Nucleus accumbens

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Nucleus accumbens
Gray727-Brodman.png
Medial surface, person facing to the left. Nucleus accumbens is very roughly in Brodmann area 34
Details
Latin nucleus accumbens septi
Part of Mesolimbic pathway
Basal ganglia (Ventral striatum)
Components Nucleus accumbens shell
Nucleus accumbens core
Identifiers
Acronym(s) NAc or NAcc
MeSH A08.186.211.730.885.105.683
NeuroNames hier-259
NeuroLex ID Nucleus accumbens
Dorlands
/Elsevier		 n_11/12580142
TA Lua error in Module:Wikidata at line 744: attempt to index field 'wikibase' (a nil value).
TH {{#property:P1694}}
TE {{#property:P1693}}
FMA {{#property:P1402}}
Anatomical terms of neuroanatomy
[[[d:Lua error in Module:Wikidata at line 863: attempt to index field 'wikibase' (a nil value).|edit on Wikidata]]]

The nucleus accumbens (NAc or 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, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Different NAcc subregions (core vs shell) and neuron subpopulations within each region (D1-type vs D2-type medium spiny neurons) are responsible for different cognitive functions.[3][4] As a whole, the nucleus accumbens has a significant role in the cognitive processing of aversion, motivation, pleasure, reward and reinforcement learning;[5][6][7] hence, it has a significant role in addiction.[6][7] It plays a lesser role in processing fear (a form of aversion), impulsivity, and the placebo effect.[8][9][10] It is involved in the encoding of new motor programs as well.[6]

Structure

The nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core.[6]

Input

Major inputs to the nucleus accumbens include the prefrontal cortex, 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, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).[11][12]

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.[13]

The nucleus accumbens is one of the few regions that receive histaminergic projections from the tuberomammillary nucleus (the sole source of histamine neurons in the brain).[14]

Output

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 tail of the ventral tegmental area,[15] substantia nigra, and the reticular formation of the pons.[1]

Shell

The nucleus accumbens shell is a substructure of the nucleus accumbens. The shell and core together form the entire nucleus accumbens.

Location: The shell is the outer region of the nucleus accumbens, and – unlike the core – is considered to be part of the extended amygdala, located at its rostral pole.

Cell types: Neurons in the nucleus accumbens are mostly medium spiny neurons containing mainly D1-type (i.e., DRD1 and DRD5) or D2-type (i.e., DRD2, DRD3, and DRD4) dopamine receptors. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA.[16][17][18] Mixed type NAcc MSNs with both D1-type and D2-type receptors are mostly confined in the NAcc shell.[16] 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.[19][20][21]

Function: The shell of the nucleus accumbens is involved in the cognitive processing of motivational salience (wanting) as well as reward perception and positive reinforcement effects.[6] Particularly important are the effects of drug and naturally rewarding stimuli on the NAc shell because these effects are related to addiction.[6] Addictive drugs have a larger effect on dopamine release in the shell than in the core.[6] The specific subset of ventral tegmental area projection neurons that synapse onto the D1-type medium spiny neurons in the shell are responsible for the immediate perception of the rewarding property of a stimulus (e.g., drug reward).[3][4]

Core

The nucleus accumbens core is the inner substructure of the nucleus accumbens.

Location: The nucleus accumbens core is part of the ventral striatum, located within the basal ganglia.

Cell types: The core of the NAcc is made up mainly of medium spiny neurons containing mainly D1-type or D2-type dopamine receptors. The neurons in the core, as compared to the neurons in the shell, 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.[19][21]

Function: The nucleus accumbens core is involved in the cognitive processing of motor function related to reward and reinforcement.[6] Specifically, the core encodes new motor programs which facilitate the acquisition of a given reward in the future.[6]

Cell types

Approximately 95% of neurons in the NAcc are GABAergic medium spiny neurons (MSNs) which primarily express either D1-type or D2-type receptors;[11] about 1–2% of the remaining neuronal types are large aspiny cholinergic interneurons and another 1–2% are GABAergic interneurons.[11] Compared to the GABAergic MSNs 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.[19][21] These neurons are also the main projection or output neurons of the nucleus accumbens.

Neurotransmitters

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 increases 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.[22] 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.[19][23]

Phenethylamine and tyramine: Phenethylamine and tyramine are trace amine compounds which are synthesized in several types of CNS neurons, including all dopamine neurons.[24] Specifically, these neurotransmitters act within the dopaminergic inputs to the NAcc. These substances regulate the presynaptic release of dopamine through their interactions with VMAT2 and TAAR1, analogous to amphetamine.

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.[25]

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.[19][26]

Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.[27] Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.[28]

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.

