獎勵偏差條件下動態神經與行為反應的可塑性大腦皮質-紋狀體線路機制

A PLASTIC CORTICO-STRIATAL CIRCUIT MECHANISM FOR DYNAMIC NEURONAL AND BEHAVIORAL RESPONSES UNDER THE BIASED REWARD CONDITION

黃冠倫(Kuan-Lun Huang)

指導教授 ： 羅中泉

國立清華大學/生命科學院/系統神經科學研究所/碩士(2010年)

摘要

獎勵訊息會透過多巴胺的調控突觸可塑性進而影響行為與神經活性，近期的哺乳類實驗: 獎勵偏差之快速眼動測驗，實驗中證明當眼動方向可以獲得獎勵，其尾核神經活性會比較高、反應時間比較快相較於眼動方向不會獲得獎勵的測驗。而此現象的機制被提出: 在多巴胺分泌下，當前突觸與後突觸同時被活化，則神經連結強度將被增強：反之如果沒有多巴胺的作用下，則神經連結強度將減弱。然而，這個假說是否真能造成觀測到的行為與神經變化，至今尚未被檢驗過。為了回答這個問題，我們建了一個神經網路模型，其中包含接受視覺訊號的大腦皮質、抑制性調控眼動的基底核、控制眼動的上丘。大腦皮質-紋狀體線路為多巴胺主要影響區域，經由動態改變突觸可塑性，我們發現之前所提出的機制並不足夠，需要更多神經反應才能再現出實驗結果。從過去的實驗數據當中，我們以最新在齧齒動物腦切片中的紋狀體量得的STDP為基礎，在模型中加入STDP。利用我們的神經網路模型，我們提出了數個可能的動態突觸可塑性改變的可能性，其皆能模擬重現出實驗結果，相信有助於實驗學家設計實驗探索真正的突觸可塑性機制。

關鍵字

多巴胺 ； 突觸可塑性 ； 快速眼動

並列摘要

Behavioral and neuronal activity can be influenced by reward information through dopamine-modulated synaptic plasticity. Recent primate experiments (Lauereyns, Watanabe, Hikosaka 2002) using biased saccade task (BST) have demonstrated that the activity of caudate nucleus (CD) neurons are stronger and the behavioral responses are faster when the target of a saccadic eye movement indicates a reward than when it does not. It has been suggested that the observation can be explained by the following mechanism: The co-activation of the pre- and post synaptic neurons facilitates the synapses when dopamine is presented, but depresses the synapses when dopamine is absent (Hikosaka 2007; Hikosaka, Nakamura 2005). However, whether the proposed mechanism is sufficient to produce the observed behavioral and neuronal changes has not been tested. To address this problem, we built a spiking neural circuit model (Lo & Wang 2006) which includes a cortical module (Cx) that processes the visual stimulus, a basal ganglia module that employs the inhibitory control over eye movements and a superior colliculus module that drives the eye movements. By implementing the dopamine-induced plasticity in the cortico-striatal synapses, a pathway that has been shown to be a major target of dopaminergic neurons, we found that the previously proposed mechanism is not likely to be sufficient and additional neuronal interactions are needed for reproducing the observations. To address this issue, we propose a spick-timing dependent plasticity (STDP) mechanism based on the latest observations of STDP in the brain slices of rodent striatum. The proposed mechanism is able to reproduce the observations. We further explored the neural circuit model with several possible scenarios of synaptic dynamics and proposed experiments that might help to identify the detailed mechanism underlying the observed neuronal and behavioral changes in the biased reward condition.

並列關鍵字

dopamine ； synaptic plasticity ； saccadic eye movement

參考文獻

Calabresi P, Centonze D, Gubellini P, Pisani A, Bernardi G. Blockade of M2-like muscarinic receptors enhances long-term potentiation at corticostriatal synapses. Eur J Neurosci 10:3020–3023 (1998)

Calabresi P, Maj R, Pisani A, Mercuri NB, and Bernardi G. Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci 12: 4224–4233 (1992)

Centonze D, Picconi B, Gubellini P, Bernardi G, Calabresi P. Dopaminergic control of synaptic plasticity in the dorsal striatum. Eur J Neurosci 13:1071–1077 (2001)

Charpier S and Deniau JM. In vivo activity-dependent plasticity at corticostriatal connections: evidence for physiological long-term potentiation. Proc Natl Acad Sci USA 94: 7036–7040 (1997)

Christopher D. Fiorillo, Philippe N. Tobler, Wolfram Schultz. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 299 (2003)