Nucleus accumbens

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Brain: Nucleus accumbens
Circuit du système de recompense.jpg
Nucleus accumbens visible in red.
Gray727-Brodman.png
Medial surface, person facing to the left. Nucleus accumbens is very roughly in Brodmann area 34
Latin nucleus accumbens septi
NeuroNames hier-259
MeSH Nucleus+Accumbens
NeuroLex ID birnlex_727

The nucleus accumbens (NAcc), also known as the accumbens nucleus or as the nucleus accumbens septi (Latin for nucleus adjacent to the septum) is a region in the basal forebrain rostral to the preoptic area of the hypothalamus.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.[2]

Each cerebral hemisphere has its own nucleus accumbens. It is located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. The nucleus accumbens can be divided into two structures—the nucleus accumbens core and the nucleus accumbens shell. These structures have different morphology and function.

Research has indicated the nucleus accumbens has an important role in pleasure including laughter, reward, and reinforcement learning, as well as fear, aggression, impulsivity, addiction, and the placebo effect.[3][4][5][6]

Structure[edit]

The nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core.

Cell types[edit]

The core of the NAcc is made up mainly of medium spiny neurons. Compared to the neurons in the shell, those in the core have an increased density of dendritic spines, branch segments, and terminal segments. From the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc, and GABA receptors are also abundant.[7][8] These neurons are also the main projection or output neurons of the nucleus accumbens.

While 95% of the neurons in the nucleus accumbens are medium spiny GABA-ergic projection neurons, other neuronal types are also found such as large cholinergic interneurons.

Output[edit]

The output neurons of the nucleus accumbens send axon projections to the basal ganglia and the ventral analog of the globus pallidus, known as the ventral pallidum (VP). The VP, in turn, projects to the medial dorsal nucleus of the dorsal thalamus, which projects to the prefrontal cortex as well as the striatum. Other efferents from the nucleus accumbens include connections with the substantia nigra, and the reticular formation of the pons.[1]

Input[edit]

Major inputs to the nucleus accumbens include prefrontal association cortices, basolateral amygdala, and dopaminergic neurons located in the ventral tegmental area (VTA), which connect via the mesolimbic pathway. Thus the nucleus accumbens is often described as one part of a cortico-striato-thalamo-cortical loop.

Dopaminergic input from the VTA modulate the activity of neurons within the nucleus accumbens. These neurons are activated directly or indirectly by euphoriant drugs (e.g., amphetamine, opiates, nicotine, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).[9][10]

Another major source of input comes from the CA1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. The neurons of the hippocampus have a noteworthy correlation to slight depolarizations of cells in the nucleus accumbens, which makes them more positive and therefore more excitable. The correlated cells of these excited states of the medium spiny neurons in the nucleus accumbens are shared equally between the subiculum and CA1. The subiculum neurons are found to hyperpolarize (increase negativity) while the CA1 neurons "ripple" (fire > 50 Hz) in order to accomplish this priming.[11]

Shell[edit]

The nucleus accumbens shell is a structure that, together with the nucleus accumbens core, makes up the entire nucleus accumbens (NAc), an important area of the brain related to motor function, reward, and emotionality.

Location: The shell of the nucleus accumbens is located in the rostral pole of the extended amygdala.

Cell types: Neurons in the nucleus accumbens are mostly medium spiny neurons. The neurons in the shell, as compared to the core, have a lower density of dendritic spines, less terminal segments, and less branch segments than those in the core. The shell neurons project to the subcommissural part of the ventral pallidum as well as the ventral tegmental area and to extensive areas in the hypothalamus and extended amygdala.[12][13][14]

Function: The shell of the nucleus accumbens plays a role in regulating motivation, reward, and psychiatric disorders related to improper regulation of these qualities. Particularly important are the effects of drug and food stimuli on the NAc shell because these effects are related to addiction and behavioral inhibition.

