중림동 경로

Mesolimbic pathway
"Return center"는 여기서 리다이렉트 됩니다.이 경로를 포함하는 보상 제도에 대해서는 보상 제도를 참조하십시오.

때때로 보상 경로라고 불리는 중림부 경로는 뇌의 [1]도파민 작동 경로입니다.이 경로는 중뇌의 복측 피개 부위를 전뇌의 기저 신경절의 복측 선조체와 연결합니다.복부 선조체는 핵과 후각결절을 [2]포함한다.

중림부 경로에서 핵으로 도파민의 방출은 인센티브 염증(예: 자극에 대한 동기 부여와 욕구)을 조절하고 강화 및 보상 관련 운동 기능 [3][4][5]학습을 촉진한다. 또한 [3][5]쾌락의 주관적 인식에 역할을 할 수 있다.중림부 경로와 핵의 분비 뉴런의 조절 장애는 [1][6][7][8]중독의 발달과 유지에 중요한 역할을 한다.

해부학

다른 도파민 작용 경로와 관련된 중수모충 경로 및 그 위치

중임동 경로는 복부 피개(VTA)에서 복부 선조체(NACC)로 돌출하는 도파민 작동성(즉, 도파민 방출) 뉴런의 집합이며, 이는 핵 외벽(NACC)과 [9]후각결절을 포함한다.그것은 뇌 자극 [10]보상을 중재하는 신경 경로 세트인 내측 전뇌 다발의 구성 경로 중 하나입니다.

VTA는 중뇌에 위치하며 도파민 작동성,[11] GABAergic, 그리고 글루탐산성 뉴런으로 구성되어 있습니다.이 영역의 도파민 작동성 뉴런은 전전두피질과 같은 다른 영역의 글루탐산성 뉴런뿐만 아니라 페둔쿨로폰틴 핵과 측두엽 피질의 콜린 작동성 뉴런으로부터 자극을 받는다.핵과 후각결절은 복부 선조체에 위치하고 있으며 주로 중간 가시가 [9][12][13]있는 뉴런으로 구성되어 있습니다.핵 어컴벤스는 NAcc 쉘과 NAcc [11]코어로 알려진 변연계 및 운동 서브영역으로 세분됩니다.핵의 중간 가시가 있는 뉴런은 VTA의 도파민 작동성 뉴런과 해마, 편도체, 그리고 내측 전전두피질의 글루탐산 뉴런으로부터 입력을 받습니다.이러한 입력에 의해 활성화될 때, 중간 가시가 있는 뉴런의 돌기는 복측 팔리덤에 [11]GABA를 방출합니다.

기능.

중임계 경로는 다른 인지 [14][15][16]과정들 중에서 동기 부여, 강화 학습, 그리고 두려움을 조절합니다.

중림부 경로는 동기인식에 관여한다.이 경로의 도파민 고갈 또는 원산지의 병변은 동물이 보상을 받기 위해 기꺼이 가는 정도를 감소시킨다(예를 들어, 쥐의 니코틴 정맥 분만을 위한 레버 누름 횟수 또는 먹이를 찾는데 소요되는 시간).도파민제 또한 보상을 받기 위해 동물이 기꺼이 가는 정도를 증가시킬 수 있다.게다가, 중림부 경로에서 뉴런의 발화 속도는 보상을 기대하는 동안 증가하며,[17] 이것은 갈망을 설명할 수 있다.중림부 도파민 방출은 한때 쾌락의 일차적 매개자로 생각되었지만, 지금은 쾌락 [18][19]지각에서 사소한 혹은 이차적인 역할만 하는 것으로 여겨진다.

임상적 의의

중독 메커니즘

중림부 경로와 경로의 출력 뉴런의 특정 세트(예: 핵 어컴벤스 내의 D1형 중간 가시 뉴런)는 [6][7][8]중독의 신경생물학에서 중심적인 역할을 한다.약물 중독은 습관적인 약물 복용으로 인해 뇌의 [20]회로에 화학적인 변화가 일어나게 되는 질병이다.코카인, 알코올, 니코틴과 같은 일반적인 중독성 물질은 중림부 경로 내, 우선적으로 핵 내 도파민 수치를 증가시키는 것으로 나타났습니다.이 약들이 그렇게 하는 메커니즘은 약의 프로토타입에 따라 다르다.예를 들어 코카인은 시냅스 전 도파민 수송체를 차단함으로써 시냅스 도파민의 재섭취를 막는다.또 다른 자극제인 암페타민은 도파민 운반체를 역전시켜 시냅스 소포에서 도파민 방출을 유도한다.비자극성 약물은 전형적으로 리간드 게이트 채널 또는 G 단백질 결합 수용체와 결합한다.이러한 약물에는 알코올, 니코틴, 테트라히드로카나비놀(THC)[21] 등이 포함된다.

이러한 중림부 경로의 도파민 작동 활성화는 보상에 대한 인식을 동반한다.이 자극-보상의 연관성은 멸종에 대한 저항을 보여주고 그것을 [22]야기한 것과 같은 행동을 반복할 동기를 증가시킨다.

이와 관련하여, 2017년 연구에 따르면 학대(감정적, 신체적, 성적)와 부정적인 삶의 사건들은 코카인에 대한 변연계 반응의 증가와 관련이 있는 것으로 나타났다.다시 말해, 이전에 학대를 당한 사람들은 코카인이나 약물 [23]사용을 위해 준비된 뇌 경로를 가지고 있을 가능성이 더 높았다.

신경학적 및 심리학적 장애와의 관계

중림부 경로는 정신분열증, 우울증,[24][25][26][27][28] 파킨슨병과 관련이 있다.그것은 단순히 앉아서 생활하는 [29]생활방식의 결과일 수도 있지만 디지털 미디어의 남용과 관련이 있는 것으로 이론화된다.각각은 중림부 [24]경로 내에서 뚜렷한 구조적 변화를 수반한다.

기타 도파민 경로

주요 기사:도파민 작용 경로

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레퍼런스

  1. ^ a b Dreyer JL (2010). "New insights into the roles of microRNAs in drug addiction and neuroplasticity". Genome Med. 2 (12): 92. doi:10.1186/gm213. PMC 3025434. PMID 21205279.
  2. ^ Ikemoto S (2010). "Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory". Neurosci Biobehav Rev. 35 (2): 129–50. doi:10.1016/j.neubiorev.2010.02.001. PMC 2894302. PMID 20149820. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures–the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. ... In the 1970s it was recognized that the olfactory tubercle contains a striatal component, which is filled with GABAergic medium spiny neurons receiving glutamatergic inputs form cortical regions and dopaminergic inputs from the VTA and projecting to the ventral pallidum just like the nucleus accumbens
    그림 3: 암페타민의 복부 선조체와 자가 투여
  3. ^ a b Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 147–148, 367, 376. ISBN 978-0-07-148127-4. 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.
  4. ^ 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. 266. ISBN 978-0-07-148127-4. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.
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  6. ^ a b 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.
  7. ^ a b 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". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.
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  19. ^ 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. PMC 3644539. PMID 23375169.
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  23. ^ Regier PS, Monge ZA, Franklin TR, Wetherill RR, Teitelman AM, Jagannathan K 등감정적, 신체적, 성적 학대는 코카인 신호에 대한 높은 변연계 반응과 관련이 있다.중독 생물학2017년 11월 22일 (6) : 1768-177.doi : 10.11/adb.12445
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