User:Seppi333/sandbox2

Need to wait for further research on subregion+subtype-specific cognitive functions to be published before finishing this table and adding it to nucleus accumbens.

class="wikitable" |+ Cognitive functions associated with {{abbr|NAcc|nucleus accumbens}} subregions and {{abbr|MSN|medium spiny neuron}} subtypes ! rowspan="1" colspan="1" | ! style="text-align: center;" | D1-type medium spiny neurons ! style="text-align: center;" | D2-type medium spiny neurons ! style="text-align: center;" | Mixed-type medium spiny neurons ! style="text-align: center;" | Subtype specificity not established
style="text-align: center;" | NAcc shell | Incentive salience{{#tag:ref|Incentive salience and aversive salience are forms of motivational salience that are associated with reward and aversion, respectively.{{cite book|author1=Koob GF, Moal ML|title=Neurobiology of Addiction|date=2006|publisher=Elsevier/Academic Press|location=Amsterdam|isbn=9780080497372|page=415|url=https://books.google.com/books?id=Sjn6I6QMxdwC&q=aversive+salience&pg=PA415}} Incentive salience manifests as both the desire and motivation to obtain a particular rewarding stimulus. Aversive salience manifests as both the desire and motivation to avoid a particular unpleasant stimulus.|name="motivational salience"|group="note"}} | Aversive salience | | Medial shell: pleasure (hedonic liking) Caudal shell: displeasure (pain/disgust)
style="text-align: center;" | NAcc core | Reward-related associative learning{{cite journal | vauthors = Calipari ES, Bagot RC, Purushothaman I, Davidson TJ, Yorgason JT, Peña CJ, Walker DM, Pirpinias ST, Guise KG, Ramakrishnan C, Deisseroth K, Nestler EJ | title = In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 113 | issue = 10 | pages = 2726–2731 | date = March 2016 | pmid = 26831103 | pmc = 4791010 | doi = 10.1073/pnas.1521238113 | quote = Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. ... Studies using in vivo pharmacological approaches have demonstrated differential roles of NAc D1 and D2 receptors in drug conditioning by use of selective receptor agonists or antagonists, further supporting a role for both dopamine and D1 and D2 MSN subtypes in associative learning (27). Whereas this work has focused on the VTA-to-NAc dopamine circuit, tracking postsynaptic responses in NAc MSNs is particularly important because they integrate information not only from VTA dopamine neurons but also from numerous glutamatergic projections (28, 29). From a network perspective, D1 and D2 MSNs receive inputs from several regions known to encode and store information about context or context–drug associations such as the prefrontal cortex, basolateral amygdala, and hippocampus (30). ... Our data highlight the important role played by D1 MSNs in NAc core in establishing context–reward associations and in controlling the strength of these associations after cocaine exposure. ... Here we show that regulation of associative learning, and its dysregulation by cocaine, is driven primarily through alterations in D1 MSNs in NAc core, which both impair the extinction of previously learned associations and enhance reinstatement following abstinence.}}{{cite journal | vauthors = Baliki MN, Mansour A, Baria AT, Huang L, Berger SE, Fields HL, Apkarian AV | title = Parceling human accumbens into putative core and shell dissociates encoding of values for reward and pain | journal = J. Neurosci. | volume = 33 | issue = 41 | pages = 16383–16393 | date = October 2013 | pmid = 24107968 | pmc = 3792469 | doi = 10.1523/JNEUROSCI.1731-13.2013 | quote = Recent evidence indicates that inactivation of D2 receptors, in the indirect striatopallidal pathway in rodents, is necessary for both acquisition and expression of aversive behavior, and direct pathway D1 receptor activation controls reward-based learning (Hikida et al., 2010; Hikida et al., 2013). It seems we can conclude that direct and indirect pathways of the NAc, via D1 and D2 receptors, subserve distinct anticipation and valuation roles in the shell and core of NAc, which is consistent with observations regarding spatial segregation and diversity of responses of midbrain dopaminergic neurons for rewarding and aversive conditions, some encoding motivational value, others motivational salience, each connected with distinct brain networks and having distinct roles in motivational control (Bromberg-Martin et al., 2010; Cohen et al., 2012; Lammel et al., 2013). ... Thus, the previous results, coupled with the current observations, imply that the NAc pshell response reflects a prediction/anticipation or salience signal, and the NAc pcore response is a valuation response (reward predictive signal) that signals the negative reinforcement value of cessation of pain (i.e., anticipated analgesia).}} | Aversion-related associative learning | N/A | Motor program learning Reward prediction error

