Mesolimbic system

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Mesolimbic is a combination of the mesencephalon ( midbrain = uppermost part of the brain stem ) and the limbic system (several areas around the diencephalon = above the midbrain ).

In a broader sense, the mesolimbic system describes the anatomical and functional totality of the connections between the two brain regions. In the narrower sense often used, however, the term only refers to the part that makes up the center of the reward system in the mammalian brain .

For this reason, the system is of central importance for the biological understanding of joy , pleasure and motivation . Its importance has increased markedly since the 1960s, as it turned out that almost all intoxicating drugs develop their effects through chemical manipulation of this system. It therefore plays a central role in research into addiction .

The dopaminergic mesolimbic system in the human brain, starting from the Ventral Tegmental Area (VTA) with the nucleus accumbens as the first target area ( sagittal plane ).

The mesolimbic system has its starting area in the area tegmentalis ventralis (ventral tegmental area, VTA) of the midbrain , its first target area in the nucleus accumbens and its downstream target areas in various core areas of the limbic system . The neurotransmitter of the nerves that pull from the VTA into the nucleus accumbens is dopamine .

structure

The neurons of the nucleus accumbens project with their axons mainly to the other structures of the limbic system, such as:

Nerve cell with dopamine receptors marked in red

The striatum with the basal ganglionic-thalamocortical control circuit receives information from all areas of the cerebral cortex . The striatum in the basal ganglionic-thalamocortical control circuit seems to play an important role in procedural memory and learning , such as habit formation and the development and performance of routine behavior. The projection of the neurons in the striatum is dynamically modulated by a nigrostriatal dopaminergic input and intrastriatal cholinergic input.

The striatum as such comprises part of the subcortical core area of ​​the basal ganglia and is composed of the caudate nucleus, pallidum and ventral striatum. Heimer & Wilson (1975) demonstrated the functional and neuroanatomical connection of the nucleus accumbens to the ventral striatum. Among the various cortico-striatal-thalamic loop systems of the basal ganglia, the ventral striatum is part of the anterior-cingulate loop that connects aCC, ventral striatum, amygdala, hippocampus, and entorhinal cortex.

A large number of dopamine receptors of the D2 type can be detected in the nucleus accumbens . These are stimulated by afferents from the ventral tegmentum.

function

The mesolimbic system is considered to be the center of the vertebrate brain's reward system. It registers the positive consequences of actions or events and thereby influences animal motivation. The function is primarily a modulatory effect on all areas of the limbic system, e.g. B. a positive reinforcement of a behavior (reward learning), because its activation is involved in the creation of feelings of pleasure.

Medical importance

The connections between diseases and the mesolimbic system have so far (as of 2020) only been researched to a small extent. However, it is already foreseeable that the system will play a key role here. On the one hand, dopamine has an influence on the regulation of the immune system , on the other hand, the immune system in turn influences the mesolimbic system . In the case of some diseases, there are already a large number of concrete results that are already being incorporated into medical practice.

Overview of the reward system of the human brain, the excessive sensitization of which plays a central role both in schizophrenia and in the development of dependence (addiction). The core of the system is the green signal traffic from the area tegmentalis ventralis (VTA) to the nucleus accumbens .

schizophrenia

Since the 1960s, there have been numerous indications that schizophrenia is often accompanied by overactivity of the mesolimbic system , in particular by over-excitation of the dopamine D2 receptors in the nucleus accumbens . This led to the dopamine hypothesis of schizophrenia, the main features of which were established, but which had to be further refined in the course of time.

depression

There is evidence that the mesolimbic system is involved in the mechanisms of depression . However, research on this is still at an early stage (as of 2020).

Addiction

The consumption of intoxicating drugs causes permanent biochemical , anatomical and physiological changes in the mesolimbic system . These changes are referred to as neuroadaption in their entirety and cause a sensitization (increased responsiveness) not only to the substance consumed, but also to other intoxicating drugs. The consequence is an increased susceptibility to repeated consumption and to addictive behavior as a whole, since the changes sometimes persist for years or even decades.