Function[edit]

Dopamine: Dopamine is related to recreational drugs including amphetamines, cocaine, and morphine, which increase extracellular levels of dopamine in both the NAc shell and the NAc core, but the effect of these increases is more pronounced in the shell. Only amphetamine at high levels increased extracellular levels of dopamine to similar levels in both the shell and the core. All of this points to a 'functional heterogeneity' in the nucleus accumbens between the shell region and the core region.[15] Similarly to drug rewards, non-drug rewards also increase levels of extracellular dopamine in the NAc shell, but drug induced DA increase is more resilient to habituation when exposed repeatedly to drug-stimuli, unlike non-drug rewarding stimuli induced dopamine increases, which do succumb to habituation. Recent[when?] studies have shown that the repeated influence of drug-inducing DA projection has an abnormal strengthening effect on stimulus-drug associations and increases the drug-reward stimuli’s resistance to extinction. This may be a contributing factor to addiction. This effect was more pronounced in the NAc shell than in the NAc core.[12][12][16]

Glucocorticoids and dopamine:Glucocorticoid receptors are the only corticosteroid receptors in the nucleus accumbens shell. L-DOPA, steroids, and specifically glucocorticoids are currently known to be the only known endogenous compounds that can induce psychotic problems, so understanding the hormonal control over dopaminergic projections with regards to glucocorticoid receptors could lead to new treatments for psychotic symptoms. A recent study demonstrated that suppression of the glucocorticoid receptors led to a decrease in the release of dopamine, which may lead to future research involving anti-glucocorticoid drugs to potentially relieve psychotic symptoms.[17]

GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABAA receptors in the NAc shell have inhibitory control on turning behavior influenced by dopamine, and GABAB receptors have inhibitory control over turning behavior mediated by acetylcholine.[12][18]

Serotonin (5-HT): Overall, 5-HT synapses are more abundant and have a greater number of synaptic contacts in the NAc shell than in the core. They are also larger and thicker, and contain more large dense core vesicles than their counterparts in the core.

Research[edit]

Chronic drug use and addiction[edit]

Further information: ΔFosB

Research using microdialysis has shown that the levels of dopamine in the extracellular fluid of the nucleus accumbens increase when rats are injected with addictive drugs such as cocaine, heroin, nicotine, or alcohol.[19] This increase in dopamine is believed to be responsible for the reinforcing effects that provoke substance dependency. Functional-imaging studies in humans have shown that environmental cues associated with addictive drugs release dopamine in the nucleus accumbens. However, when given methylphenidate, addicted subjects showed a much smaller release of dopamine in this area than non-addicted subjects. These findings suggest that the nucleus accumbens is associated with the beginnings of substance dependency, and that the dorsal striatum is responsible for reinforcing dependency.[19]

The nucleus accumbens has been targeted by stereotactic surgery for ablation as a treatment in China for alcoholism.[20]

Pleasure and reinforcement[edit]

Although the nucleus accumbens has traditionally been studied for its role in addiction, it plays an equal role in processing many rewards such as food and sex. The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.[21][22] A 2005 study found that it is involved in the regulation of emotions induced by music,[23] perhaps consequent to its role in mediating dopamine release. The nucleus accumbens plays a role in rhythmic timing and is considered to be of central importance to the limbic-motor interface (Mogensen).[citation needed]

In the 1950s, James Olds and Peter Milner implanted electrodes into the septal area of the rat and found that the rat chose to press a lever which stimulated it. It continued to prefer this even over stopping to eat or drink. This suggests that the area is the "pleasure center" of the brain and is involved in reinforcement learning.[24] In rats, stimulation of the ventral tegmental area causes the release of dopamine in the nucleus accumbens much in the same way as addictive drugs and natural reinforcers, such as water or food, initiate the release of dopamine in the nucleus accumbens.[25] The same results have been seen in human subjects in functional imaging studies. For example, increased dopamine concentration is seen in the extracellular fluid of the nucleus accumbens when subjects believed they were being given money[citation needed], and increased activation (i.e., increased fMRI BOLD signal-change) was observed among heterosexual males viewing pictures of attractive women.[26]

Maternal behavior[edit]

