives rise to both inhibitory and excitatory loops that run from the striatum into the globus pallidus, before carrying on to the thalamus, or into the subthalamic nucleus before heading into the thalamus. The dopaminergic neurons in this circuit increase the magnitude of phasic firing in response to positive reward error, that is when the reward exceeds the expected reward. These neurons do not decrease phasic firing during a negative reward prediction(less than expected), leading to hypothesis about serotonergic neurons encoding this. Dopamine phasic activity also increases a cue signaling negative events, however stimulation of dopaminergic neuron still induces place preference indicating its main role is in evaluating a positive stimulus. From these findings, two hypothesis have developed, as to the role of the basal ganglia and nigrostiatal dopamine circuits in action selection. The first model suggests a "critic" which encodes value, and an actor which encodes responses to stimuli based on perceived value. However, the second model proposes that the actions do not originate in the basal ganglia, and instead originate in the cortex and are selected by the basal ganglia. This model proposes that the direct pathway controls appropriate behavior and the indirect suppresses actions not suitable for the situation. This model proposes that tonic dopaminergic firing increases the activity of the direct pathway, causing a bias towards executing actions faster.

These models of the basal ganglia are thought to be relevant to the study of ADHD, Tourette syndrome, Parkinson's Disease, Schizophrenia, OCD, and Addiction. For example, Parkinson's disease is hypothesized to be a result of excessive inhibitors pathway activity, which explains the slow movement and cognitive deficits, while Tourettes is proposed to be a result of excessive excitatory activity resulting in the tics characteristic of Tourettes.

The mesolimbic pathways appear to be involved in some aspect of motivation. 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(number of lever presses for nicotine, or time searching for food). Dopaminergic drugs are also able to increase the extent an animal is willing to go to get a reward, and the firing rate of neurons in the mesolimbic pathway increases during anticipation of reward.

The mesolimbic pathways, once thought to be the primary controller of pleasure, is now known to have no role in pleasure. Rather dopamine pathways controls learning, prediction, and motivation. However, to reconcile this with the pleasure inducing aspects of drugs like amphetamines, it has been proposed that dopaminergic activity of the mesolimbic pathway can facilitate release of endogenous opioid peptides into the nucleus accumbens yielding pleasure.

Mesocorticolimbic pathways, as mentioned above in relation to the basal ganglia, are thought to mediate learning. Various models have been proposed, however the dominant one is that of temporal difference learning, in which a prediction is made before a reward and afterwards adjustment is made based off of a learning factor and reward yield versus expectation leading to a learning curve.

Mesocortical dopaminergic projections are though to be involved in goal directed behavior, motivation, salience, and attention, so it is particularly relevant to ADHD. The mechanism of stimulants, the current ADHD treatment is, is to increase dopaminergic activity. Mesolimbic dopaminergic activity increases caused by stimulants are thought to increase signaling for salience, creating an improvement in attention. -->

See also

• Dopaminergic cell groups

References

Template:Research help

1. "Beyond the Reward Pathway". Retrieved 2009-10-23.
2. ^ Le Moal, Michel. "Mesocorticolimbic Dopaminergic Neurons". Neuropsychopharmacology: The Fifth Generation of Progress. Retrieved 4 November 2013.
3. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 249. ISBN 9780071481274. Relationship of the hypothalamus and the pituitary gland. The anterior pituitary, or adenohypophysis, receives rich blood flow from the capillaries of the portal hypophyseal system. This system delivers factors released by hypothalamic neurons into portal capillaries at the median eminence. The figure shows one such projection, from the tuberal (arcuate) nuclei via the tuberoinfundibular tract to the median eminence.
4. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 147–148, 154–157. ISBN 9780071481274. Neurons from the SNc densely innervate the dorsal striatum where they play a critical role in the learning and execution of motor programs. Neurons from the VTA innervate the ventral striatum (nucleus accumbens), olfactory bulb, amygdala, hippocampus, orbital and medial prefrontal cortex, and cingulate cortex. VTA DA neurons play a critical role in motivation, reward-related behavior, attention, and multiple forms of memory. ... Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). ... DA has multiple actions in the prefrontal cortex. It promotes the "cognitive control" of behavior: the selection and successful monitoring of behavior to facilitate attainment of chosen goals. Aspects of cognitive control in which DA plays a role include working memory, the ability to hold information "on line" in order to guide actions, suppression of prepotent behaviors that compete with goal-directed actions, and control of attention and thus the ability to overcome distractions. ... Noradrenergic projections from the LC thus interact with dopaminergic projections from the VTA to regulate cognitive control.
5. Doyon WM, Thomas AM, Ostroumov A, Dong Y, Dani JA (October 2013). "Potential substrates for nicotine and alcohol interactions: a focus on the mesocorticolimbic dopamine system". Biochem. Pharmacol. 86 (8): 1181–93. doi:10.1016/j.bcp.2013.07.007. PMID 23876345.
6. Maia, Tiago V; Frank, Michael J. . Nature Neuroscience. 14 (2): 154–162. doi:10.1038/nn.2723. {{cite journal}}: Check |url= value (help)
7. Beucke, Jan C.; Sepulcre, Jorge; Talukdar, Tanveer; Linnman, Clas; Zschenderlein, Katja; Endrass, Tanja; Kaufmann, Christian; Kathmann, Norbert (1 June 2013). "Abnormally High Degree Connectivity of the Orbitofrontal Cortex in Obsessive-Compulsive Disorder". JAMA Psychiatry. 70 (6). doi:10.1001/jamapsychiatry.2013.173. ISSN 2168-622X.
8. Maia, Tiago V.; Cooney, Rebecca E.; Peterson, Bradley S. (1 January 2008). "The Neural Bases of Obsessive-Compulsive Disorder in Children and Adults". Development and psychopathology. 20 (4): 1251–1283. doi:10.1017/S0954579408000606. ISSN 0954-5794.
9. Maia, Tiago V; Frank, Michael J. . Nature Neuroscience. 14 (2): 154–162. doi:10.1038/nn.2723. {{cite journal}}: Check |url= value (help)
10. Salamone, John D.; Correa, Mercè. "The Mysterious Motivational Functions of Mesolimbic Dopamine". Neuron. 76 (3): 470–485. doi:10.1016/j.neuron.2012.10.021.
11. Berridge, Kent C; Kringelbach, Morten L (1 June 2013). "Neuroscience of affect: brain mechanisms of pleasure and displeasure". Current Opinion in Neurobiology. 23 (3): 294–303. doi:10.1016/j.conb.2013.01.017.
12. Schultz, Wolfram (1 July 2015). . Physiological Reviews. 95 (3): 853–951. doi:10.1152/physrev.00023.2014. ISSN 0031-9333. {{cite journal}}: Check |url= value (help)
13. Engert, Veronika; Pruessner, Jens C (9 January 2017). "Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate". Current Neuropharmacology. 6 (4): 322–328. doi:10.2174/157015908787386069. ISSN 1570-159X.

• Central nervous system pathways