Function

Reward and reinforcement

The nucleus accumbens, being one part of the reward system, plays an important role in processing rewarding stimuli, reinforcing stimuli (e.g., food and water), and those which are both rewarding and reinforcing (addictive drugs, sex, and exercise).[6][29] The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.[30][31] A 2005 study found that it is involved in the regulation of emotions induced by music,[32] 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.[33] 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.[34] 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.[35]

Maternal behavior

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.[36] Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.[37] When women are presented pictures of unrelated infants, fMRIs show increased brain activity in the nucleus accumbens and adjacent caudate nucleus, proportionate to the degree to which the women find these infants "cute".[38]

Clinical significance

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See also: Neurobiological effects of physical exercise § Long-term effects

Addiction

Current models of addiction from chronic drug use involve alterations in gene expression in the mesocorticolimbic projection.[11][39][40] The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB).[11] ΔFosB is the most significant gene transcription factor in addiction since its viral or genetic overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction;[11] it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, opiates, and substituted amphetamines.[11][39][41] ΔJunD is the transcription factor which directly opposes ΔFosB.[11] Increases in nucleus accumbens ΔJunD expression can reduce or, with a large increase, even block most of the neural alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[11]

ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[11][12] Natural rewards, like drugs of abuse, induce ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression.[11][12][29] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards as well;[11][12][29] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[12] Research on the interaction between natural and drug rewards suggests that psychostimulants and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess cross-sensitization effects that are mediated through ΔFosB.[29][42]

Summary of addiction-related plasticity
Form of neural or behavioral plasticity Type of reinforcer Sources
Opiates Psychostimulants High fat or sugar food Sexual intercourse Physical exercise
(aerobic)		 Environmental
enrichment
ΔFosB expression in
nucleus accumbens D1-type MSNs		 ↑ ↑ ↑ ↑ ↑ ↑ [29]
Behavioral plasticity
Escalation of intake Yes Yes Yes [29]
Psychostimulant
cross-sensitization		 Yes Not applicable Yes Yes Attenuated Attenuated [29]
Psychostimulant
self-administration		 ↑ ↑ ↓ ↓ ↓ [29]
Psychostimulant
conditioned place preference		 ↑ ↑ ↓ ↑ ↓ ↑ [29]
Reinstatement of drug-seeking behavior ↑ ↑ ↓ ↓ [29]
Neurochemical plasticity
CREB phosphorylation
in the nucleus accumbens		 ↓ ↓ ↓ ↓ ↓ [29]
Sensitized dopamine response
in the nucleus accumbens		 No Yes No Yes [29]
Altered striatal dopamine signaling ↓DRD2, ↑DRD3 ↑DRD1, ↓DRD2, ↑DRD3 ↑DRD1, ↓DRD2, ↑DRD3 ↑DRD2 ↑DRD2 [29]
Altered striatal opioid signaling ↑μ-opioid receptors ↑μ-opioid receptors
↑κ-opioid receptors		 ↑μ-opioid receptors ↑μ-opioid receptors No change No change [29]
Changes in striatal opioid peptides ↑dynorphin ↑dynorphin ↓enkephalin ↑dynorphin ↑dynorphin [29]
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens ↓ ↑ ↑ [29]
Dendritic spine density in
the nucleus accumbens		 ↓ ↑ ↑ [29]

Depression

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.[43] 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.[44] Nucleus accumbens has also been used as a target to treat small groups of patients with therapy-refractory obsessive-compulsive disorder.[45]

Ablation

To treat addiction and in an attempt to treat mental illness radiofrequency ablation of the nucleus accumbens has been performed. The results are inconclusive and controversial.[46][47]

Placebo effect

Activation of the NAcc has been shown to occur in the anticipation of effectiveness of a drug when a user is given a placebo, indicating a contributing role of the nucleus accumbens in the placebo effect.[9][48]

Additional images

  • Dopamine and serotonin

  • MRI coronal slice showing nucleus accumbens outlined in red

  • Sagittal MRI slice with highlighting (red) indicating the nucleus accumbens.

See also

References

  1. ↑ 1.0 1.1 Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print.[page needed]
  2. ↑ Nucleus Accumbens
  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ 7.0 7.1 Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ 16.0 16.1 Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ 21.0 21.1 21.2 Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ 29.00 29.01 29.02 29.03 29.04 29.05 29.06 29.07 29.08 29.09 29.10 29.11 29.12 29.13 29.14 29.15 29.16 Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  34. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  35. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  36. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  37. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  38. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  39. ↑ 39.0 39.1 Lua error in package.lua at line 80: module 'strict' not found.
  40. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  41. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  42. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  43. ↑ Brain Electrodes Help Treat Depression, Technology Review, 26 April 2007
  44. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  45. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  46. ↑ "Controversial Surgery for Addiction Burns Away Brain’s Pleasure Center" Author Maia Szalavitz. Dec. 13, 2012
  47. ↑ "China Bans Irreversible Brain Procedure" Author Zamiska Nicholas. April 28, 2008. The Wall Street Journal
  48. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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