The sensitization concerns the desire. In contrast to the desire, the desired feeling ( euphoria ) is not increased, but rather weakens (development of tolerance ).

See also

literature

Web links

Individual evidence

  1. ^ A b S. F. Volman, S. Lammel, EB Margolis, Y. Kim, JM Richard, MF Roitman, MK Lobo: New insights into the specificity and plasticity of reward and aversion encoding in the mesolimbic system. In: Journal of Neuroscience . Volume 33, number 45, November 2013, pp. 17569-17576, doi : 10.1523 / JNEUROSCI.3250-13.2013 , PMID 24198347 , PMC 3818538 (free full text) (review).
  2. ^ MR DeLong: The basal ganglia. In ER Kandel, JH Schwartz, TM Jessel (Eds.): Principles of Neural Science 4th ed., McGraw-Hill, New York 2000, pp. 853-867
  3. ↑ L. Heimer, RD Wilson: The subcortical projections of the allocortex: similarities in the neural associations of the hippocampus, the pyriform cortex and the neocortex. In M. Santini (Ed.): Golgi Centennial Symposium Raven Press, New York 1975, pp. 177-192
  4. ^ GE Alexander, MR DeLong, PL Strick: Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 9: 357-381 (1986)
  5. ↑ G. Bergamini, J. Mechtersheimer u. a .: Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behavior in mice. In: Neurobiology of stress. Volume 8, February 2018, pp. 42–56, doi : 10.1016 / j.ynstr.2018.01.004 , PMID 29888303 , PMC 5991330 (free full text).
  6. ↑ SM Matt, PJ Gaskill: Where Is Dopamine and how do Immune Cells See it ?: Dopamine-Mediated Immune Cell Function in Health and Disease. In: Journal of neuroimmune pharmacology: the official journal of the Society on NeuroImmune Pharmacology. [Electronic publication before printing] May 2019, doi : 10.1007 / s11481-019-09851-4 , PMID 31077015 , PMC 6842680 (free full text) (review).
  7. ↑ MT Treadway, JA Cooper, AH Miller: Can't or Won't? Immunometabolic Constraints on Dopaminergic Drive. In: Trends in cognitive sciences. Volume 23, number 5, May 2019, pp. 435–448, doi : 10.1016 / j.tics.2019.03.003 , PMID 30948204 , PMC 6839942 (free full text) (review), PDF .
  8. ↑ Stahl SM: Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. . In: CNS Spectr . 23, No. 3, 2018, pp. 187–191. doi : 10.1017 / S1092852918001013 . PMID 29954475 .
  9. ↑ EJ Nestler, WA Carlezon: The mesolimbic dopamine reward circuit in depression. In: Biological psychiatry. Volume 59, Number 12, June 2006, pp. 1151-1159, doi : 10.1016 / j.biopsych.2005.09.018 , PMID 16566899 (review), PDF .
  10. ↑ JW Koo, D. Chaudhury, MH Han, EJ Nestler: Role of Mesolimbic Brain-Derived Neurotrophic Factor in Depression. In: Biological psychiatry. Volume 86, number 10, November 2019, pp. 738-748, doi : 10.1016 / j.biopsych.2019.05.020 , PMID 31327473 , PMC 6814503 (free full text) (review).
  11. ↑ JJ Szczypiński, M. Gola: Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia? In: Reviews in the neurosciences. Volume 29, number 7, 09 2018, pp. 727-744, doi : 10.1515 / revneuro-2017-0091 , PMID 29573379 (review).
  12. ↑ Ralf Brandes u. a. (Ed.): Human physiology: with pathophysiology . Springer, Berlin Heidelberg, 2019, ISBN 978-3-662-56468-4 , p. 860, OCLC 1104934728 . , Preview Google Books .
  13. ^ MJ Robinson, AM Fischer, A. Ahuja, EN Lesser, H. Maniates: Roles of "Wanting" and "Liking" in Motivating Behavior: Gambling, Food, and Drug Addictions. In: Current topics in behavioral neurosciences. Volume 27, 2016, pp. 105-136, doi : 10.1007 / 7854_2015_387 . PMID 26407959 (Review), (PDF)