An fMRI study conducted in 2005 found that when mother rats were in the presence of their pups the regions of the brain involved in reinforcement, including the nucleus accumbens, were highly active.[27] Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.[28] When human mothers are presented pictures of their children, fMRIs show an increased brain activity in the nucleus accumbens and other reinforcing brain regions and a decrease in activity in areas of the brain involved with negative emotions.[citation needed]

Deep brain stimulation[edit]

In April 2007, two research teams reported on having inserted electrodes into the nucleus accumbens in order to use deep brain stimulation to treat severe depression.[29] In 2010 experiments reported that deep brain stimulation of the nucleus accumbens was successful in decreasing depression symptoms in 50% of patients who did not respond to other treatments such as electroconvulsive therapy.[30] Nucleus accumbens has also been used as a target to treat small groups of patients with therapy-refractory obsessive-compulsive disorder.[31]

Placebo effect[edit]

One research team found a correlation between the activation of the NAcc and the anticipation of effectiveness of a placebo, indicating a central role of the nucleus accumbens in the placebo effect.[32]

Additional images[edit]

References[edit]

  1. ^ a b Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print.
  2. ^ Nucleus Accumbens
  3. ^ Schwienbacher I, Fendt M, Richardson R, Schnitzler HU (2004). "Temporary inactivation of the nucleus accumbens disrupts acquisition and expression of fear-potentiated startle in rats". Brain Res. 1027 (1–2): 87–93. doi:10.1016/j.brainres.2004.08.037. PMID 15494160. 
  4. ^ The Placebo Effect in the NAC
  5. ^ Dopamine Involved In Aggression - Medical News Today
  6. ^ Basar, Koray, Thibaut Sesia, Henk Groenewegen, Harry W.M. Steinbusch, Veerle Visser-Vandewalle, and Yasin Temel. (2010) "Nucleus Accumbens and Impulsivity." Progress in Neurobiology 92.4 533-57.
  7. ^ Shirayama, Yukihiko, and Shigeyuki Chaki. "Neurochemistry of the Nucleus Accumbens and Its Relevance to Depression and Antidepressant Action in Rodents." Current Neuropharmocology 4.4 (2006): 277-91. Bentham Science Publishers Ltd. Web. 16 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475798/>.
  8. ^ Meredith, G. E., C. M. Pennartz, and H. J. Groenewegen. "The Cellular Framework for Chemical Signalling in the Nucleus Accumbens." Progress in Brain Research 99 (1993): 3-24. Web. 16 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7906426>.
  9. ^ Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. "ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states." 
  10. ^ Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". J. Psychoactive Drugs 44 (1): 38–55. PMC 4040958. PMID 22641964. 
  11. ^ O'Donnell, P., Goto, Y. (2001). "Synchronous activity in the hippocampus and nucleus accumbens in vivo". J. Neurosci. 21 (4): RC131. PMID 11160416. 
  12. ^ a b c d Shirayama, Y; Chaki, S (2006). "Neurochemistry of the Nucleus Accumbens and its Relevance to Depression and Antidepressant Action in Rodents". Current Neuropharmacology 4 (4): 277–291. doi:10.2174/157015906778520773. PMC 2475798. PMID 18654637. 
  13. ^ Meredith, GE; Agolia, R; Arts, MP; Groenewegen, HJ; Zahm, DS (1992). "Morphological differences between projection neurons of the core and shell in the nucleus accumbens of the rat". Neuroscience 50 (1): 149–62. doi:10.1016/0306-4522(92)90389-j. PMID 1383869. 
  14. ^ Meredith, GE; Pennartz, CM; Groenewegen, HJ (1993). "The cellular framework for chemical signalling in the nucleus accumbens". Progress in brain research 99: 3–24. doi:10.1016/s0079-6123(08)61335-7. PMID 7906426. 