{{cot|Bulleted list of refs that are already used in the article|bg=white}}

• {{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 147–148, 367, 376 | edition = 2nd | quote= VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. 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). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
  The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
  The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.}}
• {{cite journal | vauthors = Saddoris MP, Cacciapaglia F, Wightman RM, Carelli RM | title = Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation | journal = J. Neurosci. | volume = 35 | issue = 33 | pages = 11572–82 | date = August 2015 | pmid = 26290234 | pmc = 4540796 | doi = 10.1523/JNEUROSCI.2344-15.2015 | quote = Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). }}
• {{cite journal | vauthors = Berridge KC, Kringelbach ML | title = Pleasure systems in the brain | journal = Neuron | volume = 86 | issue = 3 | pages = 646–664 | date = May 2015 | pmid = 25950633 | doi = 10.1016/j.neuron.2015.02.018 | quote = | pmc=4425246}}
• {{cite journal | vauthors = Richard JM, Castro DC, Difeliceantonio AG, Robinson MJ, Berridge KC | title = Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley | journal = Neurosci. Biobehav. Rev. | volume = 37 | issue = 9 Pt A | pages = 1919–1931 | date = November 2013 | pmid = 23261404| pmc = 3706488 | doi = 10.1016/j.neubiorev.2012.12.008 | quote =
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706488/figure/F3/ Figure 3: Neural circuits underlying motivated 'wanting' and hedonic 'liking'.] }}

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• Complete set of brain structures that constitute the addiction system (need to determine neural pathways + primary pathway neurotransmitters that connect these structures):
• "[http://www.sciencedirect.com/science/article/pii/S0149763414002632 Studies have shown that cravings are underpinned by activation of the reward and motivation circuits (McBride et al., 2006, Wang et al., 2007, Wing et al., 2012, Goldman et al., 2013, Jansen et al., 2013 and Volkow et al., 2013). According to these authors, the main neural structures involved are: the nucleus accumbens, dorsal striatum, orbitofrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), amygdala, hippocampus and insula.]" - quote from linked review
• Medial PFC ←→ Basolateral amygdala - bidirectional glutamatergic projections (http://www.jneurosci.org/content/25/32/7429.full) [pathway impaired by stims]
• Basolateral amygdala → Medial PFC - minor GABAergic interneuron projection (http://www.jneurosci.org/content/25/32/7429.full) [pathway impaired by stims]
• Basolateral amygdala → Central medial amygdala - glutamatergic projection (http://www.jneurosci.org/content/25/32/7429.full)
• Large series of these connections listed in this figure caption (+in the paper): http://perspectivesinmedicine.cshlp.org/content/2/10/a011957/F1.expansion.html

:[http://www.ncbi.nlm.nih.gov/pubmed/25446562 ∆FosB: A transcriptional regulator of stress and antidepressant responses]

:[http://www.ncbi.nlm.nih.gov/pubmed/24240473 Fluoxetine epigenetically alters the CaMKIIα promoter in nucleus accumbens to regulate ΔFosB binding and antidepressant effects]

Random papers:

:PMID 23085449

:PMID 22484409

:PMID 22013150

:PMID 23576888

:PMID 24354721

:PMID 24382886

• {{cite journal | vauthors = Haile CN, Kosten TR, Kosten TA | title = Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine | journal = Am J Drug Alcohol Abuse | volume = 35 | issue = 3 | pages = 161–77 | year = 2009 | pmid = 19462300 | pmc = 2754046 | doi = 10.1080/00952990902825447 | quote = Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment. }}
• {{cite journal | vauthors = Berwid OG, Halperin JM | title = Emerging support for a role of exercise in attention-deficit/hyperactivity disorder intervention planning | journal = Curr Psychiatry Rep | volume = 14 | issue = 5 | pages = 543–51 | year = 2012 | pmid = 22895892 | pmc = 3724411 | doi = 10.1007/s11920-012-0297-4 | url = }}
• [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC58680/figure/F1/] DeltaFosB Isoforms induction graph

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