  15. ^ Pontieri, FE; Tanda, G; Di Chiara, G (1995). "Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens". Proceedings of the National Academy of Sciences of the United States of America 92 (26): 12304–12308. doi:10.1073/pnas.92.26.12304. PMC 40345. PMID 8618890. 
  16. ^ Di Chiara, G (2002). "Nucleus accumbens shell and core dopamine: Differential role in behavior and addiction". Behavioural Brain Research 137 (1–2): 75–114. doi:10.1016/s0166-4328(02)00286-3. PMID 12445717. 
  17. ^ Barrot, M; Marinelli, M; Abrous, DN; Rougé-Pont, F; Le Moal, M; Piazza, PV (2000). "The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent". The European Journal of Neuroscience 12 (3): 973–9. doi:10.1046/j.1460-9568.2000.00996.x. PMID 10762327. 
  18. ^ Akiyama, G; Ikeda, H; Matsuzaki, S; Sato, M; Moribe, S; Koshikawa, N; Cools, AR (2004). "GABAA and GABAB receptors in the nucleus accumbens shell differentially modulate dopamine and acetylcholine receptor-mediated turning behaviour". Neuropharmacology 46 (8): 1082–8. doi:10.1016/j.neuropharm.2004.02.007. PMID 15111014. 
  19. ^ a b Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print
  20. ^ Wu HM, Wang XL, Chang CW, Li N, Gao L, Geng N, Ma JH, Zhao W, Gao GD. (2010). Preliminary findings in ablating the nucleus accumbens using stereotactic surgery for alleviating psychological dependence on alcohol. Neurosci Lett. 473: 77–81 doi:10.1016/j.neulet.2010.02.019 PMID 20156524
  21. ^ Costa, VD, Lang, PJ, Sabatinelli, D, Bradley MM, and Versace, F (2010). "Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitry". Human Brain Mapping 31 (9): 1446–1457. doi:10.1002/hbm.20948. PMID 20127869. 
  22. ^ Sabatinelli, D, Lang, PJ, Bradley, MM, Costa, VD, and Versace, F (2007). "Pleasure rather than salience activates human nucleus accumbens and medial prefrontal cortex". Journal of Neurophysiology 98 (9): 1374–1379. doi:10.1152/jn.00230.2007. PMID 17596422. 
  23. ^ Menon, Vinod & Levitin, Daniel J. (2005) The rewards of music listening: Response and physiological connectivity of themesolimbic system." NeuroImage 28(1), pp. 175-184
  24. ^ Olds J, Milner P (1954). "Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain". J Comp Physiol Psychol 47 (6): 419–27. doi:10.1037/h0058775. PMID 13233369.  article
  25. ^ Nakahara, D., Ozaki, N., Miura, Y., Miura, H., et al. Increased dopamine and serotonin metabolism in rat nucleus accumbens produced by intracranial sel-stimulation of medial forebrain bundle as measured by in vivo microdialysis. Brain Research', 1989 495: 178-181.
  26. ^ Aharon, L., Etcoff, N., Ariely, D., CHabris, C. F., et al. Beautiful faces have variable reward value: fMRI and behavioral evidence. Neuron 2001, 32, 357-551.
  27. ^ Ferris, C.F., Kulkarni, P., Sullivan, J.M., Harder, J.A., et al. Pup sucking is more rewarding than cocaine: Evidence from functional magnetic resonance imaging and three-dimensional computational analysis. Journal of Neuroscience', 2005 25: 149-156.
  28. ^ Numan, M. Motivational systems and the neural circuitry of maternal behavior in the rat. Developmental Psychobiology', 2007 49: 12-21.
  29. ^ Brain Electrodes Help Treat Depression, Technology Review, 26 April 2007
  30. ^ Bewernick, B. H., Hurlemann, R., Matusch, A., et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anciety in treatment-resistant depression. Biological Psychiatry', 2009 67: 110-116.
  31. ^ Ooms P, Mantione M, Figee M, Schuurman PR, van den Munckhof P, Denys D. Deep brain stimulation for obsessive-compulsive disorders: long-term analysis of quality of life. J Neurol Neurosurg Psychiatry. 2014;85(2):153-8.
  32. ^ http://www.eurekalert.org/pub_releases/2007-07/cp-brc071607.php Brain region central to placebo effect identified

External links[edit]